Higher Risk Of Type 2 Diabetes Research Articles

576-P: Maintenance of Time-Restricted Eating in Daily Life to Lose Weight and Lower Risk of Type 2

Background: Effective weight loss maintenance interventions are a key factor to lower the risk of type 2 diabetes (T2D), and time-restricted eating (TRE) is a novel strategy which has proven successful in obtaining a weight loss in a few studies. This study examined if people with overweight or obesity at high risk of T2D were able to maintain TRE in real-life settings. Methods: Participants were recruited from the randomized controlled RESET study, an RCT investigating effects of TRE on body weight and other cardiometabolic risk factors. Semi-structured interviews were conducted with a subgroup of 20 participants allocated to 12 weeks of TRE (i.e., consuming all foods and beverages within a 10-h window). The intervention was followed by a 12-week follow-up period with no intervention. All participants were interviewed at the end of intervention and again at 12-week follow-up. Data were analyzed using a thematic analysis approach. Result: Participants had a positive attitude towards TRE, and seven wished to maintain it stringently during the follow-up period. Half of the participants wished to maintain an individually adjusted TRE concept by e.g., drinking coffee outside the interval or exceeding it at social events. Some participants found it easy to maintain TRE stringently, while two struggled to do so. A few participants were able to maintain their individually adjusted TRE concept, while seven found it too intrusive. Particularly the degree of daily life structure, meal pattern organization and social support determined maintenance success. The three remaining participants chose not to maintain TRE in the follow-up period and experienced a relief when going back to usual rhythms. Conclusion: Elements from the TRE concept were highly valued by most participants, but it often required individual adjustments in order to undertake TRE on a longer-term basis. A tailored fit to daily life activities is therefore crucial to maintain TRE which underlines the complexity of long-term maintenance. Disclosure N. Bjerre: None. L. Holm: None. J. S. Quist: None. K. Færch: Board Member; Self; ChemoMetec, Research Support; Self; Novo Nordisk Foundation, Stock/Shareholder; Self; Novo Nordisk A/S. N. F. Hempler: None. Funding Novo Nordisk Foundation; Helsefonden (20-B-0109)

Association of adiposity and diabetes mellitus type 2 by education level in the Chilean population

Adiposity and education are two independent risk factors for type 2 diabetes (T2D). However, there is limited evidence whether both education and adiposity are associated with T2D in an additive manner in the Chilean population. To investigate the joint association between adiposity and education with T2D in the Chilean adult population. Analysis of data of the Chilean National Health Survey 2016-2017, which included 5,033 participants with a mean age of 43 years, (51% women). Poisson regression analyses with robust standard error were used to investigate the joint association of the education level and general and central adiposity with T2D. The results were reported as Prevalence Ratio and their 95% confidence intervals (PR, 95% CI). Obesity was associated with a higher probability of having T2D in men than in women, however central adiposity was associated with a higher probability of having T2D in women than in men. Compared with men who had higher education (> 12 years) and had normal body weight, those with the same educational level and who were obese had 2.3-times higher probability of having T2D (PR: 2.35 [95% CI: 1.02; 5.39]). For women, having a low education and being obese was associated with 4.4-times higher probability of having T2D compared to those with higher education and normal body mass index (BMI) (PR: 4.47 [95% IC: 2.12; 9.24]). Similar results were observed when waist circumference was used as a marker of obesity rather than BMI. Women and men with higher BMI and low education had a higher risk of T2D. However, this risk was higher in women than in men.

Plasma Metabolomic Signatures of Sugar-Sweetened Beverage Consumption and Risk of Type 2 Diabetes Among US Adults

