Incident Type 2 Diabetes Research Articles

IDF2022-0476 Effectiveness of a screening program of type 2 diabetes (T2D) in Primary Care, and long-term incidence of T2D in Spain

IDF2022-0476 Effectiveness of a screening program of type 2 diabetes (T2D) in Primary Care, and long-term incidence of T2D in Spain

Mediation of an association between neighborhood socioeconomic environment and type 2 diabetes through the leisure-time physical activity environment in an analysis of three independent samples

IntroductionInequitable access to leisure-time physical activity (LTPA) resources may explain geographic disparities in type 2 diabetes (T2D). We evaluated whether the neighborhood socioeconomic environment (NSEE) affects T2D through the LTPA...

Abstract P157: Genetically Determine Gut Microbiome Abundance, Obese, and Incident Type 2 Diabetes

Introduction: Gut microbiota has been linked to the body’s adiposity and the development of type 2 diabetes (T2D). A recent genome-wide association study identified that genetic variants at the ABO locus (SNPs rs8176645 and rs550057) were associated with the abundance of gut microbiome (i.e., Bifidobacterium bifidum and Collinsella aerofaciens, respectively). Hypothesis: We assessed the hypothesis that the genetically determined gut microbiome abundance was associated with incident T2D, and such association could be modified by obese status. Methods: A total of 339,465 European ancestry participants who are initially free of T2D at baseline and have available information on genetic variants from the UK Biobank population were included in this study. The genetic risk score (GRS) was constructed by the risk alleles of the two genetic variants at the ABO locus. Cox proportional hazard models were used to estimate the associations between the genetic variants/GRS and incident T2D. Results: During a median of 11.8 years of follow-up, 11,566 incident T2D were documented. We observed that the gut microbiome-related variants rs8176645 and rs550057 were both significantly associated with incident T2D after adjustment for sex, age, body mass index (BMI), Townsend deprivation index, smoking, drinking, regular physical activity, and diet score at baseline (hazard ratio [HR] per copy of risk allele A of rs8176645 1.05, 95% CI [1.02-1.09], P -value=0.001; HR per copy of risk allele T of rs550057 1.06, 95% CI [1.03-1.09], P -value<0.001; respectively). The GRS also showed a significant association with T2D incidence in the fully adjusted model (HR=1.03, 95% CI [1.01-1.05], P -value<0.001). In addition, we found that BMI significantly modified the associations between GRS and T2D, which were more pronounced in non-obese participants ( P -interaction=0.008). Conclusion: Our findings indicate that the genetically determined gut microbiome abundance significantly predicts T2D risk, independent of traditional risk factors.

Abstract 66: Clonal Hematopoiesis of Indeterminate Potential and Incident Type 2 Diabetes Risk

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in elevated risks for coronary heart disease (CHD) and death, but its association with incident type 2 diabetes (T2D) is unknown. Hypothesis: We hypothesized that CHIP is associated with elevated risk of incident T2D. Methods: CHIP was derived from whole genome sequencing of blood DNA in NHLBI Trans-omics for Precision Medicine (TOPMed) cohorts. We analyzed 17,637 participants without prior T2D, cardiovascular disease, or cancer at blood draw, with prospective follow-up for incident T2D. We evaluated baseline prevalence of CHIP vs. no CHIP with incident T2D risk using Cox regression. We also investigated CHIP variants previously related to CHD: DNMT3A , TET2 , ASXL1 , JAK2 , and TP53 . We estimated multivariable-adjusted hazard ratios and 95% confidence intervals (HR [CI]) adjusted for age, sex, body mass index, smoking, alcohol, and education. We combined cohort estimates via fixed effects meta-analysis. Results: On average, participants were age 63.4 years (SD=11.5) and 76% female. Prevalence of CHIP was 6.0% (1,055) at baseline. There were 2,467 incident T2D cases over mean=9.8 years follow-up. Compared to those without a mutation, having CHIP was associated with a 23% higher T2D risk, both overall (combined HR=1.23; 95% CI=1.04, 1.45), and among those with CHD-related CHIP mutations (87% of total CHIP): HR=1.23 (1.03, 1.46). Although those with CHIP mutations of TET2 (HR=1.48; 1.05, 2.08) and ASXL1 (HR=1.76; 1.03, 2.99) had larger elevations in T2D risk, and DNMT3A was suggestive of increased T2D risk (HR=1.15; 0.93, 1.43), statistical power was limited for JAK2 and TP53 mutation analyses. Conclusions: CHIP was associated with higher incidence of T2D. CHIP mutations located on loci previously implicated in aging and CHD were also related to T2D, suggesting shared pathology of atherosclerosis and T2D.

