Risk Factors For Type 2 Diabetes Research Articles

Increased Body Mass Index is Independently Associated with Chronic Kidney Disease among People with Type 2 Diabetes

Background The alarming increase in the prevalence of obesity has implications for chronic kidney disease (CKD) progression in type 2 diabetes (T2D). This study aimed to assess if increased body mass index (BMI) can be an independent risk factor for CKD and T2D in the Indian context. Materials and Methods In this cross-sectional study, 602 (M:F = 378:224) participants were screened using Kidney Disease Improving Global Outcomes (KDIGO) from January to October 2023 in Chennai. Demographic, anthropometric, biochemical, clinical details, and comorbidities were recorded. T2D with CKD low risk was taken as control group, and CKD moderate and high risks were the study groups. BMI was classified based on the Asian criteria into normal (18.5–22.9), overweight (23–24.9), and obese (≥25 kg/m2). Results Majority of participants in moderate and high risk categories were obese compared to the low risk category (60.5% and 66.4% vs. 39.1%; p < 0.001). A higher proportion of participants was on antihypertensive drugs in the high risk group and in the obese category (p < 0.001). Comorbidities and diabetic complications were higher in the high risk group (p < 0.001). Multivariate logistic regression revealed that age of ≥ 60 years [OR(95% CI); 6.3(2.2–18); p = 0.009]; increased BMI as overweight [3.6(2.1–6.3); p < 0.001] and obese [5.2(3.3–8.3); p < 0.001]; smoking [4.2(1.7–10.2); p = 0.002]; increased duration of diabetes of 5–15 years [2.3(1.2–4.5); p = 0.013], 16–25 years [4.8(2.2–10.4); p < 0.001], and >25 years [4.2(1.4–13); p = 0.011]; systolic blood pressure [1.01(1.0–1.03); p = 0.02]; and hemoglobin A1c [1.2(1.1–1.3); p < 0.001] were independent risk factors for the progression of CKD. Conclusion Increased BMI was independently associated with CKD in T2D. Overweight and obese individuals are four to five times at risk for CKD progression. Early identification, lifestyle intervention, and weight-lowering drugs may reduce the complications of obesity in T2D and CKD.

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

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

Integrated clinical risk prediction of type 2 diabetes with a multifactorial polygenic risk score.

Combining information from multiple GWASs for a disease and its risk factors has proven a powerful approach for development of polygenic risk scores (PRSs). This may be particularly useful for type 2 diabetes (T2D), a highly polygenic and heterogeneous disease where the additional predictive value of a PRS is unclear. Here, we use a meta-scoring approach to develop a metaPRS for T2D that incorporated genome-wide associations from both European and non-European genetic ancestries and T2D risk factors. We evaluated the performance of this metaPRS and benchmarked it against existing genome-wide PRS in 620,059 participants and 50,572 T2D cases amongst six diverse genetic ancestries from UK Biobank, INTERVAL, the All of Us Research Program, and the Singapore Multi-Ethnic Cohort. We show that our metaPRS was the most powerful PRS for predicting T2D in European population-based cohorts and had comparable performance to the top ancestry-specific PRS, highlighting its transferability. In UK Biobank, we show the metaPRS had stronger predictive power for 10-year risk than all individual risk factors apart from BMI and biomarkers of dysglycemia. The metaPRS modestly improved T2D risk stratification of QDiabetes risk scores for 10-year risk prediction, particularly when prioritising individuals for blood tests of dysglycemia. Overall, we present a highly predictive and transferrable PRS for T2D and demonstrate that the potential for PRS to incrementally improve T2D risk prediction when incorporated into UK guideline-recommended screening and risk prediction with a clinical risk score.

Adipose tissue–derived adipsin marks human aging in non-type 2 diabetes population

IntroductionAdipsin or complement factor D is an adipokine that augments insulin secretion, is altered in various degrees of obesity, and is involved in alternative complement pathway. However, whether adipsin has...

