Incident Type 2 Diabetes Research Articles

The mediatory role of androgens on sex differences in glucose homeostasis and incidence of type 2 diabetes: the KORA study.

Sex differences exist in type 2 diabetes (T2D), and androgens have been implicated in the etiology of T2D in a sex-specific manner. We therefore aimed to investigate whether androgens play a role in explaining sex differences in glucose homeostasis and incidence of T2D. We used observational data from the German population-based KORA F4 study (n = 1975, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1412). T2D was determined through self-reporting and confirmed by contacting the physicians and/or reviewing the medical charts. Multivariable linear and logistic regression models were employed to explore associations. Mediation analyses were performed to assess direct effects (DE) and indirect effects (IE), and the mediating role of androgens (total testosterone (TT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAs)) in the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis). After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower levels of TT, DHEAs, fasting glucose levels, fasting insulin levels, 2h-glucose levels and HOMA-IR, compared to men. An inverse association was observed for TT and glucose- and insulin-related traits in men, while a positive association was observed for TT and fasting glucose levels in women. We found a mediatory role of TT on the association of sex with fasting glucose levels (IE: β = 3.08, 95% CI: 2.04, 4.30), fasting insulin levels (IE: β = 0.39, 95% CI:0.30, 0.47), 2h-glucose levels (IE: β = 12.77, 95% CI: 9.01, 16.03) and HOMA-IR (IE: β = 0.41, 95% CI: 0.33, 0.50). Also, the inconsistent mediatory role of TT was seen on the association of sex with incidence of T2D (DE: 0.12, 95% CI: 0.06, 0.20 and IE: OR = 7.60, 95% CI: 3.43, 24.54). The opposing DE and IE estimates suggest that the association between sex and either glucose homeostasis or the incidence of T2D may differ when TT is considered as a potential mediator, with higher TT levels being beneficial for glucose metabolism or incidence of T2D in men, while in women, detrimental. No mediatory role was observed for either DHEA or DHEAs on glucose homeostasis or the incidence of T2D. The dimorphic mediatory role of TT highlights its complex role in metabolic health, contributing differently to the glucose dysregulation and risk of T2D in men and women.

Abstract 4135352: Neighborhood-level Determinants and Disparities in Incident Type 2 Diabetes in a Population-Based Cohort, 2015–2020

Introduction: Living in an area with high Area Deprivation Index (ADI) is linked to worse cardiovascular disease (CVD) outcomes. However, the association of ADI with type 2 diabetes (T2D), a major CVD risk factor, is incompletely described. This knowledge may guide primary CVD prevention. Method: Rochester Epidemiology Project is a medical record linkage system of persons in southeast Minnesota and southwest Wisconsin. We identified 253,890 persons (aged 4–98 yrs on July 1, 2015) in 9 counties with >90% population coverage. ADI scores, from 2015 home addresses, were grouped into quartiles of low (Q1) to high (Q4) deprivation. We excluded persons with type 1 diabetes (T1D) or history of T2D and identified new T2D cases (2015-2020) using ICD codes, HbA1c and medications. We examined the association between ADI quartile and risk of incident T2D using Cox regression with persons right censored at death, T2D, T1D or last visit. Models were adjusted for age and gender, and reported adjusted hazard ratios (aHR [95% confidence interval]). Results: Age, gender, and race statistically differed across ADI quartiles (Table). Age × ADI interaction was significant ( P <.001). T2D incidence ranged from 6.3 (Q1) to 9.0 (Q4) per 1000 person-years ( P <.001). Women vs. men/non-binary persons (combined due to limited non-binary persons) had 30% lower risk of incident T2D (aHR 0.70 [0.67–0.72]). Risk of incident T2D was higher in persons from higher ADI areas. At median age of 48.6 yrs, the risk was 30% higher in Q2 (aHR 1.3 [1.22–1.38]), 38% higher in Q3 (aHR 1.38 [1.30–1.47]) and 53% higher in Q4 (aHR 1.53 [1.43–1.62]) vs. Q1. Higher ADI was associated with higher incident T2D in younger persons, with risk attenuation with increasing age (Figure). Conclusion: In this population cohort, persons, particularly of younger age, living in more deprived areas had a higher risk of incident T2D. ADI may help identify areas for targeted T2D screening, with implications for CVD screening and prevention.