Abstract P324: Female Reproductive Factors and Risk of Type 2 Diabetes and Cardiovascular Disease Among Women With a History of Gestational Diabetes

Introduction: The link between gestational diabetes mellitus (GDM) and long-term risk of type 2 diabetes (T2D) and cardiovascular disease (CVD) is well established; however, risk factors underlying the progression of disease remain uncertain. Hypothesis: Female reproductive factors including ages at menarche, menopause, and first birth, number of live births, and surgically-induced menopause (uni- or bilateral oophorectomy or hysterectomy) are associated with higher risk of progression, while breastfeeding is associated with lower risk of progression from GDM to T2D/CVD. Methods: Participants in the Nurses’ Health Study II reported reproductive history at cohort baseline and over follow-up, including 5346 women with a history of GDM. Self-reported incident T2D or CVD (myocardial infarction, coronary revascularization or stroke) were confirmed via questionnaire or medical records. We estimated the hazard ratios (HR [95%]) across quintiles of each reproductive factor with incident T2D and CVD using Cox models adjusting for age, race/ethnicity, smoking, BMI at 18 years, physical activity, family history of T2D or CVD, alcohol intake, menopausal status, aspirin use, and Alternate Healthy Eating Index. Results: We documented 988 incident T2D and 149 CVD cases over 25 years of follow-up. In adjusted models, higher total lactation duration was associated with lower risk of T2D (5 categories: 0, 1-6, 7-12, 13-24, >24 months, p for trend=0.01; highest vs. lowest category: HR 0.77 [95%CI: 0.60, 0.98]) and CVD (p for trend=0.03, HR 0.39 [95%CI: 0.19, 0.80]). Early age at menarche was linearly associated with higher risk of T2D (5 categories: ≤11, 12, 13, 14, >14 y: p for trend <0.0001), lowest (≤11 y) vs. reference (13 y) category: HR 1.28 [95%CI: 1.06, 1.53], while no trend could be observed for CVD outcomes (p for trend=0.48). Higher age at 1 st birth was associated with lower CVD risk (5 categories: <23, 23-25 [reference], 26-29, 30-34, ≥35 y, p for trend=0.001; highest vs reference category: HR 0.17 [95%CI: 0.05, 0.57]), but not T2D). Compared with natural menopause, surgically induced menopause was associated with higher T2D risk: 1.32 (1.00, 1.73). Number of live births and age at menopause were not associated with T2D or CVD among women with GDM history. Conclusions: Breastfeeding was associated with lower T2D and CVD risks among women with GDM history, suggesting some shared risk factors or etiologies across reproductive lifespan and long-term cardiometabolic health. Ages at menarche and 1 st birth showed differential associations with T2D and CVD.

Abstract P346: Adherence to the French Dietary Guidelines and Type 2 Diabetes Risk: The E3n-Epic Prospective Cohort Study

Background: Recently, a dietary index reflecting adherence to the 2017 French food-based dietary guidelines, the Programme National Nutrition Santé - guidelines score 2 (PNNS-GS2), has been developed, but evidence on its level of adherence and incident type 2 diabetes (T2D) risk is limited. Objective: We aimed to investigate the association between adherence to the simplified PNNS-GS2 (sPNNS-GS2) and the risk of incident T2D in a French cohort of women. Methods: Between 1993 and 2014, 71,450 women aged over 18 years were examined, and thereafter followed up for the occurrence of T2D within the E3N-EPIC prospective cohort. Dietary data were collected at baseline via a food frequency questionnaire, and the sPNNS-GS2 was derived for each participant. Multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of T2D for continuous and quintile groups of the sPNNS-GS2. Effect modification by body mass index (BMI) and mediation by BMI and waist-hip ratio (WHR) were explored. Results: The mean age was 52.9 years (SD 6.7). During a mean follow-up of 19 years, 3679 incident T2D cases were identified and validated. There was a linear association between adherence to sPNNS-GS2 and T2D risk (P non-linear = 0.85). In the fully adjusted model, each 1-SD increase in the sPNNS-GS2 was associated with a 8% decrease risk of T2D [HR (95% CI), 0.92 (0.89, 0.95)]. Compared to those with the lowest adherence (first quintile), the third [HR (95% CI), 0.91 (0.82, 1.00)] up to the fifth quintile group [HR (95% CI), 0.79 (0.71, 0.88)] had a lower T2D risk. There was a sPNNS-GS2 x BMI interaction on T2D risk (P interaction < 0.01) but not with WHR. The overall association was partly mediated by BMI (18%) and WHR (59%). Conclusion: Higher adherence to the 2017 French food-based dietary guidelines was associated with a lower risk of T2D in women. Furthermore, our mediation analysis suggests that the lower risk of T2D in women associated with adherence to the sPNNS-GS2 is partly mediated by obesity measured by BMI or WHR.

