Risk Of Type 2 Diabetes Mellitus Research Articles

Association of plasma vitamin A level with type 2 diabetes mellitus: a community aging population-based cross-sectional study

Recent studies indicated that vitamin A (VA) might be involved in the pathology of type 2 diabetes mellitus (T2DM). This cross-sectional study was conducted to explore the association between circulating VA level and T2DM. A total of 1 818 subjects aged 50 years old and above were recruited from the community. Binomial logistic regression and restricted cubic spline (RCS) were applied to analyze the association of plasma VA level with the risk of T2DM. Serum VA and lipid-adjusted VA levels of T2DM patients were significantly higher than that of non-T2DM subjects (P < 0.05). The ratios of plasma VA/total cholesterol (TC), VA/high-density lipoprotein cholesterol (HDL-c) and VA/low-density lipoprotein cholesterol (LDL-c) were positively associated with the risk of T2DM in the aging population (P < 0.05). Compared with the Q1 level, subjects with Q2 to Q3 levels of plasma VA/triglyceride (TG) have decreased risk of T2DM (odds ratio (OR)Q2 = 0.68, PQ2 = 0.021; ORQ3 = 0.59, PQ3 < 0.01). Our results indicated that the imbalance of circulating lipids and VA might affect the relationship between VA and T2DM. The middle and aging subjects with higher ratios of plasma VA/TC, VA/HDL-c, and VA/LDL-c displayed increased risk for T2DM, but the moderate ratio of VA/TG might protect against risk of T2DM.

Risk of diabetes mellitus based on the interactive association between G6PD rs72554664 polymorphism and sex in Taiwan Biobank individuals

The presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may increase the risk of type 2 diabetes mellitus (T2DM), with differing prevalence between males and females. Although G6PD deficiency is an X-linked genetic condition, its interaction with sex regarding T2DM risk among the Taiwanese population has not been fully explored. This study aimed to investigate the association between G6PD deficiency and T2DM risk in the Taiwanese population, focusing on the potential influence of sex. Data were obtained from the Taiwan Biobank (TWB) database, involving 85,334 participants aged 30 to 70 years. We used multiple logistic regression analysis to assess the interaction between G6PD rs72554664 and sex in relation to T2DM risk. The T2DM cohort comprised 55.35% females and 44.65% males (p < 0.001). The TC + TT genotype of rs72554664 was associated with an increased risk of T2DM, with an odds ratio (OR) of 1.95 (95% CI: 1.39–2.75), and males showed an OR of 1.31 (95% CI: 1.19–1.44). Notably, the G6PD rs72554664-T allelic variant in hemizygous males significantly elevated the T2DM risk (OR), 4.57; p < 0.001) compared to females with the CC genotype. Our findings suggest that the G6PD rs72554664 variant, in conjunction with sex, significantly affects T2DM risk, particularly increasing susceptibility in males. The association of the G6PD rs72554664-T allelic variant with a higher risk of T2DM highlights the importance of sex-specific mechanisms in the interplay between G6PD deficiency and T2DM.

Metabolic Score for Insulin Resistance and New-Onset Type 2 Diabetes in a Middle-Aged and Older Adult Population: Nationwide Prospective Cohort Study and Implications for Primary Care.

