Estimated effects of reductions in processed meat consumption and unprocessed red meat consumption on occurrences of type 2 diabetes, cardiovascular disease, colorectal cancer, and mortality in the USA: a microsimulation study.

BACKGROUND: High consumption of processed meat and unprocessed red meat is associated with increased risk of multiple chronic diseases, although there is substantial uncertainty regarding the relationship for unprocessed red meat. We developed a microsimulation model to estimate how reductions in processed meat and unprocessed red meat consumption could affect rates of type 2 diabetes, cardiovascular disease, colorectal cancer, and mortality in the US adult population. METHODS: We used data from two versions of the US National Health and Nutrition Examination Survey, one conducted during 2015-16 and one conducted during 2017-18, to create a simulated US population. The starting cohort was restricted to respondents aged 18 years or older who were not pregnant and had 2 days of dietary-recall data. First, we used previously developed risk models to estimate the baseline disease risk of an individual. For type 2 diabetes we used a logistic-regression model and for cardiovascular disease and colorectal cancer we used Cox proportional-hazard models. We then multiplied baseline risk by relative risk associated with individual processed meat and unprocessed red meat consumption. Prevented occurrences of type 2 diabetes, cardiovascular disease, colorectal cancer, and mortality were computed by taking the difference between the incidence in the baseline and intervention scenarios. All stages were repeated for ten iterations to correspond to a 10-year time span. Scenarios were reductions of 5%, 10%, 30%, 50%, 75%, and 100% in grams consumed of processed meat, unprocessed red meat, or both. Each scenario was repeated 50 times for uncertainty analysis. FINDINGS: The total number of individual respondents included in the simulated population was 8665, representing 242 021 876 US adults. 4493 (51·9%) of 8665 individuals were female and 4172 (48·1%) were male; mean age was 49·54 years (SD 18·38). At baseline, weighted mean daily consumption of processed meat was 29·1 g, with a 30% reduction being 8·7 g per day, and of unprocessed red meat was 46·7 g, with a 30% reduction being 14·0 g per day. We estimated that a 30% reduction in processed meat intake alone could lead to 352 900 (95% uncertainty interval 345 500-359 900) fewer occurrences of type 2 diabetes, 92 500 (85 600-99 900) fewer occurrences of cardiovascular disease, 53 300 (51 400-55 000) fewer occurrences of colorectal cancer, and 16 700 (15 300-17 700) fewer all-cause deaths during the 10-year period. A 30% reduction in unprocessed red meat intake alone could lead to 732 600 (725 700-740 400) fewer occurrences of type 2 diabetes, 291 500 (283 900-298 800) fewer occurrences of cardiovascular disease, 32 200 (31 500-32 700) fewer occurrences of colorectal cancer, and 46 100 (45 300-47 200) fewer all-cause deaths during the 10-year period. A 30% reduction in both processed meat and unprocessed red meat intake could lead to 1 073 400 (1 060 100-1 084 700) fewer occurrences of type 2 diabetes, 382 400 (372 100-391 000) fewer occurrences of cardiovascular disease, 84 400 (82 100-86 200) fewer occurrences of colorectal cancer, and 62 200 (60 600-64 400) fewer all-cause deaths during the 10-year period. INTERPRETATION: Reductions in processed meat consumption could reduce the burden of some chronic diseases in the USA. However, more research is needed to increase certainty in the estimated effects of reducing unprocessed red meat consumption. FUNDING: The Wellcome Trust.

Is it time to revise the fighting strategy toward type 2 diabetes? Sex and pollution as new risk factors.