Associations of sugary beverage intake with type 2 diabetes and the role of physical activity: a prospective cohort study

BackgroundHigher consumption of sugary beverages (SB) has been associated with type 2 diabetes (T2D), but whether these associations are modified by physical activity remains unclear. This study aimed to examine the associations of SB intake, including sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), and natural juices (NJ) with the risk of incident T2D, and the potential role of physical activity.MethodsWe included 153,862 diabetes-free participants in the UK Biobank who completed both the International Physical Activity Questionnaire at recruitment (2006–2010) and at least one 24-h dietary recall questionnaire in 2009–2012. We assessed the associations of each SB with the risk of incident T2D using Cox proportional hazard models, and explored the interactions between each SB and physical activity.ResultsDuring a median follow-up of 11.8 years, 6631 participants developed incident T2D. Participants consuming more SSB and ASB (comparing > 2 to 0 unit/d) had a higher hazard of T2D (hazard ratio [HR]: 1.17, 95% confidence interval [CI]: 1.05–1.31 for SSB; 1.54, 1.37–1.74 for ASB), while medium intake of NJ showed an inverse association (HR> 0–1 vs. 0 unit/d: 0.87, 95% CI: 0.82–0.92; HR> 1–2 vs. 0 unit/d: 0.88, 95% CI: 0.81–0.97) with incident T2D. No significant interactions between physical activity and SSB/ASB were found (P-interaction=0.204 for SSB, 0.926 for ASB), but the protective association of medium NJ intake with T2D was stronger among participants with higher level of physical activity (P-interaction = 0.043).ConclusionsHigher intake of SSB and ASB was related to higher risks of T2D. Medium NJ intake was associated with a lower risk of T2D, particularly among individuals with higher physical activity level. These findings emphasized the importance of healthy beverage intake and adequate physical activity in diabetes prevention.

Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study

BackgroundGraves’ disease (GD) is an autoimmune disease associated with an increased incidence of other autoimmune diseases. To investigate the causality between GD and Diabetes mellitus (DM), we designed bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) studies.MethodsSingle-nucleotide polymorphisms (SNPs) associated with GD, thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid-stimulating hormone (TSH), type 1 diabetes (T1D), and type 2 diabetes (T2D) were obtained from the IEU Open GWAS and FinnGen biobank databases. For the forward MR study, we used GD (sample size = 458,620) as the exposure and T1D (sample size = 520,580) and T2D (sample size = 211,766) as the outcomes. Next, high risk of T1D and T2D were used as exposure variables, and GD was used as the outcome variable for the reverse MR analysis. Finally, MVMR analysis was conducted to investigate the probable relationship between DM and indicators for thyroid function like TPO, Tg, and TSH. The inverse variance weighting (IVW) was used as the main method. Finally, the heterogeneity and sensitivity were assessed.ResultsThere were 27, 88, and 55 SNPs associated with GD, T1D, and T2D, respectively. A significant causal connection between higher genetic liability of GD and the risk of T2D (OR [95% CI] = 1.059 [1.025–1.095], P = 5.53e-04) was found in the forward MR analysis. Comparatively, the significant causal relationship between higher genetic liability of GD and the risk of T1D was not demonstrated (OR [95% CI] = 0.998[0.927,1.074], P=0.949). However, reverse MR suggested that there was a genetic susceptibility to T1D that increased the likelihood of developing GD (OR [95% CI] = 1.173[1.117,1.231], P = 1.913e-10), while T2D did not (OR [95% CI] = 0.963 [0.870–1.066], P = 0.468). Furthermore, there was inadequate evidence to suggest that abnormal TSH, TPO, and Tg levels increase the risk of incident T1D or T2D in individuals with GD. MVMR revealed no causal relationship among Tg, TSH, TPO, T1D, or T2D.ConclusionThere was no increased risk of T1D with an increase in genetic susceptibility to GD, although higher genetic susceptibility to T1D has been shown to be associated with increased risk of developing GD. A unidirectional causal relationship between the genetic liability for GD and increased risk of T2D was observed using MR analyses. MVMR analysis showed no statistically relevant causality between the genetic liability for TSH, TPO, or Tg and the risk of either T1D or T2D.

Biomarkers of glucose-insulin homeostasis and incident type 2 diabetes and cardiovascular disease: results from the Vitamin D and Omega-3 trial

BackgroundDysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline levels of insulin, C-peptide, HbA1c, and a novel insulin resistance score (IRS) with incident cardiometabolic diseases, and whether randomized vitamin D or n-3 FA modify these associations.MethodsVITamin D and OmegA-3 TriaL (NCT01169259) was a randomized clinical trial testing vitamin D and n-3 FA for the prevention of CVD and cancer over a median of 5.3 years. Incident cases of T2D and CVD (including cardiovascular death, myocardial infarction, stroke, and coronary revascularization) were matched 1:1 on age, sex, and fasting status to controls. Conditional logistic regressions adjusted for demographic, clinical, and adiposity-related factors were used to assess the adjusted odds ratio (aOR) per-standard deviation (SD) and 95%CI of baseline insulin, C-peptide, HbA1c, and IRS (Insulin×0.0295 + C-peptide×0.00372) with risk of T2D, CVD, and coronary heart disease (CHD).ResultsWe identified 218 T2D case-control pairs and 715 CVD case-control pairs including 423 with incident CHD. Each of the four biomarkers at baseline was separately associated with incident T2D, aOR (95%CI) per SD increment: insulin 1.46 (1.03, 2.06), C-peptide 2.04 (1.35, 3.09), IRS 1.72 (1.28, 2.31) and HbA1c 7.00 (3.76, 13.02), though only HbA1c remained statistically significant with mutual adjustments. For cardiovascular diseases, we only observed significant associations of HbA1c with CVD (1.19 [1.02, 1.39]), and IRS with CHD (1.25 [1.04, 1.50]), which persisted after mutual adjustment. Randomization to vitamin D and/or n-3 FA did not modify the association of these biomarkers with the endpoints.ConclusionsEach of insulin, C-peptide, IRS, and HbA1c were associated with incident T2D with the strongest association noted for HbA1c. While HbA1c was significantly associated with CVD risk, a novel IRS appears to be associated with CHD risk. Neither vitamin D nor n-3 FA modified the associations between these biomarkers and cardiometabolic outcomes.

Characterizing metabolomic signatures related to coffee and tea consumption and their association with incidence and dynamic progression of type 2 diabetes: A multi-state analysis.

Our study aimed to investigate the impact of tea and coffee consumption and related metabolomic signatures on dynamic transitions from diabetes-free status to incident type 2 diabetes (T2D), and subsequently to T2D-related complications and death. We included 438,970 participants in the UK Biobank who were free of diabetes and diabetes complications at baseline. Of these, 212,146 individuals had information on all metabolic biomarkers. We identified tea- and coffee-related metabolomic signatures using elastic net regression models. We examined associations of tea and coffee intake and related metabolomic signatures with the onset and progression of T2D using multi-state regression models. We observed that tea and coffee consumption and related metabolomic signatures were inversely associated with the risk of five T2D transitions. For example, HRs (95% CIs) per SD increase of the tea-related metabolomic signature were 0.87 (0.85, 0.89), 0.97 (0.95, 0.99), 0.91 (0.90, 0.92), 0.92 (0.91, 0.94), and 0.91 (0.90, 0.92) for transitions from diabetes-free state to incident T2D, from diabetes-free state to total death, from incident T2D to T2D complications, from incident T2D to death, and from T2D complications to death. These findings highlight the benefit of tea and coffee intake in reducing the risk of occurrence and progression of T2D.

Childhood maltreatment, adulthood obesity and incident type 2 diabetes: a retrospective cohort study using UK Biobank.

This study aims to explore the association of childhood maltreatment with obesity and type 2 diabetes (T2D) in adulthood, and whether obesity is a mediator of the latter. In a retrospective cohort study using UK Biobank data, participants recalled childhood maltreatment. Linear regression, logistic regression, and Cox proportional hazard models were used to investigate the associations with body mass index (BMI), obesity, and T2D, adjusted for sociodemographic factors. Decomposition analysis was used to examine the extent to which T2D excess risk was attributed to BMI. Of the 153,601 participants who completed the childhood maltreatment questions, one-third reported some form of maltreatment. Prevalence of adult obesity and incidence of T2D were higher with the number of reported childhood maltreatment types. People who reported ≥3 types of childhood maltreatment were at higher risk of obesity (OR 1.55, 95% CI 1.47-1.63) and incident T2D (HR 1.65, 95% CI 1.52-1.80). Excess T2D risk among those reporting maltreatment could be reduced by 39% if their BMI was comparable to participants who had not been maltreated, assuming causality. People who recalled maltreatment in childhood are at higher risk of T2D in adulthood, partly due to obesity.

SARS-CoV-2 Infection and New-Onset Type 2 Diabetes Among Pediatric Patients, 2020 to 2022

