Incident Type 2 Diabetes Cases Research Articles

High adherence to the French dietary guidelines decreases type 2 diabetes risk in females through pathways of obesity markers: Evidence from the E3N-EPIC prospective cohort study

Obesity and type 2 diabetes (T2D) have been associated with low adherence to the 2017 French food-based dietary guidelines, as assessed by the Programme National Nutrition Santé - guidelines score 2 (PNNS-GS2). Whether the association between T2D and PNNS-GS2 is direct or mediated by obesity has been little investigated. The study included 71,450 women from the E3N-EPIC cohort, mean age of 52.9 y (SD 6.7). The simplified PNNS-GS2 was derived via food history questionnaire. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D. Causal mediation analyses were used to decompose the total effect of sPNNS-GS2 on T2D into a direct effect and indirect effect mediated by body mass index (BMI) or the waist-hip ratio (WHR). During a mean follow-up of 19 y, 3679 incident T2D cases were identified and validated. There was a linear association between adherence to sPNNS-GS2 and T2D (P-nonlinearity = 0.92). In the fully adjusted model, each 1-SD increase in the sPNNS-GS2 was associated with a lower T2D risk [HR (95% CI), 0.92 (0.89, 0.95)]. The overall associations were mainly explained by sPNNS-GS2-associated excess weight, with BMI and WHR mediating 52% and 58% of the associations, respectively. Higher adherence to French food-based dietary guidelines was associated with a lower risk of T2D in women, and a significant portion of this effect could be attributed to excess weight measured by BMI or WHR. This finding helps better understand the mechanisms underlying the diet-T2D association.

Fresh fruit, dried fruit, raw vegetables, and cooked vegetables consumption associated with progression trajectory of type 2 diabetes: a multi-state analysis of a prospective cohort.

To examine the effects of fresh fruit, dried fruit, raw vegetables, and cooked vegetables on type 2 diabetes (T2D) progression trajectory. We included 429,886 participants in the UK Biobank who were free of diabetes and diabetes complications at baseline. Food groups were determined using a validated food frequency questionnaire. Outcomes were T2D incidence, complications, and mortality. Multi-state model was used to analyze the effects of food groups on T2D progression. During a follow-up of 12.6 years, 10,333 incident T2D cases were identified, of whom, 3961 (38.3%) developed T2D complications and 1169 (29.5%) died. We found that impacts of four food groups on T2D progression varied depending on disease stage. For example, compared to participants who ate less than one piece of dried fruit per day, the hazard ratios and 95% confidence intervals for those who ate ≥ 2 pieces of dried fruit per day were 0.82 (0.77, 0.87), 0.88 (0.85, 0.92), and 0.86 (0.78, 0.95) for transitions from diabetes-free state to incident T2D, from diabetes-free state to total death, and from incident T2D to T2D complications, respectively. Higher intake of fresh fruit was significantly associated with lower risk of disease progression from diabetes-free state to all-cause death. Higher intake of raw and cooked vegetables was significantly associated with lower risks of disease progression from diabetes-free state to incident T2D and to total death. These findings indicate that higher intake of fresh fruit, dried fruit, raw vegetables, and cooked vegetables could be beneficial for primary and secondary prevention of T2D.

Association between Protein Intake and Diabetes Complications Risk Following Incident Type 2 Diabetes: The EPIC-Potsdam Study.

Our knowledge about the connection between protein intake and diabetes-related complications comes largely from studies among those already diagnosed with type 2 diabetes (T2D). However, there is a lack of information on whether changing protein intake after diabetes diagnosis affects complications risk. We aimed to explore the association between protein intake (total, animal, and plant) and vascular complications in incident T2D patients considering pre-diagnosis intake and changes in intake after diagnosis. This prospective cohort study included 1064 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort who developed T2D during follow-up (physician-verified). Dietary protein intake was measured with a food frequency questionnaire at baseline and follow-up. We included physician-reported incident diabetes complications (myocardial infarction, stroke, nephropathy, and neuropathy). A total of 388 participants developed complications, 82 macrovascular complications, and 343 microvascular complications. Substituting carbohydrates with protein showed a trend towards lower complications risk, although this association was not statistically significant (hazard ratio (HR) for 5% energy (E) substitution: 0.83; 95% confidence intervals (CI): 0.60-1.14). Increasing protein intake at the expense of carbohydrates after diabetes diagnosis was not associated with total and microvascular complications (HR for 5% E change substitution: 0.98; 95% CI: 0.89-1.08 and HR for 5% E change substitution: 1.02; 95% CI: 0.92-1.14, respectively). Replacing carbohydrates with protein did not elevate the risk of diabetes complications in incident T2D cases.