Abstract P152: Joint Association of Sugar- and Artificially-Sweetened Beverage Consumption and Physical Activity and Risk of Type 2 Diabetes in US Adults

Background: Consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) and physical activity are independently associated with type 2 diabetes (T2D) risk; however, it is unknown whether there is an interaction of SSB/ASB intake and physical activity on risk of T2D. Methods: We examined the independent and joint associations between habitual SSB/ASB intake and physical activity with incident T2D risk among 196,101 women and men from the Nurses’ Health Study (NHS, 1980-2016), NHSII (1991-2017), and Health Professional’s Follow-up Study (HPFS, 1986-2016), who were free from chronic diseases at baseline. Cox proportional hazards regressions were used to estimate hazard ratios and 95% confidence intervals (HR; CI), adjusting for demographic and lifestyle T2D risk factors. Results: There were 20,430 incident T2D cases over follow-up of 36, 26, and 30 years in NHS, NHSII, and HPFS, respectively. In multivariable-adjusted models, we confirmed that participants with higher SSBs, ASBs and lower physical activity were independently at higher T2D risk, compared to lower intakes and higher activity levels. In joint analyses for these exposures, participants who did not meet physical activity guidelines and consumed gt 2 servings/day of SSBs had a significantly higher risk of T2D than those who met physical activity guidelines and never/rarely consumed SSBs (1.51; 1.43, 1.60); we observed similar findings for ASBs: 1.29; 1.23, 1.36). Among participants who met physical activity guidelines, those who consumed gt 2 servings/day of SSBs had a HR of 1.23 (1.16, 1.30); the HR for ASBs was 1.07 (1.02, 1.13). Consistent results were observed for women and men. Conclusions: Long-term habitual intake of SSBs or ASBs combined with lower physical activity was associated with higher risk of T2D in three large prospective cohort studies. These findings suggest that even when individuals are physically active, higher consumption of SSBs is associated with a higher risk of T2D. Our results support recommendations and policies to limit the intake of SSB and increase physical activity levels.

Abstract MP56: Intake of Ultra-Processed Foods is Associated With an Increase in Risk for Type Two Diabetes: Results From Three U.S. Cohort Studies and a Meta-Analysis

Introduction: There is limited evidence on the association between long-term consumption of ultra-processed foods (UPF) and the risk of type 2 diabetes (T2D), among the U.S population. The overall strength of this association has also not been established. Hypothesis: Higher intake of UPF is associated with a higher risk of T2D in U.S. adults. The pooled risk estimates from published literature reinforce the positive relationship between the UPF intakes and T2D. Methods: We first assessed this relationship among 71,871 women from the Nurses’ Health Study (NHS, 1984-2016), 87,918 women from NHSII (1991-2017), and 38,847 men from the Health Professionals Follow-up Study (HPFS, 1986-2016) who were all free of T2D at baseline. Diet was assessed using food frequency questionnaires, every 2-4 years. UPF were categorized according to the Nova classification. Information on incident cases of T2D was obtained through follow-up questionnaires every 2 years. The association between UPF intake and incident T2D was examined using Cox proportional hazards models. Second, after conducting a systematic review of prospective cohort studies, risk estimates from all included cohorts were pooled in a random-effects, dose-response, meta-analysis to assess nonlinearity of the association between total UPF intake and T2D risk. Finally, the strength of the meta-evidence was assessed using NutriGrade. Results: During 5,187,678 person-years of follow-up across the three cohorts, 19,503 T2D cases were documented. The pooled multivariable-adjusted hazard ratios (HRs) for T2D between the extreme quintiles of total UPF intake (% of grams/day), was 1.36 (95% confidence interval (CI): 1.29, 1.44; P trend <0.0001). This relationship was driven by intakes of ultra-processed animal-based products, ready-to-eat mixed dishes and artificially- and sugar-sweetened beverages. Ultra-processed cereals and ultra-processed dark breads and whole-grain breads were inversely associated with T2D risk. In the meta-analysis (7 risk estimates, 415,554 participants and 21,932 T2D cases), a significant positive dose-response association between total UPF intake and T2D was observed (P=0.90 for non-linearity): a 10% increase in total UPF intake (% grams from UPF/day) was associated with a 10% higher risk of T2D (95%CI: 8%, 12%; I 2 =23.1%; P heterogeneity =0.25). Per NutriGrade, the evidence supporting the positive relationship between total UPF intake and T2D was of high quality. Conclusions: High quality evidence shows that total UPF consumption is associated with higher risk of T2D, although not all individual foods classified as ultra-processed were associated with a higher risk in these U.S. cohorts.