Diabetes mellitus, a metabolic condition affecting around 537 million individuals worldwide, poses significant challenges, particularly among the elderly population. The etiopathogenesis of type 2 diabetes (T2D) depends on a combination of the effects driven by advancing age, genetic background, and lifestyle habits, e.g. overnutrition. These factors influence the development of T2D differently in men and women, with an obvious sexual dimorphism possibly underlying the diverse clinical features of the disease in different sexes. More recently, environmental pollution, estimated to cause 9 million deaths every year, is emerging as a novel risk factor for the development of T2D. Indeed, exposure to atmospheric pollutants such as PM2.5, O3, NO2, and Persistent Organic Pollutants (POP)s, along with their combination and bioaccumulation, is associated with the development of T2D and obesity, with a 15 % excess risk in case of exposure to very high levels of PM2.5. Similar data are available for plasticizer molecules, e.g. bisphenol A and phthalates, emerging endocrine-disrupting chemicals. Even though causality is still debated at this stage, preclinical evidence sustains the ability of multiple pollutants to affect pancreatic function, promote insulin resistance, and alter lipid metabolism, possibly contributing to T2D onset and progression. In addition, preclinical findings suggest a possible role also for plastic itself in the development of T2D. Indeed, pioneeristic studies evidenced that micro- or nanoplastics (MNP)s, particles in the micro- or nano- range, promote cellular damage, senescence, inflammation, and metabolic disturbances, leading to insulin resistance and impaired glucose metabolism in animal and/or in vitro models. Here we synthesize recent knowledge relative to the association between air-related or plastic-derived pollutants and the incidence of T2D, discussing also the possible mechanistic links suggested by the available literature. We then anticipate the need for future studies in the field of candidate therapeutic strategies limiting pollution-induced damage in preclinical models, such as SGLT-2 inhibitors. We finally postulate that future guidelines for T2D prevention should consider pollution and sex an additional risk factors to limit the diabetes pandemic.

Molecular Aspects of Cardiometabolic Diseases: From Etiopathogenesis to Potential Therapeutic Targets.

Cardiometabolic diseases (CMDs) encompass a range of prevalent, often preventable, non-communicable illnesses, including myocardial infarction, stroke, cardiac insufficiency, arterial hypertension, obesity, type 2 diabetes mellitus, insulin resistance, chronic renal dysfunction, non-alcoholic fatty liver disease, and rare metabolic disorders [...].

Correlation between Long-Term Exposure to Traffic Noise and Risk of Type 2 Diabetes Mellitus.

OBJECTIVE: This study aimed to probe the correlation of long-term exposure to traffic noise with the risk of type 2 diabetes mellitus (T2DM). METHODS: The data of 480 community residents collected from April 2017 to April 2018 were retrospectively analyzed. Exposure levels for traffic noise were defined using 24-h mean traffic noise. Logistic regression calculated the association between long-term exposure to traffic noise and the risk of T2DM. RESULTS: Overall, 480 enrolled participants were divided into T2DM (n = 45) and non-T2DM (n = 435) groups. Participants with T2DM were older and more likely to be male, had higher BMI, and were frequent drinkers (P < 0.001). The T2DM group displayed higher exposure to traffic noise than the non-T2DM group (P < 0.001). According to quartiles of traffic noise, all participants were categorized into four groups: Q1 (<51.5 dB), Q2 (51.5-<53.9 dB), Q3 (53.9-<58.0 dB), and Q4 (≥58.0 dB). Prevalence of T2DM was 5.4% in Q1, 7.7% in Q2, 10.3% in Q3, and 14.1% in Q4 groups. Multifactor regression analysis showed that age, BMI, drinking history, and traffic noise exposure are risk factors for T2DM (P < 0.05), whereas sex does not seem to have a significant impact on T2DM (P > 0.05). CONCLUSION: Long-term exposure to traffic noise may elevate the risk of T2DM. This suggests that long-term exposure to high levels of traffic noise can increase the incidence of diabetes mellitus, which deserves further consideration.

Overnutrition, Hyperinsulinemia and Ectopic Fat: It Is Time for A Paradigm Shift in the Management of Type 2 Diabetes.

The worldwide incidence of prediabetes/type 2 has continued to rise the last 40 years. In the same period, the mean daily energy intake has increased, and the quality of food has significantly changed. The chronic exposure of pancreatic ß-cells to calorie excess (excessive energy intake) and food additives may increase pancreatic insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing chronic hyperinsulinemia and peripheral insulin resistance. Chronic calorie excess and hyperinsulinemia may promote lipogenesis, inhibit lipolysis and increase lipid storage in adipocytes. In addition, calorie excess and hyperinsulinemia can induce insulin resistance and contribute to progressive and excessive ectopic fat accumulation in the liver and pancreas by the conversion of excess calories into fat. The personal fat threshold hypothesis proposes that in susceptible individuals, excessive ectopic fat accumulation may eventually lead to hepatic insulin receptor resistance, the loss of pancreatic insulin secretion, hyperglycemia and the development of frank type 2 diabetes. Thus, type 2 diabetes seems (partly) to be caused by hyperinsulinemia-induced excess ectopic fat accumulation in the liver and pancreas. Increasing evidence further shows that interventions (hypocaloric diet and/or bariatric surgery), which remove ectopic fat in the liver and pancreas by introducing a negative energy balance, can normalize insulin secretion and glucose tolerance and induce the sustained biochemical remission of type 2 diabetes. This pathophysiological insight may have major implications and may cause a paradigm shift in the management of type 2 diabetes: avoiding/reducing ectopic fat accumulation in the liver and pancreas may both be essential to prevent and cure type 2 diabetes.

