Incident Type 2 Diabetes Research Articles

Risk prediction models for type 2 diabetes using either fasting plasma glucose or HbA1c in Chinese, Malay, and Indians: Results from three multi-ethnic Singapore cohorts

AimsTo assess three well-established type 2 diabetes (T2D) risk prediction models based on fasting plasma glucose (FPG) in Chinese, Malays, and Indians, and to develop simplified risk models based on either FPG or HbA1c. MethodsWe used a prospective multiethnic Singapore cohort to evaluate the established models and develop simplified models. 6,217 participants without T2D at baseline were included, with an average follow-up duration of 8.3 years. The simplified risk models were validated in two independent multiethnic Singapore cohorts (N = 12,720). ResultsThe established risk models had moderate-to-good discrimination (area under the receiver operating characteristic curves, AUCs 0.762 – 0.828) but a lack of fit (P-values < 0.05). Simplified risk models that included fewer predictors (age, BMI, systolic blood pressure, triglycerides, and HbA1c or FPG) showed good discrimination in all cohorts (AUCs ≥ 0.810), and sufficiently captured differences between the ethnic groups. While recalibration improved fit the simplified models in validation cohorts, there remained evidence of miscalibration in Chinese (p ≤ 0.012). ConclusionsSimplified risk models including HbA1c or FPG had good discrimination in predicting incidence of T2D in three major Asian ethnic groups. Risk functions with HbA1c performed as well as those with FPG.

Neighbourhood deprivation and type 2 diabetes in patients with bipolar disorder: A nationwide follow-up study.

Patients with bipolar disorder have higher rates of type 2 diabetes (T2D) compared to the general population. Neighbourhood deprivation is associated with T2D and bipolar disorder. The aim of this study was to explore the potential effect of neighbourhood deprivation on incident T2D in patients with bipolar disorder. This nationwide open cohort study (1997-2018) included adults in Sweden ≥20years with bipolar disorder (90,780 patients) to examine the subsequent risk of T2D. The association between neighbourhood deprivation and T2D was explored using Cox regression analysis, with hazard ratios (HRs) and 95% confidence intervals (95% CIs). All models were conducted in both men and women and adjusted for individual-level sociodemographic factors and comorbidities. Neighbourhood deprivation was significantly associated with T2D in patients with bipolar disorder. The HRs were 1.61 (95% CI 1.40-1.86) for men and 1.83 (1.60-2.10) for women living in high deprivation neighbourhoods compared to those from low deprivation neighbourhoods. After adjustment, these results remained significant: 1.35 (1.17-1.56) in men and 1.39 (1.20-1.60) in women living in high deprivation neighbourhoods. The suggested graded association of higher incident T2D among patients with bipolar disorder, observed when levels of neighbourhood deprivation increased, raises important clinical and public health concerns. The results may help develop a contextual approach to prevention of T2D in patients with bipolar disorder that includes the neighbourhood environment.

Associations between Metabolomic Biomarkers of Avocado Intake and Glycemia in the Multi-Ethnic Study of Atherosclerosis

BackgroundAvocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes. ObjectivesTo identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia. MethodsBaseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an ∼18 y follow-up period. A metabolome-wide association study of avocado consumption status (consumer compared with nonconsumer) was conducted, and the relationship of these features with glycemia via cross-sectional associations with fasting insulin and glucose and longitudinal associations with incident T2D was examined. ResultsThree highly-correlated spectral features were associated with avocado intake at metabolome-wide significance levels (P < 5.3 ∗ 10–7) and combined into a single biomarker. We did not find evidence that these features were additionally associated with overall dietary quality, nor with any of 47 other food groups (all P > 0.001), supporting their suitability as a biomarker of avocado intake. Avocado intake showed a modest association only with lower fasting insulin (β = –0.07 +/- 0.03, P = 0.03), an association that was attenuated to nonsignificance when additionally controlling for body mass index (kg/m2). However, our biomarker of avocado intake was strongly associated with lower fasting glucose (β = –0.22 +/- 0.02, P < 2.0 ∗ 10–16), lower fasting insulin (β = –0.17 +/- 0.02, P < 2.0 ∗ 10–16), and a lower incidence of T2D (hazard ratio: 0.68; 0.63–074, P < 2.0 ∗ 10–16), even when adjusting for BMI. ConclusionsHighly significant associations between glycemia and avocado-related metabolomic features, which serve as biomarkers of the physiological impact of dietary intake after digestion and absorption, compared to modest relationships between glycemia and avocado consumption, highlights the importance of considering individual differences in metabolism when considering diet-health relationships.