ObjectivesSugar-sweetened beverage (SSB) consumption is associated with a higher risk of type 2 diabetes (T2D), but the metabolic changes linking SSB consumption to T2D are not fully understood. Thus, we aimed to identify a plasma metabolomic signature of SSB consumption and evaluate its association with incident T2D. MethodsWe used liquid chromatography–mass spectrometry to measure plasma metabolites (>200) among 3,434 participants from three US cohorts: Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study (HPFS). SSB consumption (servings/day; sodas, fruit punches, and other sugary drinks) was estimated from food frequency questionnaires. We used elastic net regression with 10-fold-cross-validation to identify metabolites associated with higher SSB consumption among a training set of participants (n = 2068) and replicated the association in a testing set (n = 1366). A metabolomic signature score was calculated as the weighted sum of SSB-associated metabolites. Pearson correlation (r) coefficients and 95% confidence intervals (CI) between the metabolomic signature and self-reported SSB consumption were calculated. We used multivariable Cox regression models to estimate hazard ratios (HR) and CI of the identified metabolomic signature with incident T2D among all participants. ResultsWe identified an SSB plasma metabolomic signature of 71 metabolites, primarily lipids and amino acids. Pearson correlation (r) coefficients between self-reported SSBs and the plasma metabolomic signature were 0.18 (95% CI: 0.14, 0.22; P < 0.0001) and 0.19 (95% CI: 0.14, 0.24; P < 0.0001) in the training and testing sets, respectively. After a median follow-up of 22 years, the metabolomic signature was significantly associated with higher T2D risk [HR for quartile (Q) 1 versus 4 (95% CI): 1.45 (1.02, 2.05); P = 0.04] in models adjusting for factors related to demographics, lifestyle, diet, and body mass index. The association persisted when further adjusting for self-reported SSB consumption [HR for Q1 versus Q4 (95% CI): 1.42 (1.00, 2.02); P = 0.05]. ConclusionsWe identified a novel metabolomic signature of SSB consumption in US adults that associated with elevated incident T2D risk. This signature may reflect both SSB consumption and metabolic changes related to T2D risk, although residual confounding cannot be ruled out. Funding SourcesNIH.

Cumulative Consumption of Sulfur Amino Acids Intake and Incidence of Diabetes

ObjectivesIncreasing evidence in animal models and humans suggests that diets high in sulfur-containing amino acids (SAA) could be associated a greater risk for type 2 diabetes (T2D). However, data from longitudinal human studies linking dietary SAA intake with T2D is lacking. The present study aimed to examine the association between long-term dietary intake of SAA including total SAAs, methionine, and cysteine and incident T2D in participants of the Framingham Heart Study (FHS). MethodsAdult participants were selected from two prospective FHS cohorts: The Offspring Cohort (followed from 1991 to 2015, n = 3799) and the Third Generation Cohort (followed from 2002 to 2011, n = 4096). Individuals identified as diabetes patients before baseline, having missing diet or covariates data, or reported extreme daily energy intake were excluded. Energy-adjusted intake of dietary SAAs was calculated from responses to a 131-item food frequency questionnaire. Cox proportional hazards models were used to evaluate associations between intakes of SAAs (in quintiles) and risk of T2D in each cohort. A combined analysis was also performed pooling subjects from both cohorts. ResultsOverall, we documented 471 T2D events during 9–23 years of follow-up. In both cohorts, higher SAA intake was associated with a higher risk of T2D after adjustment for demographics, traditional risk factors and related nutrients. Comparing participants in the highest quintile with those in the lowest quintile of intake, adjusted hazard ratios (95% CI) were 1.98 (1.15–3.41) for total intake (P for trend = 0.04) in the Offspring cohort, and 4.37 (1.40–13.67) (P for trend = 0.01) in the Third Generation cohort. In the combination analysis of two cohorts, adjusted hazard ratios (95% CI) were 1.98 (1.23–3.21) for total intake, 2.21 (1.38–3.53) for methionine, and 1.79 (1.12–2.87) for cysteine (P for trends < 0.03). ConclusionsHigher long-term SAA intake was associated with higher risk for T2D in humans, suggesting that dietary patterns emphasizing low SAA intake are protective against development of T2D. Funding SourcesNo funding.

Higher risk of type 2 diabetes in women with hyperandrogenic polycystic ovary syndrome

To assess the risk of type 2 diabetes (T2D) in women with polycystic ovary syndrome (PCOS) in relation to body mass index (BMI) and the hyperandrogenic (HA) PCOS phenotype. Population-based cohort study. Data from six Swedish national registers, with participants being followed for a maximum of 19 years. All women with an International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of PCOS, androgen excess, or anovulatory infertility born between 1950 and 1999 (n = 52,535) were identified in the Patient Register. The HA PCOS phenotype was defined by two filled prescriptions for anti-androgenic drugs. For each woman with PCOS, five control women (n = 254,624) were randomly chosen from the Total Population Register, matched for age and geographic area. No interventions were performed. International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of T2D or prescription of antidiabetic treatment other than metformin. The cumulative incidence rates of T2D were 1.3%, 4.4%, and 14.2% in controls (non-PCOS women) and women with normoandrogenic (NA) and HA PCOS, respectively. After adjustment for BMI, women with PCOS had a twofold higher rate of T2D than non-PCOS women (adjusted hazard ratio, 2.52 [95% confidence interval, 2.15-2.96]). Women with HA PCOS had a higher rate of T2D than those with NA PCOS (adjusted hazard ratio, 3.86 [95% confidence interval, 3.16-4.72]). Polycystic ovary syndrome is an independent risk factor for T2D, even after adjustment for BMI. Women with the HA PCOS phenotype face an even higher risk of T2D than those with the NA PCOS phenotype.

