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Lactobacillus rhamnosus GG and HbA1c in middle age and older adults without type 2 diabetes mellitus: A preliminary randomized study

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Abstract

Background and aims Probiotic supplementation improves glycemic control in persons with diabetes and the current study examined whether these benefits extend to healthy individuals. Methods The current study was a 90-day placebo-controlled, double-blind, randomized clinical trial of Lactobacillus rhamnosus GG in healthy middle-aged and older adults. Fasting blood glucose and HbA1c were quantified at baseline and follow up. Results ANCOVA controlling for baseline values showed group differences in follow up HbA1c [F (1,90) = 8.44, p = 0.005]; HbA1c values increased in the placebo group, though remained stable in the probiotic group. Conclusions If replicated, Lactobacillus rhamnosus GG may protect against changes in glycemic control.

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... Probiotic supplementation in T2DM patients has demonstrated an improvement in glycemic control, lower glycated hemoglobin (HbA1c), and fasting blood glucose. Supplementation with Lactobacillus rhamnosus GG has shown to promote stable HbA1c levels over time (Sanborn, Azcarate-Peril, & Gunstad, 2020). Bifidobacterium adolescentis is another species with probiotic potential; it has reported activities such as inhibition of pro-inflammatory cytokines and inhibition of α-glucosidase and α-amylase. ...
Article
Diabetes mellitus type 2 (T2DM) is associated with hyperglycemia, insulin resistance, and gut dysbiosis. Probiotics and prebiotics can ameliorate T2DM through different mechanisms of action, such as reducing oxidative stress, or the inhibition of pro-inflammatory markers, among others. Multiple studies in vitro and in vivo have demonstrated the reduction of hyperglycemia, depressive behaviors, obesity, oxidative stress, and insulin resistance in diabetic patients through the consumption of dairy products, such as yogurt, fermented milk, and cheese, enriched with potential probiotic strains, prebiotic ingredients, and synbiotics (understood as a combination of both). Therefore, this review aims to provide an updated overview about the impact of dairy foods with probiotics, prebiotics, or synbiotics to prevent and manage T2DM, the mechanism of action related to the host health, and the future tendencies for developing new dairy foods. Despite the addition of probiotics, prebiotics, and synbiotics to dairy products could be highly beneficial, more evidence, especially from clinical trials, is needed to develop evidence-based T2DM prevention guidelines.
... 6,7 Furthermore, healthy middle-aged and older adults who took L. rhamnosus GG for 3 months showed stable glycated hemoglobin values. 8 Moreover, Lactobacillus rhamnosus not only alleviates the hyperglycemia but also modulates the gut microbiota to obtain multiple health benefits. Oral administration of Lactobacillus rhamnosus GG could reduce conditional pathogenic bacteria (such as Proteobactria and Deferribacteres) to alleviate mortality of sepsis. ...
... Concerning liquid formulations, five trials used probiotic yogurt [21-23, 31, 32], three studies used fermented milk [33][34][35], one used soy milk [36], one used a shake [37], one used a syrup [38] and one used a decoction [39] as the carrier. Regarding solid pharmaceutical formulations, ten studies used capsules [24,[40][41][42][43][44][45][46][47][48], six studies used sachets [49][50][51][52][53][54], and five used powder package [29,[55][56][57][58] as the source of probiotics. Four studies used other types of foods for supplementation [20,[59][60][61]. ...
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Chapter
“Probiotics” are defined as the live microorganisms that exhibit a beneficial effect on the host health when administered in adequate amount. The science of probiotics has emerged very rapidly since the last few decades and acquired much acceptance as a source of viable therapeutics that serves a successful way for the treatment of various intestinal, nonintestinal (urinary, vaginal, respiratory, hepatic, and neurological), and other metabolic diseases. Several studies have demonstrated probiotics to be the most potent way to combat central components of metabolic syndrome, such as diabetes including type 1 diabetes (T1D) and type 2 diabetes (T2D), along with obesity issues. These diseases are life-threatening as they provide a source of other associated diseases, namely cardiovascular diseases, metabolic syndrome, and other possible disorders. In the situation of T1D and T2D, most of these probiotics possess certain antidiabetic characteristics, which lead to the reduction of glycemic index, oxidative stress, triglyceride levels, inhibition of proinflammatory cytokines, α-amylase, and α-glucosidase, and amelioration of gut dysbiosis. The productions of short-chain fatty acids (SCFAs), as end products of complex interactions between prebiotics and the gut microbiota, have been shown to exert multiple effects on host energy homeostasis through the production of glucagon-like peptide 1 (GLP-1), which downregulates lipogenesis and insulin resistance in the host body along with the enhancement of gut integrity. On the other hand, probiotics also present several antiobesity effects by regulating adipogenesis and increasing energy expenditure. Several probiotics alter the consequences of overweight through improved production of conjugated linoleic acid, decreased total cholesterol, free fatty acids, and endotoxins with improved mucosal integrity through modulation of gut microbiota. Therefore probiotics offer a very promising role in the treatment of diabetes and obesity diseases. Hence, this chapter emphasizes mainly the crucial role of probiotics in the prevention and management of diabetes (T1D and T2D) as well as obesity.
