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Obesity and Diabetes
Abstract
Obesity is the most significant risk factor for the development of diabetes. Both obesity and diabetes rates have continued to increase in tandem and pose increased mortality for patients and increased health care costs for the community. Weight loss of 5% or more of total body weight renders improvements in glycemic control, decreases in the need for diabetes medications, and improved quality of life. Cotreatment of obesity and diabetes requires a comprehensive medical approach that encompasses intensive lifestyle modification including behavioral changes, nutrition, and physical activity, as well as pharmacotherapy and possible surgical management.
... However, the etiology of T2DM and its connection with obesity is still not clearly defined. It is believed that T2DM results from environmental and lifestyle factors, such as poor diet, reduced physical activity, short or disturbed sleep, smoking, stress, depression, exposure to environmental chemicals [3], and obesity [4,5]. Recently, several studies have indicated that exposure to environmental pollutants may also be involved in the development of insulin resistance and T2DM. ...
... 3T3-L1 cells were seeded on 96-well plates at a density of 5 × 10 3 cells/well (for toxicity tests) or 1 × 10 3 cells/well (for cell proliferation tests). After 24 h of incubation, the medium was replaced with the fresh one, which contained 2% BCS (for toxicity tests) or 10% BCS (for cell proliferation tests) and appropriate concentrations of CPF (5,10,25,50,75,100,150,200, and 250 µM). After 24 h of incubation in the case of the toxicity test, and after 24, 48, or 72 h incubation in the case of proliferation assessment, the medium was discarded and neutral red (NR) solution (40 µg/mL; 100 µL/well) was added and incubated for 3 h at 37 • C in a humidified atmosphere of 95% air and 5% CO 2 . ...
Organophosphorus pesticides (OPs) are important factors in the etiology of many diseases, including obesity and type 2 diabetes mellitus. The aim of this study was to investigate the effect of a representative of OPs, chlorpyrifos (CPF), on viability, proliferation, differentiation, and fatty acid uptake in 3T3-L1 cells. The effect of CPF exposure on preadipocyte proliferation was examined by the MTT, NR, and BrdU assays. The impact of CPF exposure on the differentiation of preadipocytes into mature adipocytes was evaluated by Oil Red O staining and RT-qPCR. The effect of CPF on free fatty acid uptake in adipocytes was assessed with the fluorescent dye BODIPY. Our experiments demonstrated that exposure to CPF decreased the viability of 3T3-L1 cells; however, it was increased when the cells were exposed to low concentrations of the pesticide. Exposure to CPF inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. CPF exposure resulted in decreased lipid accumulation, accompanied by down-regulation of the two key transcription factors in adipogenesis: C/EBPα and PPARγ. Exposure to CPF increased basal free fatty acid uptake in fully differentiated adipocytes but decreased this uptake when CPF was added during the differentiation process. Increased free fatty acid accumulation in fully differentiated adipocytes may suggest that CPF leads to adipocyte hypertrophy, one of the mechanisms leading to obesity, particularly in adults. It can therefore be concluded that CPF may disturb the activity of preadipocytes and adipocytes, although the role of this pesticide in the development of obesity requires further research.
... Obesity is a metabolic disorder characterized by either an excessive accumulation of body fat (BF) or an improper distribution of BF that is associated with adverse effects [32,48,49]. Obesity can be both a result of and a cause of oxidative stress [50]. ...
... The proinflammatory cytokines TNF-α, IL-1, and IL-6 have been linked to adiposity [68]. TNF-α regulates the inflammatory response, immune system, adipose cell apoptosis, lipid metabolism, hepatic lipogenesis, insulin signaling, and oxidative stress [43,49,69]. Obesity increases serum TNF-α, which induces the release of IL-6 from immune cells and adipocytes and reduces systemic anti-inflammatory cytokines, promoting systemic inflammation [50,70]. ...
Metabolic syndrome is a cluster of conditions associated with the risk of diabetes mellitus type 2 and cardiovascular diseases (CVDs). Metabolic syndrome is closely related to obesity. Increased adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving metabolic syndrome components, namely insulin resistance, hypertension, and hyperlipidemia. An increasing number of studies confirm the importance of oxidative stress and chronic inflammation in the etiology of metabolic syndrome. However, few studies have reviewed the mechanisms underlying the role of oxidative stress in contributing to metabolic syndrome. In this review, we highlight mechanisms by which reactive oxygen species (ROS) increase mitochondrial dysfunction, protein damage, lipid peroxidation, and impair antioxidant function in metabolic syndrome. Biomarkers of oxidative stress can be used in disease diagnosis and evaluation of severity.
... Введение в современных условиях ожирение и часто следующий за ним сахарный диабет (сд) 2 типа (сд2) представляют собой взаимосвязанную неконтролируемую неинфекционную пандемию, охватившую многие страны мира [1]. сд2 (около 90% всех случаев сд) развивается в результате сочетания генетических факторов и факторов окружающей среды, а нездоровое питание и отсутствие физической активности признаются наиболее значимыми факторами риска его развития [2]. ...
... сд2 требует пожизненного лечения, но инвалидизирующие и сокращающие жизнь осложнения наступают, несмотря проводимую терапию [6]. без стратегических сдвигов к эффективным профилактическим действиям на глобальном уровне, согласно прогнозам, распространённость сд у взрослых (20-79 лет) в мире к 2030 г. составит 643, а к 2045 г. -783 миллиона человек 1 . ...
Weight loss and lifestyle changes can reverse the pathophysiological processes underlying type 2 diabetes, including achieving remission of the disease. A search and analysis of 9109 literature sources from the Scopus, Web of Science, PubMed/ MedLine, The CochraneLibrary databases was carried out for the keywords «diabetes remission», «diabetes reversal», «bariatric surgery», «very low-calorie diet», «low carbohydrate diet». The review presents and critically evaluates the current possibilities of achieving remission of type 2 diabetes mellitus with the help of bariatric surgery, medications, very low-calorie and lowcarbohydrate diets, and exercise.
... In this regard, it has been estimated that the patient is responsible for more than 95% of the actions related to disease management. Patients manage their diabetes on a daily basis within the context of the other objectives, priorities, health issues, family demands, and other personal concerns that make up their lives [24,25]. ...
... Thus, obesity appears to be highly prevalent but homogeneously represented in both genders. This result is in line with findings in the literature [25,28,29]. ...
Prevention of diabetes mellitus is mainly based on a healthy lifestyle. The lockdown
measures imposed during the COVID-19 pandemic resulted in major changes in daily life and social behavior, which may have an influence on diabetes self-management and glycemic control. The present work aims to assess the relationship between diabetic patients’ knowledge, attitudes, and behaviors towards proper nutrition and lifestyles in order to plan strategies for educational intervention from a health literacy perspective. Attitudes, behaviors, and knowledge of diabetic patients attending the Diabetes and Metabolic Diseases Department of the Local Health Authority of Sassari (ASL1-SS) were assessed with a cognitive survey conducted from April to July 2022. Three hundred twenty-one questionnaires were administered during the survey period. Fifty-two percent of diabetic patients were female and 48% male, with a mean age of 61.1 ± 18.5 years and 62.0 ± 15.1 years, respectively. The overall level of knowledge about the role of food and proper nutrition with respect to the risk of diabetes and its complications appeared to be generally unsatisfactory and inadequate. Nonetheless, females showed a significantly higher level of knowledge than males (p < 0.0001). Moreover, knowledge was seen to decrease according to the age of the patients (p = 0.035). As for the possible impact played by the COVID-19 pandemic on lifestyles, it should be noted that about 70% of
the respondents stated that they had maintained a reasonable dietary standard or even improved it throughout. Thus, the study underlines the need to improve the knowledge of diabetic subjects about nutrition and, in particular, their self-management, positively influencing behaviors and attitudes.
... However, chronic inflammation could lead to adipocyte accumulation and insulin resistance through inflammatory factors such as TNF-a and CRP, thereby causing changes in body weight and albumin levels (3, 4). In addition, albumin level, obesity is associated with the development of DM and complications (7,8). Thus, relying on a single inflammatory index might not provide sufficient accuracy to estimate the prognosis of patients with DM. ...
Background
Type 2 diabetes mellitus (T2DM) was a major global health threat. As a chronic low-grade inflammatory disease, the prognosis of diabetes was associated with inflammation. The advanced lung cancer inflammation index (ALI) served as a comprehensive index to assess inflammation. This study aimed to estimate the association between ALI and all-cause, cardiovascular disease (CVD), and cancer mortality in T2DM patients.
Methods
We extracted cohort data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2018 for analysis. The weighted Kaplan-Meier analysis and multivariate-adjusted Cox analysis were utilized to evaluate the relationship between ALI and all-cause, CVD, and cancer mortality in T2DM patients. Restricted cubic spline (RCS) analysis was employed to assess their non-linear relationship. Stratified analysis and interaction analysis were conducted to enhance the robustness of the results.
Results
The study incorporated a total of 3,888 patients. An increase in ALI was associated with a reduced risk of all-cause and CVD mortality in T2DM patients, but not related to cancer mortality. There were J-shaped and L-shaped non-linear relationships between ALI and all-cause, CVD mortality in T2DM patients, respectively. The inflection points were 90.20 and 93.06, respectively. For values below the inflection point, every 10U increase in ALI, both all-cause and CVD mortality risk decreased by 9%. Beyond the inflection point, all-cause mortality rose by 3%, while CVD mortality remained unaffected. Gender-stratified RCS analysis indicated a linear negative relationship between CVD mortality and ALI in female T2DM patients, whereas the trend in males aligned with the overall population.
Conclusion
Our research initially identified a significant correlation between increased ALI levels with decreased all-cause and CVD mortality in T2DM patients. There were J-shaped and L-shaped non-linear relationships between ALI and all-cause, CVD mortality in T2DM patients, respectively. For female patients, there was a linear negative relation between CVD mortality and ALI, whereas the trend in males aligned with the overall population. These findings suggested that maintaining ALI (for example, control body weight and keep albumin in the normal range) within a certain range in the clinical settings was crucial for improving all-cause and CVD mortality in T2DM patients.
... Obesity is characterized by expanded adipose tissues and metabolic disorders. It becomes a major risk factor of various diseases even cancers [3,[33][34][35]. Adipose tissue is mainly composed of adipocytes, which are full of triglycerides droplets. ...
Obesity, a worldwide epidemic in recent years, is mainly due to the uncontrolled development of adipose tissues, which includes adipocyte hypertrophy and hyperplasia. Adipocyte differentiation is a process involving multiple transcription factor cascades, and the exact mechanism has not yet been defined. As a bHLH transcription factor, Twist1 exerts its activity by forming homo- or heterodimers with other factors. In this study, we showed Twist1 restricts adipogenesis through PPARγ. Expression of various differentiation markers (including PPARγ and adiponectin) and triglyceride-containing lipid droplets were decreased with overexpression of Twist1. Pathway enrichment analysis of RNA-seq data showed that differentially expressed genes (DEGs) caused by Twist1 overexpression were significantly related to lipolysis and PPARγ signaling. This implicates that Twist1 plays important regulatory roles in these processes. ChIP and dual luciferase assays showed that Twist1 could bind either PPARγ or adiponectin promoter to repress their respective transcription or directly to PPARγ protein to regulate its transcriptional activity. Furthermore, Twist1 directly interacted RXRα, which usually forms heterodimer with PPARγ to regulate adipogenesis. Taken together, our results suggest that Twist1 is an inhibitory modulator of adipogenesis and its function is likely through direct interaction with PPARγ protein or its gene promoter.
... In our study, we observed that diabetic patients had higher weight and BMI. This finding is consistent with other published studies [16,17]. This association can be attributed to the link between obesity and insulin resistance [18]. ...
Patients with chronic obstructive pulmonary disease (COPD) may experience exacerbations. During severe exacerbations, nutritional and endocrinological comorbidities can play an important role in the clinical and functional aspects of these patients. The aim of this study was to analyse the influence of the presence of diabetes mellitus (DM) and nutritional parameters on the deterioration of symptoms and quality of life during a severe exacerbation in patients with COPD. An observational study was conducted on COPD patients admitted due to an exacerbation. The COPD Assessment Test (CAT) questionnaire was administered, and clinical and functional parameters were compared based on the presence of nutritional and endocrinological alterations. A total of 50 patients were included, of whom 30 (60%) were male. The mean age was 70.5 years (standard deviation (SD) 9.6). The median CAT score during exacerbation was 25 (interquartile range (IQR) 17.5–30), and the baseline score was 13.5 (IQR 7–19), which represented a statistically significant difference (p < 0.001). Patients with iron deficiencies had a lower total CAT score (p = 0.041), specifically for items related to daily activity (p = 0.009) and energy (p = 0.007). Diabetic patients exhibited a greater decline in pulmonary function during exacerbation (p = 0.016), while patients with high thyroid-stimulating hormone (TSH) levels had a shorter hospital stay (p = 0.016). For COPD patients admitted due to an exacerbation, the metabolic assessment is useful and relevant in the clinical set-up, as endocrinological comorbidities negatively affect clinical and functional aspects of these patients.
