Aims Epigenetic regulators, including microRNAs(miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes(GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy(range 7-23 weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index(ppBMI) or offspring sex. Methods In a case-control analysis(36 GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early–mid-pregnancy plasma levels of 10 miRNAs chosen for potential roles in pregnancy course and complications(miR-126-3p, -155-5p, -21-3p, -146b-5p, -210-3p, -222-3p, -223-3p, -517-5p, -518a-3p, and 29a-3p) using qRT-PCR. Logistic regression models adjusted for gestational age at blood draw (GA) were fit to compare circulating miRNAs between cases and controls. We repeated analyses among overweight/obese(ppBMI≥25kg/m2) or lean(ppBMI<25kg/m2) women, and women with male or female offspring separately. Results Mean age was 34.3 years(cases) and 32.9 years(controls). GA-adjusted miR-155-5p(β=0.260/p=0.028) and - 21-3p(β=0.316/p=0.005) levels were positively associated with GDM. MiR-146b-5p(β=0.266/p=0.068) and miR-517-5p(β=0.196/p=0.074) were borderline. Associations of miR-21-3p and miR-210-3p with GDM were observed among overweight/obese but not lean women. Associations of six miRNAs(miR-155-5p, -21-3p, - 146b-5p, -223-3p, -517-5p, and -29a-3p) with GDM were present only among women carrying male fetuses(all p<0.05). Conclusions Circulating early–mid-pregnancy miRNAs are associated with GDM, particularly among women who are overweight/obese pre-pregnancy or pregnant with male offspring. This area has potential to clarify mechanisms underlying GDM pathogenesis and identify at-risk mothers earlier in pregnancy.

OBJECTIVE—Visceral adiposity is an important risk factor for cardiovascular disease and type 2 diabetes. We sought to determine whether change in intraabdominal fat area (IAF) over time predicts subsequent development of diabetes.RESEARCH DESIGN AND METHODS—We followed up 436 nondiabetic Japanese-American subjects (mean age 51.9 years, mean BMI 24.2 kg/m2, 54% male) for development of diabetes. We fit a logistic regression model to examine the association over a 10-year follow-up between change in IAF at 5-year follow-up and other fat areas (measured by computed tomography) and development of incident diabetes, adjusted for age, sex, family history of diabetes in a first-degree relative, second-generation versus third-generation Japanese American (Nisei vs. Sansei), baseline IAF, BMI, weight change over time, smoking status, physical activity level, and subcutaneous fat (SCF) depot areas.RESULTS—Cumulative incidence of diabetes was 20.4% at 10 years. Mean change in IAF was 10.9 cm2. An increase of 1 SD in IAF was associated with a 1.65-fold increase in the odds of diabetes over 10 years (OR = 1.65, 95% CI 1.21–2.25) after adjusting for the above covariates. This association was also independent of changes in thoracic, thigh, and abdominal SCF, as well as change in weight.CONCLUSIONS—We conclude that baseline IAF and accumulation of fat in this area over time are independent predictors of the development of type 2 diabetes in Japanese Americans.

Aims Much is known about body composition and type 2 diabetes risk but less about body function such as strength. We assessed whether hand-grip strength predicted incident diabetes. Methods We followed 394 nondiabetic Japanese-American subjects (mean age 51.9) for the development of diabetes. We fit a logistic regression model to examine the association between hand-grip strength at baseline and type 2 diabetes risk over 10 years, adjusted for age, sex, and family history. Results A statistically significant (p = 0.008) and negative (coefficient -0.208) association was observed between hand-grip strength and diabetes risk that diminished at higher BMI levels. Adjusted ORs for a 10-pound hand-grip strength increase with BMI set at the 25th, 50th or 75th percentiles were 0.68, 0.79, and 0.98, respectively. Conclusions Among leaner individuals, greater hand-grip strength was associated with lower risk of type 2 diabetes, suggesting it may be a useful marker of risk in this population.

SARS-CoV-2, the virus causing COVID-19, has infected millions and has caused hundreds of thousands of fatalities. Risk factors for critical illness from SARS-CoV-2 infection include male gender, obesity, diabetes, and age &gt;65. The mechanisms underlying the susceptibility to critical illness are poorly understood. Of interest, these comorbidities have previously been associated with increased signaling of Th17 cells. Th17 cells secrete IL-17A and are important for clearing extracellular pathogens, but inappropriate signaling has been linked to acute respiratory distress syndrome. Currently there are few treatment options for SARS-CoV-2 infections. This review describes evidence linking risk factors for critical illness in COVID-19 with increased Th17 cell activation and IL-17 signaling that may lead to increased likelihood for lung injury and respiratory failure. These findings provide a basis for testing the potential use of therapies directed at modulation of Th17 cells and IL-17A signaling in the treatment of COVID-19.