Association of Obesity and Type 2 Diabetes with Non-Hodgkin Lymphoma: The Multiethnic Cohort.

Given the role of the immune system in non-Hodgkin lymphoma (NHL) etiology, obesity and type 2 diabetes (T2D) may impact NHL development. We examined the association of body mass index (BMI) and T2D with NHL in the multiethnic cohort (MEC). The MEC recruited >215,000 participants in Hawaii and Los Angeles from five racial/ethnic groups; NHL cases were identified through cancer registry linkages. T2D status, and BMI at age 21 and cohort entry were derived from repeated self-reports; for T2D, Medicare claims were also applied. HRs and 95% confidence intervals (CI) for BMI and T2D as predictors of NHL were determined using Cox regression adjusted for relevant covariates. Among 192,424 participants, 3,472 (1.8%) with NHL and 68,850 (36%) with T2D after 19.2±6.6 years follow-up, no significant association between T2D and NHL (HR, 1.04; 95% CI, 0.96-1.13) was observed. Stratification by BMI at cohort entry showed a significant association of T2D with NHL among individuals with normal weight only (HR, 1.18; 95% CI, 1.03-1.37). In a model with both BMI values plus T2D, only overweight (HR, 1.13; 95% CI, 1.01-1.26) and obesity (HR, 1.25; 95% CI, 0.99-1.59) at age 21 were associated with NHL incidence. Stratification by sex, race/ethnicity, and NHL subtype indicated no differences. Our findings suggest an association between T2D and NHL incidence in several subgroups but not in the total population and an elevated risk related to early-life BMI. Excess body weight in early life, rather than T2D, may be a predictor of NHL incidence.

Visit-to-Visit Glucose Variability, Cognition, and Global Cognitive Decline: The Multi-Ethnic Study of Atherosclerosis.

Higher visit-to-visit glucose variability (GV) is associated with dysglycemia and type 2 diabetes (T2D), key risk factors for cognitive decline. Evaluate the association of GV with cognitive performance and decline in racially/ethnically diverse older populations with and without T2D. We calculated the standard deviation of glucose (SDG), average real variability (ARV), and variability independent of the mean (VIM) among 4367 Multi-Ethnic Study of Atherosclerosis participants over 6 clinical examinations. Participants completed a cognitive assessment at the fifth examination, and a subset completed a second assessment 6 years later. We used multivariable linear regression to estimate the association of intraindividual GV with cognitive test scores after adjustments for cardiovascular risk factors and mean glucose level over the study period. Two-fold increments in the VIM and SDG were associated with worse Cognitive Abilities Screening Instrument (CASI) performance, while two-fold increments in VIM and ARV were associated with worse Digit Symbol Coding test score. GV measures were not associated with change in CASI performance among 1834 participants with repeat CASI data 6 years later. However, among 229 participants with incident T2D, the SDG and VIM were associated with decline in CASI (-1.7 [95% CI: -3.1, -0.3] and -2.1 [-3.7, -0.5] points, respectively). In contrast, single-timepoint glucose and HbA1c were not associated with CASI decline among participants with or without incident T2D. Higher visit-to-visit GV over 16 to 18 years is associated with worse cognitive performance in the general population, and with modest global cognitive decline in participants with T2D.

The healthy beverage index is not associated with insulin resistance, prediabetes and type 2 diabetes risk in the Rotterdam Study.