The metabolic score for insulin resistance (METS-IR) has emerged as a noninsulin-based index for the approximation of insulin resistance (IR), yet longitudinal evidence supporting the utility of METS-IR in the primary prevention of type 2 diabetes mellitus (T2DM) remains limited. We aimed to investigate the longitudinal association between METS-IR, which combines fasting plasma glucose (FPG), lipid profiles, and anthropometrics that can be routinely obtained in resource-limited primary care settings, and the incidence of new-onset T2DM. We conducted a closed-cohort analysis of a nationwide, prospective cohort of 7583 Chinese middle-aged and older adults who were free of T2DM at baseline, sampled from 28 out of 31 provinces in China. We examined the characteristics of participants stratified by elevated blood pressure (BP) at baseline and new-onset T2DM at follow-up. We performed Cox proportional hazard regression analysis to explore associations of baseline METS-IR with incident T2DM in participants overall and in participants stratified by baseline BP. We also applied net reclassification improvement and integrated discrimination improvement to examine the incremental value of METS-IR. During a mean follow-up period of 6.3 years, T2DM occurred in 527 participants, among which two-thirds (332/527, 62.9%; 95% CI 58.7%-67.1%) had baseline FPG<110 mg/dL. A SD unit increase in baseline METS-IR was associated with the first incidence of T2DM (adjusted hazard ratio [aHR] 1.33, 95% CI 1.22-1.45; P<.001) in all participants. We obtained similar results in participants with normal baseline BP (aHR 1.41, 95% CI 1.22-1.62; P<.001) and elevated baseline BP (aHR 1.29, 95% CI 1.16-1.44; P<.001). The predictive capability for incident T2DM was improved by adding METS-IR to FPG. In study participants with new-onset T2DM whose baseline FPG was <126 mg/dL and <110 mg/dL, 62.9% (332/527; 95% CI 60%-65.9%) and 58.1% (193/332; 95% CI 54.3%-61.9%) of participants had baseline METS-IR above the cutoff values, respectively. METS-IR was significantly associated with new-onset T2DM, regardless of baseline BP level. Regular monitoring of METS-IR on top of routine blood glucose in clinical practice may add to the ability to enhance the early identification of primary care populations at risk for T2DM.

Risk of Cardiovascular Complications Among Type 2 Diabetes Mellitus Patients with GSTP1 Genetic Polymorphism: A Nested Case-Control Study and Docking Studies.

The genetic alteration in the antioxidant gene Glutathione-S-Transferases Pi 1 (GSTP1) namely GSTP1*IIe105Val (rs1695) and GSTP1*Ala114Val (rs1138272) changes the individual susceptibility to cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) by altering the substrate binding and catalytic activity. This study aims to investigate the association of GSTP1 rs1695 and rs1138272 polymorphism with CVD development in T2DM patients. Genotyping was performed with 400 study participants-group I: control; group II: T2DM; group III: CVD; and group IV: T2DM/CVD [n = 100 each] by PCR-RFLP. The rs1695 and rs1138272 polymorphism were docked against NPACT and NUBBE database and virtually screened using glide. The study reported that rs1695 polymorphism was associated with T2DM risk under dominant and allelic genetic models [OR = 1.97(1.08-3.59) p = 0.02 and OR = 1.79(1.20-2.66) p = 0.003, respectively]. The val/val genotype, dominant, recessive model, and T allelic genetic model were associated with increased CVD risk [OR = 4.15(1.97-8.73) p = < 0.01; OR = 3.16(1.65-6.04) p = < 0.01; OR = 3.47(1.91-6.31) p = < 0.01; and OR = 2.94(1.95-4.43) p = < 0.01, respectively]. In contrast, rs1695 polymorphism was not associated with CVD development among patients with T2DM. In rs1138272, the wild genotype was only detected and neither heterozygous nor val/val genotype was observed. The docking analysis revealed that the Ile105Val mutation plays a significant role in altering the GSTP1 capacity compared to the Ala115Val mutation. This suggests that the Ile105Val mutation has a greater impact on the protein's structure, function, or susceptibility to diseases compared to the Ala115Val mutation. In summary, genetic alteration in GSTP1 rs1695 potentially contributes to an increased risk of T2DM and CVD.

Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study.

Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM. We linked 659 906 individuals born in Denmark 1990-2000 to their parents, grandparents, and aunts/uncles using population-based registers. We compared rates of T2DM in relatives of children with and without a diagnosis of any or one of 11 specific psychiatric disorders, including neuropsychiatric and neurodevelopmental disorders, using Cox regression. In a genotyped sample (iPSYCH2015) of individuals born 1981-2008 (n = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders. Among 5 235 300 relative pairs, relatives of individuals with a psychiatric disorder had an increased risk for T2DM with stronger associations for closer relatives (parents:hazard ratio = 1.38, 95% confidence interval 1.35-1.42; grandparents: 1.14, 1.13-1.15; and aunts/uncles: 1.19, 1.16-1.22). In the genetic sample, one standard deviation increase in T2DM-PRS was associated with an increased risk for any psychiatric disorder (odds ratio = 1.11, 1.08-1.14). Both familial T2DM and T2DM-PRS were significantly associated with seven of 11 psychiatric disorders, most strongly with attention-deficit/hyperactivity disorder and conduct disorder, and inversely with anorexia nervosa. Our findings of familial co-aggregation and higher T2DM polygenic liability associated with psychiatric disorders point toward shared familial risk. This suggests that part of the comorbidity is explained by shared familial risks. The underlying mechanisms still remain largely unknown and the contributions of genetics and environment need further investigation.