Virus-induced diabetes mellitus: revisiting infection etiology in light of SARS-CoV-2.

Diabetes mellitus (DM) is comprised of two predominant subtypes: type 1 diabetes mellitus (T1DM), accounting for approximately 5 % of cases worldwide and resulting from autoimmune destruction of insulin-producing ß-cells, and type 2 (T2DM), accounting for approximately 95 % of cases globally and characterized by the inability of pancreatic ß-cells to meet the demand for insulin due to a relative ß-cell deficit in the setting of peripheral insulin resistance. Both types of DM involve derangement of glucose metabolism and are metabolic diseases generally considered to be initiated by a combination of genetic and environmental factors. Viruses have been reported to play a role as infectious etiological factors in the initiation of both types of DM in predisposed individuals. Among the reported viral infections causing DM in humans, the most studied include coxsackie B virus, cytomegalovirus and hepatitis C virus. The recent COVID-19 pandemic has highlighted the diabetogenic potential of SARS-CoV-2, rekindling interest in the field of virus-induced diabetes (VID). This review discusses the reported mechanisms of viral-induced DM, addressing emerging concepts in VID, as well as highlighting areas where knowledge is lacking, and further investigation is warranted.

Investigating the Effects of Diet-Induced Prediabetes on Skeletal Muscle Strength in Male Sprague Dawley Rats.

Type 2 diabetes mellitus, a condition preceded by prediabetes, is documented to compromise skeletal muscle health, consequently affecting skeletal muscle structure, strength, and glucose homeostasis. A disturbance in skeletal muscle functional capacity has been demonstrated to induce insulin resistance and hyperglycemia. However, the modifications in skeletal muscle function in the prediabetic state are not well elucidated. Hence, this study investigated the effects of diet-induced prediabetes on skeletal muscle strength in a prediabetic model. Male Sprague Dawley rats were randomly assigned to one of the two groups (n = 6 per group; six prediabetic (PD) and six non-pre-diabetic (NPD)). The PD group (n = 6) was induced with prediabetes for 20 weeks. The diet that was used to induce prediabetes consisted of fats (30% Kcal/g), proteins (15% Kcal/g), and carbohydrates (55% Kcal/g). In addition to the diet, the experimental animals (n = 6) were supplied with drinking water that was supplemented with 15% fructose. The control group (n = 6) was allowed access to normal rat chow, consisting of 35% carbohydrates, 30% protein, 15% fats, and 20% other components, as well as ordinary tap water. At the end of week 20, the experimental animals were diagnosed with prediabetes using the American Diabetes Association (ADA) prediabetes impaired fasting blood glucose criteria (5.6-6.9 mmol/L). Upon prediabetes diagnosis, the animals were subjected to a four-limb grip strength test to assess skeletal muscle strength at week 20. After the grip strength test was conducted, the animals were euthanized for blood and tissue collection to analyze glycated hemoglobin (HbA1c), plasma insulin, and insulin resistance using the homeostatic model of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) concentration. Correlation analysis was performed to examine the associations of skeletal muscle strength with HOMA-IR, plasma glucose, HbA1c, and MDA concentration. The results demonstrated increased HbA1c, FBG, insulin, HOMA-IR, and MDA concentrations in the PD group compared to the NPD group. Grip strength was reduced in the PD group compared to the NPD group. Grip strength was negatively correlated with HbA1c, plasma glucose, HOMA-IR, and MDA concentration in the PD group. These observations suggest that diet-induced prediabetes compromises muscle function, which may contribute to increased levels of sedentary behavior during prediabetes progression, and this may contribute to the development of hyperglycemia in T2DM.

Accelerated Aging Induced by an Unhealthy High-Fat Diet: Initial Evidence for the Role of Nrf2 Deficiency and Impaired Stress Resilience in Cellular Senescence.