Whether beverage quality affects changes in glycaemic traits and type 2 diabetes (T2D) risk is unknown. We examined associations of a previously developed Healthy Beverage Index (HBI) with insulin resistance, and risk of prediabetes and T2D. We included 6769 participants (59% female, 62.0 ± 7.8years) from the Rotterdam Study cohort free of diabetes at baseline. Diet was assessed using food-frequency questionnaires at baseline. The HBI included 10 components (energy from beverages, meeting fluid requirements, water, coffee and tea, low-fat milk, diet drinks, juices, alcohol, full-fat milk, and sugar-sweetened beverages), with a total score ranging from 0 to 100. A higher score represents a healthier beverage pattern. Data on study outcomes were available from 1993 to 2015. Multivariable linear mixed models and Cox proportional-hazards regression models were used to examine associations of the HBI (per 10 points increment) with two measurements of HOMA-IR (a proxy for insulin resistance), and risk of prediabetes and T2D. During follow-up, we documented 1139 prediabetes and 784 T2D cases. Mean ± SD of the HBI was 66.8 ± 14.4. Higher HBI score was not associated with HOMA-IR (β: 0.003; 95% CI -0.007, 0.014), or with risk of prediabetes (HR: 1.01; 95% CI 0.97, 1.06), or T2D (HR: 1.01; 95% CI 0.96, 1.07). Our findings suggest no major role for overall beverage intake quality assessed with the HBI in insulin resistance, prediabetes and T2D incidence. The HBI may not be an adequate tool to assess beverage intake quality in our population.

Artificial Sweeteners and Risk of Type 2 Diabetes in the Prospective NutriNet-Santé Cohort.

To study the relationships between artificial sweeteners, accounting for all dietary sources (total and by type of artificial sweetener) and risk of type 2 diabetes (T2D), in a large-scale prospective cohort. The analyses included 105,588 participants from the web-based NutriNet-Santé study (France, 2009-2022; mean age 42.5 ± 14.6 years, 79.2% women). Repeated 24-h dietary records, including brands and commercial names of industrial products, merged with qualitative and quantitative food additive composition data, enabled artificial sweetener intakes to be accurately assessed from all dietary sources. Associations between artificial sweeteners (total, aspartame, acesulfame potassium [K], and sucralose) and T2D were investigated using Cox proportional hazard models adjusted for potential confounders, including weight variation during follow-up. During a median follow-up of 9.1 years (946,650 person-years, 972 incident T2D), compared with nonconsumers, higher consumers of artificial sweeteners (i.e., above the sex-specific medians of 16.4 mg/day in men and 18.5 mg/day in women) had higher risks of developing T2D (hazard ratio [HR] 1.69; 95% CI 1.45-1.97; P-trend <0.001). Positive associations were also observed for individual artificial sweeteners: aspartame (HR 1.63 [95% CI 1.38-1.93], P-trend <0.001), acesulfame-K (HR 1.70 [1.42-2.04], P-trend <0.001), and sucralose (HR 1.34 [1.07-1.69], P-trend = 0.013). Potential for reverse causality cannot be eliminated; however, many sensitivity analyses were computed to limit this and other potential biases. These findings of positive associations between artificial sweetener intakes and increased T2D risk strengthen the evidence that these additives may not be safe sugar alternatives. This study provides important insights in the context of on-going reevaluation of artificial sweeteners by health authorities worldwide.

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.

Supra-additive effect of chronic inflammation and atherogenic dyslipidemia on developing type 2 diabetes among young adults: a prospective cohort study

BackgroundBoth elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia.MethodsAge-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study).ResultsDuring a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident T2D in the entire cohort and across all age subgroups. Both CumAIP and CumCRP were jointly associated with an increased risk of diabetes (P-interaction = 0.0126). Compared to CumAIP < -0.0699 and CumCRP < 1 mg/L, co-exposure to CumAIP ≥ − 0.0699 and CumCRP ≥ 3 mg/L had a significant hazard ratio (HR) [2.55 (2.23–2.92)] after adjusting for socio-demographic, life-style factors, family history of diabetes, blood pressure, renal function and medication use. The co-exposure-associated risks varied greatly by age distribution (P-interaction = 0.0193): < 40 years, 6.26 (3.47–11.28); 40–49 years, 2.26 (1.77–2.89); 50–59 years, 2.51 (2.00–3.16); 60–69 years, 2.48 (1.86–3.30); ≥ 70 years, 2.10 (1.29–3.40). In young adults (< 45 years), both exposures had a significant supra-additive effect on diabetogenesis (relative excess risk due to interaction: 0.80, 95% CI 0.10–1.50).ConclusionsThese findings highlight the need for age-specific combined assessment and management of chronic inflammation and dyslipidemia in primary prevention against T2D, particularly for young adults. The clinical benefit derived from dual-target intervention against dyslipidemia and inflammation will exceed the sum of each part alone in young adults.