... Over the past few decades, the prevalence of diabetes has risen significantly, representing a burden in worldwide healthcare [36]. Also, obesity remains the main risk factor for the development of diabetes [37]. Surprisingly, bioactive peptides derived from many insects show antidiabetic properties both in vitro and in vivo. ...
Novel foods, including edible insects, are emerging because of their nutritional characteristics and low environmental impacts and could represent a valid alternative source of food in a more sustainable way. Edible insects have been shown to have beneficial effects on human health. Insect-derived bioactive peptides exert antihypertensive, antioxidant, anti-inflammatory, and antimicrobial properties and have protective effects against common metabolic conditions. In this review, the roles of edible insects in human health are reported, and the possible applications of these peptides in clinical practice are discussed. A special mention is given to the role of antimicrobial peptides and their potential applications in controlling infections in orthodontic procedures. In this context, insects’ antimicrobial peptides might represent a potential tool to face the onset of infective endocarditis, with a low chance to develop resistances, and could be manipulated and optimized to replace common antibiotics used in clinical practice so far. Although some safety concerns must be taken into consideration, and the isolation and production of insect-derived proteins are far from easy, edible insects represent an interesting source of peptides, with beneficial effects that may be, in the future, integrated into clinical and orthodontic practice.
... The World Obesity Foundation estimates that by 2030, approximately one billion people worldwide will be living with obesity [4]. The increase in the prevalence, incidence, and morbidity of obesity is directly related to the global rise in diabetes [5]. In 2017, approximately 462 million people were affected by type 2 diabetes, accounting for 6.28% of the world's population (4.4% of those aged 15-49, 15% of those aged 50-69, and 22% of those aged 70 and older). ...
Plant-based therapies are widely utilized for treating diseases in approximately 80% of the global population, including Colombia’s Chocó Department. This study aimed to identify and evaluate plants with significant therapeutic value for obesity and diabetes in Chocó. The inhibitory effects of these plants on pancreatic lipase (PL), α-glucosidase (AG), and α-amylase (AA) were assessed, and the most promising species were selected to isolate and identify bioactive components. Artocarpus altilis, Momordica balsamina, Bauhinia picta, Neurolaena lobata, and Vismia macrophylla emerged as key species based on their traditional usage among the Chocó population. Notably, the extract derived from Vismia macrophylla demonstrated the most encouraging outcomes as a digestive enzyme inhibitor, exhibiting IC50 values of 0.99 ± 0.21 μg/mL, 5.61 ± 0.82 mg/mL, and 28.91 ± 2.10 μg/mL for AG, AA, and PL, respectively. Further chemical analysis led to the isolation of three bioactive compounds: 5′-demethoxycadensin G 1, para-hydroxybenzoic acid methyl ester 2, and para-hydroxybenzoic acid butyl ester 3. Compound 1 displayed the highest activity against AG (IC50 = 164.30 ± 0.11 μM), while compounds 2 (IC50 = 28.50 ± 4.07 μM) and 3 (IC50 = 10.15 ± 3.42 μM) exhibited potent inhibitory effects on PL. Molecular docking and enzymatic kinetics studies indicate that these bioactive compounds primarily act as mixed inhibitors of AG and non-competitive inhibitors of PL. These findings underscore the potential of V. macrophylla and its compounds as effective inhibitors of digestive enzymes associated with obesity and type 2 diabetes.
... 21 Obesity is the most significant risk factor for the onset of diabetes. 22 The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is a predictor of IR in a Chinese population with different glucose tolerance statuses. 23,24 Dyslipidemia is multifactorial and related to poor glycemic control, IR, inflammation, and genetic susceptibility. ...
Objective: The aim of this research was to probe the effect of isobavachalcone inhibiting the high-fat diet (HFD) and streptozotocin (STZ) induced hyperglycemia and hyperlipemia in mice and its underlying mechanisms. Methods: A mouse model with type 2 diabetes mellitus (T2DM) was established by the HFD and low-dose streptozotocin. T2DM mice were treated with 10 mg/kg of isobavachalcone for 4 weeks. The levels of fasting blood glucose (FBG), blood lipids, and relative proteins in the PI3K/AKT signaling pathway as well as the histological structural changes in the liver were determined. Results: The results showed that the expression levels of FBG (42%, P < .001), triglyceride (70%, P < .001), and glucose transporter 2 were significantly reduced by isobavachalcone. The proteinic and mRNA expressions of IRS1, PI3K, and AKT genes of T2DM mice were dramatically increased with the isobavachalcone treatment. Furthermore, isobavachalcone ameliorated the morphology of the liver in T2DM model mice. Conclusion: The results suggested that isobavachalcone controls the development of T2DM as well as the regulatory mechanism involved in glucose and lipid metabolism through the PI3K/AKT signal pathway in the liver.
... Obesity has the capacity to trigger insulin resistance, thereby facilitating the development of diabetes. Additionally, there exists a mutually reinforcing relationship between obesity and diabetes in terms of promoting the differentiation of macrophages into the M1 phenotype [61]. Consequently, it becomes imperative to investigate the therapeutic potential of anti-hyperglycemia and anti-hyperlipidemia medications in the context of wound healing in individuals with diabetes. ...
Macrophages play a crucial role in regulating wound healing, as they undergo a transition from the proinflammatory M1 phenotype to the proliferative M2 phenotype, ultimately contributing to a favorable outcome. However, in hyperglycemic and hyper-reactive oxygen species environments, the polarization of macrophages becomes dysregulated, hindering the transition from the inflammatory to proliferative phase and consequently delaying the wound healing process. Consequently, regulating macrophage polarization is often regarded as a potential target for the treatment of diabetic wounds. The role of macrophages in wound healing and the changes in macrophages in diabetic conditions were discussed in this review. After that, we provide a discussion of recent therapeutic strategies for diabetic wounds that utilize macrophage polarization. Furthermore, this review also provides a comprehensive summary of the efficacious treatment strategies aimed at enhancing diabetic wound healing through the regulation of macrophage polarization. By encompassing a thorough understanding of the fundamental principles and their practical implementation, the advancement of treatment strategies for diabetic wounds can be further facilitated.
... The largest risk factor for T2D is obesity [6,7], especially when left untreated [8]. Associated with an unhealthy diet [9] and a sedentary lifestyle [10], obesity escalates the pathogenesis of T2D by increasing insulin resistance [11,12]. ...
Type 2 diabetes (T2D) in youth is a global health concern characterized by an increasing incidence and prevalence, especially among disadvantaged socioeconomic subgroups. Moreover, youth-onset T2D is more aggressive and causes earlier, more severe long-term cardio-renal complications compared with T2D in adults. The therapeutic options available are limited and often inadequate, partially due to the numerous challenges in implementing clinical trials for this vulnerable patient population. Over the last few years, a significant effort has been made to develop new effective drugs for children and adolescents with T2D. Specifically, a number of studies are currently generating new data to address the urgent unmet medical need for optimal management of this disease. This review describes the central features of youth-onset T2D and summarizes the available treatments and ongoing studies in pediatric patients.
... Among different interventions to prevent diabetes, weight loss is regarded as an important component, since substantial research has revealed a high association between obesity and T2DM, and it could also compound other health problems and complicate the management of T2DM. 4,5 The most commonly used methods for high-risk people to control and lose weight are lifestyle changes and metformin. In comparison, lifestyle interventions have demonstrated better applicability in diverse populations and are superior to the use of metformin in older adults and lower body mass index (BMI) groups. ...
Trial‐based economic value of prevention programs for diabetes is inexplicit. We aimed to review the cost‐effectiveness of nonpharmacological interventions to prevent type‐2 diabetes mellitus (T2DM) for high‐risk people. Six electronic databases were searched up to March 2022. Studies assessing both the cost and health outcomes of nonpharmacological interventions for people at high‐risk of T2DM were included. The quality of the study was assessed by the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. The primary outcome for synthesis was incremental cost‐effectiveness ratios (ICER) for quality‐adjusted life years (QALYs), and costs were standardized in 2022 US dollars. Narrative synthesis was performed, considering different types and delivery methods of interventions. Sixteen studies included five based on the US diabetes prevention program (DPP), six on non‐DPP‐based lifestyle interventions, four on health education, and one on screening plus lifestyle intervention. Compared with usual care, lifestyle interventions showed higher potential of cost‐effectiveness than educational interventions. Among lifestyle interventions, DPP‐based programs were less cost‐effective (median of ICERs: $27,077/QALY) than non‐DPP‐based programs (median of ICERs: $1395/QALY) from healthcare perspectives, but with larger decreases in diabetes incidence. Besides, the cost‐effectiveness of interventions was more possibly realized through the combination of different delivery methods. Different interventions to prevent T2DM in high‐risk populations are both cost‐effective and feasible in various settings. Nevertheless, economic evidence from low‐ and middle‐income countries is still lacking, and interventions delivered by trained laypersons and combined with peer support sessions or mobile technologies could be potentially a cost‐effective solution in such settings with limited resources.
... One of the main potential factors in the development of these implications is oxidative stress. The main sources of oxidative stress in obesity are altered glucose and lipid homeostasis and inflammatory responses mediated by various cytokines [2][3][4]. ...
Background:
An imbalance between adipokines and micronutrient concentrations, such as those of copper (Cu), has been linked to dysregulation of energy homeostasis leading to weight gain and the development of other comorbidities; however, information on this issue remains limited. Our aim was to investigate the correlation between Cu status and serum adipokine levels and their relationship in normal-weight, overweight, and obese adult women.
Methods:
Sixty patients were evaluated and classified according to their body mass index (BMI) and biochemical parameters; adipokines and Cu were measured at fasting.
Results:
Leptin (Lep) and resistin (Res) levels were elevated, whereas adiponectin (Adpn) and ghrelin (Ghr) values were decreased in overweight and obese women (p = 0.001). The mean Adpn/Lep ratio was <0.5 in overweight and obese subjects, while the Lep/Ghr ratio increased significantly in relation to weight gain, suggesting an inverse link between the ratios of these hormones in the regulation of obesity. The analysis revealed a positive association between BMI and Cu levels in obese women. Moreover, a negative association between Cu and Res in normal-weight subjects was found.
Conclusions:
Circulating fasting Res levels are negatively associated with serum Cu concentration in normal-weight adult women. We also observed a close relationship between Adpn/Lep and Lep/Ghr ratios with obesity. However, more observational studies are required to confirm these results in future research.
... Adult type 2 diabetes has been considered a serious threat as it is frequently accompanied by several major complications, such as a higher prevalence of cancers, cardiovascular diseases, chronic kidney disease, osteoporosis, and neurodegenerative diseases. Thus, the increase in obesity prevalence has led to increases in diabetes and other comorbid conditions, along with a related increase in community health care costs and patient mortality [6,7]. ...
Excessive weight and obesity are the leading risk factors for the development of chronic diseases, including diabetes. Metformin is capable of significantly improving coexisting complications of diabetes. We used a metabolomics approach to examine the effects of metformin administration on lean and obese (fa/fa) Zucker rats. After 1 week of acclimation, twenty-eight 5-week-old female lean and obese rats were randomly assigned to and maintained in the following four groups (seven rats/group) for 10 weeks: (1) lean control (LC); (2) obese control (OC); (3) lean metformin (LM); and (4) obese metformin (OM). At the end of 10 weeks, serum was collected and analyzed using HPLC with electrochemical detection, HPLC with UV detection, and liquid chromatography mass spectrometry. We selected 50 metabolites’ peaks that were shared by all four groups of rats. Peak heights, as a defining factor, generally decreased in metformin-treated lean rats vs. untreated lean controls (3 LM:16 LC). Peak heights generally increased in metformin-treated obese rats vs. untreated obese controls (14 OM:5 OC). Overall, individual peaks were distributed as 11 that represented only lean rats, 11 that represented only obese rats, and 8 that were common among both lean and obese rats. In future studies, we will use a targeted metabolomics approach to identify those metabolites, map them to biochemical pathways and create a list of biomarkers. In summary, the current study contributed to a better understanding of the basic metabolic changes of lean and obese rats and demonstrated that both obesity and metformin make a significant impact on the metabolome of Zucker rats.
... Overweight or obesity is associated with a higher risk of developing T2D and diabetes complications and more difficulty achieving glycemic control 27 . Therefore, weight reduction is a central component of T2D management. ...
