No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Understanding human diet, disease, and insulin resistance: scientific and evolutionary perspectives 1.1 Understanding human diet and disease -the scientific and evolutionary evidence 1.1.1 Evolutionary evidence: the species-specific natural human diet 1.1.1.1 Defining a species specific diet
ResearchGate has not been able to resolve any citations for this publication.
Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these processes are dysregulated, such as in type 2 diabetes (T2DM), cardiovascular disease (CVD), certain cancers and dementias. Chronic hyperinsulinaemia enforces glucose fueling, depleting the NAD+ dependent antioxidant activity that increases mitochondrial reactive oxygen species (mtROS). Consequently, beta-cell mitochondria increase uncoupling protein expression, which decreases the mitochondrial ATP surge generation capacity, impairing bolus mediated insulin exocytosis. Excessive ROS increases the Drp1:Mfn2 ratio, increasing mitochondrial fission, which increases mtROS; endoplasmic reticulum-stress and impaired calcium homeostasis ensues. Healthy individuals in habitual ketosis have significantly lower glucagon and insulin levels than T2DM individuals. As beta-hydroxybutyrate rises, hepatic gluconeogenesis and glycogenolysis supply extra-hepatic glucose needs, and osteocalcin synthesis/release increases. We propose insulin’s primary role is regulating beta-hydroxybutyrate synthesis, while the role of bone regulates glucose uptake sensitivity via osteocalcin. Osteocalcin regulates the alpha-cell glucagon secretory profile via glucagon-like peptide-1 and serotonin, and beta-hydroxybutyrate synthesis via regulating basal insulin levels. Establishing metabolic phenotypes aids in resolving basal insulin secretion regulation, enabling elucidation of the pathological changes that occur and progress into chronic diseases associated with ageing.
Importance
Obesity is associated with a number of noncommunicable chronic diseases and is purported to cause premature death.
Objective
To summarize evidence on the temporality of the association between higher body mass index (BMI) and 2 potential mediators: chronic inflammation and hyperinsulinemia.
Data Sources
MEDLINE (1946 to August 20, 2019) and Embase (from 1974 to August 19, 2019) were searched, although only studies published in 2018 were included because of a high volume of results. The data analysis was conducted between January 2020 and October 2020.
Study Selection and Measures
Longitudinal studies and randomized clinical trials that measured fasting insulin level and/or an inflammation marker and BMI with at least 3 commensurate time points were selected.
Data Extraction and Synthesis
Slopes of these markers were calculated between time points and standardized. Standardized slopes were meta-regressed in later periods (period 2) with standardized slopes in earlier periods (period 1). Evidence-based items potentially indicating risk of bias were assessed.
Results
Of 1865 records, 60 eligible studies with 112 cohorts of 5603 participants were identified. Most standardized slopes were negative, meaning that participants in most studies experienced decreases in BMI, fasting insulin level, and C-reactive protein level. The association between period 1 fasting insulin level and period 2 BMI was positive and significant (β = 0.26; 95% CI, 0.13-0.38; I² = 79%): for every unit of SD change in period 1 insulin level, there was an ensuing associated change in 0.26 units of SD in period 2 BMI. The association of period 1 fasting insulin level with period 2 BMI remained significant when period 1 C-reactive protein level was added to the model (β = 0.57; 95% CI, 0.27-0.86). In this bivariable model, period 1 C-reactive protein level was not significantly associated with period 2 BMI (β = –0.07; 95% CI, –0.42 to 0.29; I² = 81%).
Conclusions and Relevance
In this meta-analysis, the finding of temporal sequencing (in which changes in fasting insulin level precede changes in weight) is not consistent with the assertion that obesity causes noncommunicable chronic diseases and premature death by increasing levels of fasting insulin.
PUFAs are known to regulate cholesterol synthesis and cellular uptake by multiple mechanisms that do not involve SFAs. Polymorphisms in any of the numerous proteins involved in cholesterol homeostasis, as a result of genetic variation, could lead to higher or lower serum cholesterol. PUFAs are susceptible to lipid peroxidation, which can lead to oxidative stress, inflammation, atherosclerosis, cancer, and disorders associated with inflammation, such as insulin resistance, arthritis, and numerous inflammatory syndromes. Eicosanoids from arachidonic acid are among the most powerful mediators that initiate an immune response, and a wide range of PUFA metabolites regulate numerous physiological processes. There is a misconception that dietary SFAs can cause inflammation, although endogenous palmitic acid is converted to ceramides and other cell constituents involved in an inflammatory response after it is initiated by lipid mediators derived from PUFAs. This article will discuss the many misconceptions regarding how dietary lipids regulate serum cholesterol, the fact that all-cause death rate is higher in humans with low compared with normal or moderately elevated serum total cholesterol, the numerous adverse effects of increasing dietary PUFAs or carbohydrate relative to SFAs, as well as metabolic conversion of PUFAs to SFAs and MUFAs as a protective mechanism. Consequently, dietary saturated fats seem to be less harmful than the proposed alternatives.
Background:
Ultra-processed foods have now become dominant in the global food system. Whether their consumption is associated with cardiovascular mortality remains controversial. Moreover, data on ultra-processed foods and cardiovascular outcomes are scarce in the US population. We aimed to examine the association of ultra-processed food consumption with cardiovascular mortality in a US population.
Methods:
A population-based cohort of 91,891 participants was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary data were collected through a validated 137-item food frequency questionnaire. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Restricted cubic spline regression was used to test nonlinearity. Subgroup analyses were conducted to identify the potential effect modifiers.
Results:
After an average follow-up of 13.5 years (1,236,049.2 person-years), 5490 cardiovascular deaths were documented, including 3985 heart disease deaths and 1126 cerebrovascular deaths. In the fully adjusted model, participants in the highest vs. the lowest quintiles of ultra-processed food consumption had higher risks of death from cardiovascular disease (HRquintile 5 vs. 1, 1.50; 95% CI, 1.36-1.64) and heart disease (HRquintile 5 vs. 1, 1.68; 95% CI, 1.50-1.87) but not cerebrovascular disease (HRquintile 5 vs. 1, 0.94; 95% CI, 0.76-1.17). A nonlinear dose-response pattern was observed for overall cardiovascular and heart disease mortality (all Pnonlinearity < 0.05), with a threshold effect observed at ultra-processed food consumption of 2.4 servings/day and 2.3 servings/day, respectively; below the thresholds, no significant associations were observed for these two outcomes. Subgroup analyses showed that the increased risks of mortality from ultra-processed foods were significantly higher in women than in men (all Pinteraction < 0.05).
Conclusions:
High consumption of ultra-processed foods is associated with increased risks of overall cardiovascular and heart disease mortality. These harmful associations may be more pronounced in women. Our findings need to be confirmed in other populations and settings.
Background
Consumption of ultra-processed food (UPF) is gaining growing attention in relation to disease/mortality risk, but less is known on the main nutritional factors or biological mechanisms potentially underlying such associations.
Objectives
We aimed to assess the association between UPF and mortality risk in a large sample of the Italian adult population and test which nutritional factors were on the pathway of this relation. Established risk factors for cardiovascular disease (CVD) were analyzed as potential biological mechanisms linking UPF to mortality.
Methods
Longitudinal analysis was conducted on 22,475 men and women (mean ± SD age: 55 ± 12 y) recruited in the Moli-sani Study (2005–2010, Italy) and followed for 8.2 y. Food intake was assessed using a semiquantitative FFQ. UPF was defined using the NOVA classification according to degree of processing, and UPF intakes were categorized as quartiles of the ratio (%) of UPF (g/d) to total food consumed (g/d).
Results
Individuals reporting the highest intake of UPF (Q4, >14.6% of total food), as opposed to the lowest (Q1, UPF < 6.6%), experienced increased risks of CVD mortality (HR: 1.58; 95% CI: 1.23, 2.03), death from ischemic heart disease (IHD)/cerebrovascular disease (HR: 1.52; 95% CI: 1.10, 2.09), and all-cause mortality (HR: 1.26; 95% CI: 1.09, 1.46). High sugar content explained 36.3% of the relation of UPF with IHD/cerebrovascular mortality, whereas other nutritional factors (e.g., saturated fats) were unlikely to be on the pathway. Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality, and 12.0% for that of UPF with CVD mortality.