In adults, diagnoses of new-onset type 2 diabetes (T2D) have increased following diagnosis with COVID-19, but whether this occurs in children is unclear. To determine whether risk of incident T2D diagnosis is increased during the 6 months after SARS-CoV-2 infection among children. This retrospective cohort study used electronic health records from the TriNetX analytics platforms between January 1, 2020, and December 31, 2022. Pediatric patients aged 10 to 19 years without preexisting diabetes were eligible for inclusion. Data were analyzed from August 15 to September 15, 2023, with supplemental analyses January 20 and August 8 to 13, 2024. Diagnosis of COVID-19 or a non-COVID-19 respiratory infection. New diagnosis of T2D compared by risk ratios (RRs) and 95% CIs at 1, 3, and 6 months after index infection. The main study population included 613 602 patients, consisting of 306 801 with COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.8% female) and 306 801 with other respiratory infections (ORIs) but no documented COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.6% female) after propensity score matching. Risk of a new diagnosis of T2D was significantly increased from day of infection to 1, 3, and 6 months after COVID-19 diagnosis compared with the matched cohort with ORIs (RR at 1 month, 1.55 [95% CI, 1.28-1.89]; RR at 3 months: 1.48 [95% CI, 1.24-1.76]; RR at 6 months: 1.58 [95% CI, 1.35-1.85]). Similar results were found in the subpopulation classified as having overweight or obesity (RR at 1 month: 2.07 [95% CI, 1.12-3.83]; RR at 3 months: 2.00 [95% CI, 1.15-3.47]; RR at 6 months: 2.27 [95% CI, 1.38-3.75]) and the hospitalized subpopulation (RR at 1 month: 3.10 [95% CI, 2.04-4.71]; RR at 3 months: 2.74 [95% CI, 1.90-3.96]; RR at 6 months: 2.62 [95% CI, 1.87-3.66]). Similar elevation in risk was found at 3 and 6 months when excluding patients diagnosed during the interval from the index date to 1 month after infection. In this retrospective cohort study of children and adolescents aged 10 to 19 years, the risk of an incident diagnosis of T2D was greater following a COVID-19 diagnosis than in children diagnosed with ORIs. Further study is required to determine whether diabetes persists or reverses later in life.

Sleep Irregularity and the Incidence of Type 2 Diabetes: A Device-Based Prospective Study in Adults.

To prospectively examine the association between device-measured sleep regularity and incidence of type 2 diabetes (T2D) in a population-based sample of adults. We also examined if meeting sleep duration recommendations attenuated or eliminated the effects of irregular sleep on T2D. We conducted a prospective cohort study of adults aged 40-79 years participating in the UK Biobank accelerometer substudy. Participants wore wrist-attached accelerometers for a duration of 7 days, which was used to compute the Sleep Regularity Index (SRI). Participants were categorized as irregular (SRI <71.6), moderately irregular (SRI between 71.6 and 87.3), and regular (SRI >87.3) sleepers. T2D diagnosis was obtained through self-reports and health records. We analyzed data from 73,630 individuals observed for 8 years, without a history of T2D and without an event in the first year of follow-up. Compared with regular sleepers, irregular (hazard ratio [HR] 1.38; 95% CI 1.20-1.59) and moderately irregular sleepers (HR 1.35; 95% CI 1.19-1.53) were at higher risk of T2D incidence. Dose-response analyses treating SRI as a continuous measure showed higher T2D incidence with SRI scores <80. Meeting current sleep duration recommendations did not counteract the adverse effects of irregular (HR 1.35; 95% CI 1.09-1.66) or moderately irregular (HR 1.29; 95% CI 1.08-1.54) sleep on T2D incidence. Moderate and high sleep irregularity were deleteriously associated with T2D risk, even in participants who slept ≥7 h per night. Future sleep interventions will need to pay more attention to consistency in bedtimes and wake-up times, in addition to sleep duration and quality.

12374 A Prospective Study Of Plasma Levels Of Asprosin And Incident Type 2 Diabetes Among Postmenopausal Women In The Women’s Health Initiative

Abstract Disclosure: B. Yang: None. J. Li: None. E.S. Silva: None. L.S. Phillips: None. J.E. Manson: None. A.P. Reiner: None. A.R. Chopra: None. S. Liu: None. Background: Asprosin, a 30-kDa hormone identified from white adipose tissue, has been shown to play key roles in regulating hepatic glucose release and appetite stimulation. Despite an increasing body of experimental studies demonstrating asprosin as a promising therapeutic target, little is known about its distribution in the general population particularly concerning its association with incident type 2 diabetes (T2D). Objectives: To evaluate whether higher plasma levels of asprosin are associated with incident T2D among postmenopausal women independently of known risk factors for T2D. Methods: We conducted a case-control study nested in the Women’s Health Initiative (WHI), including 5,198 participants free of diabetes, cardiovascular diseases, and cancer at baseline (2,602 incident T2D cases and 2,596 controls). Plasma levels of asprosin were measured using a sandwich enzyme-linked immunosorbent (ELISA) assay. We used conditional logistic regression models to estimate the association between asprosin and T2D risk with adjustment for matching variables (age, race, sampling batch), education, body mass index (BMI), physical activity, tobacco smoking, alcohol drinking, family history of diabetes, age at menopause, total energy intake, the Alternate Healthy Eating Index (AHEI), and multivitamin use. Results: Approximately 43% of participants were white and the mean age at baseline was 63 years. The median plasma levels of asprosin were 38 (IQR: 30, 50) pmoL/L in the controls and 39 (IQR: 31, 50) pmoL/L among those who developed T2D during follow-up. Compared with the participants in the lowest quintile of plasma levels of asprosin at baseline, those in the highest quintile had a 26% increased risk of T2D (adjusted odds ratio: OR: 1.26 [95% CIs, 1.01, 1.57], p for trend=0.03) in the fully adjusted model. The OR estimates exhibited a large variation across race and BMI, although there was a linear dose-response relation between levels of asprosin and T2D risk (p for nonlinear=0.44). Genetic analysis revealed that women with the heterozygous allele (CG) at single nucleotide polymorphisms (SNP) rs56407701 had higher levels of asprosin compared to women with the homozygous reference allele (CC). Further, Mendelian Randomization analysis revealed that genetically predicted asprosin levels were associated with higher T2D risk. Conclusion: Among postmenopausal women, higher plasma levels of asprosin were prospectively associated with elevated T2D risk independent of known T2D risk factors. Further work is needed to confirm the potential causal role of this peptide hormone in the clinical risk stratification and potential prevention of T2D. Presentation: 6/2/2024