Abstract P143: Lignan Intake and Mortality Among Adults With Incident Type 2 Diabetes

Introduction: Lignans are polyphenolic compounds abundant in plant-based foods such as seeds, whole grains, and certain fruits and vegetables and may lead to better metabolic health. It remains elucidated regarding the role of lignan consumption in the etiology of premature deaths among diabetes patients. Hypothesis: We hypothesize that a higher intake of post-diagnosis lignans is associated with lower risk of mortality among individuals with incident type 2 diabetes (T2D). Design: Data from two prospective U.S. cohorts were analyzed, including the Nurses' Health Study (1984-2020) and Health Professionals Follow-up Study (1986-2022). Average daily consumption of total and individual lignans were calculated, and post-diagnosis lignan intakes were cumulatively averaged. Multivariable-adjusted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between post-diagnosis lignan intake and mortality. Results: Among 8,691 incident T2D cases contributing 119,065 person-years of follow-up, 4,502 deaths were documented, among which 1,379 cases were attributed to cardiovascular disease (CVD) and 777 to cancer. The pooled multivariable-adjusted HRs (95% CIs) of all-cause mortality comparing extreme quintiles of post-diagnosis lignan intake were 0.83 (0.74, 0.94) for total lignans, 0.87 (0.78, 0.96) for matairesinol (MAT), 0.77 (0.69, 0.86) for secoisolariciresinol (SECO), 0.92 (0.82, 1.03) for pinoresinol (PINO), and 0.92 (0.82, 1.03) for lariciresinol (LARIC). Higher post-diagnosis intakes of SECO were also significantly associated with lower CVD and cancer mortality. The HRs (95% CIs) of total mortality comparing extreme quintiles of changes in lignan intake from pre- to post-diagnosis were 0.84 (0.75, 0.93) for total lignans, 0.85 (0.76, 0.94) for MAT, and 0.79 (0.71, 0.89) for SECO. No significant associations were observed for PINO and LARIC. Stratified analyses showed that the associations of lignans were significantly stronger among non-white individuals. Conclusions: In conclusion, among individuals diagnosed with T2D, a higher intake of lignans, particularly SECO, was significantly associated with reduced overall, cardiovascular, and cancer mortality. Minority groups may particularly benefit from lignan intake, although further studies are warranted to substantiate this observation.

Maternal smoking, nutritional factors at different life stage, and the risk of incident type 2 diabetes: a prospective study of the UK Biobank

BackgroundThis study aims to investigate potential interactions between maternal smoking around birth (MSAB) and type 2 diabetes (T2D) pathway-specific genetic risks in relation to the development of T2D in offspring. Additionally, it seeks to determine whether and how nutritional factors during different life stages may modify the association between MSAB and risk of T2D.MethodsThis study included 460,234 participants aged 40 to 69 years, who were initially free of T2D from the UK Biobank. MSAB and breastfeeding were collected by questionnaire. The Alternative health eating index(AHEI) and dietary inflammation index(DII) were calculated. The polygenic risk scores(PRS) of T2D and pathway-specific were established, including β-cell function, proinsulin, obesity, lipodystrophy, liver function and glycated haemoglobin(HbA1c). Cox proportion hazards models were performed to evaluate the gene/diet-MSAB interaction on T2D. The relative excess risk due to additive interaction (RERI) were calculated.ResultsDuring a median follow-up period of 12.7 years, we identified 27,342 cases of incident T2D. After adjustment for potential confounders, participants exposed to MSAB had an increased risk of T2D (HR=1.11, 95%CI:1.08-1.14), and this association remained significant among the participants with breastfeeding (HR= HR=1.10, 95%CI: 1.06-1.14). Moreover, among the participants in the highest quartile of AHEI or in the lowest quartile of DII, the association between MSAB and the increased risk of T2D become non-significant (HR=0.94, 95%CI: 0.79-1.13 for AHEI; HR=1.09, 95%CI:0.99-1.20 for DII). Additionally, the association between MSAB and risk of T2D became non-significant among the participants with lower genetic risk of lipodystrophy (HR=1.06, 95%CI:0.99-1.14), and exposed to MSAB with a higher genetic risk for β-cell dysfunction or lipodystrophy additively elevated the risk of T2D(RERI=0.18, 95%CI:0.06-0.30 for β-cell function; RERI=0.16, 95%CI:0.04-0.28 for lipodystrophy).ConclusionsThis study indicates that maintaining a high dietary quality or lower dietary inflammation in diet may reduce the risk of T2D associated with MSAB, and the combination of higher genetic risk of β-cell dysfunction or lipodystrophy and MSAB significantly elevate the risk of T2D in offspring.