Conclusions
A high proportion of UPF in the diet was associated with increased risk of CVD and all-cause mortality, partly through its high dietary content of sugar. Some established biomarkers of CVD risk were likely to be on the pathway of such associations. These findings should serve as an incentive for limiting consumption of UPF, and encouraging natural or minimally processed foods, as several national nutritional policies recommend.
Past public health crises (e.g., tobacco, alcohol, opioids, cholera, human immunodeficiency virus (HIV), lead, pollution, venereal disease, even coronavirus (COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCDs) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation—abuse, toxicity, ubiquity, and externalities (How does your consumption affect me?). To their credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCDs within their borders. This article also supplies scientific counters to food industry talking points, and sample intervention strategies, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.
Background
Rapid simultaneous increases in ultra-processed food sales and obesity prevalence have been observed worldwide, including in Australia. Consumption of ultra-processed foods by the Australian population was previously shown to be systematically associated with increased risk of intakes of nutrients outside levels recommended for the prevention of obesity. This study aims to explore the association between ultra-processed food consumption and obesity among the Australian adult population and stratifying by age group, sex and physical activity level.
Methods
A cross-sectional analysis of anthropometric and dietary data from 7411 Australians aged ≥20 years from the National Nutrition and Physical Activity Survey 2011–2012 was performed. Food consumption was evaluated through 24-h recall. The NOVA system was used to identify ultra-processed foods, i.e. industrial formulations manufactured from substances derived from foods and typically added of flavours, colours and other cosmetic additives, such as soft drinks, confectionery, sweet or savoury packaged snacks, microwaveable frozen meals and fast food dishes. Measured weight, height and waist circumference (WC) data were used to calculate the body mass index (BMI) and diagnosis of obesity and abdominal obesity. Regression models were used to evaluate the association of dietary share of ultra-processed foods (quintiles) and obesity indicators, adjusting for socio-demographic variables, physical activity and smoking.
Results
Significant (P-trend ≤ 0.001) direct dose–response associations between the dietary share of ultra-processed foods and indicators of obesity were found after adjustment. In the multivariable regression analysis, those in the highest quintile of ultra-processed food consumption had significantly higher BMI (0.97 kg/m²; 95% CI 0.42, 1.51) and WC (1.92 cm; 95% CI 0.57, 3.27) and higher odds of having obesity (OR = 1.61; 95% CI 1.27, 2.04) and abdominal obesity (OR = 1.38; 95% CI 1.10, 1.72) compared with those in the lowest quintile of consumption. Subgroup analyses showed that the trend towards positive associations for all obesity indicators remained in all age groups, sex and physical activity level.
Conclusion
The findings add to the growing evidence that ultra-processed food consumption is associated with obesity and support the potential role of ultra-processed foods in contributing to obesity in Australia.
African consumers have purchased increasing amounts of processed food over the past 50 years. The opportunity cost of time of women and men has increased as more of them work outside the home, driving them to buy processed food and food prepared away from home to save arduous home-processing and preparation labor. In the past several decades, this trend has accelerated with a surge on the supply side of the processing sector and small and medium enterprises (SMEs) and large private companies making massive aggregate investments. Packaged, industrialized, ultra-processed foods and sugar-sweetened beverages (SSBs) are a growing proportion of the processed food consumed. Also, in the past several decades, overweight and obesity have joined the long-standing high levels of stunting and wasting among children and extreme thinness among women of childbearing age. Together these phenomena have formed a double burden of malnutrition (DBM). The DBM has emerged as an important health problem in sub-Saharan Africa. The rise of the DBM and the increase in ultra-processed food consumption are linked. Policy makers face a dilemma. On the one hand, purchases of processed food are driven by long-term factors, such as urbanization, increased income, and employment changes, and thus policy cannot change the pursuit of convenience and labor-saving food. Moreover, much processed food, like packaged milk, is a boon to nutrition, and the processed food system is a major source of jobs for women. On the other hand, the portion (some 10-30%) of processed food that is ultra-processed is a public health challenge, and policy must address its detrimental effects on disease burden. The global experience suggests that double duty actions are most important as are selected policies focused on healthy weaning foods for addressing stunting and taxes on SSBs, nutrition labeling, and other measures can steer consumers away from unhealthy ultra-processed foods to addressing obesity and possibly child nutrition and stunting. We recommend that African governments consider these policy options, but note that the current extreme fragmentation of the processing sector, consisting of vast numbers of informal SMEs in sub-Saharan Africa, and the limited administrative/implementation capacity of many African governments require pursuing this path only gradually.
Aims/hypothesis:
In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells during chronic glucose stress.
Methods:
Respiration and cytosolic ATP changes were measured in human islet cell clusters after culture for 4 days in 11.1 mmol/l glucose. Metabolomics was applied to analyse intracellular metabolite changes as a result of glucose stress conditions. Alterations in beta cell function were followed using insulin secretion assays or cytosolic calcium signalling after expression of the calcium probe YC3.6 specifically in beta cells of islet clusters.
Results:
At early stages of glucose stress, mitochondrial energy metabolism was augmented in contrast to the previously described mitochondrial dysfunction in beta cells from islets of diabetic donors. Following chronic glucose stress, mitochondrial respiration increased (by 52.4%, p < 0.001) and, as a consequence, the cytosolic ATP/ADP ratio in resting human pancreatic islet cells was elevated (by 27.8%, p < 0.05). Because of mitochondrial overactivation in the resting state, nutrient-induced beta cell activation was reduced. In addition, chronic glucose stress caused metabolic adaptations that resulted in the accumulation of intermediates of the glycolytic pathway, the pentose phosphate pathway and the TCA cycle; the most strongly augmented metabolite was glycerol 3-phosphate. The changes in metabolites observed are likely to be due to the inability of mitochondria to cope with continuous nutrient oversupply. To protect beta cells from chronic glucose stress, we inhibited mitochondrial pyruvate transport. Metabolite concentrations were partially normalised and the mitochondrial respiratory response to nutrients was markedly improved. Furthermore, stimulus-secretion coupling as assessed by cytosolic calcium signalling, was restored.
Conclusion/interpretation:
We propose that metabolic changes and associated mitochondrial overactivation are early adaptations to glucose stress, and may reflect what happens as a result of poor blood glucose control. Inhibition of mitochondrial pyruvate transport reduces mitochondrial nutrient overload and allows beta cells to recover from chronic glucose stress. Graphical abstract.
Increasing evidence suggests that high consumption of ultra-processed foods (UPF) is associated with an increase in non-communicable diseases , overweight and obesity. The present study systematically reviewed all observational studies that investigated the association between UPF consumption and health status. A comprehensive search of MEDLINE, Embase, Scopus, Web of Science and Google Scholar was conducted, and reference lists of included articles were checked. Only cross-sectional and prospective cohort studies were included. At the end of the selection process, twenty-three studies (ten cross-sectional and thirteen prospective cohort studies) were included in the systematic review. As regards the cross-sectional studies, the highest UPF consumption was associated with a significant increase in the risk of overweight/obesity (þ39 %), high waist circumference (þ39 %), low HDL-cholesterol levels (þ102 %) and the metabolic syndrome (þ79 %), while no significant associations with hypertension, hyperglycaemia or hypertriacylglycerolaemia were observed. For prospective cohort studies evaluating a total population of 183 491 participants followed for a period ranging from 3·5 to 19 years, highest UPF consumption was found to be associated with increased risk of all-cause mortality in five studies (risk ratio (RR) 1·25, 95 % CI 1·14, 1·37; P < 0·00001), increased risk of CVD in three studies (RR 1·29, 95 % CI 1·12, 1·48; P = 0·0003), cerebrovascular disease in two studies (RR 1·34, 95 % CI 1·07, 1·68; P = 0·01) and depression in two studies (RR 1·20, 95 % CI 1·03, 1·40; P = 0·02). In conclusion, increased UPF consumption was associated, although in a limited number of studies, with a worse cardiometabolic risk profile and a higher risk of CVD, cerebrovascular disease, depression and all-cause mortality.