Associations of Clinical Risk Factors and Novel Biomarkers With Age at Onset of Type 2 Diabetes.

Younger onset of type 2 diabetes (T2D) was associated with higher risks of vascular complications and mortality. To prospectively assess risk profiles for incident T2D stratified by age at onset. A total of 471 269 participants free of T2D at baseline were included from the UK Biobank. Approximately 70 clinical, lipid, lipoprotein, inflammatory, and metabolic markers, and genetic risk scores (GRSs) were analyzed. Stratified Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) for T2D with age of diagnosis divided into 4 groups (≤50.0, 50.1-60.0, 60.1-70.0, and >70.0 years). During 11 years of follow-up, 15 805 incident T2D were identified. Among clinical risk factors, obesity had the highest HR at any age, ranging from 13.16 (95% CI, 9.67-17.91) for 50.0 years and younger to 4.13 (3.78-4.51) for older than 70.0 years. Other risks associated with T2D onset at age 50.0 years and younger included dyslipidemia (3.50, 2.91-4.20), hypertension (3.21, 2.71-3.80), cardiovascular disease (2.87, 2.13-3.87), parental history of diabetes (2.42, 2.04-2.86), education lower than college (1.89, 1.57-2.27), physical inactivity (1.73, 1.43-2.10), smoking (1.38, 1.13-1.68), several lipoprotein particles, inflammatory markers, liver enzymes, fatty acids, amino acids, as well as GRS. Associations of most risk factors and biomarkers were markedly attenuated with increasing age at onset (P interaction <.05), and some were not significant for onset at age older than 70.0 years, such as smoking, systolic blood pressure, and apolipoprotein B. Most risk factors or biomarkers had stronger relative risks for T2D at younger ages, which emphasizes the necessity of promoting primary prevention among younger individuals. Moreover, obesity should be prioritized.

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.

Association between dietary carbohydrate intake and risk of type 2 diabetes: a systematic review and meta-analysis of cohort studies.

Previous meta-analyses have assessed the relationship between carbohydrate intake and type 2 diabetes (T2D) risk; however, they included few studies of Asian populations who have a higher carbohydrate intake and lower insulin secretory capacity than non-Asians. Since the publication of the previous meta-analyses, three further studies of Asian populations have been conducted. Based on this background, the present study aimed to perform an updated systematically examine observational studies concerning the link between dietary carbohydrate intake and T2D risk. We conducted a systematic search for cohort studies that investigated the target association. For each analyzed study, parameter-adjusted risk ratios were used to compare the lowest and highest carbohydrate-intake groups in terms of their risk of incident T2D. The risk ratios were calculated using a random-effects model. Ten publications were analyzed. Overall, carbohydrate intake was found not to be associated with increased risk ratios of incident T2D (risk ratio [RR] = 1.07; 95% confidence interval [95% CI] = 0.94, 1.21; P < 0.01, I2 = 61.9%). However, studies of Asian populations reported that high carbohydrate intake is significantly associated with this risk (RR = 1.29; 95% CI 1.15, 1.45; P = 0.59, I2 = 0.0%). This updated meta-analysis showed that, overall, carbohydrate intake is not associated with the risk of T2D; nevertheless, a significant association exists among Asian populations. To confirm the association between dietary carbohydrate intake and T2D risk observed in this study, further evidence from long-term observational studies of Asian populations is required. The online version contains supplementary material available at 10.1007/s13340-023-00642-0.