Adipose tissue-derived metabolite risk scores and risk for type 2 diabetes in South Asians

BackgroundSouth Asians are at higher risk for type 2 diabetes (T2D) than many other race/ethnic groups. Ectopic adiposity, specifically hepatic steatosis and visceral fat may partially explain this. Our objective was to derive metabolite risk scores for ectopic adiposity and assess associations with incident T2D in South Asians.MethodsWe examined 550 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort study aged 40–84 years without known cardiovascular disease or T2D and with metabolomic data. Computed tomography scans at baseline assessed hepatic attenuation and visceral fat area, and fasting serum specimens at baseline and after 5 years assessed T2D. LC-MS-based untargeted metabolomic analysis was performed followed by targeted integration and reporting of known signals. Elastic net regularized linear regression analyses was used to derive risk scores for hepatic steatosis and visceral fat using weighted coefficients. Logistic regression models associated metabolite risk score and incident T2D, adjusting for age, gender, study site, BMI, physical activity, diet quality, energy intake and use of cholesterol-lowering medication.ResultsAverage age of participants was 55 years, 36% women with an average body mass index (BMI) of 25 kg/m2 and 6% prevalence of hepatic steatosis, with 47 cases of incident T2D at 5 years. There were 445 metabolites of known identity. Of these, 313 metabolites were included in the MET-Visc score and 267 in the MET-Liver score. In most fully adjusted models, MET-Liver (OR 2.04 [95% CI 1.38, 3.03]) and MET-Visc (OR 2.80 [1.75, 4.46]) were associated with higher odds of T2D. These associations remained significant after adjustment for measured adiposity.ConclusionsMetabolite risk scores for intrahepatic fat and visceral fat were strongly related to incident T2D independent of measured adiposity. Use of these biomarkers to target risk stratification may help capture pre-clinical metabolic abnormalities.

Type 2 diabetes metabolomics score and risk of progression to type 2 diabetes among women with a history of gestational diabetes mellitus.

Several metabolites are individually related to incident type 2 diabetes (T2D) risk. We prospectively evaluated a novel T2D-metabolite pattern with a risk of progression to T2D among high-risk women with a history of gestational diabetes mellitus (GDM). The longitudinal Nurses' Health Study II cohort enroled 116,429 women in 1989 and collected blood samples from 1996 to 1999. We profiled plasma metabolites in 175 incident T2D cases and 175 age-matched controls, all with a history of GDM before the blood draw. We derived a metabolomics score from 21 metabolites previously associated with incident T2D in the published literature by scoring according to the participants' quintile (1-5 points) of each metabolite. We modelled the T2D metabolomics score categorically in quartiles and continuously per 1 standard deviation (SD) with the risk of incident T2D using conditional logistic regression models adjusting for body mass index at the blood draw, and other established T2D risk factors. The percentage of women progressing to T2D ranged from 10% in the bottom T2D metabolomics score quartile to 78% in the highest score quartile. Adjusting for established T2D risk factors, women in the highest quartile had more than a 20-fold greater diabetes risk than women in the lowest quartile (odds ratios [OR]=23.1 [95% CI=8.6, 62.1]; p for trend<0.001). The continuous T2D metabolomics score was strongly and positively associated with incident T2D (adjusted OR=2.7 per SD [95% CI=1.9, 3.7], p<0.0001). A pattern of plasma metabolites among high-risk women is associated with a markedly elevated risk of progression to T2D later in life.