Evidence shows a strong relationship between obesity, cancer and cardiovascular disease (CVD) risk. However, there is not enough evidence of the role of visceral obesity on both CVD and cancer. Visceral obesity may be more pro-oncogenic than total body fat. Therefore, it is important to know whether abdominal obesity can lead to both CVD and cancer. The present integrative review aimed at evaluating epidemiological evidence on the potential connection of visceral obesity in the occurrence of cancer and CVD. The following databases were searched: SCOPUS, PubMed, Science Direct, Lilacs, SciELO, Google Scholar, Web of Science, Scopus and ProQuest. The presence of visceral obesity can increase the risk of some specific cancer types, but there is controversial evidence about CVD risk based on sex-specific and ageing analyses. There is enough evidence that visceral obesity increases the risk of colorectal, pancreatic and gastro-oesophageal cancer. However, for some types of cancer such as breast, endometrial and renal, visceral obesity is a risk only in post-menopausal women. Regarding prostate cancer, the evidence is controversial. Despite the risk of visceral obesity being consistently associated with CVD in adults, this association disappears in sex-specific and older adults analyses. Moreover, in older adults, the results are controversial due to the use of different measures such as waist circumference and visceral adipose tissue. However, the evidence showing visceral obesity as a risk factor to CVD remains controversial. Sex differences, ageing and body mass index (BMI) category can potentially modify this association. Therefore, further epidemiological studies with analyses stratified by sex and samples including older adults aged 65 and older are needed. K E Y W O R D S aging, body composition, visceral adiposity, waist circumference
Background:
The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly. It is nowadays recognized as the most frequent liver disease, affecting a quarter of global population and regularly coexisting with metabolic disorders such as type 2 diabetes, hypertension, obesity, and cardiovascular disease. In a more simplistic view, NAFLD could be defined as an increase in liver fat content, in the absence of secondary cause of steatosis. In fact, the clinical onset of the disease is a much more complex process, closely related to insulin resistance, limited expandability and dysfunctionality of adipose tissue. A fatty liver is a main driver for a new recognized liver-pancreatic α-cell axis and increased glucagon, contributing to diabetes pathophysiology.
Main text:
This review will focus on the clinical and pathophysiological connections between NAFLD, insulin resistance and type 2 diabetes. We reviewed non-invasive methods and several scoring systems for estimative of steatosis and fibrosis, proposing a multistep process for NAFLD evaluation. We will also discuss treatment options with a more comprehensive view, focusing on the current available therapies for obesity and/or type 2 diabetes that impact each stage of NAFLD.
Conclusion:
The proper understanding of NAFLD spectrum-as a continuum from obesity to metabolic syndrome and diabetes-may contribute to the early identification and for establishment of targeted treatment.
Objective
There are concerns that some non-profit organisations, financed by the food industry, promote industry positions in research and policy materials. Using Freedom of Information (FOI) requests, we test the proposition that the International Life Sciences Institute (ILSI), one prominent non-for profit in international health and nutrition research, promotes industry positions.
Design
U.S. Right to Know filed five FOI from 2015 to 2018 covering communications with researchers at four US institutions: Texas A&M, University of Illinois, University of Colorado and North Carolina State University. It received 15 078 pages, which were uploaded to the University of California San Francisco’s Industry Documents Library. We searched the Library exploring it thematically for instances of: (1) funding research activity that supports industry interests; (2) publishing and promoting industry-sponsored positions or literature; (3) disseminating favourable material to decision makers and the public and (4) suppressing views that do not support industry.
Results
Available emails confirmed that ILSI’s funding by corporate entities leads to industry influence over some of ILSI activities. Emails reveal a pattern of activity in which ILSI sought to exploit the credibility of scientists and academics to bolster industry positions and promote industry-devised content in its meetings, journal and other activities. ILSI also actively seeks to marginalise unfavourable positions.
Conclusions
We conclude that undue influence of industry through third-party entities like ILSI requires enhanced management of conflicts of interest by researchers. We call for ILSI to be recognised as a private sector entity rather than an independent scientific non-profit, to allow for more appropriate appraisal of its outputs and those it funds.
The exact connection between Alzheimer’s disease (AD) and type 2 diabetes is still in debate. However, poorly controlled blood sugar may increase the risk of developing Alzheimer’s. This relationship is so strong that some have called Alzheimer’s “diabetes of the brain” or “type 3 diabetes (T3D)”. Given more recent studies continue to indicate evidence linking T3D with AD, this review aims to demonstrate the relationship between T3D and AD based on the fact that both the processing of amyloid-β (Aβ) precursor protein toxicity and the clearance of Aβ are attributed to impaired insulin signaling, and that insulin resistance mediates the dysregulation of bioenergetics and progress to AD. Furthermore, insulin-related therapeutic strategies are suggested to succeed in the development of therapies for AD by slowing down their progressive nature or even halting their future complications.
Maize and its derived fermented products, as with other cereals, are fundamental for human nutrition in many countries of the world. Mixed cultures, principally constituted by lactic acid bacteria (LAB) and yeasts, are responsible for maize fermentation, thus increasing its nutritional value and extending the products’ shelf-life. Other microorganisms involved, such as molds, acetic acid bacteria, and Bacillus spp. can contribute to the final product characteristics. This review gives an overview of the impact of the activities of this complex microbiota on maize product development and attributes. In particular, starting from amylolytic activity, which is able to increase sugar availability and influence the microbial succession and production of exopolysaccharides, vitamins, and antimicrobial compounds, which improve the nutritional value. Further activities are also considered with positive effects on the safety profile, such as phytates detoxification and mycotoxins reduction.
Parkinson's disease (PD) is a neurodegenerative disorder that results in the death of dopaminergic neurons within the substantia nigra pars compacta and the reduction in dopaminergic control over striatal output neurons, leading to a movement disorder most commonly characterized by akinesia or bradykinesia, rigidity and tremor. Also, PD is less frequently depicted by sensory symptoms (pain and tingling), hyposmia, sleep alterations, depression and anxiety, and abnormal executive and working memory related functions. On the other hand, insulin-like growth factor 1 (IGF-1) is an endocrine, paracrine and autocrine hormone with several functions including tissue growth and development, insulin-like activity, proliferation, pro-survival, anti-aging, antioxidant and neuroprotection, among others. Herein this review tries to summarize all experimental and clinical data to understand the pathophysiology and development of PD, as well as its clear association with IGF-1, supported by several lines of evidence: (1) IGF-1 decreases with age, while aging is the major risk for PD establishment and development; (2) numerous basic and translational data have appointed direct protective and homeostasis IGF-1 roles in all brain cells; (3) estrogens seem to confer women strong protection to PD via IGF-1; and (4) clinical correlations in PD cohorts have confirmed elevated IGF-1 levels at the onset of the disease, suggesting an ongoing compensatory or "fight-to-injury" mechanism.
Background
Low carbohydrate high fat (LCHF) diets are increasing in popularity amongst patients with type 2 diabetes (T2D), however it is unclear what constitutes a sustainable LCHF diet in a real-world setting.
Methods
This descriptive multi-method study characterized the diets, T2D status, and personal experiences of individuals with T2D who claimed to have followed an LCHF diet for at least 6 months. Participants completed a medications history, mixed-method dietary assessment, provided a blood sample, and were interviewed in-depth about their experiences with the diet (First-Assessment). Past medical records were obtained corresponding to T2D diagnosis and prior to starting their LCHF diets. Additionally, participants were followed up 15 months later to assess T2D remission (Follow-Up).