A Prediction Model Based on Noninvasive Indicators to Predict the 8-Year Incidence of Type 2 Diabetes in Patients with Nonalcoholic Fatty Liver Disease: A Population-Based Retrospective Cohort Study.

Background The prevention of type 2 diabetes (T2D) and its associated complications has become a major priority of global public health. In addition, there is growing evidence that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of diabetes. Therefore, the purpose of this study was to develop and validate a nomogram based on independent predictors to better assess the 8-year risk of T2D in Japanese patients with NAFLD. Methods This is a historical cohort study from a collection of databases that included 2741 Japanese participants with NAFLD without T2D at baseline. All participants were randomized to a training cohort (n = 2058) and a validation cohort (n = 683). The data of the training cohort were analyzed using the least absolute shrinkage and selection operator method to screen the suitable and effective risk factors for Japanese patients with NAFLD. A cox regression analysis was applied to build a nomogram incorporating the selected features. The C-index, receiver operating characteristic curve (ROC), calibration plot, decision curve analysis, and Kaplan-Meier analysis were used to validate the discrimination, calibration, and clinical usefulness of the model. The results were reevaluated by internal validation in the validation cohort. Results We developed a simple nomogram that predicts the risk of T2D for Japanese patients with NAFLD by using the parameters of smoking status, waist circumference, hemoglobin A1c, and fasting blood glucose. For the prediction model, the C-index of training cohort and validation cohort was 0.839 (95% confidence interval (CI), 0.804-0.874) and 0.822 (95% CI, 0.777-0.868), respectively. The pooled area under the ROC of 8-year T2D risk in the training cohort and validation cohort was 0.811 and 0.805, respectively. The calibration curve indicated a good agreement between the probability predicted by the nomogram and the actual probability. The decision curve analysis demonstrated that the nomogram was clinically useful. Conclusions We developed and validated a nomogram for the 8-year risk of incident T2D among Japanese patients with NAFLD. Our nomogram can effectively predict the 8-year incidence of T2D in Japanese patients with NAFLD and helps to identify people at high risk of T2D early, thus contributing to effective prevention programs for T2D.

Dietary potato intake and risks of type 2 diabetes and gestational diabetes mellitus

Evidence regarding associations between potato consumption and type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) risks is accumulating. This study aims to synthesize the evidence by conducting a meta-analysis of available studies.PubMed, Web of Science, EMBASE and Cochrane Library were searched (up to August 2020) to retrieve all eligible studies on the associations of interest. The risk estimates with 95% confidence intervals (CIs) were summarized using random- or fixed-effects model based on heterogeneity. Meta-analyses were performed for East and West regions separately. Dose-response relationship was assessed using data from all intake categories in each study.A total of 19 studies (13 for T2D; 6 for GDM) were identified, including 21,357 T2D cases among 323,475 participants and 1516 GDM cases among 29,288 pregnancies. Meta-analysis detected a significantly positive association with T2D risk for total potato (RR: 1.19 [1.06, 1.34]), baked/boiled/mashed potato (RR: 1.08 [1.00, 1.16]), and French fries/fried potato (RR: 1.33 [1.03, 1.70]) intakes among Western populations. Dose-response meta-analysis demonstrated a significantly increased T2D risk by 10% (95% CI: 1.07, 1.14; P for trend<0.001), 2% (95% CI: 1.00, 1.04; P for trend = 0.02) and 34% (95% CI: 1.24, 1.46; P for trend<0.001) for each 80 g/day (serving) increment in total potato, unfried potato, and fried potato intakes, respectively. As for GDM, summarized estimates also suggested a higher though non-significant GDM risk for total potato (RR: 1.19 [0.89, 1.58]), and French fries/fried potato (RR: 1.03 [0.97, 1.09]) intakes in Western countries. In the dose-response meta-analysis, a significantly increased GDM risk was revealed for each daily serving (80 g) intakes of total potato (RR: 1.22; 95% CI: 1.06, 1.42; P for trend = 0.007) and unfried potato (RR: 1.26; 95% CI: 1.07, 1.48; P for trend = 0.006).This study suggests that higher potato intake is associated with higher T2D risk among Western populations. The positive relationship presents a significant dose-response manner. Wisely controlled potato consumption may confer potential glucometabolic benefits.