Abstract 16868: Genetic Regulation of Branched-Chain Amino Acid Levels Does Not Increase Type 2 Diabetes Risk

Introduction: The branched-chain amino acids (BCAAs) valine, leucine, and isoleucine are associated with incident type 2 diabetes (T2D). Prior genetic studies have provided conflicting results as to whether the BCAAs are causally related to T2D but are limited by a small number of genetic instruments associated with BCAA levels. Hypothesis: We hypothesized that polygenic predictors that capture a broad set of genetic mechanisms regulating BCAA levels would clearly define the etiological relationship with T2D. Methods: We constructed and validated instrumental variables for each BCAA using well-powered datasets and tested their association with T2D using two-sample inverse variance weighted (IWV) Mendelian randomization (MR). Sensitivity analyses were performed to ensure the accuracy of the findings. We also tested whether instrumental variables for T2D, fasting insulin, and body mass index (BMI) were associated with BCAA levels. Finally, logistic regression was used to test whether a polygenic risk score (PRS) for T2D was associated with measured BCAA levels among 1220 participants in the Framingham offspring study (FOS) without prevalent T2D. Results: There were no significant associations with T2D for valine (beta=0.17 change in log-odds per standard deviation change in valine, [95% CI, -0.28 - 0.62], p=0.45), leucine (beta=0.19 [-0.30 - 0.68] p=0.45) or isoleucine (beta=0.02 [-0.54 - 0.59], p=0.94). In contrast, T2D was associated with each BCAA (valine: beta=0.08 per standard deviation change in levels per log-odds change in type 2 diabetes, [0.05 - 0.10], p=1.8x10 -9 ), (leucine: beta= 0.06 [0.04 - 0.09], p=4.5x10 -8 ) and isoleucine (beta= 0.06 [0.04 - 0.08], p=2.8x10 -8 ). The T2D associations were replicated in an independent population but not in a second population where T2D cases were removed. Similarly, a T2D PRS was associated with measured BCAA levels in the FOS study but not when incident T2D cases were removed. Positive associations were seen for fasting insulin and BMI, and the BCAAs by MR, and, in multivariable MR analyses, T2D and fasting insulin had independent associations with each BCAA. Conclusions: These data suggest that BCAAs are not mediators of T2D risk but may rather serve as biomarkers of T2D and higher insulin levels.

Dietary Sodium Intake and Risk of Incident Type 2 Diabetes

ObjectiveTo fill the knowledge gap of the relation between long-term dietary sodium intake and type 2 diabetes (T2D), we evaluate the association between the frequency of adding salt to foods, a surrogate marker for evaluating the long-term sodium intake, and incident T2D risk. MethodsA total of 402,982 participants from UK Biobank (March 13, 2006 – October 10, 2010) who were free of diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline, and had completed information on adding salt were analyzed in this study. ResultsDuring a median of 11.9 years of follow-up, 13,120 incident cases of T2D were documented. Compared with participants who “never/rarely” added salt to foods, the adjusted HRs were 1.11 (95% CI, 1.06 to 1.15), 1.18 (95% CI, 1.12 to 1.24), and 1.28 (95% CI, 1.20 to 1.37) across the groups of “sometimes,” “usually,” and “always,” respectively (P-trend<.001). We did not find significant interactions between the frequency of adding salt to foods and baseline hypertension status and other covariates on the risk of incident T2D. The observed positive association was partly mediated by body mass index, waist to hip ratio, and C-reactive protein, with a significant mediation effect of 33.8%, 39.9%, and 8.6%, respectively. The significant mediation effect of body mass index was largely driven by the body fat mass rather than the body fat-free mass. ConclusionOur findings for the first time indicate that higher frequency of adding salt to foods, a surrogate marker for a person’s long-term salt taste preference and intake, is associated with a higher T2D risk.

Adherence to the EAT-Lancet reference diet and risk of type 2 diabetes, mediation by body mass index