A positive correlation of serum SFRP1 levels with the risk of developing type 2 diabetes mellitus: a case-control study.

Secreted frizzled-related protein 1 (SFRP1) is an adipokine whose production is significantly altered in metabolic disorders. Considering the relationship between dysfunction of Wnt/β-catenin signaling and metabolic disorders as well as the inhibitory effects of SFRP1 on this signaling pathway, the present work aimed to investigate the correlation between serum SFRP1 levels and type 2 diabetes mellitus (T2DM) and its developing risk factors for the first time. This case-control study measured serum levels of SFRP1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, adiponectin, and fasting insulin using enzyme-linked immunosorbent assay kits in 80 T2DM patients and 80 healthy individuals. Biochemical parameters were determined using the AutoAnalyzer instrument. The T2DM group had higher levels of SFRP1 compared with the controls (146.8100±43.61416 vs 81.9531±32.78545 pg/mL; P<.001). There was a positive correlation between SFRP1 and insulin (r=0.327, P=.003), TNF-α (r=0.420, P<.001) as well as homeostatic model assessment for insulin resistance (r=0.328, P=.003) in the T2DM group. In addition, 10-unit changes in SFRP1 levels showed the risk of T2DM in both the unadjusted (odds ratio [OR] [95% CI]=1.564 [1.359-1.800]) and adjusted models accounting for age, gender, and body mass index (OR [95% CI]=1.564 [1.361-1.799]; P<.001). A cut-off value of SFRP1 (105.83 pg/mL) was identified to distinguish between the T2DM patients and the healthy subjects, with sensitivity of 75.0% and specificity of 80.0%. According to our research, there was a significant and positive link between the amount of SFRP1 and the likelihood of developing T2DM as well as the related factors like insulin resistance index and TNF-α. These results indicated that SFRP1 might have a potential role in the development of T2DM.

The Association Between Overall, Healthy, and Unhealthy Plant-Based Diet Index and Risk of Prediabetes and Type 2 Diabetes Mellitus: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

The global incidence of prediabetes and type 2 diabetes mellitus (T2DM) has increased substantially in recent years. Among the established, modifiable lifestyle factors associated with favorable prediabetes and T2DM risk, healthy dietary patterns have attracted considerable attention. The association between adherence to plant-based dietary pattern indices (PDIs), including the overall PDI (O-PDI), healthy PDI (H-PDI), and unhealthy PDI (U-PDI), and the risk of prediabetes and T2DM was investigated in this study. A literature search was conducted of the PubMed/Medline, Scopus, and Web of Sciences databases from their inception to February 2024. A systematic review and meta-analysis were conducted using random effects models and dose-response analyses. The Cochran Q test and the I2 statistic were used to evaluate heterogeneity between studies. A total of 16 publications, with data on a total of 721 012 participants, were identified for the meta-analysis. According to a pooled analysis, compared with the lowest category of O-PDI and H-PDI adherence, the highest category was associated with a 14% and 19% reduction in T2DM risk, respectively, for O-PDI (effect size [ES] = 0.86; 95%CI, 0.82-0.90; I2 = 57.7) and H-PDI (ES = 0.81; 95%CI, 0.75-0.88; I2 = 82.6). Greater adherence to U-PDI was significantly associated with an 10% increase in the risk of T2DM (ES = 1.10; 95%CI, 1.04-1.16). Consistent associations were found within the predetermined subgroups. As well, there was a nonlinear inverse association between O-PDI, H-PDI, and T2DM risk. No significant association was found between adherence to O-PDI (ES = 0.87; 95%CI, 0.75-1.01; I2 = 68%), H-PDI (ES = 0.99; 95%CI, 0.87-1.13; I2 = 0.0%), and U-PDI (ES = 1.09; 95%CI, 0.94-1.21; I2 = 22.9%) and risk of prediabetes. These findings underscore the importance of dietary selections within the framework of a plant-based dietary pattern, particularly when incorporating healthful, plant-based foods, which may have potential benefits in reducing the T2DM risk. PROSPERO registration no. CRD42023459851.