Results
Twenty-eight participants completed First-Assessment and 24 completed Follow-Up. Habitual carbohydrate intake was 20 to 50 g/d for 10 participants and 50 to 115 g/d for 17 participants. Commonly reported foods were full-fat dairy, non-starchy vegetables, coconut oil, eggs, nuts, olives and avocados, olive oil, and red meat and poultry with fat. Median (interquartile range) for HbA1c was 7.5 (6.5–9.5) % prior to starting their diets, 5.8 (5.4–6.2) % at First-Assessment and 5.9 (5.3–6.6) % at Follow-Up. Reported body weight and glucose-lowering medication requirements were considerably lower at both assessments than when starting the diet. At Follow-Up, 24 participants had been following their LCHF diets for 35 (26–53) months, the majority of which were in full or partial T2D remission. Participants perceived reduced hunger and cravings as one of the most important aspects of their diets. Of concern, many participants felt unsupported by their doctors.
Conclusion
This study described the foods and characteristics of an LCHF “lifestyle” that was sustainable and effective for certain T2D patients in a real-world setting.
Objective
To evaluate the association of ultra-processed food (UPF) consumption with gains in weight and waist circumference, and incident overweight/obesity, in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort.
Design
We applied FFQ at baseline and categorized energy intake by degree of processing using the NOVA classification. Height, weight and waist circumference were measured at baseline and after a mean 3·8-year follow-up. We assessed associations, through Poisson regression with robust variance, of UPF consumption with large weight gain (1·68 kg/year) and large waist gain (2·42 cm/year), both being defined as ≥90th percentile in the cohort, and with incident overweight/obesity.
Setting
Brazil.
Participants
Civil servants of Brazilian public academic institutions in six cities ( n 11 827), aged 35–74 years at baseline (2008–2010).
Results
UPF provided a mean 24·6 ( sd 9·6) % of ingested energy. After adjustment for smoking, physical activity, adiposity and other factors, fourth (>30·8 %) v . first (<17·8 %) quartile of UPF consumption was associated (relative risk (95 % CI)) with 27 and 33 % greater risk of large weight and waist gains (1·27 (1·07, 1·50) and 1·33 (1·12, 1·58)), respectively. Similarly, those in the fourth consumption quartile presented 20 % greater risk (1·20 (1·03, 1·40)) of incident overweight/obesity and 2 % greater risk (1·02; (0·85, 1·21)) of incident obesity. Approximately 15 % of cases of large weight and waist gains and of incident overweight/obesity could be attributed to consumption of >17·8 % of energy as UPF.
Conclusions
Greater UPF consumption predicts large gains in overall and central adiposity and may contribute to the inexorable rise in obesity seen worldwide.
Purpose
Recent studies suggest that the quality and quantity of visceral adipose tissue (VAT) play significant roles in adipocyte function, and are related to insulin resistance. We tested the hypothesis that high amounts of upper VAT (aVAT) and low-quality VAT worsen treatment outcomes via altered insulin metabolism.
Methods
Cohort 1 included 106 women with breast cancer who were undergoing surgery. Homeostasis model assessment of insulin resistance (HOMA-R), insulin-like growth factor (IGF)-1, and IGF-binding protein 3 (IGFBP3) were measured before the initiation of treatment. aVAT was measured via computed tomography (CT). VAT quality was assessed using CT-determined Hounsfield units (VAT-HU). Associations between the variables investigated and VAT quality and quantity were analyzed. Cohort 2 included 271 patients who underwent chemotherapy. Associations between the variables investigated and survival outcomes after chemotherapy were analyzed via retrospective chart review.
Results
In cohort 1, aVAT was significantly correlated with insulin and HOMA-R levels. As body mass index (BMI) class increased, mean IGF-1 increased and mean IGFBP3 decreased, but these trends were not statistically significant. In cohort 2, aVAT was significantly positively correlated with BMI. The patients in the third aVAT tertiles had significantly shorter distant disease-free survival (dDFS) after neoadjuvant chemotherapy setting. In multivariate analysis, aVAT and VAT-HU were significantly associated with shorter dDFS.
Conclusions
High aVAT and low-quality VAT were associated with poor survival outcome, increased insulin levels, and insulin resistance. The present study suggests the importance of evaluating the quality and quantity of VAT when estimating insulin resistance and treatment outcomes.
Background:
Insulin resistance (IR) is considered as a risk factor for atrial fibrillation (AF) even before diabetes develops. The pathophysiology and underlying mechanism are largely unclear.
Methods:
We investigated the corresponding mechanism in two IR models of rats fed 15-week high-fat (HFa) and high-fructose/cholesterol (HFr) diets. AF was evaluated and induced by burst atrial pacing. Isolated atrial myocytes were used for whole-cell patch clamp and calcium assessment. Ex vivo whole heart was used for optical mapping. Western blot and immunofluorescence were used for quantitative protein evaluation.
Results:
Both HFa and HFr rat atria were vulnerable to AF evaluated by burst atrial pacing. Isolated atrial myocytes from HFa and HFr rats revealed significantly increased sarcoplasmic reticulum calcium content and diastolic calcium sparks. Whole-heart mapping showed prolonged calcium transient duration, conduction velocity reduction, and repetitive ectopic focal discharge in HFa and HFr atria. Protein analysis revealed increased TGF-β1 and collagen expression; increased superoxide production; abnormal upregulation of calcium-homeostasis-related proteins, including oxidized CaMKIIδ, phosphorylated-phospholamban, phosphorylated-RyR-2, and sodium-calcium exchanger; and increased Rac1 activity in both HFa and HFr atria. We observed that inhibition of CaMKII suppressed AF in both HF and HFr diet-fed rats. In vitro palmitate-induced IR neonatal cardiomyocytes and atrial fibroblasts expressed significantly more TGF-β1 than did controls, suggesting paracrine and autocrine effects on both myocytes and fibroblasts.
Conclusions:
IR engenders both atrial structural remodeling and abnormal intracellular calcium homeostasis, contributing to increased AF susceptibility. The inhibition of CaMKII may be a potential therapeutic target for AF in insulin resistance.
In the last decade, much attention has been devoted to the effects of nutrient-related signals on brain development and cognitive functions. A turning point was the discovery that brain areas other than the hypothalamus expressed receptors for hormones related to metabolism. In particular, insulin signaling has been demonstrated to impact on molecular cascades underlying hippocampal plasticity, learning and memory. Here, we summarize the molecular evidence linking alteration of hippocampal insulin sensitivity with changes of both adult neurogenesis and synaptic plasticity. We also review the epidemiological studies and experimental models emphasizing the critical role of brain insulin resistance at the crossroad between metabolic and neurodegenerative disease. Finally, we brief novel findings suggesting how biomarkers of brain insulin resistance, involving the study of brain-derived extracellular vesicles and brain glucose metabolism, may predict the onset and/or the progression of cognitive decline.
To date, type 2 diabetes is considered to be a “bi-hormonal disorder” rather than an “insulin-centric disorder,” suggesting that glucagon is as important as insulin. Although glucagon increases hepatic glucose production and blood glucose levels, paradoxical glucagon hypersecretion is observed in diabetes. Recently, insulin resistance in pancreatic α cells has been proposed to be associated with glucagon dysregulation. Moreover, cell autonomous dysfunction of α cells is involved in the etiology of diabetes. In this review, we summarize the current knowledge about the physiological and pathological roles of glucagon.
Humans carry a much larger percentage of body fat than other primates. Despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. Phenotypic divergence is often caused by genetic divergence in cis-regulatory regions. We examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using rhesus macaque as an outgroup. We find that many regions that have decreased accessibility in humans are enriched for promoter and enhancer sequences, are depleted for signatures of negative selection, are located near genes involved with lipid metabolism, and contain a short sequence motif involved in the beigeing of fat, the process in which lipid-storing white adipocytes are transdifferentiated into thermogenic beige adipocytes. The collective closing of many putative regulatory regions associated with beigeing of fat suggests a mechanism that increases body fat in humans.