Tirzepatide is a once-weekly GIP/GLP-1 receptor agonist. In this phase 3, randomized, open-label trial, insulin-naive adults (≥18 years of age) with type 2 diabetes (T2D) uncontrolled on metformin (with or without a sulphonylurea) were randomized 1:1:1:1 to weekly tirzepatide 5 mg, 10 mg or 15 mg or daily insulin glargine at 66 hospitals in China, South Korea, Australia and India. The primary endpoint was non-inferiority of mean change in hemoglobin A1c (HbA1c) from baseline to week 40 after treatment with 10 mg and 15 mg of tirzepatide. Key secondary endpoints included non-inferiority and superiority of all tirzepatide doses in HbA1c reduction, proportions of patients achieving HbA1c < 7.0% and weight loss at week 40. A total of 917 patients (763 (83.2%) in China) were randomized to tirzepatide 5 mg (n = 230), 10 mg (n = 228) or 15 mg (n = 229) or insulin glargine (n = 230). All doses of tirzepatide were non-inferior and superior to insulin glargine for least squares mean (s.e.) reduction in HbA1c from baseline to week 40: tirzepatide 5 mg, 10 mg and 15 mg, −2.24% (0.07), −2.44% (0.07) and −2.49% (0.07), respectively, and insulin glargine, −0.95% (0.07), with a treatment difference ranging from −1.29% to −1.54% (all P < 0.001). Proportions of patients achieving HbA1c < 7.0% at week 40 were greater in tirzepatide 5-mg (75.4%), 10-mg (86.0%) and 15-mg (84.4%) groups compared to insulin glargine (23.7%) (all P < 0.001). All tirzepatide doses led to superior body weight reduction at week 40: tirzepatide 5 mg, 10 mg and 15 mg, −5.0 kg (−6.5%), −7.0 kg (−9.3%) and −7.2 kg (−9.4%), respectively, compared to insulin glargine, 1.5 kg (+2.1%) (all P < 0.001). The most common adverse events with tirzepatide were mild to moderate decreased appetite, diarrhea and nausea. No severe hypoglycemia was reported. Tirzepatide demonstrated superior reductions in HbA1c versus insulin glargine in an Asia-Pacific, predominately Chinese, population with T2D and was generally well tolerated. ClinicalTrials.gov registration: NCT04093752.
... This approach can be seen in the '40+' initiative which encompasses blood glucose tests in patients over the age of 40 and with risk factors, as a part of preventive health services provided under the general health insurance scheme. Obesity, the greatest single risk factor for the onset of type 2 diabetes [24], is considered a reason to administer a blood glucose test in patients under the general age for screening tests (35 years according to ADA and USPSTF, 45 years according to PTD). The prevalence of adult female obesity is often higher than the prevalence of adult male obesity in most populations [25]. ...
Introduction and objective:
The number of patients diagnosed with diabetes is constantly increasing. Opportunistic screening for diabetes, based on blood glucose tests, can result in early diagnosis and mitigation of its complications. The aim of the study was to assess the frequency of blood-glucose tests in adults in Poland, and factors associated with the frequency of blood-glucose tests, including respondents’ knowledge about diabetes.
Material and methods:
In June 2022, a nationwide cross-sectional survey was carried out among adults in Poland.` The survey used a computer-assisted web interview technique and a self-developed questionnaire that included questions on respondents’ self-reported knowledge of diabetes, time since last blood glucose test and socio-demographic characteristics of participants.
Results:
The study population comprised 1,051 individuals aged 18–85 years, among whom 53.3% were females. Over a third of respondents (36.3%) declared a bad or rather bad knowledge about diabetes. Almost half of the respondents (48.7%) had a blood glucose test in the last 12 months, and 12.4% declared that they had never had a blood glucose test. Among respondents without diagnosed diabetes, female gender (OR=1.30, 0.96–1.76; p=0.009), age over 50 years (p<0.05), history of diabetes in the respondent’s family (OR=1.83, 1.33–2.51; p<0.001), and good or at least moderate level of knowledge of diabetes were significantly associated (p<0.05) on blood glucose test frequency.
Conclusions:
The presented data manifest the need to intensify screening for diabetes combined with implementing a comprehensive education strategy regarding diabetes in Poland.
... However, there has been no consensus as to whether the underlying mechanisms of obesity are definite risk factors for kidney dysfunction. Obesity is usually accompanied by metabolic abnormalities, including elevated blood glucose [9], elevated blood pressure [10], and lipid disorders [11]. Most studies declare that the metabolic abnormalities induced by obesity played a key role in kidney dysfunction [12,13]. ...
Background
The impact of metabolically healthy obesity (MHO) on kidney dysfunction remains debatable. Moreover, few studies have focused on the early stages of kidney dysfunction indicated by hyperfiltration and mildly reduced eGFR. Thus, we aimed to investigate the association between the MHO and early kidney dysfunction, which is represented by hyperfiltration and mildly reduced estimated glomerular filtration rate (eGFR), and to further explore whether serum uric acid affects this association.
Methods
This cross-sectional study enrolled 1188 residents aged ≥ 40 years old from Yonghong Communities. Metabolically healthy phenotypes were categorized based on Adult Treatment Panel III criteria. Obesity was defined as body mass index (BMI) ≥ 25 kg/m². Mildly reduced eGFR was defined as being in the range 60 < eGFR ≤ 90 ml/min/1.73m². Hyperfiltration was defined as eGFR > 95th percentile after adjusting for sex, age, weight, and height.
Results
Overall, MHO accounted for 12.8% of total participants and 24.6% of obese participants. Compared to metabolically healthy non-obesity (MHNO), MHO was significantly associated with an increased risk of mildly reduced eGFR (odds ratio [OR] = 1.85, 95% confidence interval [CI] 1.13–3.01) and hyperfiltration (OR = 2.28, 95% CI 1.03–5.09). However, upon further adjusting for uric acid, the association between the MHO phenotype and mildly reduced eGFR was reduced to null. Compared with MHNO/non-hyperuricemia, MHO/non-hyperuricemia was associated with an increased risk of mildly reduced eGFR (OR = 2.04, 95% CI 1.17–3.58), whereas MHO/hyperuricemia was associated with an observably increased risk (OR = 3.07, 95% CI 1.34–7.01).
Conclusions
MHO was associated with an increased risk of early kidney dysfunction, and the serum uric acid partially mediated this association. Further prospective studies are warranted to clarify the causality.
... The occurrence of macrosomia is an increased risk factor for maternal postpartum infections, and it is associated with several adverse perinatal outcomes, including prolonged labor and increased rates of cesarean delivery [165]. Compared to otherwise healthy infants, macrosomia leads to higher risks for childhood obesity, adult obesity, hypertension, diabetes, and other agerelated diseases [166,167]. Existing research recognizes the critical role of regulating fetal growth played by placental ncRNAs ( Table 4). The exploration of the correlation between placental ncRNAs and the birth outcome of macrosomia is beneficial to further understand the mechanism of macrosomia and to provide interventions and treatments. ...
Non-coding RNAs (ncRNAs) are transcribed from the genome and do not encode proteins. In recent years, ncRNAs have attracted increasing attention as critical participants in gene regulation and disease pathogenesis. Different categories of ncRNAs, which mainly include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are involved in the progression of pregnancy, while abnormal expression of placental ncRNAs impacts the onset and development of adverse pregnancy outcomes (APOs). Therefore, we reviewed the current status of research on placental ncRNAs and APOs to further understand the regulatory mechanisms of placental ncRNAs, which provides a new perspective for treating and preventing related diseases.
... They both generate a great impact on health and the economy [4]. Obesity is defined as an increase in body mass index (BMI) greater than or equal to 30 kg/m 2 , and it can be divided into different degrees obesity implies an increased risk for developing T2DM and cardiovascular events with respect to the population with a normal BMI [5,6]. ...
The prevalence of type 2 diabetes mellitus (T2DM) is rising in the general population. This increase leads to higher cardiovascular risk, with cardiovascular diseases being the main cause of death in diabetic patients. New therapeutic weapons for diabetes mellitus are now available. Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are novel drugs that are widely used due to their strong benefit in preventing hospitalization for decompensated heart failure and renal protection, limiting the deterioration of the glomerular filtration rate, independently of the presence of diabetes mellitus. These drugs have also shown benefit in the prevention of atherosclerotic cardiovascular events and cardiovascular mortality in diabetic patients with established cardiovascular disease. On the other hand, patients with T2DM usually present a high burden of associated comorbidities. Some of these entities are arterial hypertension, dyslipidemia, hyperuricemia, obesity, non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), vascular aging, respiratory diseases, or osteoporosis and fractures. Healthcare professionals should treat these patients from an integral point of view, and not manage each pathology separately. Therefore, as potential mechanisms of SGLT2 inhibitors in metabolic diseases have not been fully reviewed, we conducted this review to know the current evidence of the use and effect of SGLT2 inhibitors on these metabolic diseases.
... Obesity is considered the most significant risk factor for the development of type 2 diabetes [75]. In this regard, antidiabetic drugs usually have an effect on body weight control. ...
The obesity pandemic is one of society's most urgent public health concerns. A third of the global adult population may fall under obese or overweight by 2025, suggesting a rising demand for medical care and an exorbitant cost of healthcare expenditure in the coming years. Generally, the treatment strategy for obese patients is largely patient-centric and needs dietary, behavioral, pharmacological, and sometimes even surgical interventions. Given that obesity cases are rising in adults and children and lifestyle modifications have failed to produce desired results, so the need for medical therapy adjunct to lifestyle modifications is vital for better managing of obesity. Most existing or past drugs for obesity treatment target satiety or monoamine pathways and induce a feeling of fullness in patients, while drugs like orlistat are targeted against intestinal lipases. However, many medications targeted against neurotransmitters showed adverse events in patients, thus being withdrawn from the market. Alternatively, the combination of some drugs has been successfully tested in obesity management. However, the demand for novel, safer, and more efficacious pharmaceutical drugs for weight management does exist. The present review elucidates the current understanding of the available anti-obesity medicines of synthetic and natural origin, their main mechanisms of action, and the shortcomings associated with current weight-management drugs.
... Obesity prevalence has nearly tripled worldwide since the 1970s [1], and is now recognized as a major contributor to the development of a number of cardio-metabolic disorders, including type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) [2,3]. Excess energy storage as fat in adipocytes is the hallmark of obesity, with adipocytes undergoing cellular hypertrophy and hyperplasia under conditions of a chronic positive energy balance [4]. ...
Adipose tissue is a dynamic endocrine organ, secreting a plethora of adipokines which play a key role in regulating metabolic homeostasis and other physiological processes. An altered adipokine secretion profile from adipose tissue depots has been associated with obesity and related cardio-metabolic diseases. Asprosin is a recently described adipokine that is released in response to fasting and can elicit orexigenic and glucogenic effects. Circulating asprosin levels are elevated in a number of cardio-metabolic diseases, including obesity and type 2 diabetes. In vitro studies have reported pro-inflammatory effects of asprosin in a variety of tissues. The present study aimed to further elucidate the role of asprosin in inflammation by exploring its potential effect(s) in THP-1 macrophages. THP-1 monocytes were differentiated to macrophages by 48 h treatment with dihydroxyvitamin D3. Macrophages were treated with 100 nM recombinant human asprosin, 100 ng/mL lipopolysaccharide (LPS), and 10 μM caffeic acid phenethyl ester (CAPE; an inhibitor of NFκB activation) or 1 µM TAK-242 (a Toll-like receptor 4, TLR4, inhibitor). The expression and secretion of pertinent pro-inflammatory mediators were measured by qPCR, Western blot, ELISA and Bioplex. Asprosin stimulation significantly upregulated the expression and secretion of the pro-inflammatory cytokines: tumour necrosis factor α (TNFα), interleukin-1β (IL-1β), IL-8 and IL-12 in vitro. This pro-inflammatory response in THP-1 macrophages was partly attenuated by the treatments with CAPE and was significantly inhibited by TAK-242 treatment. Asprosin-induced inflammation is significantly counteracted by TLR4 inhibition in THP-1 macrophages, suggesting that asprosin exerts its pro-inflammatory effects, at least in part, via the TLR4 signalling pathway.
... Excess weight and obesity are risk factors for diabetes, hypertension, ischemic heart disease, stroke, sleep apnea, cancer, as well as other lifestyle diseases [1][2][3][4][5]. Excessive intake of calories and physical inactivity are the major causes of excess weight [6], so complex lifestyle changes (reduced calorie intake and increased physical activity) combined with bariatric surgery and/or pharmacological treatment can reduce body weight. ...