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Acentral principle in science and medicine is that the more independent pieces of evidence there are that agree, the more convincing it is that a hypothesis—or diagnosis—is valid. The opposite is also true: discordant information leads to uncertainty. Unfortunately, it is not uncommon for clinicians caring for people with diabetes to encounter individuals in whom HbA1c and blood glucose simply do not match. Sometimes, there is an obvious explanation such as hemolytic anemia. But when it occurs in people with reliable blood glucose records and ostensibly normal peripheral blood and reticulocyte counts, without evidence of hemoglobinopathy, hemolytic disorder, blood loss/transfusion, or nutritional deficiency such as iron, folate, or vitamin B12, we are left with the questions of how the discordant information should be treated and what it means for patient care. Part of the challenge is that even the best characterization of the association between HbA1c and blood glucose shows an imperfect relationship in populations. For example, at an HbA1c of 6.0%, the mean blood glucose has a 95% CI ranging from 100 to 152 mg/dL. This overlaps with the 95% CI for the mean blood glucose at an HbA1c of 7.0%, which is 123–185 mg/dL (1). Such wide variation reinforces the notion that HbA1c and blood glucose are not exactly equivalent. Moreover, it raises the question of whether a binary cut point for HbA1c in the diagnosis of diabetes, such as 6.5% (2), is an adequate representation of blood glucose and suggests that reliance only on HbA1c could miss persons with diabetes and falsely diagnose those without (3,4). But, if we obtain both glucose measurements and HbA1c, we are left with what to do with discordant information. Three explanations are commonly advanced to explain the spread in the …
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Objective: We sought to examine associations in older adults among diabetes, glycemic control, diabetes duration, and biomarkers of hyperglycemia with incident mild cognitive impairment (MCI) and incident dementia. Research design and methods: We conducted a prospective analysis of 5,099 participants from the Atherosclerosis Risk in Communities (ARIC) Study who attended the fifth (2011-2013) exam. Cognitive status was assessed during follow-up via telephone calls, death certificate codes, surveillance, and a follow-up examination (2016-2017). We defined incident cognitive impairment as incident MCI or incident dementia in persons dementia-free at the index examination; we also examined each outcome separately. Diabetes was defined using self-report, medications, or HbA1c ≥6.5%; poor glycemic control in persons with diabetes was defined as HbA1c ≥7%. We examined the following biomarkers of hyperglycemia: HbA1c, fructosamine, glycated albumin, and 1,5-anhydroglucitol. Results: Mean age at baseline was 76 years, 59% were female, and 21% were black. Diabetes (hazard ratio [HR] 1.14 [95% CI 1.00, 1.31]), poor glycemic control in persons with diabetes (HR 1.31 [95% CI 1.05, 1.63]), and longer diabetes duration (≥5 vs. <5 years; HR 1.59 [95% CI 1.23, 2.07]) were significantly associated with incident cognitive impairment. We found a J-shaped association between HbA1c and incident dementia. Glycated albumin and fructosamine were also associated with incident dementia, independently of HbA1c. HbA1c and fructosamine were also associated with incident MCI. Conclusions: Diabetes status, poor glycemic control, and longer diabetes duration were associated with worse cognitive outcomes over a median follow-up of 5 years.