High-fat diets (HFDs) have pervaded modern dietary habits, characterized by their excessive saturated fat content and low nutritional value. Epidemiological studies have compellingly linked HFD consumption to obesity and the development of type 2 diabetes mellitus. Moreover, the synergistic interplay of HFD, obesity, and diabetes expedites the aging process and prematurely fosters age-related diseases. However, the underlying mechanisms driving these associations remain enigmatic. One of the most conspicuous hallmarks of aging is the accumulation of highly inflammatory senescent cells, with mounting evidence implicating increased cellular senescence in the pathogenesis of age-related diseases. Our hypothesis posits that HFD consumption amplifies senescence burden across multiple organs. To scrutinize this hypothesis, we subjected mice to a 6-month HFD regimen, assessing senescence biomarker expression in the liver, white adipose tissue, and the brain. Aging is intrinsically linked to impaired cellular stress resilience, driven by dysfunction in Nrf2-mediated cytoprotective pathways that safeguard cells against oxidative stress-induced senescence. To ascertain whether Nrf2-mediated pathways shield against senescence induction in response to HFD consumption, we explored senescence burden in a novel model of aging: Nrf2-deficient (Nrf2+/-) mice, emulating the aging phenotype. Our initial findings unveiled significant Nrf2 dysfunction in Nrf2+/- mice, mirroring aging-related alterations. HFD led to substantial obesity, hyperglycemia, and impaired insulin sensitivity in both Nrf2+/- and Nrf2+/+ mice. In control mice, HFD primarily heightened senescence burden in white adipose tissue, evidenced by increased Cdkn2a senescence biomarker expression. In Nrf2+/- mice, HFD elicited a significant surge in senescence burden across the liver, white adipose tissue, and the brain. We postulate that HFD-induced augmentation of senescence burden may be a pivotal contributor to accelerated organismal aging and the premature onset of age-related diseases.

Visceral Adipose Tissue: The Hidden Culprit for Type 2 Diabetes.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by insulin resistance in various tissues. Though conventionally associated with obesity, current research indicates that visceral adipose tissue (VAT) is the leading determining factor, wielding more influence regardless of individual body mass. The heightened metabolic activity of VAT encourages the circulation of free fatty acid (FFA) molecules, which induce insulin resistance in surrounding tissues. Individuals most vulnerable to this preferential fat deposition are older males with ancestral ties to Asian countries because genetics and sex hormones are pivotal factors for VAT accumulation. However, interventions in one's diet and lifestyle have the potential to strategically discourage the growth of VAT. This illuminates the possibility that the expansion of VAT and, subsequently, the risk of T2D development are preventable. Therefore, by reducing the amount of VAT accumulated in an individual and preventing it from building up, one can effectively control and prevent the development of T2D.

An adipocentric perspective of pancreatic lipotoxicity in diabetes pathogenesis.

Obesity and diabetes represent two increasing and invalidating public health issues that often coexist. It is acknowledged that fat mass excess predisposes to insulin resistance and type 2 diabetes mellitus (T2D), with the increasing incidence of the two diseases significantly associated. Moreover, emerging evidence suggests that obesity might also accelerate the appearance of type 1 diabetes (T1D), which is now a relatively frequent comorbidity in patients with obesity. It is a common clinical finding that not all patients with obesity will develop diabetes at the same level of adiposity, with gender, genetic, and ethnic factors playing an important role in defining the timing of diabetes appearance. The adipose tissue (AT) expandability hypothesis explains this paradigm, indicating that the individual capacity to appropriately store energy surplus in the form of fat within the AT determines and prevents the toxic deposition of lipids in other organs, such as the pancreas. Thus, we posit that when the maximal storing capacity of AT is exceeded, individuals will develop T2D. In this review, we provide insight into mechanisms by which the AT controls pancreas lipid content and homeostasis in case of obesity to offer an adipocentric perspective of pancreatic lipotoxicity in the pathogenesis of diabetes. Moreover, we suggest that improving AT function is a valid therapeutic approach to fighting obesity-associated complications including diabetes.

Sociodemographic disparities in sodium-glucose cotransporter-2 inhibitor use among US kidney transplant recipients: An observational study of real-world pharmacy records.

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

BACKGROUND: Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS: We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS: Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).

Usual intake of dairy products and the chance of pre-diabetes regression to normal glycemia or progression to type 2 diabetes: a 9-year follow-up.