BACKGROUND
Metabolic syndrome (MetS) is highly correlated with obesity and cardiovascular risk, but the importance of dietary carbohydrate independent of weight loss in MetS treatment remains controversial. Here, we test the theory that dietary carbohydrate intolerance (i.e., the inability to process carbohydrate in a healthy manner) rather than obesity per se is a fundamental feature of MetS.METHODS
Individuals who were obese with a diagnosis of MetS were fed three 4-week weight-maintenance diets that were low, moderate, and high in carbohydrate. Protein was constant and fat was exchanged isocalorically for carbohydrate across all diets.RESULTSDespite maintaining body mass, low-carbohydrate (LC) intake enhanced fat oxidation and was more effective in reversing MetS, especially high triglycerides, low HDL-C, and the small LDL subclass phenotype. Carbohydrate restriction also improved abnormal fatty acid composition, an emerging MetS feature. Despite containing 2.5 times more saturated fat than the high-carbohydrate diet, an LC diet decreased plasma total saturated fat and palmitoleate and increased arachidonate.CONCLUSION
Consistent with the perspective that MetS is a pathologic state that manifests as dietary carbohydrate intolerance, these results show that compared with eucaloric high-carbohydrate intake, LC/high-fat diets benefit MetS independent of whole-body or fat mass.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02918422.FUNDINGDairy Management Inc. and the Dutch Dairy Association.
Objective
To evaluate the association of changes in red meat consumption with total and cause specific mortality in women and men.
Design
Two prospective cohort studies with repeated measures of diet and lifestyle factors.
Setting
Nurses’ Health Study and the Health Professionals Follow-up Study, United States.
Participants
53 553 women and 27 916 men without cardiovascular disease or cancer at baseline.
Main outcome measure
Death confirmed by state vital statistics records, the national death index, or reported by families and the postal system.
Results
14 019 deaths occurred during 1.2 million person years of follow-up. Increases in red meat consumption over eight years were associated with a higher mortality risk in the subsequent eight years among women and men (both P for trend<0.05, P for heterogeneity=0.97). An increase in total red meat consumption of at least half a serving per day was associated with a 10% higher mortality risk (pooled hazard ratio 1.10, 95% confidence interval 1.04 to 1.17). For processed and unprocessed red meat consumption, an increase of at least half a serving per day was associated with a 13% higher mortality risk (1.13, 1.04 to 1.23) and a 9% higher mortality risk (1.09, 1.02 to 1.17), respectively. A decrease in consumption of processed or unprocessed red meat of at least half a serving per day was not associated with mortality risk. The association between increased red meat consumption and mortality risk was consistent across subgroups defined by age, physical activity, dietary quality, smoking status, or alcohol consumption.
Conclusion
Increases in red meat consumption, especially processed meat, were associated with higher overall mortality rates.
Background:
Industry sponsorship of public health research has received increasing scrutiny, and, as a result, many multinational corporations (MNCs), such as The Coca-Cola Company and Mars Inc., have committed to transparency with regard to what they fund, and the findings of funded research. However, these MNCs often fund charities, both national and international, which then support research and promote industry-favourable policy positions to leaders. We explore whether one industry funded charity, the International Life Sciences Institute ('ILSI'), is the scientifically objective, non-lobby, internationally-credible body that it suggests it is, so as to aid the international health and scientific communities to judge ILSI's outputs.
Methods:
Between June 2015 and February 2018, U.S. Right to Know), a non-profit consumer and public health group, submitted five U.S. state Freedom of Information requests (FOIs) to explore ILSI engagement with industry, policy makers, and/or researchers, which garnered a total of 17,163 pages for analysis. Two researchers explored these documents to assess the activities and conduct of ILSI against its purported objectives.
Results:
Within the received documents we identified instances of ILSI seeking to influence research, conferences, public messages, and policy, including instances of punishments for ILSI bodies failing to promote industry-favourable messaging. We identified ILSI promoting its agenda with national and international bodies to influence policy and law, causing the World Health Organization to withdraw from official relations with what it now considers a private sector entity.
Conclusions:
ILSI seeks to influence individuals, positions, and policy, both nationally and internationally, and its corporate members deploy it as a tool to promote their interests globally. Our analysis of ILSI serves as a caution to those involved in global health governance to be wary of putatively independent research groups, and to practice due diligence before relying upon their funded studies and/or engaging in relationship with such groups.
AIMS/HYPOTHESIS: We aimed to investigate the role of insulin in regulating human skeletal muscle metabolism in health and diabetes.
METHODS: We conducted a systematic review and meta-analysis of published data that examined changes in skeletal muscle protein synthesis (MPS) and/or muscle protein breakdown (MPB) in response to insulin infusion. Random-effects models were used to calculate weighted mean differences (WMDs), 95% CIs and corresponding p values. Both MPS and MPB are reported in units of nmol (100 ml leg vol.)(-1) min(-1).
RESULTS: A total of 104 articles were examined in detail. Of these, 44 and 25 studies (including a total of 173 individuals) were included in the systematic review and meta-analysis, respectively. In the overall estimate, insulin did not affect MPS (WMD 3.90 [95% CI -0.74, 8.55], p = 0.71), but significantly reduced MPB (WMD -15.46 [95% CI -19.74, -11.18], p < 0.001). Overall, insulin significantly increased net balance protein acquisition (WMD 20.09 [95% CI 15.93, 24.26], p < 0.001). Subgroup analysis of the effect of insulin on MPS according to amino acid (AA) delivery was performed using meta-regression analysis. The estimate size (WMD) was significantly different between subgroups based on AA availability (p = 0.001). An increase in MPS was observed when AA availability increased (WMD 13.44 [95% CI 4.07, 22.81], p < 0.01), but not when AA availability was reduced or unchanged. In individuals with diabetes and in the presence of maintained delivery of AA, there was a significant reduction in MPS in response to insulin (WMD -6.67 [95% CI -12.29, -0.66], p < 0.05).
CONCLUSIONS/INTERPRETATION: This study demonstrates the complex role of insulin in regulating skeletal muscle metabolism. Insulin appears to have a permissive role in MPS in the presence of elevated AAs, and plays a clear role in reducing MPB independent of AA availability.
Purpose of Review
Dietary obesity is primarily attributed to an imbalance between food intake and energy expenditure. Adherence to lifestyle interventions reducing weight is typically low. As a result, obesity becomes a chronic state with increased co-morbidities such as insulin resistance and diabetes. We review the effects of brain insulin action and dopaminergic signal transmission on food intake, reward, and mood as well as potential modulations of these systems to counteract the obesity epidemic.
Recent Findings
Central insulin and dopamine action are interlinked and impact on food intake, reward, and mood. Brain insulin resistance causes hyperphagia, anxiety, and depressive-like behavior and compromises the dopaminergic system. Such effects can induce reduced compliance to medical treatment. Insulin receptor sensitization and dopamine receptor agonists show attenuation of obesity and improvement of mental health in rodents and humans.
Summary
Modulating brain insulin and dopamine signaling in obese patients can potentially improve therapeutic outcomes.
This commentary contains a clear and simple guide designed to identify ultra-processed foods. It responds to the growing interest in ultra-processed foods among policy makers, academic researchers, health professionals, journalists and consumers concerned to devise policies, investigate dietary patterns, advise people, prepare media coverage, and when buying food and checking labels in shops or at home. Ultra-processed foods are defined within the NOVA classification system, which groups foods according to the extent and purpose of industrial processing. Processes enabling the manufacture of ultra-processed foods include the fractioning of whole foods into substances, chemical modifications of these substances, assembly of unmodified and modified food substances, frequent use of cosmetic additives and sophisticated packaging. Processes and ingredients used to manufacture ultra-processed foods are designed to create highly profitable (low-cost ingredients, long shelf-life, emphatic branding), convenient (ready-to-consume), hyper-palatable products liable to displace all other NOVA food groups, notably unprocessed or minimally processed foods. A practical way to identify an ultra-processed product is to check to see if its list of ingredients contains at least one item characteristic of the NOVA ultra-processed food group, which is to say, either food substances never or rarely used in kitchens (such as high-fructose corn syrup, hydrogenated or interesterified oils, and hydrolysed proteins), or classes of additives designed to make the final product palatable or more appealing (such as flavours, flavour enhancers, colours, emulsifiers, emulsifying salts, sweeteners, thickeners, and antifoaming, bulking, carbonating, foaming, gelling and glazing agents).