Abstract Background Prevalence of diabetes has more than tripled since 1980. Urbanization, more sedentary lifestyles, and modern diets high in fat, sugar and salt are among the main causes of this increased incidence. A diet rich in healthy plant-based products is a way to prevent T2D (4) but has also impact on the natural resources and environment. In 2019 the EAT-Lancet Commission proposed a planetary, healthy, and reference diet, designed to reduce the global health-environmental double burden of current dietary patterns. The objective of this study was to investigate the association between the EAT-Lancet reference diet and type 2 diabetes (T2D) risk. Methods The study was conducted using data from 88,964 adults participating to the French NutriNet-Santé cohort 2009-2022 (78.8 % female; mean (SD) baseline age of participants was 43.8 (14.5) y). The endpoint was incident T2D. The main exposure was the EAT-Lancet Diet Index (ELD-I) modelled as sex-specific quintiles (Qs). Hazard Ratios (HRs) and Confidence Intervals (CIs) were assessed by Cox proportional hazards models adjusted for potential confounders. A mediation analysis was also implemented. The role of body mass index (BMI) as a potential mediating factor in the relationship was investigated. Findings During follow-up (median = 6.79 y), 812 incident T2D cases occurred. The ELD-I ranged from −192 to 429 points with a mean (SD) score of 43.4 (25.7) points. Compared with the participants who had lower adherence to the EAT-Lancet reference diet, those with higher had a 29 % lower risk of T2D (HRQ5vs.Q1: 0.71; 95% CI: 0.56, 0.89; Ptrend = 0.0024). The association studied was mediated up to 58 % by BMI. Interpretation In this large cohort study, higher adherence to the EAT-Lancet reference diet was associated with a decreased risk of T2D beyond body weight change. These results support previous findings and highlights the interest of the EAT-Lancet reference diet as a healthy and sustainable diet. Key messages • Higher adherence level to the EAT-Lancet reference diet was associated with a decreased of type 2 diabetes risk. • The association between the EAT-Lancet reference diet and the occurrence of type 2 diabetes is partially mediated by BMI.

Association of plasma advanced glycation end-products and their soluble receptor with type 2 diabetes among Chinese adults.

Population-based evidence regarding circulating advanced glycation end-products (AGEs) and the risk of type 2 diabetes (T2D) is conflicting and insufficient. We aimed to examine the association of plasma AGEs and plasma soluble receptors for AGEs (sRAGE) with T2D. We conducted a hospital-based case-control study including 1072 pairs (53.9±9.7years, 56.0% male) of newly diagnosed T2D and age- and sex-matched controls. We further performed a nested case-control study within an ongoing prospective cohort consisting of 127 incident T2D cases and 381 well-matched controls (62.2±5.1years, 71.7% male). Plasma AGEs were detected using liquid chromatography-tandem mass spectrometry, and plasma sRAGE was measured by enzyme-linked immunosorbent assay. Conditional logistic regression was used to evaluate the association of plasma AGEs and sRAGE concentrations with T2D. Higher plasma AGEs and lower sRAGE concentrations were associated with higher odds of T2D. The multivariable-adjusted odds ratios of T2D comparing the highest with the lowest quartile levels were 3.28 (95% CI: 2.14, 5.02) for plasma AGEs and 0.25 (95% CI: 0.16, 0.39) for plasma sRAGE. Participants in the highest quartile of plasma AGEs and the lowest quartile of sRAGE concentrations had the greatest odds of T2D. The positive association of AGEs and inverse association of sRAGE with T2D risk was confirmed in the replication-nested case-control study. Increased circulating AGEs and decreased sRAGE concentrations were associated with elevated T2D risk. Our findings may have implications for the strategies of T2D prevention and management.

Exposure to airborne polychlorinated biphenyls and type 2 diabetes in a Danish cohort

BackgroundPrevious research indicates an association between higher-chlorinated polychlorinated biphenyls (PCBs) and type 2 diabetes (T2D). However, less is known about the extent to which PCB exposure in indoor air, composed primarily of lower-chlorinated PCBs, affects T2D risk. We assessed the association between indoor air exposure to PCBs in residential buildings and T2D incidence. MethodsThe register-based ‘Health Effects of PCBs in Indoor Air’ (HESPAIR) cohort comprises 51,921 Danish residents of two residential areas with apartments built with and without PCB-containing materials (reference apartments). We assessed exposure status by combining register-based information on relocation history with extrapolated values of exposure based on PCB-measurements in indoor air from subsets of the apartments. T2D cases were identified in the Danish registers during 1977–2018. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression analyses with time-varying exposure. ResultsWe identified 2737 incident T2D cases during the follow-up. Exposure to ≥3300 ng/m3 PCB × year (3rd tertile of PCByear) was associated with higher risk of T2D (HR 1.15, 95% CI 1.02–1.30) compared with exposure to <300 ng/m3 PCB × year (reference). However, among individuals with lower cumulated PCByear, the risk was similar to residents with exposure <300 ng/m3 PCB × year (300–899 ng/m3 PCB × year: HR 0.98, 95% CI 0.87–1.11; 900–3299 ng/m3 PCB × year: HR 0.96, 95% CI 0.83–1.10). DiscussionWe observed a marginally higher risk of T2D, but there was no evidence of an exposure-response relationship. The results should be interpreted with caution until confirmed in other independent studies of PCB exposure in indoor air.