BACKGROUND: We assessed the possible effect of usual dairy consumption on pre-diabetes (Pre-DM) remission or progression to type 2 diabetes (T2D). METHODS: Pre-DM adults (n = 334, mean age of 49.4 years, and 51.5% men) were assessed for dairy intakes (2006-2008) and followed up to 9 years for incidence of T2D or normal glycemia (NG). All biochemical measurements were done at baseline and all subsequent examinations with 3-y follow-up intervals. Multinomial regression models with adjustment of confounding variables were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) of incident T2D and NG for each serving/d dairy consumption. RESULTS: The odds of NG was significantly elevated by 69% (OR = 1.69, 95% CI = 1.00-2.86, P = 0.05) per 200 g/d increased high-fat dairy intake, while the amount of total dairy or low-fat dairy was not related to the outcomes. Higher intakes of yogurt were more likely to be associated with an increased odds of NG (OR = 1.82, 95% CI = 1.20-2.74, P = 0.01). Usual intakes of milk, cheese, or cream-butter were not associated to Pre-DM remission or progression to T2D. CONCLUSION: Regular dairy consumption may increase the chance of Pre-DM regression to NG.

A review of air pollution as a driver of cardiovascular disease risk across the diabetes spectrum.

The prevalence of diabetes is estimated to reach almost 630 million cases worldwide by the year 2045; of current and projected cases, over 90% are type 2 diabetes. Air pollution exposure has been implicated in the onset and progression of diabetes. Increased exposure to fine particulate matter air pollution (PM2.5) is associated with increases in blood glucose and glycated hemoglobin (HbA1c) across the glycemic spectrum, including normoglycemia, prediabetes, and all forms of diabetes. Air pollution exposure is a driver of cardiovascular disease onset and exacerbation and can increase cardiovascular risk among those with diabetes. In this review, we summarize the literature describing the relationships between air pollution exposure, diabetes and cardiovascular disease, highlighting how airborne pollutants can disrupt glucose homeostasis. We discuss how air pollution and diabetes, via shared mechanisms leading to endothelial dysfunction, drive increased cardiovascular disease risk. We identify portable air cleaners as potentially useful tools to prevent adverse cardiovascular outcomes due to air pollution exposure across the diabetes spectrum, while emphasizing the need for further study in this particular population. Given the enormity of the health and financial impacts of air pollution exposure on patients with diabetes, a greater understanding of the interventions to reduce cardiovascular risk in this population is needed.

Effects of Excessive High-fructose Corn Syrup Drink Intake in Middle-aged Mice.

BACKGROUND/AIM: The global prevalence of type 2 diabetes (T2D) continues to increase, necessitating the need for understanding the causes of its development. The widespread use of high-fructose corn syrup (HFCS) in drinks and diets is suspected to play a role in metabolic disorders. Although many studies have reported on the effects of excessive HFCS and excessive energy intakes in middle-aged individuals, few have focused on energy restriction. This study aimed to investigate the effects of excessive HFCS drink intake under energy restriction on developing T2D in early middle-aged mice. MATERIALS AND METHODS: Early middle-aged mice were divided in HFCS and control groups; they were provided either 10% HFCS water or deionized water ad libitum for 12 weeks, respectively. Total energy intake was controlled using a standard rodent diet. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), tissue weight measurements, serum parameter analyses, and mRNA expression assessments were performed. RESULTS: No increase in body and adipose tissue weight was observed with excessive HFCS intake under energy restriction. Moreover, serum lipid parameters did not differ from those of controls. However, in the OGTT and ITT, the HFCS group showed higher blood glucose levels than the control group. Moreover, the pancreatic weight and insulin II mRNA expression were reduced. CONCLUSION: The excessive HFCS drink intake under energy restriction did not induce obesity; however, it induced impaired glucose tolerance, indicating its negative effects on the pancreas in early middle-aged mice. When translated in human physiology, our results show that even if one does not become obese, excessive HFCS may affect the overall metabolic mechanism; these effects may vary depending on age.

Associations of birth weight, plasma metabolome in adulthood and risk of type 2 diabetes.