Adherence to a healthy Nordic diet and risk of type 2 diabetes among men: the Kuopio Ischaemic Heart Disease Risk Factor Study

PurposeTo investigate the association between healthy Nordic diet and risk of type 2 diabetes (T2D) in middle-aged and older men from eastern Finland.MethodsA total of 2332 men aged 42–60 years and free of T2D at baseline in 1984–1989 were included. Diet was assessed with 4-day food records at baseline and the healthy Nordic diet score was calculated based on a modified Baltic Sea Diet Score. T2D diagnosis was based on self-administered questionnaires, fasting and 2-h oral glucose tolerance test blood glucose measurements, or by record linkage to national health registries. Cox proportional hazards regression and analysis of covariance were used for analyses.ResultsDuring the mean follow-up of 19.3 years, 432 men (18.5%) were diagnosed with T2D. The multivariable-adjusted hazard ratio for T2D in the lowest vs. the highest quartile of the healthy Nordic diet score was 1.35 (95% CI 1.03–1.76) (P trend across quartiles 0.028). Lower adherence to healthy Nordic diet was also associated with higher plasma glucose and insulin concentrations.ConclusionsIn this prospective population-based cohort study among middle-aged and older men from eastern Finland, lower adherence to healthy Nordic diet was associated with higher risk of T2D and higher plasma glucose and serum insulin concentrations.

Contribution of Adipose Tissue Oxidative Stress to Obesity-Associated Diabetes Risk and Ethnic Differences: Focus on Women of African Ancestry

Adipose tissue (AT) storage capacity is central in the maintenance of whole-body homeostasis, especially in obesity states. However, sustained nutrients overflow may dysregulate this function resulting in adipocytes hypertrophy, AT hypoxia, inflammation and oxidative stress. Systemic inflammation may also contribute to the disruption of AT redox equilibrium. AT and systemic oxidative stress have been involved in the development of obesity-associated insulin resistance (IR) and type 2 diabetes (T2D) through several mechanisms. Interestingly, fat accumulation, body fat distribution and the degree of how adiposity translates into cardio-metabolic diseases differ between ethnicities. Populations of African ancestry have a higher prevalence of obesity and higher T2D risk than populations of European ancestry, mainly driven by higher rates among African women. Considering the reported ethnic-specific differences in AT distribution and function and higher levels of systemic oxidative stress markers, oxidative stress is a potential contributor to the higher susceptibility for metabolic diseases in African women. This review summarizes existing evidence supporting this hypothesis while acknowledging a lack of data on AT oxidative stress in relation to IR in Africans, and the potential influence of other ethnicity-related modulators (e.g., genetic-environment interplay, socioeconomic factors) for consideration in future studies with different ethnicities.

In-Silico Study of Immune System Associated Genes in Case of Type-2 Diabetes With Insulin Action and Resistance, and/or Obesity.

Type-2 diabetes and obesity are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches and are among the most frequent and highly complex and heterogeneous in nature. Based on epidemiological evidence, it is known that the patients suffering from obesity are considered to be at a significantly higher risk of type-2 diabetes. There are several pieces of evidence that support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of type-2 diabetes. Multi-level unwanted alterations such as (epi-) genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major sources that promote several complex diseases, and such a heterogeneous level of complexity is considered as a major barrier in the development of therapeutics. With so many known challenges, it is critical to understand the relationships and the shared causes between type-2 diabetes and obesity, and these are difficult to unravel and understand. For this purpose, we have selected publicly available datasets of gene expression for obesity and type-2 diabetes, have unraveled the genes and the pathways associated with the immune system, and have also focused on the T-cell signaling pathway and its components. We have applied a simplified computational approach to understanding differential gene expression and patterns and the enriched pathways for obesity and type-2 diabetes. Furthermore, we have also analyzed genes by using network-level understanding. In the analysis, we observe that there are fewer genes that are commonly differentially expressed while a comparatively higher number of pathways are shared between them. There are only 4 pathways that are associated with the immune system in case of obesity and 10 immune-associated pathways in case of type-2 diabetes, and, among them, only 2 pathways are commonly altered. Furthermore, we have presented SPNS1, PTPN6, CD247, FOS, and PIK3R5 as the overexpressed genes, which are the direct components of TCR signaling.