Association of variability in metabolic parameters with the incidence of type 2 diabetes: evidence from a functional community cohort

BackgroundTo investigate the association of variability in metabolic parameters such as total cholesterol concentrations (TC), uric acid (UA), body mass index (BMI), visceral adiposity index (VAI) and systolic blood pressure (SBP) with incident type 2 diabetes (T2D) and whether variability in these metabolic parameters has additive effects on the risk of T2D.MethodsBased on the Beijing Functional Community Cohort, 4392 participants who underwent three health examinations (2015, 2016, and 2017) were followed up for incident T2D until the end of 2021. Variability in metabolic parameters from three health examinations were assessed using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability index. Participants were grouped according to the number of high-variability metabolic parameters. Cox proportional hazards models were performed to assess the hazard ratio (HR) and 95% confidence interval (CI) for incident T2D.ResultsDuring a median follow-up of 3.91 years, 249 cases of incident T2D were identified. High variability in TC, BMI, VAI and SBP was significantly associated with higher risks of incident T2D. As for UA, significant multiplicative interaction was found between variability in UA and variability in other four metabolic parameters for incident T2D. The risk of T2D significantly increased with the increasing numbers of high-variability metabolic parameters. Compared with the group with low variability for 5 parameters, the HR (95% CI) for participants with 1–2, 3, 4–5 high-variability metabolic parameters were 1.488 (1.051, 2.107), 2.036 (1.286, 3.222) and 3.017 (1.549, 5.877), respectively. Similar results were obtained in various sensitivity analyses.ConclusionsHigh variability of TC, BMI, VAI and SBP were independent predictors of incident T2D, respectively. There was a graded association between the number of high-variability metabolic parameters and incident T2D.

Differences in DNA methylation of HAMP in blood cells predicts the development of type 2 diabetes

ObjectivesBetter disease management can be achieved with earlier detection through robust, sensitive, and easily accessible biomarkers. The aim of the current study was to identify novel epigenetic biomarkers determining the risk of type 2 diabetes (T2D). MethodsLivers of 10-week-old female New Zealand Obese (NZO) mice, slightly differing in their degree of hyperglycemia and liver fat content and thereby in their diabetes susceptibility were used for expression and methylation profiling. We screened for differences in hepatic expression and DNA methylation in diabetes-prone and -resistant mice, and verified a candidate (HAMP) in human livers and blood cells. Hamp expression was manipulated in primary hepatocytes and insulin-stimulated pAKT was detected. Luciferase reporter assays were conducted in a murine liver cell line to test the impact of DNA methylation on promoter activity. ResultsIn livers of NZO mice, the overlap of methylome and transcriptome analyses revealed a potential transcriptional dysregulation of 12 hepatokines. The strongest effect with a 52% decreased expression in livers of diabetes-prone mice was detected for the Hamp gene, mediated by elevated DNA methylation of two CpG sites located in the promoter. Hamp encodes the iron-regulatory hormone hepcidin, which had a lower abundance in the livers of mice prone to developing diabetes. Suppression of Hamp reduces the levels of pAKT in insulin-treated hepatocytes. In liver biopsies of obese insulin-resistant women, HAMP expression was significantly downregulated along with increased DNA methylation of a homologous CpG site. In blood cells of incident T2D cases from the prospective EPIC-Potsdam cohort, higher DNA methylation of two CpG sites was related to increased risk of incident diabetes. ConclusionsWe identified epigenetic changes in the HAMP gene which may be used as an early marker preceding T2D.

Disrupted Pediatric Diabetes Trends in the Second Year of the COVID-19 Pandemic.