Association between two novel anthropometric measures and type 2 diabetes in a Chinese population.

To investigate the associations of conicity index (C-index) and relative fat mass (RFM) with incident type 2 diabetes mellitus (T2DM) among adults in China. A total of 10 813 participants aged over 18 years in Shenzhen Longhua district were enrolled in a follow-up study conducted from 2018 to 2022. The participants were categorized based on quartiles (Q) of C-index and RFM. The Cox proportional hazards model was performed to examine the relationships between C-index, RFM and the risk of T2DM. After adjusting for potential confounding factors, including age, sex, occupation, marital status, education level, smoking status, alcohol consumption, physical exercise, hypertension status, fasting blood glucose (FBG) and total cholesterol (TC), both C-index and RFM showed positive and independent associations with risk of T2DM. The multivariable-adjusted hazard ratios (95% confidence intervals) for T2DM risk in participants in C-index Q3 and Q4 compared with those in C-index Q1 were 1.50 (1.12, 2.02) and 1.73 (1.29, 2.30), and 1.94 (1.44, 2.63), 3.18 (1.79, 5.64), 4.91 (2.68, 9.00) for participants in RFM Q2, Q3 and Q4 compared with RFM Q1. These differences were statistically significant (all p < 0.05). C-index and RFM are strongly associated with new-onset T2DM and could be used to identify the risk of diabetes in large-scale epidemiological studies.

Association of ADIPOQ Gene Polymorphisms with Type 2 Diabetes and Obesity Risk in the Kazakh Population: A Case-Control and Population-Based Study.

Type 2 diabetes mellitus (T2DM) is a socially significant disease with increasing prevalence worldwide. It is characterized by heterogeneous metabolic disorders and is associated with various risk factors, including BMI, abnormal lipid levels, hypertension, smoking, dietary preferences, physical inactivity, sedentary lifestyle, family history of diabetes, prediabetes or gestational diabetes, inflammation, intrauterine environment, age, sex, ethnicity, and socioeconomic status. Assessing the genetic risk of developing T2DM in specific populations remains relevant. The ADIPOQ gene, encoding adiponectin, is directly related to the risk of developing T2DM, obesity, and cardiovascular diseases. Our study demonstrated significant associations of ADIPOQ gene polymorphisms with the risk of developing T2DM and obesity, as well as with fasting glucose levels and BMI, in the Kazakh population. Specifically, rs266729 was significantly associated with T2DM and obesity in the Kazakh population, while other studied polymorphisms (rs1501299, rs2241766, and rs17846866) did not show a significant association. These findings suggest that ADIPOQ gene polymorphisms may influence T2DM risk factors and highlight the importance of genetic factors in T2DM development. However, further research in larger cohorts is needed to confirm these associations.

Dietary Modulations in Preventing Cardiometabolic Risk in Individuals with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a complex health issue include obesity, high cholesterol, high blood pressure, and chronic inflammation that increase the risk of cardiovascular diseases (CVDs). CVDs are of great concern in the disease progression and prognosis of T2DM. This review is a comprehensive examination of the literature on the relationship between T2DM and cardiovascular risk, nutrition-related cardiometabolic risk (CMR) factors, and impact of dietary modulations on CMR. In recent years the researches has been focus on the importance of a comprehensive treatment approach like dietary modulations to address multiple cardiovascular risk reductions, including hypertension and dyslipidemia. Modulation of dietary patterns are the most promising interventions to prevent CMR factors and T2DM via affecting the body weight, glucose control, and microbial diversity of individuals. Current evidence suggests that high-quality dietary patterns such as the Dietary Approaches to Stop Hypertension (DASH) eating plan and the Mediterranean diet is important in the metabolic control processes of T2DM with anti-inflammatory and antioxidant compounds, glucagon-like peptide agonist compounds, and intestinal microbiota changes. Nutrition plays a critical role in preventing and improving CVD outcomes in patients with T2DM. Dietary modulations should be planned considering individual differences in responses to dietary composition and nutritional changes, personal preferences, eating behaviors and gut microbiota differences.