When, why, and how early humans began to eat meat are three of the most fundamental unresolved questions in the study of human origins. Before 2.5 million years ago the presence and importance of meat in the hominid diet is unkown. After stone tools appear in the fossil record it seems clear that meat was eaten in increasing quantities, but whether it was obtained through hunting or scavenging remains a topic of intense debate. This book takes a novel and strongly interdisciplinary approach to the role of meat in the early hominid diet, inviting well-known researchers who study the human fossil record, modern hunter-gatherers, and nonhuman primates to contribute chapters to a volume that integrates these three perspectives. Stanford’s research has been on the ecology of hunting by wild chimpanzees. Bunn is an archaeologist who has worked on both the fossil record and modern foraging people. This will be a reconsideration of the role of hunting, scavening, and the uses of meat in light of recent data and modern evolutionary theory. There is currently no other book, nor has there ever been, that occupies the niche this book will create for itself.
When, why, and how early humans began to eat meat are three of the most fundamental unresolved questions in the study of human origins. Before 2.5 million years ago the presence and importance of meat in the hominid diet is unkown. After stone tools appear in the fossil record it seems clear that meat was eaten in increasing quantities, but whether it was obtained through hunting or scavenging remains a topic of intense debate. This book takes a novel and strongly interdisciplinary approach to the role of meat in the early hominid diet, inviting well-known researchers who study the human fossil record, modern hunter-gatherers, and nonhuman primates to contribute chapters to a volume that integrates these three perspectives. Stanford’s research has been on the ecology of hunting by wild chimpanzees. Bunn is an archaeologist who has worked on both the fossil record and modern foraging people. This will be a reconsideration of the role of hunting, scavening, and the uses of meat in light of recent data and modern evolutionary theory. There is currently no other book, nor has there ever been, that occupies the niche this book will create for itself.
As ultraprocessed foods (i.e., foods composed of mostly cheap industrial sources of dietary energy and nutrients plus additives) have become more abundant in our food supply, rates of obesity and diet-related disease have increased simultaneously. Food addiction has emerged as a phenotype of significant empirical interest within the past decade, conceptualized most commonly as a substance-based addiction to ultraprocessed foods. We detail ( a) how approaches used to understand substance-use disorders may be applicable for operationalizing food addiction, ( b) evidence for the reinforcing potential of ingredients in ultraprocessed foods that may drive compulsive consumptions, ( c) the utility of conceptualizing food addiction as a substance-use disorder versus a behavioral addiction, and ( d) clinical and policy implications that may follow if ultraprocessed foods exhibit an addictive potential. Broadly, the existing literature suggests biological and behavioral parallels between food addiction and substance addictions, with ultraprocessed foods high in both added fat and refined carbohydrates being most implicated in addictive-like eating. Future research priorities are also discussed, including the need for longitudinal studies and the potential negative impact of addictive ultraprocessed foods on children.
Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Importance
Risk profiles for premature coronary heart disease (CHD) are unclear.
Objective
To examine baseline risk profiles for incident CHD in women by age at onset.
Design, Setting, and Participants
A prospective cohort of US female health professionals participating in the Women’s Health Study was conducted; median follow-up was 21.4 years. Participants included 28 024 women aged 45 years or older without known cardiovascular disease. Baseline profiles were obtained from April 30, 1993, to January 24, 1996, and analyses were conducted from October 1, 2017, to October 1, 2020.
Exposures
More than 50 clinical, lipid, inflammatory, and metabolic risk factors and biomarkers.
Main Outcomes and Measures
Four age groups were examined (<55, 55 to <65, 65 to <75, and ≥75 years) for CHD onset, and adjusted hazard ratios (aHRs) were calculated using stratified Cox proportional hazard regression models with age as the time scale and adjusting for clinical factors. Women contributed to different age groups over time.
Results
Of the clinical factors in the women, diabetes had the highest aHR for CHD onset at any age, ranging from 10.71 (95% CI, 5.57-20.60) at CHD onset in those younger than 55 years to 3.47 (95% CI, 2.47-4.87) at CHD onset in those 75 years or older. Risks that were also noted for CHD onset in participants younger than 55 years included metabolic syndrome (aHR, 6.09; 95% CI, 3.60-10.29), hypertension (aHR, 4.58; 95% CI, 2.76-7.60), obesity (aHR, 4.33; 95% CI, 2.31-8.11), and smoking (aHR, 3.92; 95% CI, 2.32-6.63). Myocardial infarction in a parent before age 60 years was associated with 1.5- to 2-fold risk of CHD in participants up to age 75 years. From approximately 50 biomarkers, lipoprotein insulin resistance had the highest standardized aHR: 6.40 (95% CI, 3.14-13.06) for CHD onset in women younger than 55 years, attenuating with age. In comparison, weaker but significant associations with CHD in women younger than 55 years were noted (per SD increment) for low-density lipoprotein cholesterol (aHR, 1.38; 95% CI, 1.10-1.74), non–high-density lipoprotein cholesterol (aHR, 1.67; 95% CI, 1.36-2.04), apolipoprotein B (aHR, 1.89; 95% CI, 1.52-2.35), triglycerides (aHR, 2.14; 95% CI, 1.72-2.67), and inflammatory biomarkers (1.2- to 1.8-fold)—all attenuating with age. Some biomarkers had similar CHD age associations (eg, physical inactivity, lipoprotein[a], total high-density lipoprotein particles), while a few had no association with CHD onset at any age. Most risk factors and biomarkers had associations that attenuated with increasing age at onset.
Conclusions and Relevance
In this cohort study, diabetes and insulin resistance, in addition to hypertension, obesity, and smoking, appeared to be the strongest risk factors for premature onset of CHD. Most risk factors had attenuated relative rates at older ages.
There is an ongoing scientific debate about whether unhealthy, highly processed foods are addictive and whether this contributes to overeating and obesity. Through this debate series, we identified numerous points of consensus, including that 1) addictive-like eating exists, 2) mechanisms implicated in substance-related and addictive disorders contribute to overeating and obesity, and 3) food industry practices are also a key contributor to this phenomenon. We also agree that obesity, a multifaceted condition, is not synonymous with addictive-like eating and that further research is needed to clarify the understanding of addictive-like eating. Disagreements remain regarding the strength of evidence that highly processed foods are addictive, the appropriate framework for conceptualizing addictive-like eating, and the societal implications of identifying unhealthy, highly processed foods as addictive. Finally, we highlight future research needed to address existing gaps in the scientific literature that underlie continuing controversies, most notably the need for scientific consensus about what measures should be used to evaluate whether highly processed foods are addictive.
Background
Ultra-processed foods account for more than 50% of daily calories consumed in several high-income countries, with sales of ultra-processed foods soaring globally, especially in middle-income countries. The objective of this study is to investigate the association between ultra-processed food (UPF) consumption and risk of type 2 diabetes (T2D) in a UK-based prospective cohort study.
Methods
Participants of the UK Biobank (2007–2019) aged 40–69 years without diabetes at recruitment who provided 24-h dietary recall and follow-up data were included. UPFs were defined using the NOVA food classification. Multivariable Cox proportional hazards regression models were used to evaluate the association between UPF consumption and the risk of T2D adjusting for socio-demographic, anthropometric and lifestyle characteristics.
Results
A total of 21,730 participants with a mean age of 55.8 years and mean UPF intake of 22.1% at baseline were included. During a mean follow-up of 5.4 years (116,956 person-years), 305 incident T2D cases were identified. In the fully adjusted model, compared with the group in the lowest quartile of UPF intake, the hazard ratio for T2D was 1.44, 1.04–2.02 in the group with the highest quartile of UPF consumption. A gradient of elevated risk of T2D associated with increasing quartiles of UPF intake was consistently observed (p value for trend < 0.028). A significantly increased risk of T2D was observed per 10 percentage points increment in UPF consumption ([adjusted HR]: 1.12, 95% confidence interval [CI]: 1.04–1.20).
Conclusions
Our findings demonstrate that a diet high in UPFs is associated with a clinically important increased risk of T2D. Identifying and implementing effective public health actions to reduce UPF consumption in the UK and globally are urgently required.