Ultra-processed foods and type-2 diabetes risk in the SUN project: A prospective cohort study

The association between ultra-processed foods (UPF) consumption and the risk of type 2 diabetes (T2D) has not been much explored. We aimed to evaluate the association between consumption of UPF and the incidence of T2D. We assessed 20,060 participants (61.5% women) from the SUN project (Seguimiento Universidad de Navarra) followed-up every two years (median follow-up 12 years). Food and drink consumption were evaluated through a validated 136-item food frequency questionnaire and grouped according to their degree of processing by the NOVA classification. Participants were categorized into tertiles of UPF consumption adjusted for total energy intake. We fitted Cox proportional hazard models with repeated dietary measurements at baseline and updating information on food consumption after 10 years of follow-up to minimise the potential effect of diet variation. During 215,149 person-years of follow-up, 175 new-onset T2D cases were confirmed. Participants in the highest baseline tertile (high consumption) of UPF consumption had a higher risk of T2D as compared to those in the lowest tertile (multivariable adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI]: 1.06 to 2.22) with a significant dose-response relationship (p for linear trend=0.024). The multivariable adjusted HR using repeated measurements of UPF intake was 1.65 (95% CI 1.14-2.38) when comparing extreme tertiles. In a highly-educated Mediterranean cohort with a low absolute risk, a higher intake of UPF was independently associated with a higher risk for T2D. These results provide more evidence to encourage the limitation of UPF consumption to reduce the population burden of T2D.

Could social prescribing contribute to type 2 diabetes prevention in people at high risk? Protocol for a realist, multilevel, mixed methods review and evaluation

IntroductionSocial prescribing is an innovation being widely adopted within the UK National Health Service policy as a way of improving the management of people with long-term conditions, such as type...

The Utility of a Type 2 Diabetes (T2D) Polygenic Score in Addition to Clinical Variables for Prediction of T2D Incidence in Birth, Youth, and Adult Cohorts

Background: There is limited information on how polygenic scores (PSs) — based on variants from genome-wide association studies (GWAS) of T2D — add to clinical variables in predicting T2D incidence. Methods: For participants in a longitudinal study in an Indigenous population from the Southwest United States (US) with high T2D prevalence, we analyzed 10 constructions of PS using publicly available GWAS summary statistics. T2D incidence was examined in three cohorts of individuals without T2D at baseline. The adult cohort, comprised of 2333 participants followed from age≥20y, had 640 T2D cases. The youth cohort was comprised of 2229 participants followed from age 5-19y (228 cases). The birth cohort was comprised of 2894 participants followed from birth (438 cases). We assessed contributions of the PS and clinical variables in predicting T2D incidence. Results: Of the 10 PS constructions, a PS using 293 genome-wide significant variants from a large T2D GWAS meta-analysis in European-ancestry populations performed best. In the adult cohort, area under the receiver operating characteristic curve (AUC) for clinical variables for prediction of T2D incidence was 0·728; with the PS, 0·735. The PS’s hazard ratio (HR) was 1.27 per SD (p=1·6×10-8; 95% CI 1·17-1·38). In the youth cohort, the analogous model’s AUC was 0·805; with the PS, 0·812. The PS’s HR was 1·49 (p=4·3×10-8; 95% CI 1·29-1·72). In the birth cohort, AUC for the clinical variables was 0·614; with the PS, 0·685. The PS’s HR was 1·48 (p=2·8×10-16; 95% CI 1·35-1·63). To further assess the potential impact of including PS for assessing individual T2D risk, the net reclassification improvement (NRI) was calculated: NRI for the PS was 0·264, 0·249, and 0·309 for adult, youth, and birth cohorts, respectively. For comparison, NRI for HbA1c was 0·292 and 0·150 for adult and youth cohorts, respectively. Across all cohorts, as estimated using decision curve analyses, the net benefit of including the PS in addition to clinical variables was most pronounced at moderately stringent threshold probability (pt) values for instituting a preventive intervention. Discussion: This study demonstrates that the PS contributes significantly to prediction of T2D incidence in addition to the information provided by clinical factors; however, overall improvement of the prediction model was modest. Discriminatory power of the PS for predicting incident T2D was similar to that of other commonly measured clinical factors (e.g. HbA1c). Including T2D PS in addition to clinical factors may be clinically beneficial for identifying individuals at higher risk for T2D, especially at younger ages. Funding Statement: This study used computational resources of the Biowulf system at the National Institutes of Health (NIH), Bethesda, MD. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Intramural Research Program provided support for NIDDK-based coauthors. The NIH Oxford-Cambridge Scholars Program provided funding support for L.E.W.’s doctoral programme. M.I.M. was a Wellcome Senior Investigator and an NIHR Senior Investigator. This work was funded in Oxford by the Wellcome Trust (098381, 106130, 203141), NIH (U01- DK105535; U01-DK085545) and National Institute for Health Research (NIHR) (NF-SI-0617- 10090) and Oxford Biomedical Research Centre (BRC). Declaration of Interests: The views expressed in this article are those of the author(s) and not necessarily those of NIH, NHS, NIHR, or UK Department of Health. M.I.M. has served on advisory panels for Pfizer, Novo Nordisk, and Zoe Global; has received honoraria from Merck, Pfizer, Novo Nordisk, and Eli Lilly; and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, M.I.M. and A.M. are employees of Genentech and holders of Roche stock. Ethics Approval Statement: Protocols were approved by the institutional review board of the National Institute of Diabetes and Digestive and Kidney Diseases.