Abstract P606: Effectiveness of Randomized Dietary Interventions for the Primary Prevention of Incident Cardiovascular Disease and Type 2 Diabetes

Objective: Randomized controlled trials (RCTs) provide opportunities to estimate the causal effects of interventions on disease risk; however, large-scale, long-term RCTs of diet for the prevention of major chronic disease endpoints are sparse. We sought to summarize RCTs comparing the effectiveness of dietary interventions for the primary prevention of clinical cardiovascular disease (CVD) events and type 2 diabetes (T2D) in adults. Methods: We conducted a systematic review and meta-analysis (PROSPERO #CRD42021283728) of RCTs exclusively with dietary interventions with outcomes of incident primary CVD events and/or T2D among adults. We searched MEDLINE and other databases and references. Eligible interventions included those providing instruction, education, and/or provisions to modify intakes of nutrients, foods, or overall dietary patterns. We excluded meal replacement products, dietary supplements, interventions with concomitant comprehensive lifestyle programs, exercise regimens, etc., trials in secondary prevention populations, and trials assessing risk factor or biomarker changes only, rather than clinical events. Two investigators performed screening and data extraction in parallel. We conducted a random effects meta-analysis to estimate the pooled effectiveness of dietary interventions compared with usual diet or low-fat control groups for CVD and T2D outcomes, separately. Results: Among the 5365 citations generated in our searches, we identified 4 eligible RCTs, representing 56,721 participants with mean ages ranging from 44.7 to 67.9 years. Mean intervention duration was 2.3 to 8.1 years, resulting in 3,151 CVD events and 3,603 T2D cases. Compared with the control diets, the various healthy dietary patterns were related to a combined 7% (relative risk [RR] = 0.93, confidence interval [CI] = 0.87-1.00) lower CVD risk and 8% (RR = 0.92, CI = 0.86-0.98) lower T2D risk. Conclusion: Despite major morbidity and mortality from CVD and T2D, there have been few large, population-based, long-term RCTs assessing the exclusive effectiveness of dietary modification for the primary prevention of clinical CVD events or T2D. Results, however, indicate that various healthy diets may be modestly effective for primary prevention.

Abstract P216: Carbohydrate Quantity and Quality, and Risk of Type 2 Diabetes: Results From Three Large Prospective US Cohorts

Background: High-quality carbohydrate sources, such as whole grains, have been associated with a lower risk of type 2 diabetes (T2D), whereas low-quality carbohydrate sources, such as refined grains and added sugar, have been associated with a higher T2D risk. However, few studies have considered how replacing dietary carbohydrate with other macronutrients may influence T2D risk. Objective: We examined whether isocaloric substitution of high- or low-quality carbohydrate for fat, protein, and their subtypes is associated with T2D risk. Methods: We included 75,430 women from the Nurses' Health Study (1984-2016), 85,630 women from the Nurses' Health Study II (1991-2017), and 40,261 men from the Health Professionals Follow-Up Study (1986-2016) who were free of T2D, CVD, and cancer at baseline. Dietary data were collected every 2-4 years using a validated, semi-quantitative food frequency questionnaire. High-quality carbohydrate was defined as carbohydrate from whole grains, fruits, vegetables, and legumes. Low-quality carbohydrate was defined as carbohydrate from refined grains, added sugars, and potatoes. We used Cox proportional hazards regression with time-varying covariates to model the substitution of 5% of energy intake from high- and low-quality carbohydrate for isocaloric amounts of fat, protein, and their subtypes [polyunsaturated fat (PUFA), animal and plant monounsaturated fat (MUFA), saturated fat, trans fat, and animal and plant protein]. Cohort-specific estimates were combined using inverse variance-weighted fixed effects meta-analyses. Results: During 4,859,845 years of follow-up, we documented 20,141 incident T2D cases. In multivariable-adjusted meta-analyses, isocaloric substitution of high-quality carbohydrate for total fat [HR (95% CI) 0.94 (0.93, 0.96)], total MUFA [0.95 (0.91, 0.98)], MUFA from animal sources [0.92 (0.88, 0.95)], total protein [0.91 (0.89, 0.94)], or animal protein [0.94 (0.91, 0.97] was associated with a lower T2D risk. On the other hand, the substitution of low-quality carbohydrate for plant MUFA [1.06 (1.02-1.10)] or plant protein [1.06 (1.02-1.11)] was associated with a higher risk of T2D. When we restricted high-quality carbohydrate sources to whole grains, the results were similar or stronger. Additionally, substitution of whole grain carbohydrate for saturated fat [0.87 (0.84, 0.91)], trans fat [0.87 (0.83, 0.92)], PUFA [0.88 (0.84, 0.92)], plant MUFA [0.92 (0.87, 0.96)], or plant protein [0.91 (0.86, 0.97)] was associated with lower T2D risk. Conclusions: The effect of carbohydrate substitution on T2D risk depends not only on the nutrient being substituted but also on the quality of the carbohydrate. Substitution of high-quality carbohydrate, especially carbohydrate from whole grains (i.e. whole wheat bread, oatmeal), for fat or protein, especially animal sources (i.e. beef, poultry), may lower T2D risk.