The joint effect of cumulative metabolic parameters on the risk of type 2 diabetes: a population-based cohort study

Background and aimsThis study aimed to examine the cumulative effects of body mass index (BMI), body roundness index (BRI), pulse pressure (PP), triglycerides (TG), high-density lipoprotein cholesterol (HDL) and fasting plasma glucose (FPG) on Type 2 diabetes (T2D) morbidity.MethodsA total of 78,456 participants aged older than 45 years were extracted from basic public health services in China. During the 2-year follow-up, 6,942 individuals had developed T2D. The binary logistic regression models and multinomial logistic regression models were conducted to investigate the effects of cumulative metabolic parameters on incident T2D, prediabetes regression and progression.ResultsWe found statistically deleterious impacts of exposure to high cumulative BMI, BRI, PP, TG and low cumulative HDL on T2D morbidity and prediabetes progression. Compared to the group with low cumulative of all five parameters, the adjusted ORs for new-onset T2D for participants presenting with 1–2, 3, and 4–5 elevated metabolic parameters were 1.41(1.31,1.52), 1.93(1.74,2.13) and 2.21(1.94,2.51), respectively. There was additive interaction between FPG level and cumulative metabolic parameters with T2D. Compared with participants with the lowest quartile of FPG and low cumulative of all 5 parameters, those with the highest quartile of FPG and high cumulative of 4–5 parameters had a 14.63 [95% CI (12.27, 17.42)] higher risk of incident T2D.ConclusionsParticipants with more numbers of high-cumulative metabolic parameters were associated with a higher risk of incident T2D and prediabetes progression. A high level of normal FPG could enhance these risks.

Sex-specific association between carbohydrate antigen 19–9 and incident type 2 diabetes

Carbohydrate antigen 19–9 (CA19-9) levels are associated with glycemic control, insulin resistance, and chronic complications in patients with type 2 diabetes (T2D). Women generally show higher CA19-9 levels despite a greater T2D prevalence in men. We evaluated the sex-specific longitudinal associations between CA19-9 levels and T2D incidence. Korean adults (n = 329,380) without previous cancer or T2D were categorized into four groups based on their CA19-9 levels. The study end point was the development of incident T2D during follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) according to CA19-9 levels. During a median follow-up of 6.1 years (3.3–9.3 years), the incidence rates of T2D were 9.9 per 1,000 person-years in men and 3.6 per 1,000 person-years in women. In the time-dependent analysis, adjusted HRs (95% confidence intervals) for incident T2D comparing CA19-9 levels of 10.0–19.9, 20.0–29.9, and ≥ 30 U/mL to the reference (< 10 U/mL) were 1.08 (1.04–1.13), 1.18 (1.07–1.30), and 1.64 (1.35–1.99), respectively, among men. However, this association was not observed in women. The association between CA19-9 category and incident T2D significantly differed by sex (Pinteraction = 0.006). Among young and middle-aged Korean adults, elevated CA19-9 levels were significantly associated with increased risk of type 2 diabetes in men but not in women. Elevated CA19-9 levels in men could be a useful marker for identifying individuals at high risk of developing T2D. Evaluation approaches for individuals with elevated CA19-9 levels should be sex-specific.

Prevalence of obesity and cardiovascular disease in adults with type 2 diabetes and use of diabetes medication in Germany: A claims data study.