Risk Factors for Type 2 Diabetes in the Multiethnic Cohort

ObjectivesIn this report, we investigated the association between established risk factors and type 2 diabetes (T2D) across 5 distinct ethnic groups and explored differences according to T2D definition within the Multiethnic Cohort (MEC) Study. MethodsUsing the full MEC, with participants in Hawaii and Los Angeles (N=172,230), we applied Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All participants completed questionnaires asking about demographics, anthropometrics, lifestyle factors, and regular diet. T2D status was determined from self-reported diagnosis/medication and Medicare claims. We assessed the associations between well-established risk factors and T2D in the full cohort, after stratification by ethnic group, according to the T2D definition, and in a biorepository subset. Effect modification by ethnicity was evaluated using Wald’s tests. ResultsOverall, 46,500 (27%) participants had an incident T2D diagnosis after a mean follow-up of 17.1±6.9 years. All predictors were significantly associated with T2D: overweight (HR=1.74), obesity (HR=2.90), red meat intake (HR=1.15), short (HR=1.04) and long (HR=1.08) sleep duration, and smoking (HR=1.26) predicted a significantly higher T2D incidence, whereas coffee (HR=0.90) and alcohol (HR=0.78) consumption, physical activity (HR=0.89), and diet quality (HR=0.96) were associated with lower T2D incidence. The strength of these associations was similar across ethnic groups with noteworthy disparities for overweight/obesity, physical activity, alcohol intake, coffee consumption, and diet quality. ConclusionsThese findings confirm the importance of known risk factors for T2D across ethnic groups, but small differences were detected that may contribute to disparate incidence rates in some ethnic groups, especially for obesity and physical activity.

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.

Type 2 Diabetes and Its Association With Psychiatric Disorders in Young Adults in South Korea

Because type 2 diabetes (T2D) has become increasingly prevalent among young adults, the study of the association of T2D with psychiatric disorders in young adults is important for early detection and timely intervention. To determine whether a diagnosis of a psychiatric disorder is associated with increased risk of developing T2D in young adults. This large-scale prospective cohort study used data collected by the South Korean National Health Insurance Service between 2009 and 2012, representing 97% of the South Korean population. Young adults aged 20 to 39 years with and without diagnoses of psychiatric disorders were included in the study. Young adults with missing data and those with a history of T2D were excluded from the study. The cohort was followed up to monitor development of T2D until December 2018. Data were analyzed from March 2021 to February 2022. Diagnosis of 1 of 5 psychiatric disorders, including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder. The primary outcome was newly diagnosed T2D during a follow-up period of 7.59 years. The incidence rate of T2D was calculated as the number of new cases per 1000 person-years during the follow-up period. The Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% CIs for T2D incidence. Exploratory analyses were performed for subgroups stratified by age and sex. In total, 6 457 991 young adults (mean [SD] age, 30.74 [4.98] years; 3 821 858 men [59.18%]) were followed up, including 658 430 individuals with psychiatric disorders. The cumulative incidence of T2D differed significantly between individuals with and without psychiatric disorders (log-rank test, P < .001). Incidence rates of T2D for individuals with and without psychiatric disorders were 2.89 and 2.56 per 1000 person-years, respectively. Individuals with a diagnosis of any psychiatric disorder showed a higher risk of developing T2D than those without a diagnosis (adjusted HR, 1.20; 95% CI, 1.17-1.22). The adjusted HRs for T2D were 2.04 (95% CI, 1.83-2.28) for individuals with schizophrenia, 1.91 (95% CI, 1.73-2.12) for individuals with bipolar disorder, 1.24 (95% CI, 1.20-1.28) for individuals with depressive disorder, 1.13 (95% CI, 1.11-1.16) for individuals with anxiety disorder, and 1.31 (95% CI, 1.27-1.35) for individuals with sleep disorder. In this large-scale prospective cohort study of young adults, 5 psychiatric disorders were significantly associated with an increased risk of developing T2D. Young adults with schizophrenia and bipolar disorder in particular were at a higher risk of T2D. These results have important implications for early detection of and timely intervention in T2D for young adults with psychiatric disorders.