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients.

The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM. To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM. A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers. Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients. This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.

Analysis of the risk of diabetes mellitus type 2 in women workers at a reference hospital in Asuncion, Paraguay

Introduction: Obesity, age, sedentary lifestyle, and family history of diabetes mellitus are risk factors for type 2 diabetes mellitus (T2DM). Objective: determine the probable risk of developing T2DM in the next 10 years in working women at a reference hospital in Asunción, Paraguay. Methodology: This cross-sectional observational descriptive study was conducted with physicians, nurses, and administrative staff. Data were collected over three months using the FINDRISK test to assess diabetes risk, which consists of eight questions about age, body mass index, waist circumference, physical activity, fruit and vegetable consumption, history of blood pressure, high blood pressure and high glucose, and diabetes diagnosed in family members. Descriptive statistics in the form of frequencies and percentages, as well as analytical statistics using the Mann-Whitney and Kruskal-Wallis tests, were used to analyze the data. Results: A total of 112 women participated in the study, with more than 40% in the age range of 31–40 years. The waist circumference of 80-88 cm was the most common (38.4%). It was found that 33% of participants were overweight. Almost 60% of the participants did not perform daily physical activities. More than 38% of the first-degree relatives had a history of diabetes. Of the surveyed participants, 67.9%had some risk of developing T2DM in the next 10 years and 22 had a high or very high risk according to the FINDRISK test. Participants aged 35 years had a significantly higher risk (p=0.008). Conclusion: A high prevalence of overweight and obesity was observed, with 67.9% of the respondents showing some degree of risk for developing T2DM in the next 10 years, of which nearly 20% were categorized as high or very high risk.

Untargeted lipidomics analysis in women with morbid obesity and type 2 diabetes mellitus: A comprehensive study.

There is a phenotype of obese individuals termed metabolically healthy obese that present a reduced cardiometabolic risk. This phenotype offers a valuable model for investigating the mechanisms connecting obesity and metabolic alterations such as Type 2 Diabetes Mellitus (T2DM). Previously, in an untargeted metabolomics analysis in a cohort of morbidly obese women, we observed a different lipid metabolite pattern between metabolically healthy morbid obese individuals and those with associated T2DM. To validate these findings, we have performed a complementary study of lipidomics. In this study, we assessed a liquid chromatography coupled to a mass spectrometer untargeted lipidomic analysis on serum samples from 209 women, 73 normal-weight women (control group) and 136 morbid obese women. From those, 65 metabolically healthy morbid obese and 71 with associated T2DM. In this work, we find elevated levels of ceramides, sphingomyelins, diacyl and triacylglycerols, fatty acids, and phosphoethanolamines in morbid obese vs normal weight. Conversely, decreased levels of acylcarnitines, bile acids, lyso-phosphatidylcholines, phosphatidylcholines (PC), phosphatidylinositols, and phosphoethanolamine PE (O-38:4) were noted. Furthermore, comparing morbid obese women with T2DM vs metabolically healthy MO, a distinct lipid profile emerged, featuring increased levels of metabolites: deoxycholic acid, diacylglycerol DG (36:2), triacylglycerols, phosphatidylcholines, phosphoethanolamines, phosphatidylinositols, and lyso-phosphatidylinositol LPI (16:0). To conclude, analysing both comparatives, we observed decreased levels of deoxycholic acid, PC (34:3), and PE (O-38:4) in morbid obese women vs normal-weight. Conversely, we found elevated levels of these lipids in morbid obese women with T2DM vs metabolically healthy MO. These profiles of metabolites could be explored for the research as potential markers of metabolic risk of T2DM in morbid obese women.