BACKGROUND The epidemiology of adult-onset type 1 diabetes (T1D) incidence is not well-characterized due to the historic focus on T1D as a childhood-onset disease. PURPOSE We assess the incidence of adult-onset (≥20 years) T1D, by country, from available data. DATA SOURCES A systematic review of MEDLINE, Embase, and the gray literature, through 11 May 2021, was undertaken. STUDY SELECTION We included all population-based studies reporting on adult-onset T1D incidence and published from 1990 onward in English. DATA EXTRACTION With the search we identified 1,374 references of which 46 were included for data extraction. Estimates of annual T1D incidence were allocated into broad age categories (20–39, 40–59, ≥60, or ≥20 years) as appropriate. DATA SYNTHESIS Overall, we observed the following patterns: 1) there is a paucity of data, particularly in low- and middle-income countries; 2) the incidence of adult-onset T1D is lowest in Asian and highest in Nordic countries; 3) adult-onset T1D is higher in men versus women; 4) it is unclear whether adult-onset T1D incidence declines with increasing age; and 5) it is unclear whether incidence of adult-onset T1D has changed over time. LIMITATIONS Results are generalizable to high-income countries, and misclassification of diabetes type cannot be ruled out. CONCLUSIONS From available data, this systematic review suggests that the incidence of T1D in adulthood is substantial and highlights the pressing need to better distinguish T1D from T2D in adults so that we may better assess and respond to the true burden of T1D in adults.

OBJECTIVE To examine associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/coronavirus disease 2019 with incident diabetes. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study using Veterans Health Administration data. We defined all patients without preexisting diabetes with one or more nasal swabs positive for SARS-CoV-2 (1 March 2020–10 March 2021; n = 126,710) as exposed and those with no positive swab and one or more laboratory tests (1 March 2020–31 March 2021; n = 2,651,058) as unexposed. The index date for patients exposed was the date of first positive swab and for patients unexposed a random date during the month of the qualifying laboratory test. We fit sex-stratified logistic regression models examining associations of SARS-CoV-2 with incident diabetes within 120 days and all follow-up time through 1 June 2021. A subgroup analysis was performed among hospitalized subjects only to help equalize laboratory surveillance. RESULTS SARS-CoV-2 was associated with higher risk of incident diabetes, compared with no positive tests, among men (120 days, odds ratio [OR] 2.56 [95%CI 2.32–2.83]; all time, 1.95 [1.80–2.12]) but not women (120 days, 1.21 [0.88–1.68]; all time, 1.04 [0.82–1.31]). Among hospitalized participants, SARS-CoV-2 was associated with higher risk of diabetes at 120 days and at the end of follow-up in men (OR 1.42 [95% CI 1.22–1.65] and 1.32 [1.16–1.50], respectively) but not women (0.72 [0.34–1.52] and 0.80 [0.44–1.45]). Sex ∗ SARS-CoV-2 interaction P values were all &lt;0.1. CONCLUSIONS SARS-CoV-2 is associated with higher risk of incident diabetes in men but not in women even after greater surveillance related to hospitalization is accounted for.

OBJECTIVEWe examined the association of lactation duration with incident type 2 diabetes among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODSWe monitored 4,372 women with a history of GDM participating in the Nurses' Health Study II for incident type 2 diabetes over 25 years up to 2017. Lactation history was obtained through follow-up questionnaires to calculate lactation duration. Follow-up blood samples were collected from a subset of these women at median age of 58 years through the Diabetes & Women's Health Study. RESULTSWe documented 873 incident cases of type 2 diabetes during 87,411 person-years of follow-up. Longer duration of lactation was associated with lower risk of type 2 diabetes for both total lactation (hazard ratio 1.05 [95% CI 0.83-1.34] for up to 6 months, 0.91 [0.72-1.16] for 6-12 months, 0.85 [0.67-1.06] for 12-24 months, and 0.73 [0.57-0.93] for >24 months, compared with 0 months; P-trend 5 0.003) and exclusive breastfeeding (P-trend 5 0.002) after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy BMI. Longer duration of lactation was also associated with lower HbA 1c , fasting plasma insulin, and C-peptide concentrations among women without type 2 diabetes at follow-up (all adjusted P-trend £0.04). CONCLUSIONSLonger duration of lactation is associated with a lower risk of type 2 diabetes and a favorable glucose metabolic biomarker profile among women with a history of GDM. The underlying mechanisms and impact on diabetes complications, morbidity, and mortality remain to be determined.As women undergo changes in metabolism to meet the demands of the growing fetus and to prepare for delivery and lactation (1), they often experience deterioration in insulin sensitivity during normal pregnancy (2). Although most women maintain glucose homeostasis by a compensatory increase in insulin secretion (1,3), this compensatory mechanism is insufficient in some women, resulting in gestational diabetes mellitus (GDM), which affects ;5-9% of pregnancies in the U.S. (4,5). Because women with a history of GDM are at higher risk for type 2 diabetes later in life (6,7), it is critical to identify modifiable determinants of type 2 diabetes risk prevention specific for these high-risk women.

IntroductionStudies demonstrate associations between changes in obesity-related phenotypes and cardiovascular risk. While maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes.ObjectivesWe examined associations of mppBMI and GWG with longitudinal change in offspring's BMI (ΔBMI), and assessed whether associations are explained by offspring genetics.Design and MethodsWe used a birth cohort of 1400 adults, with data at birth, age 17 and 32. After genotyping offspring, we created genetic scores, predictive of exposures and outcome, and fit linear regression models with and without scores to examine the associations of mppBMI and GWG with ΔBMI.ResultsA one SD change in mppBMI and GWG was associated with a 0.83 and a 0.75 kg/m2 increase in ΔBMI respectively. The association between mppBMI and offspring ΔBMI was slightly attenuated (12%) with the addition of genetic scores. In the GWG model, a significant substantial 28.2% decrease in the coefficient was observed.ConclusionsThis study points to an association between maternal excess weight in pregnancy and offspring BMI change from adolescence to adulthood. Genetic factors may account, in part, for the GWG/ΔBMI association. These findings broaden observations that maternal obesity-related phenotypes have long-term consequences for offspring health.