Abstract MP66: The Interplay Between Diet, Circulating Indolepropionate Concentrations, and Cardiometabolic Health in US Populations

Background: Indolepropionate (IPA), a tryptophan metabolite of human gut microbiota origin, is associated with lower risk of type 2 diabetes (T2D) in humans. The complex interplay among tryptophan intake, the gut microbiome, prebiotics, circulating IPA concentrations, and T2D risk has not been investigated. Objectives: We aimed to identify IPA-producing gut microbiota species and investigate potential diet-microbiota interaction on circulating IPA concentrations. Methods: We included 287 men from the Men’s Lifestyle Validation Study, a sub-study of the Health Professionals Follow-Up Study (HPFS), who provided up to two pairs of fecal samples and two blood samples approximately six months apart. Dietary intake was assessed using 7-day diet records. We identified microbial taxonomic features associated with plasma IPA concentrations using generalized linear regression and calculated a rank-based species score to reflect IPA-producing potential. Associations between plasma concentrations of tryptophan metabolites and T2D risk were examined in 13,032 participants from Nurses’ Health Study (NHS), NHSII, and HPFS. Results: Plasma IPA concentrations were associated with overall gut microbial profiles (permutational analysis of variance test, p=0.001). We identified 17 microbial species, such as Eubacterium eligens, Butyrivibrio crossotus , and Faecalibacterium prausnitzii , whose abundance was significantly associated with increased plasma IPA concentrations (false discovery rate < 0.05). A significant association between higher tryptophan intake and higher IPA concentrations was only observed among men who had higher fiber intake and a higher microbial species score consisting of the 17 species (p-interaction < 0.01). Similar modulation was also observed for major tryptophan food contributors including vegetables (p-interaction < 0.01), red/processed meat (p-interaction = 0.02), egg (p-interaction 0.01), dairy (p-interaction = 0.01), and whole grain (p-interaction < 0.01). Moreover, interactions persisted for all fiber subtypes (soluble/insoluble fiber and pectin). We documented 1,744 incident T2D cases during 218,603 person-years of follow-up. Plasma concentrations of tryptophan and three kynurenine-pathway metabolites (kynurenine, xanthurenate, and quinolinate) were positively associated with T2D risk while an inverse association was found for IPA. Conclusions: Specific microbial species and dietary fiber jointly modulate the associations between tryptophan intake and circulating IPA concentrations. In a subsequent analysis, IPA levels were predictive of lower T2D risk. Our findings suggest that the health effects of dietary tryptophan may depend on both gut microbiome composition and prebiotic consumption.

Type 2 Diabetes Prevention Programs-From Proof-of-Concept Trials to National Intervention and Beyond.

The prevention of type 2 diabetes (T2D) in high-risk people with lifestyle interventions has been demonstrated by several randomized controlled trials. The intervention effect has sustained up to 20 years in post-trial monitoring of T2D incidence. In 2000, Finland launched the national T2D prevention plan. For screening for high T2D risk, the non-laboratory Finnish Diabetes Risk Score was developed and widely used, also in other countries. The incidence of drug-treated T2D has decreased steadily since 2010. The US congress authorized public funding for a national diabetes prevention program (NDPP) in 2010. It was built around a 16-visit program that relies on referral from primary care and self-referral of persons with either prediabetes or by a diabetes risk test. The program uses a train-the-trainer program. In 2015 the program started the inclusion of online programs. There has been limited implementation of nationwide T2D prevention programs in other countries. Despite the convincing results from RCTs in China and India, no translation to the national level was introduced there. T2D prevention efforts in low-and middle-income countries are still limited, but results have been promising. Barriers to efficient interventions are greater in these countries than in high-income countries, where many barriers also exist. Health disparities by socioeconomic status exist for T2D and its risk factors and form a challenge for preventive interventions. It seems that a stronger commitment to T2D prevention is needed, such as the successful WHO Framework Convention on Tobacco Control, which legally binds the countries to act.