Metformin-Insulin Combination Therapy Ameliorates Hyperglycemia in a COVID-19 Type-1 Diabetic Child with Insulin Resistance: A Case Report

Introduction: Recent studies have indicated that COVID-19 may be linked with type 1 diabetes mellitus (T1DM) in children. It has been observed that not only is there a potential risk of new-onset pediatric T1DM associated with COVID-19, but numerous cases also present with insulin resistance, necessitating prompt management. Case Presentation: We report the case of a 9-year-old girl with a history of T1DM who was admitted with hyperglycemia (blood sugar &gt; 750 mg/dL) and subsequently diagnosed with COVID-19. The co-administration of metformin and intravenous insulin successfully resolved subcutaneous insulin resistance, allowing the patient to be discharged in good health. Conclusions: Insulin resistance is a recognized complication of SARS-CoV-2 infection, and metformin combined with intravenous insulin has proven effective in managing hyperglycemia and improving insulin resistance in this context. Further research is necessary to elucidate the underlying mechanisms and develop optimal therapeutic strategies.

Association between ideal cardiovascular health and abnormal glucose metabolism in the elderly: evidence based on real-world data

BackgroundLimited information is available on the effect of ideal cardiovascular health (CVH) and abnormal glucose metabolism in elderly people. We aimed to analyze the prevalence of CVH behaviors, abnormal glucose metabolism, and their correlation in 65 and older people.MethodsIn this study, randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used. Recruiting was carried out between January 2020 and December 2020, and 1984 participants aged 65 years or older completed the study.ResultsThe prevalence of abnormal glucose metabolism in this group was 26.7% (n = 529), among which the prevalence of impaired fasting glucose (IFG) was 9.5% (male vs. female: 8.7% vs 10.1%, P = 0.338), and the prevalence of type 2 diabetes mellitus (T2DM) was 19.0% (male vs. female: 17.8 vs. 19.8%, P = 0.256). The ideal CVH rate (number of ideal CVH metrics ≥ 5) was only 21.0%. The risk of IFG and T2DM decreased by 23% and 20% with each increase in one ideal CVH metrics, with OR (95%CI) of 0.77(0.65–0.92) and 0.80(0.71–0.90), respectively (P-trend < 0.001). TyG fully mediated the ideal CVH and the incidence of T2DM, and its mediating effect OR (95%CI) was 0.88(0.84–0.91).ConclusionsEach increase in an ideal CVH measure may effectively reduce the risk of abnormal glucose metabolism by more than 20%.

Additive Interaction Between Insulin Resistance, Chronic Low-Grade Inflammation and Vitamin D Deficiency on the Risk of Type 2 Diabetes Mellitus: A Cohort Study

Objectives The aim of this study was to explore, on an additive scale, the combined effect of the association between insulin resistance (IR), chronic low-grade inflammation (CLGI) and vitamin D deficiency (VDD) on the risk of type 2 Diabetes Mellitus (T2DM). Methods This is a cohort study, including 1484 non-diabetic subjects, followed for a period of four years. 25 hydroxy-vitamin D (25OHD), hypersensitive C-reactive protein (HsCRP) and triglyceride-glucose index were assessed. Based on VDD and CLGI, the population was subdivided into 4 exposure groups. Analysis was performed both in the case of IR and without IR. Cox proportional regression and additive interaction were applied to explore cumulative effects of exposure. Results At follow-up, 162 newly diagnosed cases of T2DM were identified. TYG index (RR = 4.0[2.8–5.6]), HsCRP (RR = 1.6 [1.4–1.7]) and 25OHD (RR = 0.96 [0.39–0.98]) were all significantly associated with the risk of T2DM (p < 0.01). The highest excess risk was recorded in patients cumulating simultaneously IR, CLGI and VDD (RR= 8.4[3.6–19.8], p < 0.0001). The additive interaction was significant, the excess risk linked to the interaction RERI = 10.5[1.43–19.7], the proportion attributable to the combined effect: AP = 0.61[0.37–0.85], and the interaction was synergistic: synergy index: 2.8[1.42–5.69]. Conclusion Baseline levels of TYG index, 25OHD and HsCRP are strongly predictive of future T2DM, and their joint effects are additive and synergistic. Interventional studies are therefore warranted in order to evaluate whether vitamin D supplementation, combined with appropriate anti-inflammatory therapies, is effective as a preventive strategy to reduce the risk of T2DM.