Increases in incident cases of pediatric type 1 (T1D) and type 2 diabetes (T2D) were observed during the first year of the COVID-19 pandemic. This work aimed to identify trends in incidence and presentation of pediatric new-onset T1D and T2D during the second year of the COVID-19 pandemic. A retrospective chart review was conducted. Demographics, anthropometrics, and initial laboratory results from patients aged 0 to 21 years who presented with new-onset diabetes to a pediatric tertiary care center were recorded. The incident cases of T1D (n = 46) and T2D (n = 46) in 2021-2022 (second year of the pandemic) were consistent with the incident cases of T1D (n = 46) and T2D (n = 53) in 2020 to 2021 (first year of the pandemic). Compared to the incident cases of diabetes in the prepandemic years, in the second year, the incident cases of T1D increased 48%, and the incident cases of T2D increased 188%. In the second year of the pandemic, incident cases of T2D represented half (50%) of all newly diagnosed pediatric diabetes cases. Patients with T2D were more likely to present in diabetic ketoacidosis, though this was not statistically significant (P = .08). The increase in incident cases of pediatric T1D and T2D observed during the first year of the COVID-19 pandemic persisted during the second pandemic year. This suggests that despite pediatric vaccination efforts and return to social in-person activities, we may continue to see effects of the pandemic on pediatric diabetes trends.

1399-P: Lipoprotein Subfractions and Type 2 Diabetes Incidence in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multiethnic Study of Atherosclerosis (MESA) Cohorts

Background: Atherogenic dyslipidemia is prevalent in individuals at risk for type 2 diabetes (T2D) but less is known about composition of lipoprotein subfractions in diverse racial/ethnic groups. We examined associations between lipoprotein subfractions and incident T2D among participants of the MASALA and MESA cohorts. Methods: Adults aged 45-84 years without T2D and with fasting serum, demographic and clinical data at baseline and 2-5 year follow-up were included. Lipoprotein subfractions were measured at baseline using NMR spectrometry on a common platform. LASSO regularized logistic regression models adjusted for age, sex, race/ethnicity, lipid-lowering agents and waist circumference assessed odds of incident T2D with adjustment for multiple comparisons. Results: Analyses included 3839 participants with average age of 62 years, 51% women, mean BMI 28 kg/m2 and 234 incident T2D cases. Triglycerides (TG) in LDL-5, LDL-6 and HDL-3 and HDL-4 were associated with odds of incident T2D and free cholesterol in HDL-1 was inversely associated (Table). There were no interactions by race. Conclusions: TG in small, dense HDL and LDL were positively associated, while free cholesterol in large HDL was inversely related to odds of incident T2D at first follow-up in participants of the MESA and MASALA cohort studies. Disclosure M.D.Gadgil: None. D.M.Herrington: None. S.Singh: None. N.R.Kandula: None. A.M.Kanaya: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK119404-01A1); National Heart, Lung, and Blood Institute/National Center Research Resources/National Center for Advancing Translational Sciences (R01HL093009); National Institutes of Health (UL1RR024131); Medical Research Council/National Institute for Health and Care Research (NC-PC-12025); National Institute for Health and Care Research Imperial Biomedical Research Centre; National Heart, Lung, and Blood Institute (75N92020D00001, HHSN268201500003I, N01HC-95159, 75N92020D00005, N01HC-95160, 75N92020D00002, N01HC95161, 75N92020D00003, N01HC95162, 75N92020D00006, N01HC95163, 75N92020D00004, N01HC95164, 75N92020D00007, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169); National Center for Advancing Translational Sciences (UL1TR000040, UL1TR001079, UL1TR001420)

Mediation of metabolic syndrome in the association between long-term co-exposure to road traffic noise, air pollution and incident type 2 diabetes

ObjectivesRecent studies have linked exposure to road traffic noise or air pollution with incident type 2 diabetes (T2D), but investigation on their co-exposure was limited and underlying mechanisms remain unclear. We hypothesized that long-term co-exposure to road traffic noise and air pollution increases the risk of incident T2D via the development of metabolic syndrome (MetS). MethodsThis prospective study included 390,834 participants in UK Biobank. Cumulative risk index (CRI), the health-based weighted levels of multiple exposures, was applied to characterize the co-exposure to 24-hour road traffic noise (Lden), particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5), and nitrogen dioxide (NO2). Lden was modeled by the Common Noise Assessment Methods in Europe and air pollutant levels were measured by the Land Use Regression model at participants’ residential addresses. Incident T2D was ascertained through linkages to inpatient hospital records. MetS was defined by five (central obesity, triglycerides, HDL cholesterol, glucose, and blood pressure) or six factors (C-reactive protein additionally). Cox proportional hazard models were used to assess the association between environmental exposures and incident T2D, and mediation analyses were applied to investigate the role of MetS. ResultsAfter a median of 10.9 years of follow-up, 13,214 (3.4%) incident T2D cases were ascertained. The exposure to Lden, PM2.5, and NO2, as well as their co-exposure, were significantly associated with an elevated risk of incident T2D, with HRs of 1.03 (95%CI: 1.00, 1.05) per 3.5 dB(A) increase in Lden, 1.05 (95%CI: 1.01, 1.10) per 1.3 μg/m3 increase in PM2.5, 1.07 (95%CI: 1.02, 1.11) per 9.8 μg/m3 increase in NO2, and 1.06 (95%CI: 1.02, 1.09) per interquartile range increase in CRI. MetS significantly mediated 43.5%− 54.7% of the CRI-T2D relationship. ConclusionsLong-term co-exposure to road traffic noise and air pollution is associated with an elevated risk of incident T2D, which may partly be mediated by MetS.