To identify the prevalence of cardiovascular disease (CVD) and obesity in patients with type 2 diabetes (T2D) in Germany and to evaluate if antidiabetic treatment patterns varied by comorbidity status. Patients with T2D (aged ≥18 years) were identified during the study period (2014-2020) from medical claims of 4.5 million publicly insured German residents and divided into different cohorts based on CVD and/or obesity diagnosis. Annual prevalence and incidence were estimated for each study year, while characteristics and treatments were assessed in 2020. Data were extrapolated to the German population by age and sex. The prevalence of T2D in 2020 was 11.4%. Among patients with T2D, 53.0% had CVD, 39.3% had obesity, and 20.9% had CVD and obesity. Since 2014, CVD increased by 1.4%, obesity by 4.5%, and CVD with obesity by 2.7% in patients with T2D. The incidence of T2D in 2020 was 1.0% (42.9% had CVD, 37.9% had obesity, and 15.8% had CVD and obesity). Among the prevalent T2D population in 2020, 4.9% received glucagon-like peptide-1 receptor agonists (GLP-1RAs), 9.7% received sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 13.0% received GLP-1 RAs and/or SGLT2 inhibitors. Of those with CVD, 12.9% received GLP-1 RAs and/or SGLT2 inhibitors (without CVD, 13.2%). Of those with obesity, 19.4% received GLP-1RAs and/or SGLT2 inhibitors (without obesity, 9.0%). In this retrospective claims database study, more than two thirds of patients with T2D also had CVD, obesity, or both CVD and obesity. GLP-1 RA and SGLT2 inhibitor use remained low.

Patterns of incidence and characteristics of youth with new-onset diabetes mellitus during the COVID era

Objectives: The incidence of diabetes mellitus (DM) in children, adolescents, and young adults has been on the rise for many decades. The COVID-19 pandemic has been associated with a dramatic increase in new cases of pediatric DM and a shift in the seasonal pattern of incidence. We aimed to determine the incidence of DM and its subtypes during the COVID-19 pandemic (2020–2022) and pre-pandemic (2017–2019). We sought to assess for a difference in seasonality and temporal pattern of new-onset DM between the two periods and aimed to describe and compare the clinical characteristics of the patients diagnosed during this time. Material and Methods: In this retrospective chart review, data were collected from medical records for all patients aged 1–21 years diagnosed with DM at our center between January 1, 2017 and December 31, 2022. Results: The incidence of DM at our center increased 38% during the pandemic (incidence rate ratio [IRR] 1.38, 95% confidence interval; [CI] 1.20–1.58). The incidence of type 1 diabetes (T1D) increased 11% (IRR 1.11, 95% CI 1.01–1.23) and the median body mass index percentile increased for those diagnosed during the pandemic (P = 0.012). The incidence of type 2 diabetes (T2D) increased 238% (IRR 3.38, 95% CI 2.17–5.28) during the pandemic, with the highest rate of diagnosis in a younger age group (P = 0.015). The pattern of incidence of T1D shifted from lowest in the summer pre-pandemic to highest in the summer during the pandemic (IRR 1.82, 95% CI 1.22–2.72). The overall incidence trend for DM, T1D, and T2D, peaked in spring 2021 and then declined until it stabilized in summer 2022. Conclusion: Our study showed a persistent increase in the incidence of both T1D and T2D in the pediatric population during the pandemic. Those diagnosed with T2D during the pandemic were younger than those diagnosed in the pre-pandemic period. There was a shift in seasonal pattern of T1D incidence during the pandemic with the highest rates of incidence during the summer. Further studies are needed to evaluate the underlying mechanisms of the persistent increase in incidence.

Anger Expression Styles, Cynical Hostility, and the Risk for the Development of Type 2 Diabetes or Diabetes-Related Heart Complications: Secondary Analysis of the Health and Retirement Study.

Limited research has examined associations between trait anger and hostility and incident type 2 diabetes (T2D) and diabetes-related heart complications. However, anger expression styles (i.e., anger-in, anger-out) have not been examined. The present study used secondary data to examine the associations between anger expression styles, cynical hostility, and the risk of developing T2D (objective 1) or diabetes-related heart complications (objective 2). Self-report data came from participants aged 50-75 in the Health and Retirement Study. Anger-in (anger that is suppressed and directed toward oneself), anger-out (anger directed towards other people or the environment), and cynical hostility were measured at baseline (i.e., 2006 or 2008). Follow-up data (i.e., diabetes status or diabetes-related heart complications status) were collected every two years thereafter until 2020. The objective 1 sample included 7,898 participants without T2D at baseline, whereas the objective 2 sample included 1,340 participants with T2D but without heart complications at baseline. Only anger-in was significantly associated with incident T2D after controlling for sociodemographic characteristics, HR = 1.08, 95% CI [1.01, 1.16], but the association did not hold after further adjustment for depressive symptoms. Only anger-out was significantly associated with incident diabetes-related heart complications after adjusting for sociodemographic characteristics, health-related covariates, and depressive symptoms, HR = 1.21, 95% CI [1.02, 1.39]. Anger expression styles were differentially related to diabetes outcomes. These findings demonstrate the value of expanding the operationalization of anger beyond trait anger in this literature and encourage further investigation of anger expression styles.