Exposure to high levels of PFAS through drinking water is associated with increased risk of type 2 diabetes—findings from a register-based study in Ronneby, Sweden

Epidemiological studies linking type 2 diabetes (T2D) and exposure to per- and polyfluoroalkyl substances (PFAS), are limited and have yielded conflicting results. This register-based study aimed to investigate the risk of T2D among Swedish adults who had been exposed to PFAS from highly contaminated drinking water for decades. The study included 55,032 adults (aged ≥18 years) from the Ronneby Register Cohort, who ever lived in Ronneby during 1985-2013. Exposure was assessed using the yearly residential address and the absence ("never-high") or presence ("ever-high") of high PFAS contamination in the municipal drinking water supply; the latter was subdivided into "early-high" and "late-high" exposure with cut-off at 2005. Incident T2D cases were retrieved from the National Patient Register and the Prescription Register. Cox proportional hazard models with time-varying exposure were used to estimate hazard ratios (HRs). Stratified analyses were performed based on age (18-45 vs>45). Elevated HRs for T2D were observed when comparing "ever-high" to "never-high" exposure (HR 1.18, 95% CI 1.03-1.35), as well as when comparing "early-high" (HR 1.12, 95% CI 0.98-1.50) or "late-high" (HR 1.17, 95% CI 1.00-1.37) to "never-high", after adjusting for age and sex. Individuals aged 18-45 years had even higher HRs. Adjusting for the highest-achieved education level attenuated the estimates, but the directions of associations remained. Elevated HRs were also found among those who had lived in areas with a heavily contaminated water supply for 1-5 years (HR 1.26, 95% CI 0.97-1.63) and 6-10 years (HR 1.25, 95% CI 0.80-1.94). This study suggests an increased risk of T2D after long-term high PFAS exposure through drinking water. In particular, a higher risk of early onset diabetes was found, indicating increased susceptibility to PFAS-related health effects at younger ages.

Effect of Dietary Phenolic Compounds on Incidence of Type 2 Diabetes in the “Seguimiento Universidad de Navarra” (SUN) Cohort

The global incidence of type 2 diabetes (T2D) has been steadily increasing in recent decades. The Mediterranean dietary pattern has shown a preventive effect on the risk of T2D. Evaluating the association between bioactive compounds such as phenolic compounds (PC) in a Mediterranean cohort could help to better understand the mechanisms implicated in this protection. We evaluated the association between dietary intake of PC and the risk of T2D in a relatively young cohort of 17,821 Spanish participants initially free of T2D, through the University of Navarra Follow-up Project ("Seguimiento Universidad de Navarra" or SUN cohort) after 10 years of median follow-up using time-dependent Cox models. Intake of PC was estimated at baseline and repeatedly at 10-year follow-up using a 136-item validated food frequency and the Phenol-Explorer database. The incidence of T2D was identified by a biennial follow-up, and only medically confirmed cases were included. During 224,751 person-years of follow-up, 186 cases of T2D were confirmed. A suboptimal intake of stilbenes was independently associated with a higher risk of T2D in subjects over 50 years (HR: 1.75, 95% CI: 1.06-2.90, p value < 0.05) after adjusting for potential confounders. Our results suggest that a moderate-high intake of stilbenes can decrease the risk of developing T2D in subjects over 50 years in our cohort.

Low-Carbohydrate Diet Scores and Mortality Among Adults With Incident Type 2 Diabetes.

The current study aims to prospectively examine the association between postdiagnosis low-carbohydrate diet (LCD) patterns and mortality among individuals with type 2 diabetes (T2D). Among participants with incident diabetes identified in the Nurses' Health Study and Health Professionals Follow-up Study, an overall total LCD score (TLCDS) was calculated based on the percentage of energy as total carbohydrates. In addition, vegetable (VLCDS), animal (ALCDS), healthy (HLCDS), and unhealthy (ULCDS) LCDS were further derived that emphasized different sources and quality of macronutrients. Multivariable-adjusted Cox models were used to assess the association between the LCDS and mortality. Among 10,101 incident T2D cases contributing 139,407 person-years during follow-up, we documented 4,595 deaths of which 1,389 cases were attributed to cardiovascular disease (CVD) and 881 to cancer. The pooled multivariable-adjusted hazard ratios (HRs, 95% CIs) of total mortality per 10-point increment of postdiagnosis LCDS were 0.87 (0.82, 0.92) for TLCDS, 0.76 (0.71, 0.82) for VLCDS, and 0.78 (0.73, 0.84) for HLCDS. Both VLCDS and HLCDS were also associated with significantly lower CVD and cancer mortality. Each 10-point increase of TLCDS, VLCDS, and HLCDS from prediagnosis to postdiagnosis period was associated with 12% (7%, 17%), 25% (19%, 30%), and 25% (19%, 30%) lower total mortality, respectively. No significant associations were observed for ALCDS and ULCDS. Among people with T2D, greater adherence to LCD patterns that emphasize high-quality sources of macronutrients was significantly associated with lower total, cardiovascular, and cancer mortality.