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The ratio of human to bacterial cells in the human body (microbiota) is around 1:1. As a result of co-evolution of the host mucosal immune system and the microbiota, both have developed multiple mechanisms to maintain homeostasis. However, dissociations between the composition of the gut microbiota and the human host may play a crucial role in the development of type 2 diabetes. Metformin, the most frequently administered medication to treat patients with type 2 diabetes, has only recently been suggested to alter gut microbiota composition through the increase in mucin-degrading Akkermansia muciniphila, as well as several SCFA-producing (short-chain fatty acid) microbiota. The gut microbiota of participants on metformin has exerted alterations in gut metabolomics with increased ability to produce butyrate and propionate, substances involved in glucose homeostasis. Thus, metformin appears to affect the microbiome, and an individual’s metformin tolerance or intolerance may be influenced by their microbiome. In this review, we will focus on the effects of metformin in gut microbiota among patients with T2DM.
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Context The rising prevalence of type 2 diabetes requires increased efforts to find effective therapeutic agents for this complex condition. Following the recent observation that the gut microbiota is altered in diabetic patients, researchers investigated the effect of probiotics in patients with diabetes. Objective The aim of this systematic review was to assess the effects of probiotic consumption on glycemic control in diabetic patients. Data Sources PubMed, Scopus, Web of Science (formerly ISI Web of Knowledge), Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and ProQuest Dissertations and Theses databases were searched up to November 2015. Study Selection Clinical trials in diabetic patients in whom probiotics were administered as an intervention were included. Data Extraction Primary outcomes were fasting blood glucose, insulin concentration, insulin resistance, and hemoglobin A1c. Secondary outcomes were adverse events. Data Synthesis Of the 2736 reports that were screened, 13 clinical trials met the inclusion criteria. Pooling data from eligible clinical trials revealed that probiotic supplementation significantly (P < 0.05) decreased fasting blood glucose and hemoglobin A1c in diabetic patients, although the participants’ characteristics (eg, body mass index) and the number and type of probiotic microorganisms affected the clinical response. Conclusions Administration of probiotics appears to have a beneficial role in the management of type 2 diabetes; however, more clinical studies with adequate sample sizes and sound methodology are required to inform the development of evidence-based treatment guidelines.
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Aims: To systematically review evidence of probiotic interventions against type 2 diabetes mellitus (T2DM) and analyse the effects of probiotics on glycaemic control among T2DM patients. Methods: Electronic search using five electronic databases was performed until October 2015. Relevant studies were identified, extracted and assessed for risk of bias. The primary outcomes of this review were glycated haemoglobin (HbA1c) and fasting blood glucose (FBG). Fasting plasma insulin, homeostasis model assessment-insulin resistance, C-reactive protein, interleukin-6 and malondialdehyde, were identified as the secondary outcomes. Mean differences (MD) between probiotics and control groups for all outcomes were pooled using either Fixed- or Random-Effect Model. Statistical heterogeneity was assessed using I(2) and Chi(2) tests. Results: Six randomised controlled trials (RCTs) were included in the systematic review, whereas only five were included in meta-analysis. Most RCTs were presented with low or unclear risk of bias. When compared to placebo, FBG was significantly lower with probiotic consumption (MD=-0.98mmol/L; 95% CI: -1.17, 0.78, p<0.00001), with moderate but insignificant heterogeneity noted. Insignificant changes between the groups were also noted for HbA1c and other secondary outcomes. Conclusions: A moderate hypoglycaemic effect of probiotics, with a significantly lower FBG was noted. Findings on HbA1c, anti-inflammatory and anti-oxidative effects of probiotics in the clinical setting, however, remain inconsistent. The findings imply the need for well-designed clinical studies to further assess the potential beneficial effects of probiotics in management of T2DM.