Exercise tolerance is limited in obesity and improves after weight reduction; therefore, we mutually compared the relative changes in exercise capacity variables during cardiopulmonary exercise tests (CPET) in a 12 kg sheer weight reduction model. Twenty healthy male runners underwent two CPETs: CPET1 with the actual body weight, which determined the anaerobic threshold (AT) and respiratory compensation point (RCP); and CPET2 during which the participants wore a +12 kg vest and ran at the AT speed set during the CPET1. Running after body weight reduction shifted the CPET parameters from the high-mixed aerobic-anaerobic (RCP) to the aerobic zone (AT), but these relative changes were not mutually similar. The most beneficial changes were found for breathing mechanics parameters (range 12–28%), followed by cardiovascular function (6–7%), gas exchange (5–6%), and the smallest for the respiratory exchange ratio (5%) representing the energy metabolism during exercise. There was no correlation between the extent of the relative body weight change (median value ~15%) and the changes in CPET parameters. Weight reduction improves exercise capacity and tolerance. However, the observed relative changes are not related to the magnitude of the body change nor comparable between various parameters characterizing the pulmonary and cardiovascular systems and energy metabolism.
... Visceral fat can secrete a variety of proinflammatory adipokines, which are closely related to insulin resistance, lipid disorders, cardiovascular diseases and bone metabolic diseases. 11,12 Therefore, it is of great significance to study the association between coronary artery calcification and BMD in T2DM patients with different VFA. ...
Purpose:
The relationship between coronary artery calcification and bone mineral density (BMD) in T2DM is still unclear. The aim of this study is to analyze the association between coronary artery calcium score (CACs) and BMD in T2DM with different visceral fat area (VFA), and further to explore the clinical significance of CACs in predicting osteoporosis in T2DM patients.
Patients and methods:
A total of 479 T2DM patients aged ≥50 years were included. Agatston was applied to calculate CACs to evaluate the degree of coronary artery calcification. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD. According to VFA, all subjects were divided into VFA <100cm2 and VFA ≥100cm2 group. Adjusted regression analysis was performed to analyze the association between CACs and BMD. ROC curve was used to analyze the optimal cut-off value of CACs for screening osteoporosis.
Results:
The baseline showed that in VFA ≥100cm2 group, CACs increased significantly than that in VFA <100cm2 group (212.1±195.9 vs 139.3±141.8, p<0.001) and total hip BMD decreased obviously (0.968±0.19 vs 1.021±0.184, p=0.01). After multivariable adjustment, CACs was not significantly associated with BMD in all patients (p>0.05). However, CACs was negatively associated with BMD of total hip and lumbar spine in patients with VFA ≥100cm2 (total hip β=-0.087 p=0.01; lumbar spine β=-0.052 p=0.005), but not VFA <100cm2. ROC curve analysis showed that the optimal cut-off value of CACs for screening osteoporosis was 191.505.
Conclusion:
The present study implied that associations between CACs and BMD varied by the visceral fat deposition. It is critical to evaluate the condition of visceral fat accumulation for exploring the complex interplay of coronary artery calcification and BMD in T2DM patients. It may be of some clinical value for CACs in predicting osteoporosis in T2DM with visceral obesity.
... Obesity, diet, long light and short sleep, and dysbiosis of the gut flora can promote systemic chronic low-grade inflammation and oxidative stress leading to insulin resistance and increased risk of diabetes (56,(99)(100)(101)(102). In recent years, gut flora has also been recognized as an important causative factor for diabetes (103). ...
Circadian rhythm is an inherent endogenous biological rhythm in living organisms. However, with the improvement of modern living standards, many factors such as prolonged artificial lighting, sedentarism, short sleep duration, intestinal flora and high-calorie food intake have disturbed circadian rhythm regulation on various metabolic processes, including GLP-1 secretion, which plays an essential role in the development of various metabolic diseases. Herein, we focused on GLP-1 and its circadian rhythm to explore the factors affecting GLP-1 circadian rhythm and its potential mechanisms and propose some feasible suggestions to improve GLP-1 secretion.
... Type 2 diabetes is strongly associated with obesity, with more than 80% of type 2 diabetes attributable to obesity, which also contributes to many diabetes-related deaths [27]. Weight gain after the age of 18 years for women and 20 years for men also increases the risk of type 2 diabetes [28]. ...
Obesity is a chronic disease that endangers human health. In recent years, the phenomenon of obesity has become more and more common, and it has become a global epidemic. Obesity is closely associated with many adverse metabolic changes and diseases, such as insulin resistance, type 2 diabetes mellitus, coronary heart disease, nervous system diseases and some malignant tumors, which have caused a huge burden on the country’s medical finance. In most countries of the world, the incidence of cancer caused by obesity is increasing year on year. Diabetes associated with obesity can lead to secondary neuropathy. How to treat obesity and its secondary diseases has become an urgent problem for patients, doctors and society. This article will summarize the multidisciplinary research on obesity and its complications.
... Obesity represents the comments modifiable risk for the development of T2DM. It was found that a weight loss ≥5% of the bodyweight resulted in glycemic control, decreased diabetic medications use, and enhanced the quality of life 22 . However, a recent study 23 that assessed the prevalence of overweight/obesity and DM in low-income and middle-income countries has reported that the correlation between BMI and DM risk is subject to considerable regional variations. ...
Objective:
Obesity/overweight is a major preventable cause of morbidity responsible for various health disorders. Thus, the present investigation aimed to estimate the prevalence rates of obesity and its related risk factors among the Saudi community in the Hai'l Region.
Patients and methods:
In this study, 2,438 participants were randomly recruited in the Hai'l region during a cross-sectional survey. Participants were included based on their body mass index (BMI). Only those with BMI >25 weight (kg)/height (m)2 were included.
Results:
The overall prevalence rates of overweight and obesity were 61% and 39%. The prevalence rates of males' overweight, obesity, and morbid obesity were 69%, 19%, and 12%, respectively. The prevalence rates of overweight, obesity and morbid obesity among females were 50%, 28%, and 22%, respectively.
Conclusions:
Overweight, obesity, and morbid obesity are prevalent in Hai'l region, Northern Saudi Arabia. Overweight/obesity is more prevalent among women, rural inhabitants, less educated people, and adults aged 26-40 years. Hypertension, type 2 diabetes mellitus (T2DM), and deep vein thrombosis (DVT) are significantly obesity-associated risk factors in Saudi Arabia.
... Obesity is the most significant risk factor for the development of type 2 diabetes [42]. In most populations, the prevalence of obesity in adults is greater for women than for men [43]. ...
Diabetes is one of the most common chronic diseases worldwide. The study aimed to
present an epidemiological analysis of hospitalization related to diabetes mellitus in Poland between
2014 and 2020 as well as to analyze changes in diabetes-related hospital admissions before and during
the COVID-19 pandemic. This study is a retrospective analysis of the national registry dataset of
hospital discharge reports on diabetes-related hospitalizations in Poland between 2014 and 2020.
The number of diabetes-related hospitalizations varied from 76,220 in 2016 to 45,159 in 2020. The
hospitalization rate per 100,000 has decreased from 74.6 in 2019 to 53.0 in 2020 among patients with
type 1 diabetes (percentage change: −28.9%). An even greater drop was observed among patients
with type 2 diabetes: from 99.4 in 2019 to 61.6 in 2020 (percentage change: −38%). Both among
patients with type 1 and type 2 diabetes, a decrease in hospitalization rate was higher among females
than males (−31.6% vs. −26.7% and −40.9% vs. −35.2% respectively). When compared to 2019,
in 2020, the in-hospital mortality rate increased by 66.7% (60.0% among males and 65.2% among
females) among patients hospitalized with type 1 diabetes and by 48.5% (55.2% among females and
42.1% among males) among patients hospitalized with type 2 diabetes. Markable differences in
hospitalization rate, duration of hospitalization, as well as in-hospital mortality rate by gender, were
observed, which reveal health inequalities
... Over the years as obesity has increased globally so has been the increase in the incidence of diabetes. [52] The increased deaths from COVID-19 in different countries are thus correlated. ...
... Over the years as obesity has increased globally so has been the increase in the incidence of diabetes. [52] The increased deaths from COVID-19 in different countries are thus correlated. ...
COVID-19 flu has been the worst pandemic on earth in more than a century and has thus far claimed more than six million lives worldwide. As of 19th March 2022, there were 57 major countries where one million or more COVID-19cases were registered, and the deaths reported therein constituted 92.3% of the total deaths worldwide. The high mortality rate is associated with comorbid conditions of the infected. Obesity, diabetes, cardiovascular diseases, high blood pressure, chronic obstructive pulmonary diseases, tuberculosis, and a higher percentage of the aged population (more than 65y) were identified as major morbidity conditions among others. Mycobacterium sensitized healthy people were found to resist the disease more efficiently. Prior vaccination with human influenza virus vaccines had considerable protective effects against catching or manifesting severity in COVID-19 flu. Timely vaccination with an approved vaccine against SARS-CoV-2 was considered immensely protective from the disease. All countries should therefore adopt policy measures that ensure adequate vaccination among their population.
... This result is in line with another observation from our study, namely that treatment with clinical inertia is identified in patients with higher BMI. Since obesity is in tight correlation and frequently the following comorbidity in type 2 diabetes patients [29], our patients with higher average BMIs were also identified in the group exposed to clinical inertia (BMI 28.04 vs. 27.68, with vs. without inertia, respectively, p = 0.024). ...
With the growing prevalence and complex pathophysiology of type 2 diabetes, many patients fail to achieve treatment goals despite guidelines and possibilities for treatment individualization. One of the identified root causes of this failure is clinical inertia. We explored this phenomenon, its possible predictors, and groups of patients affected the most, together with offering potential paths for intervention. Our research was a cross-sectional study conducted during 2021 involving 52 physicians and 543 patients of primary healthcare institutions in Belgrade, Serbia. The research instruments were questionnaires based on similar studies, used to collect information related to the factors that contribute to developing clinical inertia originating in both physicians and patients. In 224 patients (41.3%), clinical inertia was identified in patients with poor overall health condition, long diabetes duration, and comorbidities. Studying the changes made to the treatment, most patients (53%) had their treatment adjustment more than a year ago, with 19.3% of patients changing over the previous six months. Moreover, we found significant inertia in the treatment of patients using modern insulin analogues. Referral to secondary healthcare institutions reduced the emergence of inertia. This assessment of primary care physicians and their patients pointed to the high presence of clinical inertia, with an overall health condition, comorbidities, diabetes duration, current treatment, last treatment change, glycosylated hemoglobin and fasting glucose measuring frequency, BMI, patient referral, diet adjustment, and physician education being significant predictors.
... Biguanide metformin (MF), a first-line drug for the treatment of type 2 diabetes mellitus (T2DM), is widely used to normalize insulin sensitivity and improve glucose and lipid metabolism in patients with T2DM and metabolic syndrome [1][2][3][4]. In diabetic pathology, there is numerous evidence that MF also improves the functions of the impaired endocrine system, including the restoration of hypothalamic-pituitary-gonadal (HPG) axis, both in men and women [5][6][7][8][9]. ...
In men with type 2 diabetes mellitus (T2DM), steroidogenesis and spermatogenesis are impaired. Metformin and the agonists of luteinizing hormone/human chorionic gonadotro-pin(hCG)-receptor (LH/hCG-R) (hCG, low-molecular-weight allosteric LH/hCG-R-agonists) can be used to restore them. The aim was to study effectiveness of separate and combined administration of metformin, hCG and 5-amino-N-tert-butyl-2-(methylsulfanyl)-4-(3-(nicotinamido)phe-nyl)thieno[2,3-d]pyrimidine-6-carboxamide (TP3) on steroidogenesis and spermatogenesis in male rats with T2DM. hCG (15 IU/rat/day) and TP3 (15 mg/kg/day) were injected in the last five days of five-week metformin treatment (120 mg/kg/day). Metformin improved testicular steroidogenesis and spermatogenesis and restored LH/hCG-R-expression. Compared to control, in T2DM, hCG stimulated steroidogenesis and StAR-gene expression less effectively and, after five-day administration , reduced LH/hCG-R-expression, while TP3 effects changed weaker. In co-administration of metformin and LH/hCG-R-agonists, on the first day, stimulating effects of LH/hCG-R-agonists on testosterone levels and hCG-stimulated expression of StAR-and CYP17A1-genes were increased, but on the 3-5th day, they disappeared. This was due to reduced LH/hCG-R-gene expression and increased aromatase-catalyzed estradiol production. With co-administration, LH/hCG-R-agonists did not contribute to improving spermatogenesis, induced by metformin. Thus, in T2DM, metfor-min and LH/hCG-R-agonists restore steroidogenesis and spermatogenesis, with metformin being more effective in restoring spermatogenesis, and their co-administration improves LH/hCG-R-ago-nist-stimulating testicular steroidogenesis in acute but not chronic administration.
Maternal inulin intervention activates hypothalamic Socs3 , Npy , and Il6 gene methylation, inhibits Lepr gene methylation, and moderates the hypothalamus feeding circuit, leading to a decrease in food intake and body weight in male offspring.