Maternal DNA methylation signatures of arsenic exposure is associated with adult offspring insulin resistance in the Strong Heart Study

Exposure to low to moderate arsenic (As) levels has been associated with type 2 diabetes (T2D) and other chronic diseases in American Indian communities. Prenatal exposure to As may also increase the risk for T2D in adulthood, and maternal As has been associated with adult offspring metabolic health measurements. We hypothesized that T2D-related outcomes in adult offspring born to women exposed to low to moderate As can be evaluated utilizing a maternally-derived molecular biosignature of As exposure. Herein, we evaluated the association of maternal DNA methylation with incident T2D and insulin resistance (Homeostatic model assessment of insulin resistance [HOMA2-IR]) in adult offspring. For DNA methylation, we used 20 differentially methylated cytosine-guanine dinucleotides (CpG) previously associated with the sum of inorganic and methylated As species (ΣAs) in urine in the Strong Heart Study (SHS). Of these 20 CpGs, we found six CpGs nominally associated (p < 0.05) with HOMA2-IR in a fully adjusted model that included clinically relevant covariates and offspring adiposity measurements; a similar model that adjusted instead for maternal adiposity measurements found three CpGs nominally associated with HOMA2-IR, two of which overlapped the offspring adiposity model. After adjusting for multiple comparisons, cg03036214 remained associated with HOMA2-IR (q < 0.10) in the offspring adiposity model. The odds ratio of incident T2D increased with an increase in maternal DNA methylation at one HOMA2-IR associated CpG in the model adjusting for offspring adiposity, cg12116137, whereas adjusting for maternal adiposity had a minimal effect on the association. Our data suggests offspring adiposity, rather than maternal adiposity, potentially influences the effects of maternal DNAm signatures on offspring metabolic health parameters. Here, we have presented evidence supporting a role for epigenetic biosignatures of maternal As exposure as a potential biomarker for evaluating risk of T2D-related outcomes in offspring later in life.

Comparison of five different risk scores to predict incident type 2 diabetes in the Swiss HIV cohort study.

People with HIV (PWH) have a higher risk of type 2 diabetes (T2D) than HIV-negative individuals. In the general population, diabetes risk scores are used to identify persons at risk of developing T2D, but little is known regarding their performance in PWH. Assessment of the capacity of five diabetes risk scores to predict T2D in PWH. A prospective study including all Swiss HIV cohort study (SHCS) participants followed between 2009 and 2019. Five diabetes risk scores were assessed: FINDRISC versions 1 and 2, Balkau, Swiss Diabetes Association (SDA), and Kraege. Three thousand eight hundred fifty-three T2D-free PWH (78.5% men, 39.9 ± 11.3 years) were included. After a median follow-up of 4.8 years (interquartile range 2.2-7.8), 62 participants (1.6%) developed T2D, corresponding to an incidence rate of 3.18 per 1000 person-years (95% confidence interval = 2.47-4.08). Participants who developed T2D were older (48.7 ± 12.4 vs. 39.8 ± 11.2 years), more likely to be obese (22.6% vs. 7.4%), abdominally obese (9.7% vs. 1.5%), and to have a family history of diabetes (32.3% vs. 19.1%) than those without T2D. The AUC for incident T2D ranged between 0.72 (Kraege 16) and 0.81 (SDA, FINDRISC2 and Balkau). Sensitivity ranged between 3.2% (Balkau) and 67.7% (FINDRISC1) and specificity between 80.9% (FINDRISC1) and 98.3% (Balkau). Positive predictive values of all scores were below 20%, while negative predictive values were above 98%. Our study shows that the performance of conventional diabetes risk scores in PWH is promising, especially for Balkau and FINDRISC2, which showed good discriminatory power. These scores may help identify patients at a low risk of T2D in whom careful assessment of modifiable T2D risk factors can be spared.

Association of Fatty Liver Index with Incident Diabetes Risk in Patients Initiating Statin-Therapy: A 6-Year Retrospective Study.