Egg consumption, overall diet quality, and risk of type 2 diabetes and coronary heart disease: A pooling project of US prospective cohorts

Data on the relation of egg consumption with risk of type 2 diabetes (T2D) and coronary heart disease (CHD) are limited and inconsistent. Few studies have controlled for overall dietary patterns in egg-T2D or egg-CHD analyses, and it is unclear whether any observed elevated risks of T2D and CHD with frequent egg consumption is real or due to confounding by dietary habits. We tested the hypothesis that frequent egg consumption is associated with a higher risk of T2D and CHD risk after adjustment for overall dietary patterns among adults. We used prospective cohort design to complete time-to-event analyses. We pooled de novo, harmonized, individual-level analyses from nine US cohorts (n=103,811). Cox regression was used to estimate hazard ratios separately in each cohort adjusting for age, ethnicity, body mass index (BMI), exercise, smoking, alcohol intake, and dietary patterns. We pooled cohort-specific results using an inverse-variance weighted method to estimate summary relative risks. Median age ranged from 25 to 72 years. Median egg consumption was 1 egg per week in most of the cohorts. While egg consumption up to one per week was not associated with T2D risk, consumption of ≥2 eggs per week was associated with elevated risk [27% elevated risk of T2D comparing 7+ eggs/week with none (95% CI: 16%-37%)]. There was little evidence for heterogeneity across cohorts and we observed similar conclusions when stratified by BMI. Overall, egg consumption was not associated with the risk of CHD. However, in a sensitivity analysis, there was a 30% higher risk of CHD (95% CI: 3%-56%) restricted to older adults consuming 5-6 eggs/week. Our data showed an elevated risk of T2D with egg consumption of ≥2 eggs per week but not with <2 eggs/week. While there was no overall association of egg consumption with CHD risk, the elevated CHD observed with consumption of 5-6 eggs/week in older cohorts merits further investigation.

DNA Methylation GrimAge and Incident Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

DNA methylation (DNAm)-based biological age (epigenetic age) has been suggested as a useful biomarker of age-related conditions including type 2 diabetes (T2D), and its newest iterations (GrimAge measurements) have shown early promise. In this study, we explored the association between epigenetic age and incident T2D in the context of their relationships with obesity. A total of 1,057 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included in the current analyses. We stratified the participants into three groups: normal weight, overweight, and obese. A 1-year increase of GrimAge was associated with higher 10-year (study years 15-25) incidence of T2D (odds ratio [OR] 1.06, 95% CI 1.01-1.11). GrimAge acceleration, which represents the deviation of GrimAge from chronological age, was derived from the residuals of a model of GrimAge and chronological age, and any GrimAge acceleration (positive GrimAA: having GrimAge older than chronological age) was associated with significantly higher odds of 10-year incidence of T2D in obese participants (OR 2.57, 95% CI 1.61-4.11). Cumulative obesity was estimated by years since obesity onset, and GrimAge partially mediated the statistical association between cumulative obesity and incident diabetes or prediabetes (proportion mediated = 8.0%). In conclusion, both older and accelerated GrimAge were associated with higher risk of T2D, particularly among obese participants. GrimAge also statistically mediated the associations between cumulative obesity and T2D. Our findings suggest that epigenetic age measurements with DNAm can potentially be used as a risk factor or biomarker associated with T2D development.