Unveiling the Roles of Immune Function and Inflammation in the Associations Between Dietary Patterns and Incident Type 2 Diabetes

Objective To investigate the associations between data-driven dietary patterns, immune function, and incident type 2 diabetes (T2D) and the mediating effects of immune function. Methods This study included 375,665 participants without diabetes at baseline in the UK Biobank study. Dietary patterns were derived through principal component analysis of food frequency questionnaire data. Immune function was assessed using 14 individual inflammatory markers and an integrated low-grade inflammation score (INFLA-score). Cox proportional hazard models were used to estimate the associations of dietary patterns or immune function with incident T2D. Linear regressions were used to estimate the associations of dietary patterns with immune function. Mediating effects of immune function were quantified. Results During a median 14.6-year follow-up, 13,932 participants developed T2D. Four dietary patterns were identified: prudent diet (high in whole grains, vegetables, fruits, fish), wheat/dairy/eggs restrictive diet (limiting these foods), meat-based diet (high in red/processed meat, salt), and full-cream dairy diet (preference for full cream milk or dairy products). The prudent diet was negatively (HRQ4 vs Q1, 0.69 [95% CI, 0.65–0.72]), while the wheat/dairy/eggs restrictive diet (HRQ4 vs Q1, 1.08 [95% CI, 1.03–1.13]), meat-based diet (HRQ4 vs Q1, 1.12 [95% CI, 1.06–1.17]), and full-cream dairy diet (HRQ4 vs Q1, 1.08 [95% CI, 1.03–1.12]) were positively associated with incident T2D (all p for trend ≤0.04). The prudent diet was negatively and the full-cream dairy diet was positively associated with most inflammatory markers. Most inflammatory markers, especially INFLA-score (HR, 1.18 [95% CI, 1.16–1.20]), were positively associated with incident T2D. INFLA-score mediated 13% of the association with incident T2D for the prudent diet and 34% for the full-cream dairy diet. Conclusions This study identified four distinct dietary patterns and a range of inflammatory markers associated with incident T2D. A notable proportion of the associations between dietary patterns and T2D was mediated by immune function.

Giving a voice to “the silent killer”: a knowledge, attitude and practice study of diabetes among French Guiana’s Parikweneh people

BackgroundThe prevalence of type 2 diabetes (T2D) in the French overseas department of French Guiana, South America, nearly doubles that in its European counterpart, Metropolitan France. This region is demographically diverse and includes several populations of Indigenous Peoples. Although such populations are at particular risk of developing T2D across the Americas, very little is known about their health status in French Guiana, and accurate numbers of diabetic patients do not exist.MethodsIn light of a potential public health crisis, an ethnomedicinal study of diabetes experienced by Indigenous Parikweneh was conducted to provide better insight into the knowledge, attitudes and practices (KAP) related to this quickly emerging disease in French Guiana. Altogether, 75 interviews were conducted with community members and Elders, as well as healthcare professionals and administrators providing services to the Parikweneh population of Macouria and Saint-Georges de l’Oyapock.ResultsInterviews suggest a high incidence of T2D in this population, with cases that have risen quickly since the mid-twentieth century. Parikweneh participants linked the development of the illness to dietary changes, notably through the introduction of new and sweet foods. Recognizing the complexity of diabetes and its symptoms, diabetic patients highlighted the importance of biomedical treatments and follow-ups, though they frequently alternated or used them concomitantly with Parikweneh medicines. With the help of biomedical tools (i.e. glucometer), local medicinal practices mirrored biomedical approaches through dietary adaptation and the use of medicinal animals and plants for glycaemic control and the treatment of complications from the disease.ConclusionParikweneh are appropriating T2D into their knowledge system and adapting their health system in response to this relatively new health concern. A greater understanding of local practices and perceptions relating to T2D among medical staff may therefore be beneficial for meeting patients’ needs, providing greater autonomy in their health path, and improving treatment outcomes.

Quality and quantity of macronutrients, and their joint associations with the incidence of type 2 diabetes over a nine-year follow-up