Statins are associated with new-onset type 2 diabetes (T2D), mainly in patients with metabolic syndrome (MetS). The fatty liver index (FLI) is used as a prognostic score for the diagnosis of non-alcoholic fatty liver disease (NAFLD), which is common in patients with MetS. We aimed to investigate the association of FLI with new-onset T2D in patients initiating statin therapy. A retrospective observational study including 1241 individuals with dyslipidemia and followed up for ≥3 years. Patients with T2D and those receiving lipid-lowering treatment at the baseline visit were excluded. Models with clinical and laboratory parameters were used to assess the association of FLI with incident T2D. Among the 882 eligible subjects, 11% developed T2D during the follow-up (6 years; IQR: 4-10 years). After adjusting for sex, age and MetS parameters, a multivariate analysis revealed that age (HR:1.05; 95%CI: 1.01-1.09, p < 0.05), fasting plasma glucose (HR: 1.09; 95%CI: 1.06-1.13, p < 0.001) and FLI (HR: 1.02; 95%CI: 1.01-1.04, p < 0.01) were independently associated with T2D risk. The subjects with probable NAFLD (FLI ≥ 60) had a three-fold increased T2D risk compared with the subjects with FLI < 60 (HR: 3.14; 95%CI: 1.50-6.59, p = 0.001). A ROC curve analysis showed that FLI had a significant, although poor, predictive value for assessing T2D risk (C-Statistic: 0.67; 95%CI: 0.58-0.77, p = 0.001). Higher FLI values were associated with reduced T2D-free survival (log-rank = 15.46, p < 0.001). FLI is significantly and independently associated with new-onset T2D risk in patients initiating statin therapy.

Quantifying the Relationship Between Physical Activity Energy Expenditure and Incident Type 2 Diabetes: A Prospective Cohort Study of Device-Measured Activity in 90,096 Adults.

To investigate the association between accelerometer-derived physical activity energy expenditure (PAEE) and incident type 2 diabetes (T2D) in a cohort of middle-aged adults and within subgroups. Data were from 90,096 UK Biobank participants without prevalent diabetes (mean 62 years of age; 57% women) who wore a wrist accelerometer for 7 days. PAEE was derived from wrist acceleration using a population-specific method validated against doubly labeled water. Logistic regressions were used to assess associations between PAEE, its underlying intensity, and incident T2D, ascertained using hospital episode and mortality data up to November 2020. Models were progressively adjusted for demographic, lifestyle factors, and BMI. The association between PAEE and T2D was approximately linear (n = 2,018 events). We observed 19% (95% CI 17-21) lower odds of T2D per 5 kJ · kg-1 · d-1 in PAEE without adjustment for BMI and 11% (9-13) with BMI adjustment. The association was stronger in men than women and weaker in those with obesity and higher genetic susceptibility to obesity. There was no evidence of effect modification by genetic susceptibility to T2D or insulin resistance. For a given level of PAEE, odds of T2D were lower among those engaging in more moderate-to-vigorous activity. There was a strong linear relationship between PAEE and incident T2D. A difference in PAEE equivalent to an additional daily 20-min brisk walk was associated with 19% lower odds of T2D. The association was broadly similar across population subgroups, supporting physical activity for diabetes prevention in the whole population.

Bacille Calmette Guerin (BCG) and prevention of types 1 and 2 diabetes: Results of two observational studies.

Diabetes is a common disease marked by high blood sugars. An earlier clinical trial in type 1 diabetic subjects (T1Ds) found that repeat BCG vaccinations succeeded in lowering HbA1c values over a multi-year course. Here we seek to determine whether BCG therapy for bladder cancer may improve blood sugar levels in patients with comorbid T1D and type 2 diabetes (T2D). We also investigate whether BCG exposure may reduce onset of T1D and T2D by examining country-by-country impact of BCG childhood vaccination policies in relation to disease incidence. We first analyzed three large US patient datasets (Optum Labs data [N = 45 million], Massachusetts General Brigham [N = 6.5 million], and Quest Diagnostics [N = 263 million adults]), by sorting out subjects with documented T1D (N = 19) or T2D (N = 106) undergoing BCG therapy for bladder cancer, and then by retrospectively assessing BCG's subsequent year-by-year impact on blood sugar trends. Additionally, we performed an ecological analysis of global data to assess the country-by-country associations between mandatory neonatal BCG vaccination programs and T1D and T2D incidence. Multi-dose BCG therapy in adults with comorbid diabetes and bladder cancer was associated with multi-year and stable lowering of HbA1c in T1Ds, but not in T2Ds. The lack of a similar benefit in T2D may be due to concurrent administration of the diabetes drug metformin, which inhibits BCG's beneficial effect on glycolysis pathways. Countries with mandatory neonatal BCG vaccination policies had a lower incidence of T1D in two international databases and a lower incidence of T2D in one of the databases. The epidemiological evidence analyzed here suggests that BCG may play a role in the prevention of T1D. It does not support prevention of T2D, most likely because of interference by metformin. Our ecological analysis of global data suggests a role for neonatal BCG in the prevention of T1D and, to a lesser extent, T2D. Randomized clinical trials are needed to confirm these findings.