Dietary Diversity and Inflammatory Diet Associated with All-Cause Mortality and Incidence and Mortality of Type 2 Diabetes: Two Prospective Cohort Studies.

A higher dietary diversity score (DDS) and a lower energy-adjusted dietary inflammatory index (E-DII) may be associated with lower risks of type 2 diabetes (T2D) and mortality. This cohort study aimed to investigate the associations of DDS and E-DII with all-cause mortality, incidence of T2D, and mortality of T2D, as well as the joint effects of these two dietary factors. A total of 181,360 participants without all types of diabetes at baseline from the UK Biobank and 42,139 participants from the US NHANES were included. Cox proportional hazards models were used to assess the associations of DDS and E-DII with outcomes. In the UK Biobank data, 8338 deaths, 3416 incident T2D cases, and 353 T2D deaths occurred during a median follow-up of 12.5 years. In the US NHANES data, 6803 all-cause deaths and 248 T2D-specific deaths were recorded during a median follow-up of 9.6 years. We observed that higher DDS and lower E-DII were significantly associated with lower risks of total mortality and incident T2D. Compared with low DDS, the hazard ratios (HRs) and 95% confidence intervals (CIs) of high DDS were 0.69 (0.64, 0.74) for all-cause mortality, 0.79 (0.70, 0.88) for incident T2D in the UK Biobank, and 0.69 (0.61, 0.78) for all-cause mortality in the US NHANES. Compared with participants in tertile 3 of E-DII, those in tertile 1 had a lower risk of overall death [HR 0.86 (95% CI: 0.81, 0.91) in UK Biobank; 0.83 (0.77, 0.88) in US NHANES] and incident T2D [0.86 (0.79, 0.94)] in UK Biobank. No evidence was observed of the interactive effects of DDS and E-DII on either all-cause mortality or the incidence and mortality of T2D. There was no significant association found between any exposure and T2D mortality in this study. In conclusion, our results revealed that higher DDS and lower E-DII were associated with both total mortality and incident T2D in UK and US adults.

Partial substitution of red or processed meat with plant-based foods and the risk of type 2 diabetes

High consumption of red and processed meat has been associated with increased type 2 diabetes (T2D) risk. These kinds of diets are also environmentally unsustainable. We examined a modeled association between a partial substitution of red meat or processed meat with plant-based foods (legumes, vegetables, fruit, cereals, or a combination of these) and T2D risk among Finnish adults. We used pooled data from five Finnish cohorts (n = 41,662, 22% women, aged ≥ 25 years, 10.9 years median follow-up with 1750 incident T2D cases). Diet was assessed by a validated food frequency questionnaire. In the substitution models, 100 g/week of red meat or 50 g/week of processed meat were substituted with similar amounts of plant-based substitutes. Cohort-specific hazard ratios (HRs) were estimated by Cox proportional hazards multivariable model and pooled using a two-staged random-effects model. We observed small, but statistically significant, reductions in T2D risk in men when red or processed meat were partially substituted with fruits (red meat: HR 0.98, 95% CI 0.97–1.00, P = 0.049, processed meat: 0.99, 0.98–1.00, P = 0.005), cereals (red meat: 0.97, 0.95–0.99, P = 0.005, processed meat: 0.99, 0.98–1.00, P = 0.004) or combination of plant-based foods (only processed meat: 0.99, 0.98–1.00, P = 0.004) but not with legumes or vegetables. The findings of women were similar but not statistically significant. Our findings suggest that even small, easily implemented, shifts towards more sustainable diets may reduce T2D risk particularly in men.

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.