Multidimensional plasma lipid composition and its causal association with type 2 diabetes mellitus: A Mendelian randomization study

Background and aimRecent research extends our knowledge of plasma lipid species, building on established links between serum lipid levels and Type 2 Diabetes Mellitus (T2DM) risk. Identifying the causal roles of these lipid species is key to improving T2DM risk assessment. Methods and resultsThis study employs Mendelian randomization (MR) to investigate the causal relationship between 179 lipid species across 13 lipid categories and T2DM. Summary-level data were sourced from genome-wide association studies. The primary analytical methods included the inverse variance weighted (IVW) approach and the Wald ratio, complemented by a series of sensitivity analyses to ensure the robustness of results. The IVW analysis reveals a significant causal association between elevated levels of ceramide (d40:2) (OR = 1.071, 95% CI 1.034–1.109, P = 1.36 × 10−4), sphingomyelin (d38:1) (OR = 1.052, 95% CI 1.028–1.077, P = 1.80 × 10−5), and triacylglycerol (56:8) (OR = 1.174, 95% CI 1.108–1.243, P = 4.65 × 10−8), and an increased risk of T2DM. Conversely, Wald ratio analysis indicates that higher levels of phosphatidylcholine (O-16:1_16:0) (OR = 0.928, 95% CI 0.892–0.966, P = 2.37 × 10−4), phosphatidylcholine (O-16:1_20:4) (OR = 0.932, 95% CI 0.897–0.967, P = 2.37 × 10−4), and phosphatidylcholine (O-18:2_20:4) (OR = 0.872, 95% CI 0.812–0.935, P = 1.24 × 10−4) are significantly associated with a reduced risk of T2DM. Furthermore, suggestive causal evidence for 22 additional lipid species was identified. ConclusionsThis MR study establishes a causal relationship between specific lipid classes in modulating the risk of T2DM. It offers new insights for risk assessment and potential therapeutic targets in T2DM.

Interactions between physical activity and psychological factors in the association with the risk of lean type 2 diabetes mellitus.

Background: The extent to which physical activity and psychological factors may affect the risk of diabetes mellitus among lean individuals remains unclear.Purpose: This study aimed to investigate the associations of total physical activity (TPA) and psychological factors with lean type 2 diabetes mellitus (T2DM) risk.Research Design: A prospective cohort study.Study Sample: The study population included 1,945 Korean adults who maintained a body mass index <23kg/m2.Data Collection and Analysis: Baseline data on TPA and psychological factors were collected and T2DM incidence was assessed for 10 years. For analysis, a multivariable Cox proportional hazards regression model was used.Results: TPA was inversely associated with T2DM risk and this association was more pronounced in participants who were depressed or distressed; the top TPA quartile exhibited significant reductions in T2DM risk of 66% (95% confidence interval [CI]: 0.15, 0.78) and 65% (95% CI: 0.14, 0.88) among participants who reported depressed mood and those who perceived high distress, respectively, compared with the bottom TPA quartile.Conclusions: The current study demonstrated the preventive effects of physical activity on T2DM in lean adults through its interaction with psychological factors.