BackgroundThe association between macronutrient consumption and the risk of type 2 diabetes (T2D) remains equivocal. Here, we investigated whether the quantity and quality of macronutrient intake are associated with T2D incidence in a West Asian population.MethodsT2D-free adults (n = 2457, mean age 38.5 ± 13.6 years, 54.2% women) who participated in the third examination cycle (2005–2008) of the Tehran Lipid and Glucose Study were followed for a median of 8.6 years. We estimated the macronutrient quality index (MQI), its individual sub-indices (carbohydrate quality index (CQI), fat quality index (FQI), and healthy plate protein quality index (HPPQI)), as well as the macronutrient quantity. The risk of T2D in relation to macronutrient quantity, quality, and their combined effects was examined using Cox proportional hazard models adjusted for known risk factors for T2D.ResultsDuring the study follow-up, 257 incident cases of T2D were documented. Individuals in the highest tertiles of MQI and CQI had a 27% (HR = 0.73, 95% CI = 0.54, 0.98) and 29% (HR = 0.71, 95% CI = 0.51–0.99) lower T2D risk than those in the lowest tertiles. The T2D incidence was 35% lower in the middle HPPQI tertile than in the lowest (HR = 0.65, 95% CI = 0.47, 0.89). The multivariable adjusted model showed that individuals in the middle and highest tertiles of carbohydrate intake had 32% (HR = 0.68, 95% CI = 0.49–0.95) and 26% (HR = 0.74, 95% CI = 0.55–1.00) lower risks of T2D than individuals in the lowest tertile. A high-quantity, high-quality carbohydrate diet (≥ 58.5% of energy from carbohydrate with a CQI ≥ 13) and a low-glycemic index (GI), high-fiber diet (GI < 55 and fiber ≥ 25 g/d) were related to a reduced risk of T2D by 34% (HR = 0.66, 95% CI = 0.47, 0.93) and 42% (HR = 0.58, 95% CI = 0.38, 0.90), respectively.ConclusionA diet with a higher carbohydrate quality may be associated with a lower T2D incidence, particularly when the carbohydrate quantity is also high.

Genetic predisposition to impaired beta-cell function modifies the association between serum pyrethroid levels and the risk of type 2 diabetes: A gene-environment interaction study

Previous studies suggested that pyrethroid exposure was associated with elevated type 2 diabetes (T2D) risk, while it remains uncertain whether genetic predisposition modifies this association. A nested case-control study within the prospective Dongfeng-Tongji cohort comprised 1832 T2D cases, age- (±5 years) and sex-matched controls with qualified genotyping data. Serum pyrethroids were measured by gas chromatography-tandem mass spectrometry. Overall diabetes-related genetic risk score (GRS) or pathway-specific GRS, including unweighted GRSs (uGRS) and weighted GRSs (wGRS), was developed by genetic variants identified in Asian populations. Higher overall diabetes-related GRS and GRS specific to the pathway of impaired beta cell function (Beta-cell GRS) were associated with a higher incident T2D risk. Beta-cell uGRS significantly modified the association of serum permethrin (Pinteraction=0.04) and deltamethrin (Pinteraction=0.01) with T2D. Specifically, for each doubling increase in serum deltamethrin, the odds ratios (ORs) (95 % confidence intervals [CIs]) for T2D were 1.23 (0.98–1.56) and 0.91 (0.77–1.07) in the highest and lowest Beta-cell uGRS group, as well as 1.23 (1.02–1.47) and 0.95 (0.78–1.15) for Beta-cell wGRS group, respectively. When considering jointly, those with the highest deltamethrin levels and highest Beta-cell GRS had a substantially higher T2D risk, compared with the reference group (OR for uGRS: 3.79 [95 % CI: 2.03–7.07], Pinteraction=0.03 and 3.23 [95 % CI: 1.78–5.87], Pinteraction=0.05 for wGRS). Our findings suggested that genetic susceptibility to impaired beta-cell function should be considered for T2D prevention targeting pyrethroid exposure, particularly deltamethrin.

Bidirectional association between type 2 diabetes and irritable bowel syndrome: A large-scale prospective cohort study.

To examine the bidirectional association between type 2 diabetes (T2D) and irritable bowel syndrome (IBS) in a large prospective population cohort. Participants free of IBS at baseline in the UK Biobank were included in the analysis of T2D and incident IBS (cohort 1), with 11 140 T2D patients and 413 979 non-T2D patients. Similarly, those free of T2D at baseline were included in the analysis of IBS and incident T2D (cohort 2), with 21 944 IBS patients and 413 979 non-IBS patients. Diagnoses of T2D and IBS were based on International Classification of Disease-10 codes. The Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs). In cohort 1, 8984 IBS cases were identified during a median 14.5-year follow-up. Compared with non-T2D, T2D patients had a 39.0% increased risk of incident IBS (HR = 1.39, 95% confidence interval [CI]: 1.23-1.56, P < .001), with a higher IBS risk in those with higher fasting blood glucose levels (HR = 1.43, 95% CI: 1.19-1.72, P < .001) or longer T2D duration (HR = 1.47, 95% CI: 1.23-1.74, P < .001). In cohort 2, 29 563 incident T2D cases were identified. IBS patients had an 18.0% higher risk of developing T2D versus non-IBS patients (HR = 1.18, 95% CI: 1.12-1.24, P < .001). A similar excess T2D risk was observed in IBS patients with a duration of either less than 10 years, or of 10 years or longer. Further sensitivity analysis and subgroup analysis indicated consistent findings. T2D and IBS exhibit a bidirectional association, with an increased risk of co-morbidity. Awareness of this association may improve the prevention and management of both diseases.