Context
Exercise training is known to improve glucose tolerance and reverse insulin resistance in people with obesity. However, some individuals fail to improve or even decline in their clinical traits following exercise intervention.
Objective
This study focused on gene expression and DNA methylation signatures in skeletal muscle of low (LRE) and high responders (RES) to 8 weeks of supervised endurance training.
Methods
We performed skeletal muscle gene expression and DNA methylation analyses in LRE and RES before and after exercise intervention. Additionally, we applied the least absolute shrinkage and selection operator (LASSO) approach to identify predictive marker genes of exercise outcome.
Results
We show that the two groups differ markedly already before the intervention. RES were characterized by lower expression of genes involved in DNA replication and repair, and higher expression of extracellular matrix (ECM) components. The LASSO approach identified several novel candidates (eg, ZCWPW2, FOXRED1, STK40) that have not been previously described in the context of obesity and exercise response. Following the intervention, LRE reacted with expression changes of genes related to inflammation and apoptosis, RES with genes related to mitochondrial function. LRE exhibited significantly higher expression of ECM components compared to RES, suggesting improper remodeling and potential negative effects on insulin sensitivity. Between 45% and 70% of differences in gene expression could be linked to differences in DNA methylation.
Conclusion
Together, our data offer an insight into molecular mechanisms underlying differences in response to exercise and provide potential novel markers for the success of intervention.
Aim
Bariatric metabolic surgery (BMS) is a proven treatment option for patients with both obesity and type 2 diabetes mellitus (T2DM). However, there is a lack of comprehensive reporting on the short‐term remission rates of diabetes, and the existing data are inadequate. Hence, this study aimed to investigate the factors that may contribute to diabetes remission (DR) in patients with obesity and T2DM, 3 months after undergoing BMS. Furthermore, our objective was to develop a risk‐predicting model using a nomogram.
Methods
In total, 389 patients with obesity and T2DM, who had complete preoperative information and underwent either laparoscopic sleeve gastrectomy or laparoscopic gastric bypass surgery between January 2014 and May 2023, were screened in the Chinese Obesity and Metabolic Surgery Database. The patients were randomly divided into a training set (n = 272) and a validation set (n = 117) in a 7:3 ratio. Potential factors for DR were analysed through univariate and multivariate logistic regression analyses and then modelled using a nomogram. The model's performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Calibration plots were used to assess prediction accuracy and decision curve analyses were conducted to evaluate the clinical usefulness of the model.
Results
Glycated haemoglobin, triglycerides, duration of diabetes, insulin requirement and hypercholesterolaemia were identified as independent factors influencing DR. We have incorporated these five indicators into a nomogram, which has shown good efficacy in both the training cohort (AUC = 0.930) and validation cohort (AUC = 0.838). The calibration plots indicated that the model fits well in both the training and the validation cohorts, and decision curve analyses showed that the model had good clinical applicability.
Conclusion
The prediction model developed in this study holds predictive value for short‐term DR following BMS in patients with obesity and T2DM.
Background
The prevalence of people who are overweight or obese is increasing globally, especially in low- and middle-income countries. High body mass index (BMI) among women of reproductive age is a risk factor for various adverse reproductive and pregnancy outcomes. This study aims to describe trends over time in the distribution of BMI among Tanzanian women of reproductive age intending to conceive between 2004/5 and 2015/16, and identify factors associated with high BMI.
Methods
We used data on 20,819 women of reproductive age (15-49 years) intending to conceive who participated in the Tanzania Demographic and Health Surveys in 2004/5, 2010 and 2015/16. We estimated the prevalence of high BMI (being overweight [≥25 to <30 kg/m ² ] and obesity [≥30kg/m ² ) and trends in the prevalence of high BMI across the three surveys. Using survey-weighted multivariable logistic regression, we used the most recent 2015/16 survey data to identify factors associated with high BMI.
Results
Median BMI increased from 21.7kg/m ² (inter-quartile range, IQR=19.9-24.1 kg/m ² ) in 2004/5 to 22.0 kg/m ² (IQR=20.0-24.8 kg/m ² ) in 2010 to 22.7 kg/m ² (IQR=20.4-26.0 kg/m ² ) in 2015/16. The prevalence of overweight women increased from 11.1% in 2004/5 to 15.8% in 2015 (P <0.001). The prevalence of obesity increased from 3.1% in 2004/5 to 8.0% in 2015/16 (P<0.001). Women in the highest wealth quintile had higher odds (adjusted odds ratio, aOR= 4.5; 95%CI 3.4-6.3, P<0.001) of high BMI than women in the lowest quintile. The odds of high BMI were about four times greater (aOR=3.9; 95%CI=2.9-5.4, P<0.001) for women 40-44 years compared to 20–24-year-olds. Women in the high-paying occupations had greater odds of high BMI than those working in agriculture (aOR=1.5; 95% CI=1.1-2.2, P=0.002). Women residing in the Southern zone had 1.9 (95%CI=1.5-2.5, P<0.001) greater odds of high BMI than Lake zone residents.
Conclusions
In Tanzania, high BMI affects almost 1 in 4 women of reproductive age who intend to conceive. This contributes to the burden of poor maternal and reproductive health outcomes. We recommend developing and implementing health-system strategies for addressing high BMI, tailored to the modifiable risk factors identified among women of reproductive age.
Obesity causes significant morbidity and increases the mortality risk for both mother and fetus. With an increasing projected prevalence, it is vital that the obstetric anesthetist is equipped with the knowledge and tools to manage these women. A multi-disciplinary team approach and early planning is required. Neuraxial analgesia for labor helps to negate the need for general anesthesia, which is associated with increased risk in this subset of women. Catheter techniques for neuraxial anesthesia allow for titration, manipulation, and prolongation of the anesthetic block to reduce the risk of conversion to general anesthesia.
Bariatric bypass surgery has been an effective treatment for morbid obesity. However, there is an increasing number of reported cases of gastric cancer after bypass surgery. Our systematic review showed an increasing trend of gastric cancer cases after bariatric bypass surgery in the last decade, mostly located in the excluded stomach (77%) and diagnosed in an advanced stage. In addition to known risk factors such as tobacco smoking (17%), H. pylori infection (6%), and family history of gastric cancer (3%), bile reflux, a recently proposed cancer-promoting factor, was also estimated in 18% of the cases. Our data suggest that gastric cancer risk assessment should be considered before gastric bypass surgery, and further investigations are needed to determine the value of post-operative gastric cancer surveillance.
The prevalence and mortality rate of diabetes shows an increasing trend globally, especially in Asia regions. From 1980 to 2014, the global prevalence rate increased from 4.7% to 8.5%, while the figure for South-East Asia Region surged from 4.1% to 8.6% in the same period, which ranked the second-high rate globally. As the neighboring countries, China and Japan share many similarities. The researchers found that although there are many differences in the prevalence of diabetes between the two countries, the overall prevalence is both in a high level. Therefore, we’ll collect the data about the regional differences between China and Japan, to compare and analyze the results reasons and solutions of two region’s differences. The prevalence rate and the mortality rate are different in different gender and ages in both countries. Normally males got the greater chances to get diabetes, while females are more likely to die in this disease. As the reacerch shows that the diabetes caused by three main factors, they are smoking, high body mass index and low physical activity respectively. And the high body mass is the dominant cause. As the latest research, the scientist found some new ways to help the diabetes patients. We might could use several solutions to them in later years.
Background
The obesity rate in the Chinese population is increasing and there is a lack of short and reliable scales for measuring obesity-related eating behavior in China. The EBS-SF (Sakata Eating Behavior Scale short form) has only 7 entries and has shown good reliability in studies such as those in Japan.Objective
To translate the EBS-SF into Chinese, check its reliability, validity and explore the related factors.Method
The EBS-SF was translated into Chinese. 3,440 residents were investigated and 34 respondents were retested. Item analysis and reliability and validity tests were carried out. Personality characteristics, family health status and depression were investigated using the BFI-10, FHS-SF and PHQ-9 to investigate the factors associated with EBS-SF. The t-test, ANOVA and Pearson correlation was used to explore the related factors of its scores.ResultAmong 3,440 residents, 1,748 (50.81%) were male and 1,692 (49.19%) were female; 1,373 (39.91%) were aged 36–50 years. All 7 items were qualified in the item analysis. As for reliability, the Cronbach's α was 0.870, the split-half reliability was 0.830, the test-retest correlation coefficient was 0.868. As for the structural validity, the standardized factor loadings were above 0.50, χ2 / df = 2.081,GFI = 0.999; NFI = 0.999; RFI = 0.996; RMSEA = 0.018, all qualified. The characteristics, personality, family health and depression were correlated with the score of the Chinese version of EBS short form.Conclusion
The structural validity and reliability of the Chinese version of the EBS-SF are good and it can be used as a measurement tool to evaluate the eating behavior of Chinese. The scores of the EBS-SF may be related to the sociological characteristics, personality, family health, and depression status.
As the baby boomer cohort ages, they have an ever-increasing number of comorbidities and associated poly-pharmaceutical treatment needs. The challenge for healthcare providers is to stay current of advancements in providing for this aging population. Baby boomers can expect a longer life expectancy than any previous generation. Yet, longevity has not correlated with better health. This cohort is noted for being goal driven and more self-assured than younger generations. They are resourceful and will often attempt to fix things themselves, including their healthcare. They believe hard work deserves justifiable rewards and relaxation. These beliefs have resulted in baby boomers utilizing more alcohol and illicit drugs. Altogether this means today's healthcare providers must be aware of potential interactions from the polypharmacy of prescribed medication, and they must include and understand additional complications associated with supplemental medications and illegal drugs.
Introduction:
It is suggested that cytokines play a key role in the pathogenesis of type 2 diabetes mellitus (T2DM). Therefore, this study explored two recently discovered cytokines, interleukin (IL)-37 (anti-inflammatory) and IL-39 (pro-inflammatory), in T2DM due to limited data in this context.
Methods:
Serum IL-37 and IL-39 levels were determined in 106 T2DM patients and 109 controls using enzyme-linked immunosorbent assay kits.
Results:
Serum levels (median and interquartile range) of IL-37 (79 [47-102] vs. 60 [46-89] ng/L; probability [p] = .04) and IL-39 (66 [59-69] vs. 31 [19-42] ng/L; p < .001) were significantly elevated in T2DM patients compared to controls. As indicated by the area under the curve (AUC), IL-39 (AUC = 0.973; p < .001) was more predictable for T2DM than IL-37 (AUC = 0.582; p = .039). Elevated levels of IL-39 were significantly associated with T2DM (odds ratio = 1.30; p < .001), while IL-37 did not show this association. Classification of IL-37 and IL-39 levels by demographic and clinical characteristics of patients revealed some significant differences including gender (IL-39), body mass index (BMI; IL-37 and IL-39) and diabetic neuropathy (IL-39). BMI was positively correlated with IL-39 (correlation coefficient [rs ] = 0.27; p = .005) and glycosylated haemoglobin (rs = 0.31; p = .001), and negatively correlated with age at onset (rs = -0.24; p = .015).
Conclusions:
IL-37 and IL-39 levels were elevated in the serum of T2DM patients. Besides, IL-39 is proposed to be a novel cytokine associated with T2DM and positively correlated with BMI.
Background: The potential role of exercise in physiological cardiac hypertrophy is rooted in both hormonal and genetic components.
Objectives: The aim of this study was to determine the impact of resistance exercise on the expression of PI3K and AKT1 in cardiac tissue of type 2 diabetes (T2D) rats and their physiological cardiac hypertrophy.
Methods: First, 21 male Wistar rats (220±20 g) were obese with 6-week high-fat diet (HFD) and were randomly assigned into non-diabetes, control T2D, and exercise diabetes groups. After inducing obesity, T2D was induced by intraperitoneal injection of streptozotocin (25 mg/kg) for diabetes groups. Rats in the exercise group completed a 6-week resistance exercise program, 5 sessions per week. PI3K/AKT1 expression and the weight ratio of left ventricular to heart, heart to body, and left ventricular to body were compared by analysis of variance (ANOVA) between groups.
Results: In response to the induction of diabetes, the expression of PI3K/AKT1 in heart tissue decreased significantly compared to that of non-diabetic rats (P=0.001 and P=0.001, respectively). Further, resistance training led to a significant increase in PI3K expression (P=0.028) and AKT1 (P=0.032) and the weight ratio of left ventricular to heart (P=0.001), heart to the body (P=0.001), and left ventricular to the body (P=0.001) compared to control diabetic rats.
Conclusion: Resistance training is associated with physiological cardiac hypertrophy in diabetic rats, and this improvement may be attributed to the PI3K/AKT1 signaling pathway.