Article
AimTo determine whether using HbA1c for screening and management could be confounded by age differences, whether age effects can be explained by unrecognized diabetes and prediabetes, insulin resistance or postprandial hyperglycaemia, and whether the effects of aging have an impact on diagnostic accuracy.Methods We conducted a cross-sectional analysis in adults without known diabetes in the Screening for Impaired Glucose Tolerance (SIGT) study 2005–2008 (n=1573) and the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n=1184).ResultsBoth glucose intolerance and HbA1c levels increased with age. In univariate analyses including all subjects, HbA1c levels increased by 0.085% per AUTHOR: Please give increases in HbA1c in mmol/mol with percentages in brackets. 10 years of age in the SIGT study and by 0.094% per 10 years in the NHANES; in both datasets, the HbA1c increase was 0.08% per 10 years in subjects without diabetes, and 0.07% per 10 years in subjects with normal glucose tolerance, all P<0.001. In multivariate analyses of subjects with normal glucose tolerance, the relationship between age and HbA1c remained significant (P<0.001) after adjustment for covariates including race, BMI, waist circumference, sagittal abdominal diameter, triglyceride/HDL ratio, and fasting and 2-h plasma glucose and other glucose levels, as assessed by an oral glucose tolerance test. In both datasets, the HbA1c of an 80-year-old individual with normal glucose tolerance would be 0.35% greater than that of a 30-year-old with normal glucose tolerance, a difference that is clinically significant. Moreover, the specificity of HbA1c-based diagnostic criteria for prediabetes decreased substantially with increasing age (both P<0.0001).Conclusions In two large datasets, using different methods to measure HbA1c, the association of age with higher HbA1c levels: was consistent and similar; was both statistically and clinically significant; was unexplained by features of aging; and reduced diagnostic specificity. Age should be taken into consideration when using HbA1c for the diagnosis and management of diabetes and prediabetes.This article is protected by copyright. All rights reserved.
Article
The human gut is a huge complex ecosystem where microbiota, nutrients, and host cells interact extensively, a process crucial for the gut homeostasis and host development with a real partnership. The various bacterial communities that make up the gut microbiota have many functions including metabolic, barrier effect, and trophic functions. Hence, any dysbiosis could have negative consequences in terms of health and many diseases have been associated to impairment of the gut microbiota. These close relationships between gut microbiota, health, and disease, have led to great interest in using probiotics (i.e. live micro-organisms), or prebiotics (i.e. non-digestible substrates) to positively modulate the gut microbiota to prevent or treat some diseases. This review focuses on probiotics, their mechanisms of action, safety, and major health benefits. Health benefits remain to be proven in some indications, and further studies on the best strain(s), dose, and algorithm of administration to be used are needed. Nevertheless, probiotic administration seems to have a great potential in terms of health that justifies more research.
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Substantial epidemiological evidence shows an increased risk for developing Alzheimer's disease (AD) in people with diabetes. Yet the underlying molecular mechanisms still remain to be elucidated. This article reviews the current studies on common pathological processes of Alzheimer's disease and diabetes with a particular focus on potential mechanisms through which diabetes affects the initiation and progression of Alzheimer's disease. Impairment of insulin signaling, inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, APOEɛ4 and cholesterol appears to be important mediators and likely to act synergistically in promoting AD pathology.
Article
The aim of the present study was to examine the relationship of changes in long term glucose levels as measured by Hemoglobin A1c (HbA1c) with simultaneous changes in cognition. The sample included in the present analysis consisted of 101 community dwelling non-diabetic elderly subjects participating in ongoing longitudinal studies of cognition. Subjects were included in this study if they were cognitively normal at baseline, had at least one co-temporaneous follow-up assessment of HbA1c and the Mini Mental State Exam (MMSE), and complete data on age, gender, race, and years of education. MMSE decline over time was the main outcome measure. In TOBIT mixed regression models, MMSE was the dependent variable and HbA1c the time-varying covariate. Sociodemographic (age, gender, and education), cardiovascular (hypertension and APOE4 status), and lifestyle (smoking and physical activity) covariates were included in the statistical model. After adjusting for age at follow-up, there was a decrease of 1.37 points in the MMSE (p = 0.0002) per unit increase in HbA1c. This result remained essentially unchanged after adjusting also for gender and education (p = 0.0005), cardiovascular factors (p = 0.0003), and lifestyle (p = 0.0006). Additionally, results remained very similar after excluding subjects with potentially incipient diabetes with HbA1c between 6 and 7. These findings suggest that in non-diabetic non-demented elderly subjects, an increase in HbA1c over time is associated with cognitive decline. Such results may have broad clinical applicability since manipulation of glucose control, even in non-diabetics, may affect cognitive performance, perhaps enabling preventive measures against dementia.