Combined analysis of gestational diabetes and maternal weight status from pre-pregnancy through post-delivery in future development of type 2 diabetes

We examined the associations of gestational diabetes mellitus (GDM) and women’s weight status from pre-pregnancy through post-delivery with the risk of developing dysglycaemia [impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes (T2D)] 4–6 years post-delivery. Using Poisson regression with confounder adjustments, we assessed associations of standard categorisations of prospectively ascertained pre-pregnancy overweight and obesity (OWOB), gestational weight gain (GWG) and substantial post-delivery weight retention (PDWR) with post-delivery dysglycaemia (n = 692). Women with GDM had a higher risk of later T2D [relative risk (95% CI) 12.07 (4.55, 32.02)] and dysglycaemia [3.02 (2.19, 4.16)] compared with non-GDM women. Independent of GDM, women with pre-pregnancy OWOB also had a higher risk of post-delivery dysglycaemia. Women with GDM who were OWOB pre-pregnancy and had subsequent PDWR (≥ 5 kg) had 2.38 times (1.29, 4.41) the risk of post-delivery dysglycaemia compared with pre-pregnancy lean GDM women without PDWR. No consistent associations were observed between GWG and later dysglycaemia risk. In conclusion, women with GDM have a higher risk of T2D 4–6 years after the index pregnancy. Pre-pregnancy OWOB and PDWR exacerbate the risk of post-delivery dysglycaemia. Weight management during preconception and post-delivery represent early windows of opportunity for improving long-term health, especially in those with GDM.

The role of a traditional and western diet on glucose homeostasis in Greenlandic Inuit carriers and non-carriers of type 2 diabetes variant in the TBC1D4 gene: A protocol for a randomized clinical trial

IntroductionThe lifestyle of Inuit in Greenland and worldwide is undergoing a transition from a fisher-hunter to a westernized society and meanwhile the prevalence of type-2 diabetes (T2D) has increased dramatically. Studies have shown that a common nonsense p.Arg684Ter variant in TBC1D4, which is frequent in Greenland, confers genetic susceptibility towards high risk of T2D. The aim of the study is to investigate whether a traditional marine diet, with high fat and low carbohydrate, will improve glycemic control in Greenland Inuit compared to a western diet. Moreover, we want to examine if the response is more pronounced in carriers of the p.Arg684Ter variant. Materials and methodsWe will conduct a randomized, clinical cross-over trial with two dietary intervention periods of four weeks duration. The diet intervention comprise provision of >20E% and instruction for the remaining part of the diet. We expect to include 30 homozygous carriers and 30 homozygous non-carriers of the p.Arg684Ter variant, aged 18–80 years, across three Greenlandic towns. The primary outcome is plasma (p)-glucose 2 h post an oral glucose tolerance test and we aim to have 80% power, at α = 0.05, to detect a difference of 1.1 mmol/L. We will also include supporting measures of glucose homeostasis, assess other markers of the metabolic syndrome and perform metabolome and microbiome profiling. The statistical analysis will be performed as complete case analyses using linear mixed models. Ethics and disseminationThe study received approval by the Ethics Committee of Greenland (KVUG 2018-26) and will be disseminated via international peer-reviewed journal articles and conferences. Trial registration numberClinicaltrials.gov identifier no. NCT04011904.

Factors Associated With Low Physical Activity in Two Latin American Populations at Risk of Developing Type 2 Diabetes: An Exploratory Analysis.