1376-P: Dietary Sodium Intake and Risk of Incident Type 2 Diabetes

Background: Type 2 Diabetes (T2D) and hypertension often coexist and share many common risk factors. High dietary sodium intake is a well-established risk factor for hypertension, whereas few studies have assessed the relation between dietary sodium intake and type 2 diabetes (T2D). In this study, we aimed to 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. Methods: A total of 402,982 participants from UK biobank, 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. Cox proportional hazards models were used to estimate the association between the frequency of adding salt to foods and incident T2D. Results: During a median of 11.8 years of follow-up, 13,120 incident T2D were documented. Compared with participants who Never/Rarely added salt to foods, the adjusted Hazard Ratios (95% confidence interval) were 1.13 (1.08, 1.17), 1.20 (1.14, 1.26), and 1.39 (1.30, 1.49) across the groups of Sometimes, Usually, and Always, respectively (P-trend&amp;lt;0.001). 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 (BMI), waist to hip ratio, and C-reactive protein, with a significant mediation effect of 32.9%, 36.6% and 7.0%, respectively. The significant mediation effect of BMI was largely driven by the body fat mass rather than the body fat-free mass. Conclusions: Our 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. Disclosure X.Wang: None. H.Ma: None. R.Tang: None. Q.Xue: None. X.Li: None. Y.Heianza: None. L.Qi: None.

1418-P: Identification and Follow-up of T2D by Subtypes and Their Cardiovascular Risk in Mexican Population—The Experience of the MIDO State Registry in Guanajuato

Type 2 diabetes (T2D) is a complex and heterogeneous disease that has been categorized based on its underlying physiological mechanisms to inform treatment strategies. However, patients with T2D often exhibit a wide range of phenotypic and metabolic profiles, and the subclassification of this disease has only recently been developed, enabling the possibility of personalized management and improved outcomes. The aim of this research was to identify and follow-up T2D subtypes and their cardiovascular risk (CVR) in the Mexican population. In this study, 14,124 patients with incident T2D were assessed to characterize their phenotypic and metabolic profiles and to identify their CVR as part of the MIDO State Registry in Guanajuato, Mexico between April 2014, and April 2022. Of the 14,124 patients with incident T2D, when clustered into subtypes according to their phenotypic and metabolic profile, 3,530 (24.9%) belonged to the mild age-related diabetes (MARD) subtype, 4,304 (30.5%) to the mild obesity-related diabetes (MOD), 3,180 (22.1%) to the severe autoimmune diabetes (SIRD), and 3,111 (11.5%) to the severe insulin-resistant diabetes (SIDD). When the CVR was assessed, 1,767 (50.1%) individuals had a medium CVR and 1,763 (49.9%) had a high CVR in the MARD, 3,313 (76.9%) had a medium CVR and 990 (23.1%) had a high CVR in the MOD, 1,699 (54.6%) had a medium CVR and 1,733 (45.4%) had a high CVR in the SIRD, and 2,290 (72.0%) had a medium CVR and 890 (27.9%) had a high CVR in the SIDD. Of the 13,192 patients that were followed for 6 months, up to 61.0% of the MARD, 61.4% of the MOD, 61.2% of the SIRD, and 40.9% of the SIDD achieved metabolic control (HbA1c &amp;lt;7%). Classifying the subtypes of T2D allows for the design of personalized treatment strategies aiming to delay the progression of the disease and prevent cardiovascular complications. In Mexico, this is a novel approach that seeks to improve the overall outcomes of patients with incident T2D. Disclosure H.Gallardo-rincón: None. R.Tapia-conyer: None. A.Montoya: None. L.Morales-juarez: None. M.J.Rios-blancas: None. D.Álvarez-hernández: None. L.Martinez-juarez: None. D.Diaz-martínez: None. F.Magos-vazquez: None. E.Vargas: None.