The Effect of Thiazolidinediones in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterised by insulin resistance and is a risk for type2 diabetes mellitus (T2DM). The aim of this study was to review the literature on the effect of pioglitazone and rosiglitazone in women with PCOS. We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science in April 2020 and updated in March 2023. Studies were deemed eligible if they were randomised controlled trials (RCTs) reporting the effect of pioglitazone and rosiglitazone in PCOS. The study follows the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently extracted data and assessed the risk of bias using the Cochrane risk of bias tool. Out of 814 initially retrieved citations, 24 randomised clinical trials (RCTs) involving 976 participants were deemed eligible. Among women with PCOS, treatment with rosiglitazone compared to metformin resulted in a significant increase in the mean body weight (mean difference (MD) 1.95kg; 95%CI 0.03-3.87, p = 0.05). Metformin treatment was associated with a reduction in mean body mass index (BMI) compared to pioglitazone (MD 0.85kg/m2; 95%CI 0.13-1.57, p = 0.02). Both pioglitazone compared to placebo (MD 2.56kg/m2; 95%CI 1.77-3.34, p < 0.00001) and rosiglitazone compared to metformin (MD 0.74kg/m2; 95%CI 0.07-1.41, p = 0.03) were associated with a significant increase in BMI. Treatment with pioglitazone compared to placebo showed a significant reduction in triglycerides (MD - 0.20mmol/L; 95%CI - 0.38 to - 0.03, p = 0.02) and fasting insulin levels (MD - 11.47mmol/L; 95%CI - 20.20, - 2.27, p = 0.01). Rosiglitazone compared to metformin was marginally significantly associated with a reduction in the luteinising hormone (LH) (MD - 0.62; 95%CI - 1.25-0.00, p = 0.05). Both pioglitazone and rosiglitazone were associated with significant increases in body weight and BMI when compared with metformin or placebo. Pioglitazone significantly reduced triglycerides and fasting insulin when compared with placebo while rosiglitazone showed a modest reduction of LH when compared with metformin. CRD42020178783.

P049 Genetic liability to rheumatoid arthritis and the risk of cardiometabolic diseases

Abstract Background/Aims Patients with rheumatoid arthritis (RA) are at an increased risk of comorbidities. Previous studies have reported a positive association between RA and cardiometabolic disease risk. However, few causal inference studies have addressed the different serological subtypes of RA and their association with cardiometabolic disease risk. This Mendelian randomisation (MR) study was conducted to offer insight into the causal pathway underlying this association. Methods A two-sample MR analysis was conducted using genetic variants as instrumental variables (IVs) to estimate the causal effect of genetic liability to RA and its serological subsets (seropositive and seronegative) on cardiometabolic disease risk including hypertension, coronary artery disease (CAD), atrial fibrillation, heart failure, stroke, and type 2 diabetes mellitus (T2DM). IVs were obtained from two genome-wide association studies (GWASs) for RA (53,663 cases and 1,064,978 controls [n =177 IVs]). Summary statistics were stratified for serological status including seropositive RA (RA+; 35,240 cases, [n = 195 IVs]), and seronegative RA (RA−; 8,515 cases, [n = 12 IVs]). Both subsets were compared to 990,155 controls. Summary statistics for cardiometabolic diseases were extracted from GWASs of European ancestries. Results The inverse-variance weighted (IVW) model showed a positive association between genetic liability to RA and the risk of CAD, heart failure, and T2DM; CAD, (Odds ratio [OR] = 1.04; 95% confidence interval [CI] 1.01-1.06; P-value [P] = 2.7210-3, heart failure, OR = 1.03; 95% CI 1.01-1.06; P = 0.018, and T2DM, OR = 1.08; 95% CI 1.05-1.11; P = 4.6310-8.). A similar association direction was observed between genetic liability to RA+ and the risk of CAD and T2DM; CAD, (OR = 1.02; 95% CI 1.01-1.04; P = 0.009, T2DM, OR = 1.05; 95% CI 1.03-1.07; P = 3.9110-7). Genetic liability to RA− was positively associated with T2DM risk; (OR = 1.09; 95% CI 1.02-1.16; P = 0.011). Conclusion In this MR study, a positive association of genetic liability to RA was demonstrated with CAD, heart failure and T2DM risk. Genetic liability to RA+ was associated with an increased risk of CAD and T2DM risk while genetic liability to RA− was positively associated with T2DM risk. Future research should investigate genetic architecture of RA including its serological subsets with cardiometabolic diseases to delineate the genes associated with these comorbidities. Disclosure S. Alduhayhi: None. M. Soomro: None. S. Zhao: None. A. Barton: None. A. Morris: None. J. Bowes: None.