Background:
The pancreas is small and irregular in shape in people with type 2 diabetes. If these abnormalities are caused by the disease state itself rather than being a predisposing factor, remission of type 2 diabetes should restore normal pancreas morphology. The objective of this study was to determine whether changes in pancreas volume and shape occurred during 2 years of remission.
Methods:
For this post-hoc analysis, we included a subset of adult participants of the Diabetes Remission Clinical Trial (DiRECT), who had type 2 diabetes and were randomly assigned to a weight management intervention or routine diabetes management. Intervention group participants were categorised as responders (HbA1c <6·5% [48 mmol/mol] and fasting blood glucose <7·0 mmol/L, off all anti-diabetes medication) and non-responders, who were classified as remaining diabetic. Data on pancreas volume and irregularity of pancreas border at baseline, 5 months, 12 months, and 24 months after intervention were compared between responders and non-responders; additional comparisons were made between control group participants with type 2 diabetes and a non-diabetic comparator (NDC) group, who were matched to the intervention group by age, sex, and post-weight-loss weight, to determine the extent of any normalisation. We used a mixed-effects regression model based on repeated measures ANOVA with correction for potential confounding. Magnetic resonance techniques were employed to quantify pancreas volume, the irregularity of the pancreas borders, and intrapancreatic fat content. β-cell function and biomarkers of tissue growth were also measured.
Findings:
Between July 25, 2015, and Aug 5, 2016, 90 participants with type 2 diabetes in the DiRECT subset were randomly assigned to intervention (n=64) or control (n=26) and were assessed at baseline; a further 25 non-diabetic participants were enrolled into the NDC group. At baseline, mean pancreas volume was 61·7 cm3 (SD 16·0) in all participants with type 2 diabetes and 79·8 cm3 (14·3) in the NDC group (p<0·0001). At 24 months, pancreas volume had increased by 9·4 cm3 (95% CI 6·1 to 12·8) in responders compared with 6·4 cm3 (2·5 to 10·3) in non-responders (p=0·0008). Pancreas borders at baseline were more irregular in participants with type 2 diabetes than in the NDC group (fractal dimension 1·138 [SD 0·027] vs 1·097 [0·025]; p<0·0001) and had normalised by 24 months in responders only (1·099 [0·028]). Intrapancreatic fat declined by 1·02 percentage points (95% CI 0·53 to 1·51) in 32 responders and 0·51% (-0·17 to 1·19) in 13 non-responders (p=0·23).
Interpretation:
These data show for the first time, to our knowledge, reversibility of the abnormal pancreas morphology of type 2 diabetes by weight loss-induced remission.
Funding:
Diabetes UK.
Several blood pressure guidelines recommend low sodium intake (<2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. <2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world's population consume a moderate range of dietary sodium (2.3-4.6g/day; 1-2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of <5 g/day in populations with mean sodium intake of >5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.
Purpose of review:
This article provides an up-to-date review of the manifestations of neuropathy seen in the setting of diabetes and other metabolic disorders.
Recent findings:
Although a number of metabolic disorders cause or are associated with peripheral neuropathy, the neuropathies associated with glucose dysregulation make up the vast majority of cases. Recent investigations have determined major differences in the neuropathies associated with type 1 and type 2 diabetes. Neuropathy in type 1 diabetes is closely linked to glycemic control, whereas neuropathy in type 2 diabetes is linked to dyslipidemia, central obesity, hypertension, insulin resistance, and glucose control. Although length-dependent axonal distal symmetric polyneuropathy is the most common clinical presentation, diabetes is also associated with acute, asymmetric, painless, and autonomic neuropathies.
Summary:
The prevalence of diabetes and metabolic syndrome is increasing across the globe. The need to recognize and treat the wide array of clinical manifestations of neuropathy detected in individuals with metabolic disorders will continue to grow. As a consequence, an increasing number of well-trained physicians who can manage these patients is needed. At present, treatment is largely focused on prevention and symptomatic management. Investments into funding for both basic and clinical science are necessary to bring novel therapeutic interventions into clinical practice.
Context:
Industry influence on health science and policy is a critical issue of our day. In 2015, the New York Times revealed that Coca-Cola paid scientists to form a Global Energy Balance Network promoting the notion that exercise, not dietary restraint, is the solution to the obesity epidemic-a claim few accept. This article examines the organizational dynamics and policy process behind Coke's efforts to sway obesity policy, globally and in China, a critical market, during 1995-2015.
Methods:
In-depth, qualitative research during 2013-18 involved: 10 weeks of fieldwork in Beijing; interviews with 25 leading experts; analysis of newsletters documenting all major obesity-related activities in China; interviews with 12 Euro-American experts; extensive internet research on all major actors.
Findings:
This article tells two intertwined stories (institutional dynamics; science- and policymaking) at global and local-Chinese levels. Coke succeeded in redirecting China's obesity science and policy to emphasize physical activity. Key to its success was the industry-funded, global nonprofit, the International Life Sciences Institute (ILSI). Beneath ILSI's public narrative of unbiased science and no policy advocacy lay a maze of hidden channels companies used to advance their interests. Working through those channels, Coca-Cola influenced China's science- and policymaking during every phase in the policy process, from framing the issues to drafting official policy.
Conclusions:
Though China is exceptional, ILSI promoted exercise globally, suggesting potentially significant impacts in other ILSI-branch countries.
Purpose of review:
The aim of this study was to highlight the recent advancements and future directions for potential use of a low carbohydrate ketogenic dietary approach to treat binge eating and ultraprocessed food addiction. Herein, we explore proposed mechanisms of why a diet low in refined carbohydrates, processed sugar and higher fat content may be helpful in alleviating symptoms.
Recent findings:
Emerging evidence suggests there may be a metabolic role in development of maladaptive eating. These findings broaden our understanding of eating psychopathology causes. Ultraprocessed, refined or high glycemic index carbohydrates are a possible trigger mediating neurochemical responses similar to addiction. The carbohydrate-insulin model of obesity supports observations of these foods triggering abnormal blood sugar and insulin spikes subsequently leading to changes in metabolic and neurobiological signaling. This results in overeating symptoms and hunger exacerbation, which differs from observed effects of healthy fat consumption and lack of similar insulin spikes. As supported in recent case series, significantly reducing or abstaining from these addictive-like ultraprocessed foods and highly refined carbohydrates could be considered a treatment approach.
Summary:
The current review highlights recent and pertinent evidence with respect to theoretical and practical application of low carbohydrate ketogenic therapeutic approaches for ultraprocessed food addiction and binge eating symptoms (see supplemental video).
During the last century, there has been an increasing prevalence of hyperuricaemia noted in many populations. While uric acid is usually discussed in the context of gout, hyperuricaemia is also associated with hypertension, chronic kidney disease, hypertriglyceridaemia, obesity, atherosclerotic heart disease, metabolic syndrome, and type 2 diabetes. Here we review the connection between hyperuricaemia and cardiovascular, kidney and metabolic diseases. Contrary to the popular view that uric acid is an inert metabolite of purine metabolism, recent studies suggest serum uric acid may have a variety of pro-inflammatory, pro-oxidative and vasoconstrictive actions that may contribute to cardiometabolic diseases. Hyperuricaemia is a predictive factor for the development of hypertension, metabolic syndrome, type 2 diabetes, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, myocardial infarction, stroke, heart failure and chronic kidney disease. Treatment with uric acid-lowering therapies has also been found to improve outcomes in patients with hypertension and kidney disease, in some but not all studies. In conclusion, uric acid is emerging as a potentially treatable risk factor for cardiometabolic diseases, and more clinical trials investigating the potential benefit of lowering serum uric acid are recommended in individuals with hyperuricaemia with and without deposition and concomitant hypertension, metabolic syndrome or chronic kidney disease.
Introduction
Considerable controversy remains on the relationship between egg consumption and cardiovascular disease risk. The objective of this systematic review and meta-analysis was to explore the association between egg consumption and overall cardiovascular disease events.