Significant racial/ethnic disparities in healthcare and diabetes technology use have been observed in Type 2 diabetes mellitus (T2DM), which are associated with nonengagement in diabetes self-management and out-of-range glycemia. This study aimed to assess whether there were differences in the blood glucose levels achieved by several racial/ethnic groups using the same digital tool. Study objectives were to determine whether engagement with the digital tool and blood glucose levels differ among ethnic groups, and to determine whether any differences in the in-target-glycemia are related to engagement levels. The retrospective real-world analysis followed a group of 1000 people with Type 2 diabetes who used the DarioTM digital therapeutic platform over 12 months. Participants included in the study had a blood glucose average > 180 mg/dL (hyperglycemia, high-risk) in their first month. The differences between/within the groups’ average blood glucose level (Avg.bg) and glycemic variability were evaluated. Furthermore, three general linear models were constructed to predict the Avg.bg by the number of blood glucose measurements (Bgm) in Model 1 (with the moderator White persons (WP)/people from racial and ethnic minority groups (REM)) and by the frequency of measurements by months (F.m) within REM and WP in Model 2 and Model 3, respectively. The Avg.bg was significantly reduced in each group over a year with no differences between REM/WP users. Blood glucose measurements in Model 1 and frequency of measurements by months in Model 2 and Model 3 predicted the Avg.bg (β1 = −0.20, p = 0.045; β2 = −4.38, p = 0.009; β3= −3.77, p < 0.001, respectively). Findings indicate a positive association between digital engagement and glycemia, with no differences between REM and WP participants.
Background
Continuous glucose monitor (CGM) systems were originally intended only for people with diabetes. Recently, there has been interest in monitoring glucose concentrations in a variety of other situations. As data accumulate to support the use of CGM systems in additional states unrelated to diabetes, the use of CGM systems is likely to increase accordingly.
Methods
PubMed and Google Scholar were searched for articles about the use of CGM in individuals without diabetes. Relevant articles that included sufficient details were queried to identify what cohorts of individuals were adopting CGM use and to define trends of use.
Results
Four clinical user cases were identified: (1) metabolic diseases related to diabetes with a primary dysregulation of the insulin-glucose axis, (2) metabolic diseases without a primary pathophysiologic derangement of the insulin-glucose axis, (3) health and wellness, and (4) elite athletics. Seven trends in the use of CGM systems in people without diabetes were idenfitied which pertained to both FDA-cleared medical grade products as well as anticipated future products, which may be regulated differently based on intended populations and indications for use.
Conclusions
Wearing a CGM has been used not only for diabetes, but with a goal of improving glucose patterns to avoid diabetes, improving mental or physical performance, and promoting motivate healthy behavioral changes. We expect that clinicians will become increasingly aware of (1) glycemic patterns from CGM tracings that predict an increased risk of diabetes, (2) specific metabolic glucotypes from CGM tracings that predict an increased risk of diabetes, and (3) new genetic and genomic biomarkers in the future.
Childhood and adolescent exposure to obesogenic environments has contributed to the development of several health disorders, including neurocognitive impairment. Adolescence is a critical neurodevelopmental window highly influenced by environmental factors that affect brain function until adulthood. Post-weaning chronic exposure to a high-fat diet (HFD) adversely affects memory performance; physical activity is one approach to coping with these dysfunctions. Previous studies indicate that voluntary exercise prevents HFD's detrimental effects on memory; however, it remains to evaluate whether it has a remedial/therapeutical effect when introduced after a long-term HFD exposure. This study was conducted on a diet-induced obesity mice model over six months. After three months of HFD exposure (without interrupting the diet) access to voluntary physical activity was provided. HFD produced weight gain, increased adiposity, and impaired glucose tolerance. Voluntary physical exercise ameliorated glucose tolerance and halted weight gain and fat accumulation. Additionally, physical activity mitigated HFD-induced spatial and recognition memory impairments. Our data indicate that voluntary physical exercise starting after several months of periadolescent HFD exposure reverses metabolic and cognitive alterations demonstrating that voluntary exercise, in addition to its known preventive effect, also has a restorative impact on metabolism and cognition dysfunctions associated with obesity.
Metformin, the world’s most prescribed anti-diabetic drug, is also effective in preventing type 2 diabetes in people at high risk1,2. Over 60% of this effect is attributable to the ability of metformin to lower body weight in a sustained manner³. The molecular mechanisms by which metformin lowers body weight are unknown. In two, independent randomised controlled clinical trials, circulating levels of GDF15, recently described to reduce food intake and lower body weight through a brain stem-restricted receptor, were increased by metformin. In wild-type mice, oral metformin increased circulating GDF15 with GDF15 expression increasing predominantly in the distal intestine and the kidney. Metformin prevented weight gain in response to a high-fat diet in wild-type mice but not in mice lacking GDF15 or its receptor GFRAL. In obese, high-fat-fed mice, the effects of metformin to reduce body weight were reversed by a GFRAL antagonist antibody. Metformin had effects on both energy intake and energy expenditure that required GDF15. Metformin retained its ability to lower circulating glucose levels in the absence of GDF15 action. In summary, metformin elevates circulating levels of GDF15, which are necessary for its beneficial effects on energy balance and body weight, major contributors to its action as a chemopreventive agent.
Objective:
The development of these updated clinical practice guidelines (CPG) was commissioned by the American Association of Clinical Endocrinologists, The Obesity Society, the American Society of Metabolic and Bariatric Surgery, the Obesity Medicine Association, and the American Society of Anesthesiologists boards of directors in adherence to the American Association of Clinical Endocrinologists 2017 protocol for standardized production of CPG, algorithms, and checklists.
Methods:
Each recommendation was evaluated and updated based on new evidence from 2013 to the present and subjective factors provided by experts.
Results:
New or updated topics in this CPG include contextualization in an adiposity-based, chronic disease complications-centric model, nuance-based, and algorithm/checklist-assisted clinical decision-making about procedure selection, novel bariatric procedures, enhanced recovery after bariatric surgery protocols, and logistical concerns (including cost factors) in the current healthcare arena. There are 85 numbered recommendations that have updated supporting evidence, of which 61 are revised and 12 are new. Noting that there can be multiple recommendation statements within a single numbered recommendation, there are 31 (13%) Grade A, 42 (17%) Grade B, 72 (29%) Grade C, and 101 (41%) Grade D recommendations. There are 858 citations, of which 81 (9.4%) are evidence level (EL) 1 (highest), 562 (65.5%) are EL 2, 72 (8.4%) are EL 3, and 143 (16.7%) are EL 4 (lowest).
Conclusions:
Bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity. Clinical decision-making should be evidence-based within the context of a chronic disease. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues.
Diabetes is a major cause of morbidity and mortality in the United States (1-3). Diabetes can be present but undiagnosed, meaning that a person can have diabetes but not report having ever been told by a doctor or health professional that they have the condition. Type 2 diabetes can progress over an extended time period with gradual, often unnoticed, changes occurring before diagnosis. If left unmanaged, diabetes may contribute to serious health outcomes including neuropathy, nephropathy, retinopathy, coronary artery disease, stroke, and peripheral vascular disease (4). This report presents the prevalence of total, diagnosed, and undiagnosed diabetes in U.S. adults in 2013-2016.
Objective:
This study updates previous estimates of the economic burden of diagnosed diabetes and quantifies the increased health resource use and lost productivity associated with diabetes in 2017.
Research design and methods:
We use a prevalence-based approach that combines the demographics of the U.S. population in 2017 with diabetes prevalence, epidemiological data, health care cost, and economic data into a Cost of Diabetes Model. Health resource use and associated medical costs are analyzed by age, sex, race/ethnicity, insurance coverage, medical condition, and health service category. Data sources include national surveys, Medicare standard analytical files, and one of the largest claims databases for the commercially insured population in the U.S.
Results:
The total estimated cost of diagnosed diabetes in 2017 is $327 billion, including $237 billion in direct medical costs and $90 billion in reduced productivity. For the cost categories analyzed, care for people with diagnosed diabetes accounts for 1 in 4 health care dollars in the U.S., and more than half of that expenditure is directly attributable to diabetes. People with diagnosed diabetes incur average medical expenditures of ∼$16,750 per year, of which ∼$9,600 is attributed to diabetes. People with diagnosed diabetes, on average, have medical expenditures ∼2.3 times higher than what expenditures would be in the absence of diabetes. Indirect costs include increased absenteeism ($3.3 billion) and reduced productivity while at work ($26.9 billion) for the employed population, reduced productivity for those not in the labor force ($2.3 billion), inability to work because of disease-related disability ($37.5 billion), and lost productivity due to 277,000 premature deaths attributed to diabetes ($19.9 billion).
Conclusions:
After adjusting for inflation, economic costs of diabetes increased by 26% from 2012 to 2017 due to the increased prevalence of diabetes and the increased cost per person with diabetes. The growth in diabetes prevalence and medical costs is primarily among the population aged 65 years and older, contributing to a growing economic cost to the Medicare program. The estimates in this article highlight the substantial financial burden that diabetes imposes on society, in addition to intangible costs from pain and suffering, resources from care provided by nonpaid caregivers, and costs associated with undiagnosed diabetes.
IN BRIEF Patients with obesity and type 2 diabetes are key targets for weight loss. Given the lack of behavioral weight loss in most patients, obesity pharmacotherapy options should be considered in this patient population. This article reviews key pharmacotherapy options for patients with coexisting obesity and type 2 diabetes. Diabetes medications that are associated with weight gain should be avoided in these patients if possible.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an attractive novel therapeutic option for the treatment of type 2 diabetes. They block the reabsorption of filtered glucose in kidneys, mainly in proximal renal tubules, resulting in increased urinary glucose excretion and correction of the diabetes-related hyperglycemia. Beyond improving glucose control, SGLT2 inhibitors offer potential benefits by reducing body weight and blood pressure. On the basis of the efficacy demonstrated in clinical trials, SGLT2 inhibitors are recommended as second- or third-line agents for the management of patients with type 2 diabetes. Beneficial effects on kidney disease progression, cardiovascular and all-cause mortality, and hospitalization for heart failure have also been demonstrated with one SGLT2 inhibitor (empagliflozin). Potential adverse events resulting from their mechanism of action or related to concomitant therapies are reviewed. A treatment algorithm for the adjustment of concomitant therapies after initiating SGLT2 inhibitors is also proposed.
Aims:
Small, short studies suggest metformin influences the glucagon-like peptide (GLP)-1 axis in individuals with and without type 2 diabetes (T2DM). In the Carotid Atherosclerosis: Metformin for insulin ResistAnce (CAMERA) trial (NCT00723307) we investigated whether this effect is sustained and related to changes in glycaemia or weight. In the cross-sectional DIabetes REsearCh on patient straTification (DIRECT) study, we investigated basal and post-meal GLP-1 levels in diabetic patients.
Materials and methods:
CAMERA was a double-blinded randomized placebo-controlled trial of metformin in 173 participants without diabetes. Using six-monthly fasted total GLP-1 levels over 18 months, we evaluated metformin's effect on total GLP-1 with repeated-measures and ANCOVA analyses. In DIRECT, we examined active and total fasting and 60-minute post-meal GLP-1 levels in 775 patients recently diagnosed with T2DM treated with metformin or diet, using Student's T-tests and linear regression.
Results:
In CAMERA, metformin increased total GLP-1 at 6 (+20.7%, [95% confidence intervals 4.7-39.0%]), 12 (+26.7% [10.3-45.6%]) and 18 months (+18.7% [3.8-35.7%]), an overall increase of 23.4% (11.2-36.9%; p < 0.0001) versus placebo. Adjustment for changes in glycaemia and adiposity, individually or combined, did not attenuate this effect. In DIRECT, metformin was associated with higher fasting active (39.1% [21.3-56.4%]) and total GLP-1 (14.1% [1.2-25.9%]) but not post-meal incremental GLP-1. These changes were independent of potential confounders including age, sex, adiposity and HbA1c.
Conclusions:
In non-diabetic individuals, metformin increases total GLP-1 in a sustained manner and independently of changes in weight or glycaemia. Metformin-treated diabetic patients also have higher fasted GLP-1 independent of weight and glycaemia.
The combination of basal insulin and a glucagon-like peptide 1 receptor agonist is becoming increasingly common and offers several potential benefits to patients with type 2 diabetes. Clinical studies have demonstrated improved glycemic control and low risks of hypoglycemia and weight gain with the combination, which provides a safe and effective alternative to basal-bolus insulin with less treatment burden. Fixed-ratio combination products that administer both agents in a single injection are in the pipeline and will offer additional options for clinicians and patients. This review focuses on the rationale for, clinical evidence on, and implications of using this combination of therapies in the treatment of type 2 diabetes.
Weight loss of 5% to 10% can improve type 2 diabetes and related comorbidities. Few safe, effective weight-management drugs are currently available.