Article
Although glycemic levels are known to rise with normal aging, the nondiabetic A1C range is not age specific. We examined whether A1C was associated with age in nondiabetic subjects and in subjects with normal glucose tolerance (NGT) in two population-based cohorts. We performed cross-sectional analyses of A1C across age categories in 2,473 nondiabetic participants of the Framingham Offspring Study (FOS) and in 3,270 nondiabetic participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. In FOS, we examined A1C by age in a subset with NGT, i.e., after excluding those with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Multivariate analyses were performed, adjusting for sex, BMI, fasting glucose, and 2-h postload glucose values. In the FOS and NHANES cohorts, A1C levels were positively associated with age in nondiabetic subjects. Linear regression revealed 0.014- and 0.010-unit increases in A1C per year in the nondiabetic FOS and NHANES populations, respectively. The 97.5th percentiles for A1C were 6.0% and 5.6% for nondiabetic individuals aged <40 years in FOS and NHANES, respectively, compared with 6.6% and 6.2% for individuals aged >or=70 years (P(trend) < 0.001). The association of A1C with age was similar when restricted to the subset of FOS subjects with NGT and after adjustments for sex, BMI, fasting glucose, and 2-h postload glucose values. A1C levels are positively associated with age in nondiabetic populations even after exclusion of subjects with IFG and/or IGT. Further studies are needed to determine whether age-specific diagnostic and treatment criteria would be appropriate.
Article
Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes. We aimed to characterise trajectories of fasting and postload glucose, insulin sensitivity, and insulin secretion in individuals who develop type 2 diabetes. We analysed data from our prospective occupational cohort study (Whitehall II study) of 6538 (71% male and 91% white) British civil servants without diabetes mellitus at baseline. During a median follow-up period of 9.7 years, 505 diabetes cases were diagnosed (49.1% on the basis of oral glucose tolerance test). We assessed retrospective trajectories of fasting and 2-h postload glucose, homoeostasis model assessment (HOMA) insulin sensitivity, and HOMA beta-cell function from up to 13 years before diabetes diagnosis (diabetic group) or at the end of follow-up (non-diabetics). Multilevel models adjusted for age, sex, and ethnic origin confirmed that all metabolic measures followed linear trends in the group of non-diabetics (10,989 measurements), except for insulin secretion that did not change during follow-up. In the diabetic group (801 measurements), a linear increase in fasting glucose was followed by a steep quadratic increase (from 5.79 mmol/L to 7.40 mmol/L) starting 3 years before diagnosis of diabetes. 2-h postload glucose showed a rapid increase starting 3 years before diagnosis (from 7.60 mmol/L to 11.90 mmol/L), and HOMA insulin sensitivity decreased steeply during the 5 years before diagnosis (to 86.7%). HOMA beta-cell function increased between years 4 and 3 before diagnosis (from 85.0% to 92.6%) and then decreased until diagnosis (to 62.4%). In this study, we show changes in glucose concentrations, insulin sensitivity, and insulin secretion as much as 3-6 years before diagnosis of diabetes. The description of biomarker trajectories leading to diabetes diagnosis could contribute to more-accurate risk prediction models that use repeated measures available for patients through regular check-ups. Medical Research Council (UK); Economic and Social Research Council (UK); British Heart Foundation (UK); Health and Safety Executive (UK); Department of Health (UK); National Institute of Health (USA); Agency for Health Care Policy Research (USA); the John D and Catherine T MacArthur Foundation (USA); and Academy of Finland (Finland).
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LGG has been studied extensively in humans and experimental animals for a wide variety of uses. In some cases, data are conflicting and limited by small sample sizes. Nevertheless, the many possible indications for its use are bound to spawn continued enthusiasm for LGG clinical trials. At present, there is strong evidence that LGG can be used in acute diarrhea and antibiotic-associated diarrhea. More data are needed on the use of LGG in atopic disease and for prevention of infections in daycare, traveler's diarrhea, and dental caries. Results from studies in IBD, C difficile, and cystic fibrosis are promising. Finally, studies of LGG for cancer prevention, rheumatoid arthritis, IBS, liver disease, and diabetes warrant more research. Altering the intestinal flora with probiotics is an exciting approach to managing intestinal disorders and related conditions. LGG and other products are safe, cheap, and easy to administer. Future investigators will be challenged to define their utility in treatment and prevention of the broad array of potential clinical settings.
Standards of medical care in diabetes—2010
  • American Diabetes Association
Age as independent determinant of glucose tolerance
  • Shimokata