Methods
We systematically searched Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception from 1966 through January 2020 for observational studies that reported the association between egg consumption and cardiovascular disease events. Two investigators independently reviewed data. Conflicts were resolved through consensus. Random-effects meta-analyses were used. Sources of heterogeneity were analyzed.
Results
We identified 23 prospective studies with a median follow-up of 12.28 years. A total of 1,415,839 individuals with a total of 123,660 cases and 157,324 cardiovascular disease events were included. Compared to the consumption of no or 1 egg/day, higher egg consumption (more than 1 egg/day) was not associated with significantly increased risk of overall cardiovascular disease events (pooled hazard ratios, 0.99; 95% CI, 0.93-1.06; p<0.001; I²= 72.1%). Higher egg consumption (more than 1 egg/day) was associated with a significantly decreased risk of coronary artery disease (pooled hazard ratios, 0.89; 95% CI, 0.86-0.93; p<0.001; I²= 0%), compared to consumption of no or 1 egg/day.
Conclusions
Our analysis suggests that higher consumption of eggs (more than 1 egg/day) was not associated with increased risk of cardiovascular disease, but associated with a significant reduction in risk of coronary artery disease.
Estimates of the human trophic level and dietary quality during the Paleolithic are the basis for many hypotheses and interpretations regarding human evolution and behavior. We describe an additional factor that could have significantly influenced human evolution and behavior, the availability of large prey animals.
Given the importance of large prey and the mounting evidence of the decline in its abundance throughout the Pleistocene, we question the reliability of past reconstructions of the human trophic level that were heavily based on analogies with the recent ethnographic record.
We review the ecological and technological records of the Hadza and the Ju/’hoansi (!Kung), two recent hunter-gatherers' groups that dominate the literature as acceptable ethnographic analogs for Paleolithic Africa. We find that their dietary record reflects, as expected by our model, an adaptation to an ecological reality of increased vegetal biomass and reduced large prey biomass that differ substantially from the ecology of most of the Pleistocene but do share analogical trends with the late Upper Paleolithic when the Late Quaternary Megafauna Extinction took place.
In normal pregnancy, maternal metabolism transforms to one characterized by insulin resistance (IR) to promote nutrient availability to the fetus while supporting maternal metabolic needs. The rising global epidemic of obesity and overweight now approaches 60%, and this has changed the landscape of the pregnancy phenotype. With pre-pregnancy obesity comes heightened IR and, when compounded by pregnancy-induced IR, the intrauterine environment becomes characterized by nutrient excess in the form of glucose, lipids, and amino acids in parallel with metabolic derangements, including inflammation and oxidative stress. When a sedentary lifestyle, poor nutrition, and excess gestational weight gain (GWG) are added, the maternal metabolome and microbiome are further altered. This chapter will provide a discussion of IR in pregnancy and its mechanisms, including genetic/epigenetic, cellular, metabolic, and lifestyle factors. Importantly, the implications of IR in pregnancy on maternal and offspring outcomes will be highlighted.
The ongoing obesity epidemic places about a third of American youth at risk for developing obesity-related insulin resistance. This is manifested by reduced multiorgan effects of insulin, leading to elevated insulin concentrations and, in some cases, inappropriately elevated glucose and lipid concentrations. Many risk factors for insulin resistance—including genetics, epigenetics, obesity, diet, and lifestyle—are in common between adolescents and adults. However, adolescents have a unique risk factor in the physiologic insulin resistance of puberty, which along with obesity can pose a “double hit” to the beta-cell, causing increased burden for insulin secretion.
Background:Obese postmenopausal women are at higher breast cancer risk potentially
driven by hyperinsulinemia. However, reports of insulin level associations with breast cancer
incidence and survival are inconsistent. Therefore, we examined associations among insulin
resistance by homeostasis model assessment-insulin resistance (HOMA-IR) index and
incident breast cancer, deaths from breast cancer, and deaths after breast cancer in
postmenopausal women participating in the Women's Health Initiative (WHI).
Patients and Methods:From the 161,808 postmenopausal women, aged 50-79 years,
enrolled at 40 US clinical centers from 1993 through1998 in WHI clinical trials or the
observational study, 22,837 with available fasting serum insulin and glucose by the same
methodology and no prior breast cancer represent the current study population. The
exposure was insulin resistance (HOMA-IR index) as [fasting insulin (qIU/ml) times fasting
glucose (mg/dL) / 22.5. Survival by cause was determined by central medical record or
death certificate review, enhanced by National Death Index queries. Breast cancers, initially
ascertained by serial survey, were confirmed by medical record review. Associations
between HOMA-IR quartiles and breast cancer outcomes were examined using Cox multi-
variate proportional hazards models with results reported as hazard ratios (HR) and 95%
confidence intervals.
Results: At entry, women in the highest HOMA-IR quartile were more likely to be Black,
have lower education level, have higher body mass index (BMI), higher waist circumference
≥ 88 cm and lower physical activity levels, but have lower calculated five-year breast cancer
risk. After 18.1 years median follow-up from randomization with 1,148 incident breast
cancers, breast cancer incidence was higher in women in the highest, compared to the
lowest, HOMA-IR index quartile (HR 1.39 95% CI 1.14 -1.69, P = 0.0012). Of the women
with incident breast cancer, 353 (31%) have died, with cause of death available on 334
(95% of cases) where breast cancer was the most common cause of death (33%); followed
by cardiovascular disease (24%); and other cancers (13%). With median post-breast cancer
diagnosis follow-up of 10.5 years, breast cancer mortality was examined from breast cancer
diagnosis. No association was found between death from breast cancer and HOMA-IR.
However, women with breast cancer in the highest HOMA-IR quartile, compared to women
in the lowest, were significantly more likely to experience death after breast cancer from
any cause (HR 1.45 95% CI 1.00 - 2.09, P = 0.0488) and were at somewhat higher risk of
death from cardiovascular disease (HR 1.51 95% CI 0.67 - 3.41) and other causes (HR 1.93
95% CI 0.87-4.27).
Conclusion:In postmenopausal women, higher insulin resistance is associated with higher
breast cancer incidence and more deaths after breast cancer, likely due to insulin influence
on several causes of death. However, deaths from breast cancer, even in this older
postmenopausal population, remains a major factor limiting survival which needs to be
addressed. The findings suggest insulin resistance represented a potential intervention
target for postmenopausal women with early stage
breast cancer.
Citation Format: Chlebowski RT, Pan K, Mortimer J, Cespedes Feliciano EM, Gunter MJ, Hurria A, Rohan T, Vitolins MZ, Adams-Campbell L, Ho G, Cheng T-YD, Nelson R. Insulin resistance and breast cancer incidence and mortality in postmenopausal women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-10.
The transition of hominins to a largely meat-based diet ∼1.8 million years ago led to the exploitation of other mammals for food and resources. As hominins, particularly archaic and modern humans, became increasingly abundant and dispersed across the globe, a temporally and spatially transgressive extinction of large-bodied mammals followed; the degree of selectivity was unprecedented in the Cenozoic fossil record. Today, most remaining large-bodied mammal species are confined to Africa, where they co-evolved with hominins. Here, using a comprehensive global dataset of mammal distribution, life history and ecology, we examine the consequences of ‘body size downgrading’ of mammals over the late Quaternary on fundamental macroecological patterns. Specifically, we examine changes in species diversity, global and continental body size distributions, allometric scaling of geographic range size with body mass, and the scaling of maximum body size with area. Moreover, we project these patterns toward a potential future scenario in which all mammals currently listed as vulnerable on the IUCN's Red List are extirpated. Our analysis demonstrates that anthropogenic impact on earth systems predates the terminal Pleistocene and has grown as populations increased and humans have become more widespread. Moreover, owing to the disproportionate influence on ecosystem structure and function of megafauna, past and present body size downgrading has reshaped Earth's biosphere. Thus, macroecological studies based only on modern species yield distorted results, which are not representative of the patterns present for most of mammal evolution. Our review supports the concept of benchmarking the ‘Anthropocene’ with the earliest activities of Homo sapiens.