To investigate efficacy and safety of liraglutide vs placebo for weight management in adults with overweight or obesity and type 2 diabetes.
Fifty-six-week randomized (2:1:1), double-blind, placebo-controlled, parallel-group trial with 12-week observational off-drug follow-up period. The study was conducted at 126 sites in 9 countries between June 2011 and January 2013. Of 1361 participants assessed for eligibility, 846 were randomized. Inclusion criteria were body mass index of 27.0 or greater, age 18 years or older, taking 0 to 3 oral hypoglycemic agents (metformin, thiazolidinedione, sulfonylurea) with stable body weight, and glycated hemoglobin level 7.0% to 10.0%.
Once-daily, subcutaneous liraglutide (3.0 mg) (n = 423), liraglutide (1.8 mg) (n = 211), or placebo (n = 212), all as adjunct to 500 kcal/d dietary deficit and increased physical activity (≥150 min/wk).
Three coprimary end points: relative change in weight, proportion of participants losing 5% or more, or more than 10%, of baseline weight at week 56.
Baseline weight was 105.7 kg with liraglutide (3.0-mg dose), 105.8 kg with liraglutide (1.8-mg dose), and 106.5 kg with placebo. Weight loss was 6.0% (6.4 kg) with liraglutide (3.0-mg dose), 4.7% (5.0 kg) with liraglutide (1.8-mg dose), and 2.0% (2.2 kg) with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, -4.00% [95% CI, -5.10% to -2.90%]; liraglutide [1.8 mg] vs placebo, -2.71% [95% CI, -4.00% to -1.42%]; P < .001 for both). Weight loss of 5% or greater occurred in 54.3% with liraglutide (3.0 mg) and 40.4% with liraglutide (1.8 mg) vs 21.4% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 32.9% [95% CI, 24.6% to 41.2%]; for liraglutide [1.8 mg] vs placebo, 19.0% [95% CI, 9.1% to 28.8%]; P < .001 for both). Weight loss greater than 10% occurred in 25.2% with liraglutide (3.0 mg) and 15.9% with liraglutide (1.8 mg) vs 6.7% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 18.5% [95% CI, 12.7% to 24.4%], P < .001; for liraglutide [1.8 mg] vs placebo, 9.3% [95% CI, 2.7% to 15.8%], P = .006). More gastrointestinal disorders were reported with liraglutide (3.0 mg) vs liraglutide (1.8 mg) and placebo. No pancreatitis was reported.
Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks. Further studies are needed to evaluate longer-term efficacy and safety.
clinicaltrials.gov Identifier:NCT01272232.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are gaining ground as therapeutic modalities in combination with insulin in patients with type 2 diabetes mellitus. Exploiting the multiple benefits of incretin-based therapies in certain patient populations, especially in those who would benefit most from potential weight loss or prevention of body weight gain, has provided a valuable add-on option in diabetes management. However, caution needs to be exercised when initiating such a double injectable therapy, as evidence indicates that, in most instances, the insulin dose needs to be re-adjusted. The majority of published studies suggest reduction of insulin dose, especially related to the ‘bolus’ component; however, some have also recommended that insulin dose should actually be increased, but we found no credible evidence to support the latter. An important determinant of the titration process is the insulin formulation already in use at baseline. As more potent and long-acting GLP-1RAs are introduced, optimal insulin dose scaling is a major challenge, especially in a primary setting. We provide an overview of the current knowledge in this rapidly changing field. Based on currently reported evidence, a reduction of basal insulin by 10% and a decrease of prandial insulin by 30 – 40% is recommended on addition of GLP-1RAs.
OBJECTIVE
To assess the efficacy and safety of 32 mg naltrexone sustained-release (SR)/360 mg bupropion SR (NB) in overweight/obese individuals with type 2 diabetes with or without background oral antidiabetes drugs.
RESEARCH DESIGN AND METHODS
This was a 56-week, double-blind, placebo-controlled study in which 505 patients received standardized lifestyle intervention and were randomized 2:1 to NB or placebo. Coprimary end points were percent weight change and achievement of ≥5% weight loss. Secondary end points included achievement of HbA1c <7% (53 mmol/mol), achievement of weight loss ≥10%, and change in HbA1c, waist circumference, fasting blood glucose, and lipids.
RESULTS
In the modified intent-to-treat population (54% female, 80% Caucasian, and mean age 54 years, weight 106 kg, BMI 37 kg/m2, and HbA1c 8.0% [64 mmol/mol]), NB resulted in significantly greater weight reduction (−5.0 vs. −1.8%; P < 0.001) and proportion of patients achieving ≥5% weight loss (44.5 vs. 18.9%, P < 0.001) compared with placebo. NB also resulted in significantly greater HbA1c reduction (−0.6 vs. −0.1% [6.6 vs. 1.1 mmol/mol]; P < 0.001), percent of patients achieving HbA1c <7% (53 mmol/mol) (44.1 vs. 26.3%; P < 0.001), and improvement in triglycerides and HDL cholesterol compared with placebo. NB was associated with higher incidence of nausea (42.3 vs. 7.1%), constipation (17.7 vs. 7.1%), and vomiting (18.3 vs. 3.6%). No difference was observed between groups in the incidence of depression, suicidal ideation, or hypoglycemia.
CONCLUSIONS
NB therapy in overweight/obese patients with type 2 diabetes induced weight loss, which was associated with improvements in glycemic control and select cardiovascular risk factors and was generally well tolerated with a safety profile similar to that in patients without diabetes.
Background:
Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients.
Methods:
In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years.
Results:
The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51).
Conclusions:
An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).
Harmon S. Jordan, ScD, Karima A. Kendall, PhD, Linda J. Lux, Roycelynn Mentor-Marcel, PhD, MPH, Laura C. Morgan, MA, Michael G. Trisolini, PhD, MBA, Janusz Wnek, PhD
Jeffrey L. Anderson, MD, FACC, FAHA, Chair , Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect , Nancy M. Albert, PhD, CCNS, CCRN,
Background
No data from randomised controlled trials of metabolic surgery for diabetes are available beyond 5 years of follow-up. We aimed to assess 10-year follow-up after surgery compared with medical therapy for the treatment of type 2 diabetes.
Methods
We did a 10-year follow-up study of an open-label, single-centre (tertiary hospital in Rome, Italy), randomised controlled trial, in which patients with type 2 diabetes (baseline duration >5 years; glycated haemoglobin [HbA 1c] >7·0%, and body-mass index ≥35 kg/m ²) were randomly assigned (1:1:1) to medical therapy, Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD) by a computerised system. The primary endpoint of the study was diabetes remission at 2 years (HbA 1c <6·5% and fasting glycaemia <5·55 mmol/L without ongoing medication for at least 1 year). In the 10-year analysis, durability of diabetes remission was analysed by intention to treat (ITT). This study is registered with ClinicalTrials.gov, NCT00888836.
Findings
Between April 30, 2009, and Oct 31, 2011, of 72 patients assessed for eligibility, 60 were included. The 10-year follow-up rate was 95·0% (57 of 60). Of all patients who were surgically treated, 15 (37·5%) maintained diabetes remission throughout the 10-year period. Specifically, 10-year remission rates in the ITT population were 5·5% for medical therapy (95% CI 1·0–25·7; one participant went into remission after crossover to surgery), 50·0% for BPD (29·9–70·1), and 25·0% for RYGB (11·2–46·9; p=0·0082). 20 (58·8%) of 34 participants who were observed to be in remission at 2 years had a relapse of hyperglycaemia during the follow-up period (BPD 52·6% [95% CI 31·7–72·7]; RYGB 66·7% [41·7–84·8]). All individuals with relapse, however, maintained adequate glycaemic control at 10 years (mean HbA 1c 6·7% [SD 0·2]). Participants in the RYGB and BPD groups had fewer diabetes-related complications than those in the medical therapy group (relative risk 0·07 [95% CI 0·01–0·48] for both comparisons). Serious adverse events occurred more frequently among participants in the BPD group (odds ratio [OR] for BPD vs medical therapy 2·7 [95% CI 1·3–5·6]; OR for RYGB vs medical therapy 0·7 [0·3–1·9]).
Interpretation
Metabolic surgery is more effective than conventional medical therapy in the long-term control of type 2 diabetes. Clinicians and policy makers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes.
Funding
Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
It is unknown whether weight loss outcomes differ with metformin monotherapy in patients with obesity with or without type 2 diabetes (T2DM)/prediabetes (PreDM). In this retrospective study, 6- or 12-month weight loss outcomes were compared in 222 patients with or without T2DM/preDM who completed metformin monotherapy. Average weight loss was similar between groups, euglycemic vs. T2DM/preDM (6 months: 6.5 [6.0%] vs. 6.5 [6.1%] p = 0.97; 12 months: 7.4 [6.2%] vs. 7.3 [7.7%], p = 0.92). Categorical weight losses (≥5% and ≥10% of baseline weight) were also similar. Comparable clinically significant weight loss was achieved with metformin monotherapy in patients with obesity with or without T2DM/PreDM.
Obesity is a chronic disease caused by dysregulated energy homeostasis pathways that encourage the accumulation of adiposity, which in turn results in the development or exacerbation of weight-related comorbidities. Treatment of obesity relies on a foundation of lifestyle modification; weight loss pharmacotherapy, bariatric surgery and devices are additional tools to help patients achieve their health goals. Appropriate management of patients with obesity provides multiple metabolic benefits beyond weight loss.
Obesity shortens life expectancy. Bariatric surgery is known to reduce the long-term relative risk of death, but its effect on life expectancy is unclear.
We used the Gompertz proportional hazards regression model to compare mortality and life expectancy among patients treated with either bariatric surgery (surgery group) or usual obesity care (control group) in the prospective, controlled Swedish Obese Subjects (SOS) study and participants in the SOS reference study (reference cohort), a random sample from the general population.
In total, 2007 and 2040 patients were included in the surgery group and the control group, respectively, and 1135 participants were included in the reference cohort. At the time of the analysis (December 31, 2018), the median duration of follow-up for mortality was 24 years (interquartile range, 22 to 27) in the surgery group and 22 years (interquartile range, 21 to 27) in the control group; data on mortality were available for 99.9% of patients in the study. In the SOS reference cohort, the median duration of follow-up was 20 years (interquartile range, 19 to 21), and data on mortality were available for 100% of participants. In total, 457 patients (22.8%) in the surgery group and 539 patients (26.4%) in the control group died (hazard ratio, 0.77; 95% confidence interval [CI], 0.68 to 0.87; P<0.001). The corresponding hazard ratio was 0.70 (95% CI, 0.57 to 0.85) for death from cardiovascular disease and 0.77 (95% CI, 0.61 to 0.96) for death from cancer. The adjusted median life expectancy in the surgery group was 3.0 years (95% CI, 1.8 to 4.2) longer than in the control group but 5.5 years shorter than in the general population. The 90-day postoperative mortality was 0.2%, and 2.9% of the patients in the surgery group underwent repeat surgery.
Among patients with obesity, bariatric surgery was associated with longer life expectancy than usual obesity care. Mortality remained higher in both groups than in the general population.
Over recent decades, an improved understanding of the pathophysiology of type 2 diabetes mellitus (T2DM) and glucose regulation has led to innovative research and new treatment paradigms. The discovery of the gut peptide glucagon-like peptide-1 (GLP-1) and its role in glucose regulation paved the way for the class of GLP-1 receptor agonist compounds, or GLP-1RAs. The long-acting GLP-1RAs (dulaglutide, exenatide extended-release, liraglutide, semaglutide [injectable and oral]) are classified as such based on a minimum 24-hour duration of clinically relevant effects after administration. In phase 3 clinical trial programs of long-acting GLP-1RAs, A1C typically was reduced in the range of 1% to 1.5%, with reductions close to 2% in some studies. GLP-1RAs when used alone (without sulfonylureas or insulin) have a low risk of hypoglycemia because, like endogenous GLP-1, their insulinotropic effects are glucose-dependent. In addition to local actions in the gastrointestinal (GI) tract, GLP-1RAs stimulate receptors in the central nervous system to increase satiety, resulting in weight loss. All long-acting GLP-1RAs have, at minimum, been shown to be safe and not increase cardiovascular (CV) risk and most (liraglutide, semaglutide injectable, dulaglutide, albiglutide) have been shown in CV outcomes trials (CVOTs) to significantly reduce the risk of major cardiac adverse events. The class has good tolerability overall, with generally transient GI adverse events being most common. The weekly injectable agents offer scheduling convenience and may promote treatment adherence. One long-acting GLP-1RA is available as an oral daily tablet, which may be preferable for some patients and providers.
CONTEXT
Questions remain about bariatric surgery for type 2 diabetes mellitus (T2DM) treatment.