Low level of physical activity is a risk factor for chronic non-communicable diseases. Specifically, people at risk of Type 2 Diabetes (T2D) have shown to benefit from being physically active. The objective of this study was to explore what factors were associated with low physical activity in people at high risk of T2D living in Bogota and Barranquilla, Colombia.Methodology: Cross-sectional study using baseline data from a quasi-experimental clinical trial (PREDICOL Project). The study included 1,135 participants of Bogota and Barranquilla that presented a high risk of developing T2D according to the Finnish Diabetes Risk Score (>12 points) and who underwent an oral glucose tolerance test. The main outcome variable was the level of physical activity assessed by the International Physical Activity Questionnaire. Unadjusted and adjusted logistic regression analysis were used to calculate odds ratios (OR) and the corresponding 95% confidence intervals (CI).Results: In total, 72.5% of the study participants had low level of physical activity. Participants in the age group between 45 and 54 years showed 74% greater odds of having low physical activity compared with the youngest age group (OR 1.74, 95% CI 1.1 −2.8). People living in Barranquilla were eight times more likely to have low physical activity compared with those in Bogotá D.C. (OR 8.1, 95% CI 5.7 to 11.4).Conclusion: A large proportion of the population at risk of developing D2T in two large cities of Colombia have a sedentary lifestyle. Interventions should be designed and implemented in order to increase physical activity in these populations.

Causal Relationship and Shared Genetic Loci between Psoriasis and Type 2 Diabetes through Trans-Disease Meta-Analysis

Psoriasis and type 2 diabetes (T2D) are complex conditions with significant impacts on health. Patients with psoriasis have a higher risk of T2D (∼1.5 OR) and vice versa, controlling for body mass index; yet, there has been a limited study comparing their genetic architecture. We hypothesized that there are shared genetic components between psoriasis and T2D. Trans-disease meta-analysis was applied to 8,016,731 well-imputed genetic markers from large-scale meta-analyses of psoriasis (11,024 cases and 16,336 controls) and T2D (74,124 cases and 824,006 controls), adjusted for body mass index. We confirmed our findings in a hospital-based study (42,112 patients) and tested for causal relationships with multivariable Mendelian randomization. Mendelian randomization identified a causal relationship between psoriasis and T2D (P= 1.6× 10‒4, OR= 1.01) and highlighted the impact of body mass index. Trans-disease meta-analysis further revealed four genome-wide significant loci (P < 5× 10‒8) with evidence of colocalization and shared directions of effect between psoriasis and T2D not present in body mass index. The proteins coded by genes in these loci (ACTR2, ERLIN1, TRMT112, and BECN1) are connected through NF-κB signaling. Our results provide insight into the immunological components that connect immune-mediated skin conditions and metabolic diseases, independent of confounding factors.

Body mass index and risk of obesity-related conditions in a cohort of 2.9 million people: Evidence from a UK primary care database.

ObjectiveObesity rates in the United Kingdom are some of the highest in Western Europe, with considerable clinical and societal impacts. Obesity is associated with type 2 diabetes (T2D), osteoarthritis, cardiovascular disease, and increased mortality; however, relatively few studies have examined the occurrence of multiple obesity‐related outcomes in the same patient population. This study was designed to examine the associations between body mass index (BMI) and a broad range of obesity‐related conditions in the same large cohort from a UK‐representative primary care database.MethodsDemographic data and diagnosis codes were extracted from the Clinical Practice Research Datalink GOLD database in January 2019. Adults registered for ≥ 3 years were grouped by BMI, with BMI 18.5–24.9 kg/m2 as reference group. Associations between BMI and 12 obesity‐related outcomes were estimated using Cox proportional hazard models, adjusted for age, sex, and smoking.ResultsMore than 2.9 million individuals were included in the analyses and were followed up for occurrence of relevant outcomes for a median of 11.4 years during the study period. Generally, there was a stepwise increase in risk of all outcomes with higher BMI. Individuals with BMI 40.0–45.0 kg/m2 were at particularly high risk of sleep apnea (hazard ratio [95% confidence interval] vs. reference group: 19.8 [18.9–20.8]), T2D (12.4 [12.1–12.7]), heart failure (3.46 [3.35–3.57]), and hypertension (3.21 [3.15–3.26]).ConclusionsThis study substantiates evidence linking higher BMI to higher risk of a range of serious health conditions, in a large, representative UK cohort. By focusing on obesity‐related conditions, this demonstrates the wider clinical impact and the healthcare burden of obesity, and highlights the vital importance of management, treatment approaches, and public health programs to mitigate the impact of this disease.