AIMS: We aimed to examine the longitudinal associations of birth weight with plasma metabolites in adulthood, and further quantify the proportions of the links between birth weight and incident adult type 2 diabetes (T2D) that were mediated by plasma metabolites. MATERIALS AND METHODS: A total of 62,033 participants with complete nuclear magnetic resonance metabolomics and birth weight data from the UK Biobank were included in this study. Linear regression was used to assess the associations between birth weight and metabolites. Cox regression was used to estimate hazard ratios for T2D associated with metabolites. We further performed mediation analyses to estimate the extent to which metabolites might mediate the association between birth weight and T2D risk. RESULTS: Low birth weight was associated with the adverse metabolic responses across multiple metabolic pathways, including lipoprotein subclasses, amino acids, fatty acids (FA), and inflammation. Metabolites associated with higher birth weight tended to be associated with a lower risk of T2D (Pearson correlation coefficient: -0.85). A total of 62 metabolites showed statistically significant mediation effects in the protective association of higher birth weight and T2D risk, including large-sized very low-density lipoprotein particles and triglyceride concentrations as well as saturated, and monounsaturated FA and glycoprotein acetyls. CONCLUSIONS: We identified a range of metabolites that reflect the adult metabolic response to birth weight, some of which might lie on the pathway between birth weight and adult T2D risk.

Mendelian Randomization Analysis Identifies Inverse Causal Relationship between External Eating and Metabolic Phenotypes.

Disordered eating contributes to weight gain, obesity, and type 2 diabetes (T2D), but the precise mechanisms underlying the development of different eating patterns and connecting them to specific metabolic phenotypes remain unclear. We aimed to identify genetic variants linked to eating behaviour and investigate its causal relationships with metabolic traits using Mendelian randomization (MR). We tested associations between 30 genetic variants and eating patterns in individuals with T2D from the Volga-Ural region and investigated causal relationships between variants associated with eating patterns and various metabolic and anthropometric traits using data from the Volga-Ural population and large international consortia. We detected associations between HTR1D and CDKAL1 and external eating; between HTR2A and emotional eating; between HTR2A, NPY2R, HTR1F, HTR3A, HTR2C, CXCR2, and T2D. Further analyses in a separate group revealed significant associations between metabolic syndrome (MetS) and the loci in CRP, ADCY3, GHRL, CDKAL1, BDNF, CHRM4, CHRM1, HTR3A, and AKT1 genes. MR results demonstrated an inverse causal relationship between external eating and glycated haemoglobin levels in the Volga-Ural sample. External eating influenced anthropometric traits such as body mass index, height, hip circumference, waist circumference, and weight in GWAS cohorts. Our findings suggest that eating patterns impact both anthropometric and metabolic traits.

The Contribution of Type 2 Diabetes to Parkinson's Disease Aetiology.

Type 2 diabetes (T2D) and Parkinson's disease (PD) are chronic disorders that have a significant health impact on a global scale. Epidemiological, preclinical, and clinical research underpins the assumption that insulin resistance and chronic inflammation contribute to the overlapping aetiologies of T2D and PD. This narrative review summarises the recent evidence on the contribution of T2D to the initiation and progression of PD brain pathology. It also briefly discusses the rationale and potential of alternative pharmacological interventions for PD treatment.

Association between napping and type 2 diabetes mellitus.

As the incidence of type 2 diabetes mellitus (T2DM) is increasing rapidly and its consequences are severe, effective intervention and prevention, including sleep-related interventions, are urgently needed. As a component of sleep architecture, naps, alone or in combination with nocturnal sleep, may influence the onset and progression of T2DM. Overall, napping is associated with an increased risk of T2DM in women, especially in postmenopausal White women. Our study showed that napping >30 minutes (min) increased the risk of T2DM by 8-21%. In addition, non-optimal nighttime sleep increases T2DM risk, and this effect combines with the effect of napping. For nondiabetic patients, napping >30 min could increase the risks of high HbA1c levels and impaired fasting glucose (IFG), which would increase the risk of developing T2DM later on. For diabetic patients, prolonged napping may further impair glycemic control and increase the risk of developing diabetic complications (e.g., diabetic nephropathy) in the distant future. The following three mechanisms are suggested as interpretations for the association between napping and T2DM. First, napping >30 min increases the levels of important inflammatory factors, including interleukin 6 and C-reactive protein, elevating the risks of inflammation, associated adiposity and T2DM. Second, the interaction between postmenopausal hormonal changes and napping further increases insulin resistance. Third, prolonged napping may also affect melatonin secretion by interfering with nighttime sleep, leading to circadian rhythm disruption and further increasing the risk of T2DM. This review summarizes the existing evidence on the effect of napping on T2DM and provides detailed information for future T2DM intervention and prevention strategies that address napping.