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)

1421-P: Ten-Year Trend in Socioeconomic Inequalities in the Prevalence and Incidence of Pharmacologically Treated Type 2 Diabetes in France—2010–2020

The aim was to describe the association between socio-economic inequalities (SEI) and the prevalence/incidence of pharmacologically-treated type 2 diabetes (T2D) in France over the 2010-2020 period. Diabetes cases were identified using a validated algorithm in the French national health data system. Analyses were restricted to adults ≥45 years to focus on T2D. SEI were measured, each year, via the French Deprivation index (FDep, by population quintiles; Q1: corresponding to the less deprived municipalities) for metropolitan France. The relative risks (RR) of being T2D (prevalence) and developing T2D (incidence) in Q2, Q3, Q4 and Q5 were estimated by sex over the period via Poisson regression. Denominators were the French health consumers (from 24,228,526 in 2010 to 29,772,928 in 2020) for prevalence and the at risk population for incidence. A positive gradient was observed in the RR of T2D prevalence and incidence by FDep quintiles in all years. The influence of SEI (reference Q1) on T2D prevalence increased over the period for men in Q2, Q3, Q4 and Q5, and for women in Q3, Q4 and Q5; and on T2D incidence for men in Q4 and Q5. To conclude, SEI were positively associated with the prevalence/incidence of pharmacologically-treated T2D in metropolitan France. Further, the association increased over last decade for prevalence, and only in most deprived men for incidence. Disclosure M.Guion: None. L.Mandereau-bruno: None. S.Goria: None. S.Fosse-edorh: None. E.Cosson: Board Member; Abbott, Medtronic. Funding Fondation de France (00107045)

188-OR: Circulating Metabolites and Type 2 Diabetes (T2D) Risk—An Integrated Metabolomics and Genetics Study of ~23,000 Adults

Metabolome captures complex states of metabolic homeostasis affected by genetic and environmental factors. A systematic understanding of metabolites associated with T2D risk may offer potentials for personalized risk monitoring and prevention. Here, we integrated data for 467 harmonized circulating metabolites, genetics, and diet/lifestyle factors in up to 23,616 racially diverse individuals from 10 cohorts with up to 26-y of follow-up. Through multivariable-adjusted metabolome-wide association analyses, we identified 235 metabolites associated with incident T2D (4,000 incident cases; FDR&amp;lt;0.05). Genetic determinants of these metabolites were mapped to genes implicated in pathways of nutrient/energy metabolism and glucose/lipid dysregulation (pathway enrichment FDR&amp;lt;0.05) and highly expressed in T2D-relevent tissues e.g., liver, adipose tissues, pancreas, and muscles (tissue-specific expression enrichment FDR&amp;lt;0.05). Mendelian randomization analyses further corroborated potential causal associations between 93 of the 235 metabolites and T2D. These included previously known (e.g., valine and isoleucine) and novel associations (e.g., α-ketoisocaproate in leucine metabolism, N-acetylaspartate in glutamate metabolism, and odd-chain fatty acid heptadecanoate). Furthermore, we analyzed metabolome-wide associations with 18 mutually adjusted modifiable risk factors. Several factors e.g., physical activity and whole grain (WG) intake, explained higher proportions of inter-individual variation of T2D-associated vs. other metabolites. We identified specific metabolites as potential mediators linking each risk factor to T2D (e.g., 4 metabolites mediated 22% of the WG-T2D association). In conclusion, we found known and novel metabolites associated with T2D risk, indicating potential biological pathways through which genetic and lifestyle factors contribute to T2D. Our findings may inform future personalized T2D prevention. Disclosure J.Li: None. J.Dupuis: None. E.Selvin: None. S.Bhupathiraju: None. J.A.Brody: None. Y.Liu: None. A.Eliassen: None. J.E.Manson: None. C.B.Clish: None. R.N.Lemaitre: None. K.L.Tucker: None. J.Hu: None. J.I.Rotter: None. M.A.Martinez-gonzalez: None. K.M.Rexrode: None. J.B.Meigs: Consultant; Quest Diagnostics. E.Boerwinkle: None. R.Kaplan: None. F.Hu: None. B.Yu: None. Q.Qi: None. N.The nhlbi topmed metabolomics and proteomics worki: n/a. L.Liang: None. M.Guasch: None. J.Merino: None. M.Ruiz-canela: None. K.Luo: None. C.Rebholz: None. B.Porneala: None. Funding National Institutes of Health (R00DK122128 to J.L.)