OBJECTIVE
Compare the remission of T2DM following surgical or non-surgical treatments.
DESIGN, SETTING, AND PARTICIPANTS
Randomized Controlled Trial at the University of Pittsburgh, in the United States. Five year follow up from February 2015 until June 2016.
INTERVENTIONS
61 participants with obesity and T2DM who were initially randomized to either bariatric surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) or an intensive lifestyle weight loss intervention (LWLI) program for 1 year. Lower level lifestyle weight loss interventions (LLLI) were then delivered for 4 years.
MAIN OUTCOMES AND MEASURES
Diabetes remission assessed at 5 years.
RESULTS
The mean age of the patients was 47 ± 6.6 years, 82% were women, and 21% African American. Mean hemoglobin A1c level 7.8% ± 1.9%, BMI 35.7 ± 3.1 kg/m2 and 26 participants (43%) had Body Mass Index (BMI) <35kg/m2. Partial or complete T2DM remission was achieved by 30% (n=6) of RYGB, 19% (n=4) of LAGB, and no LWLI participants (p=0.0208). At 5 years those in the RYGB group had the largest percentage of individuals (56%) not requiring any medications for T2DM compared to those in the LAGB (45%) and LWLI (0%) groups (p=0.0065). Mean reductions in percent body weight at 5 years was the greatest after RYGB 25.2% ± 2.1%, followed by LAGB 12.7% ± 2.0% and lifestyle treatment 5.1% ± 2.5% (all pairwise p<0.01).
CONCLUSIONS
Surgical treatments are more effective than lifestyle intervention alone for T2DM treatment.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT01047735
Background:
Although the national obesity epidemic has been well documented, less is known about obesity at the U.S. state level. Current estimates are based on body measures reported by persons themselves that underestimate the prevalence of obesity, especially severe obesity.
Methods:
We developed methods to correct for self-reporting bias and to estimate state-specific and demographic subgroup-specific trends and projections of the prevalence of categories of body-mass index (BMI). BMI data reported by 6,264,226 adults (18 years of age or older) who participated in the Behavioral Risk Factor Surveillance System Survey (1993-1994 and 1999-2016) were obtained and corrected for quantile-specific self-reporting bias with the use of measured data from 57,131 adults who participated in the National Health and Nutrition Examination Survey. We fitted multinomial regressions for each state and subgroup to estimate the prevalence of four BMI categories from 1990 through 2030: underweight or normal weight (BMI [the weight in kilograms divided by the square of the height in meters], <25), overweight (25 to <30), moderate obesity (30 to <35), and severe obesity (≥35). We evaluated the accuracy of our approach using data from 1990 through 2010 to predict 2016 outcomes.
Results:
The findings from our approach suggest with high predictive accuracy that by 2030 nearly 1 in 2 adults will have obesity (48.9%; 95% confidence interval [CI], 47.7 to 50.1), and the prevalence will be higher than 50% in 29 states and not below 35% in any state. Nearly 1 in 4 adults is projected to have severe obesity by 2030 (24.2%; 95% CI, 22.9 to 25.5), and the prevalence will be higher than 25% in 25 states. We predict that, nationally, severe obesity is likely to become the most common BMI category among women (27.6%; 95% CI, 26.1 to 29.2), non-Hispanic black adults (31.7%; 95% CI, 29.9 to 33.4), and low-income adults (31.7%; 95% CI, 30.2 to 33.2).
Conclusions:
Our analysis indicates that the prevalence of adult obesity and severe obesity will continue to increase nationwide, with large disparities across states and demographic subgroups. (Funded by the JPB Foundation.).
Purpose of review:
In recent years, there have been several cardiovascular outcomes trials (CVOT) of two new classes of glucose-lowering medications: sodium-glucose cotransporter-2 inhibitors (SGLT2-i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA). It is important examine their potential for cardiovascular benefit and possible side effects among patients with type 2 diabetes (T2D) mellitus.
Recent findings:
The current article reviews the findings of recent CVOT of SGLT2-i and GLP-1 RA, including their impact on cardiovascular events and relevant side effects.
Summary:
For all T2D patients, with or without established cardiovascular disease, the SGLT2-i have demonstrated impressive reductions in hospitalization for heart failure and renoprotection. For T2D patients with established cardiovascular disease, SGLT2-i demonstrated an additional benefit of reduced major adverse cardiac events, on top of reductions in hospitalizations for heart failure, renoprotection, and in some instances, mortality. Similarly, all GLP-1 RA CVOTs demonstrated noninferiority compared with placebo for safety. In comparison, GLP-1 RA appear to preferentially reduce ischemic events (stroke or myocardial infarction) over hospitalization for heart failure, and demonstrated renoprotection in several of the CVOTs.
Objective:
The aim of this study was to obtain estimates of changes in perioperative outcomes and utilization of bariatric surgery in the United States from 1993 to 2016.
Background:
Bariatric surgery has evolved over the past 2 decades. Nationally representative information on changes of perioperative outcomes and utilization of surgery in the growing eligible population (class III obesity or class II obesity with comorbidities) is lacking.
Methods:
Adults with obesity diagnosis who underwent primary bariatric surgery in the United States from 1993 to 2016 were identified in the National Inpatient Sample database. Estimates of the yearly number, types and cost of surgeries, patients' and hospital characteristics, complications and mortality rates were obtained. Prevalence of obesity and comorbidities were obtained from the National Health and Nutrition Examination Survey and changes in utilization of surgery were estimated.
Results:
An estimated 1,903,273 patients underwent bariatric surgery in the United States between 1993 and 2016. Mean age was 43.9 years (79.9% women, 70.9% white race, 70.7% commercial insurance); these and other characteristics changed over time. Surgeries were exclusively open operations in 1993 (n = 8,631; gastric bypass and vertical banded gastroplasty, 49% each) and 98% laparoscopic (n = 162,969; 69.8% sleeve gastrectomy and 27.8% gastric bypass) in 2016. Complication and mortality rates peaked in 1998 (11.7% and 1%) and progressively decreased to 1.4% and 0.04% in 2016. Utilization increased from 0.07% in 1993 to 0.62% in 2004 and remained low at 0.5% in 2016.
Conclusions:
Perioperative safety of bariatric surgery improved over the last quarter-century. Despite growth in number of surgeries, utilization has only marginally increased. Addressing barriers for utilization may allow for greater access to surgical therapy.
Despite intensive research, the causes of the obesity epidemic remain incompletely understood and conventional calorie-restricted diets continue to lack long-term efficacy. According to the carbohydrate-insulin model (CIM) of obesity, recent increases in the consumption of processed, high–glycemic-load carbohydrates produce hormonal changes that promote calorie deposition in adipose tissue, exacerbate hunger, and lower energy expenditure. Basic and genetic research provides mechanistic evidence in support of the CIM. In animals, dietary composition has been clearly demonstrated to affect metabolism and body composition, independently of calorie intake, consistent with CIM predictions. Meta-analyses of behavioral trials report greater weight loss with reduced-glycemic load vs low-fat diets, though these studies characteristically suffer from poor long-term compliance. Feeding studies have lacked the rigor and duration to test the CIM, but the longest such studies tend to show metabolic advantages for low-glycemic load vs low-fat diets. Beyond the type and amount of carbohydrate consumed, the CIM provides a conceptual framework for understanding how many dietary and nondietary exposures might alter hormones, metabolism, and adipocyte biology in ways that could predispose to obesity. Pending definitive studies, the principles of a low-glycemic load diet offer a practical alternative to the conventional focus on dietary fat and calorie restriction.
Metabolic surgery is unrivaled by other therapeutic modalities due to its ability to foster diabetes remission. Metabolic surgery is an integral therapeutic modality in obese and morbidly obese populations because pharmacological and behavioral therapy often fail to effectively manage type II diabetes. However, given the invasiveness of the metabolic surgery relative to behavioral therapy and the need to conform to preparatory and discharge guidelines, patients must adhere to strict nutritional and diabetes management protocols. Also, the pharmacological regimen that is instituted upon discharge is distinct from the preoperative regimen. Oftentimes, the dose for insulin and oral medications are significantly decreased or withdrawn. As time elapses and depending on several factors (e.g., exercise adherence), diabetes control becomes tenuous in a small portion of the patients because there is weight regain and on-going beta cell failure. At this time interval, intensification of diabetes therapy becomes prudent. Indeed, pharmacotherapy from the preoperative to the postoperative phase is labile and may be complex. Therefore, by discussing pharmacology options during the preoperative, perioperative, and postoperative period, the goal is to guide clinician-driven care.
Background
Long-term results from randomized, controlled trials that compare medical therapy with surgical therapy in patients with type 2 diabetes are limited.
Methods
We assessed outcomes 5 years after 150 patients who had type 2 diabetes and a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 27 to 43 were randomly assigned to receive intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The primary outcome was a glycated hemoglobin level of 6.0% or less with or without the use of diabetes medications.
Results
Of the 150 patients who underwent randomization, 1 patient died during the 5-year follow-up period; 134 of the remaining 149 patients (90%) completed 5 years of follow-up. At baseline, the mean (±SD) age of the 134 patients was 49±8 years, 66% were women, the mean glycated hemoglobin level was 9.2±1.5%, and the mean BMI was 37±3.5. At 5 years, the criterion for the primary end point was met by 2 of 38 patients (5%) who received medical therapy alone, as compared with 14 of 49 patients (29%) who underwent gastric bypass (unadjusted P=0.01, adjusted P=0.03, P=0.08 in the intention-to-treat analysis) and 11 of 47 patients (23%) who underwent sleeve gastrectomy (unadjusted P=0.03, adjusted P=0.07, P=0.17 in the intention-to-treat analysis). Patients who underwent surgical procedures had a greater mean percentage reduction from baseline in glycated hemoglobin level than did patients who received medical therapy alone (2.1% vs. 0.3%, P=0.003). At 5 years, changes from baseline observed in the gastric-bypass and sleeve-gastrectomy groups were superior to the changes seen in the medical-therapy group with respect to body weight (−23%, −19%, and −5% in the gastric-bypass, sleeve-gastrectomy, and medical-therapy groups, respectively), triglyceride level (−40%, −29%, and −8%), high-density lipoprotein cholesterol level (32%, 30%, and 7%), use of insulin (−35%, −34%, and −13%), and quality-of-life measures (general health score increases of 17, 16, and 0.3; scores on the RAND 36-Item Health Survey ranged from 0 to 100, with higher scores indicating better health) (P<0.05 for all comparisons). No major late surgical complications were reported except for one reoperation.
Conclusions
Five-year outcome data showed that, among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing, or in some cases resolving, hyperglycemia. (Funded by Ethicon Endo-Surgery and others; STAMPEDE ClinicalTrials.gov number, NCT00432809.)
The adoption and maintenance of physical activity are critical foci for blood glucose management and overall health in individuals with diabetes and prediabetes. Recommendations and precautions vary depending on individual characteristics and health status. In this Position Statement, we provide a clinically oriented review and evidence-based recommendations regarding physical activity and exercise in people with type 1 diabetes, type 2 diabetes, gestational diabetes mellitus, and prediabetes.
Context:
Vitamin B12 deficiency may occur with metformin treatment, but few studies have assessed risk with long-term use.
Objective:
To assess risk of B12 deficiency with metformin use in the DPP/DPPOS Design: Secondary analysis from DPP/DPPOS. Participants were assigned to placebo (n=1082, PLA) or metformin (n=1073, MET) for 3.2 years; MET received open-label metformin for an additional 9 years.
Setting:
27 study centers in the US Patients: DPP eligibility: elevated fasting glucose, impaired glucose tolerance, and overweight/obesity. Analytic population: participants with available stored samples. B12 levels were assessed at 5 (n=857, n=858) and 13 years [n=756, n=764] in PLA and MET, respectively.
Interventions:
Metformin 850 mg twice daily versus placebo (DPP); open-label metformin in MET (DPPOS) Main Outcome Measures: B12 deficiency, anemia, peripheral neuropathy Results: Low B12 (≤203 pg/ml) occurred more often in MET than PLA at 5 years (4.3% vs 2.3%, p=0.02) but not at 13 years (7.4% vs. 5.4%, p=0.12). Combined low and borderline-low B12 (≤298 pg/ml) was more common in MET at 5 (19.1% vs 9.5%, p<0.01) and 13 years (20.3% vs 15.6%, p=0.02). Years of metformin use was associated with increased risk of B12 deficiency (OR B12 deficiency/year metformin use, 1.13, 95% CI 1.06-1.20). Anemia prevalence was higher in MET, but did not differ by B12 status. Neuropathy prevalence was higher in MET with low B12 levels.
Conclusions:
Long-term use of metformin in DPPOS was associated with biochemical B12 deficiency and anemia. Routine testing of vitamin B12 levels in metformin-treated patients should be considered.