Prevalence of Type 2 Diabetes Risk in a Higher Education Community of North-Eastern Portugal: a Prospective Cross-sectional Observational Analysis

Objectives: Type 2 diabetes (T2D) is considered one of the most prevalent diseases worldwide. The aim of this study was to analyse the risk of developing T2D in a higher education community of Bragança, North-Eastern Portugal.Methods: The observational, cross-sectional and prospective sample comprised 3021 individuals, aged between 18 and 64 years old, of whom 1759 were women (mean age 24.16 ± 8.80 years) and 1263 were men (mean age 23.37 ± 8.70 years). The Finnish Diabetes Risk Score (FINDRISC) questionnaire was employed to estimate the risk of developing T2D over the next 10 years.Results: The results indicated that approximately 37 (1%) participants in the sample exhibited a high risk of developing T2D, 117 (4%) participants exhibited a moderate risk, 660 (22%) participants exhibited a slight risk, and 2206 (73%) participants exhibited a low risk. A higher T2D risk was observed in the staff group in comparison with the other groups (p < 0.001). Furthermore, body mass index (BMI) and waist circumference (WC) were the variables that most contributed to the increased risk of developing T2D (X2 = 1034.5; p < 0.001).Conclusions: In conclusion, the study reported a low T2D risk for the higher education community of Bragança in the Portuguese North-Eastern region. However, the risk of T2D was found to be higher in the staff group than in the student group. The FINDRISK questionnaire may be applied for the early diagnosis of T2D risk factors.

Clinical profile and risk factors for type-2 diabetes – A cross-sectional study

Objectives Type 2 diabetes is a chronic metabolic disorder characterised by elevated blood glucose levels due to insulin resistance or insufficient insulin production. Understanding the prevalence, characteristics, and markers of this disease is essential for effective prevention, management and treatment. The study aims to explore the association between type 2 diabetes and its prevalence, characteristics and markers. Material and Methods Adults with type 2 diabetes and matched healthy controls were enrolled in the study. Statistical calculations were used to establish the sample size. Information on demographics, physical examinations and lab tests were collected. We assessed plasma glucose, glycated haemoglobin (HbA1c), serum lipids and serum DPP4. Results The mean age (SD) of the population under research was 55.7 (6.12) years for the study subjects and 55.7 (6.11) years for the controls. A positive family history of diabetes was present in 34 (or 33%) of the diabetes patients compared to 11 (or 11%) of the non-diabetic patients (p 0.001). The mean HbA1c in the diabetic group was substantially greater than that of the non-diabetic controls (5.47 1.89%), as expected (7.23 2.69%), p 0.001. It’s interesting to note that total cholesterol was markedly higher in the diabetes participants (5.59 2.24 mmol/L) than in the non-diabetic controls (6.48 1.54 mmol/L), p = 0.001. Conclusion Due to common risk factors and underlying mechanisms, type 2 diabetes and hypertension may be related, as suggested by the high prevalence of hypertension in the diabetic group. Type 2 diabetes was substantially related to elevated HbA1c and fasting plasma glucose levels, indicating poor glycaemic control. The higher mean serum Dipeptidyl peptidase-4 (DPP4) level in the group with type 2 diabetes shows a link between high DPP4 levels and the disease, which may have an effect on incretin hormone activity, insulin resistance and therapeutic options.

DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes

ObjectiveYouth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes.MethodsWe performed an epigenome-wide analysis of DNAm on whole blood from 218 youth with T2D and 77 normoglycemic controls from the iCARE (improving renal Complications in Adolescents with type 2 diabetes through REsearch) cohort. Associations were tested using multiple linear regression models while adjusting for maternal diabetes, sex, age, BMI, smoking status, second-hand smoking exposure, cell-type proportions and genetic ancestry.ResultsWe identified 3830 differentially methylated sites associated with youth T2D onset, of which 3794 were moderately (adjusted p-value < 0.05 and effect size estimate > 0.01) associated and 36 were strongly (adjusted p-value < 0.05 and effect size estimate > 0.05) associated. A total of 3725 of these sites were not previously reported in the EWAS Atlas as associated with T2D, adult obesity or youth obesity. Moreover, three CpGs associated with youth-onset T2D in the PFKFB3 gene were also associated with maternal T2D exposure (FDR < 0.05 and effect size > 0.01). This is the first study to link PFKFB3 and T2D in youth.ConclusionOur findings support that T2D in youth has different impacts on DNAm than adult-onset, and suggests that changes in DNAm could provide an important link between in utero exposure to maternal diabetes and the onset of T2D.

Inflammation and immunological disarrays are associated with acute exercise in type 2 diabetes.

Type 2 diabetes (T2D) is the most common metabolic disorder that is associated with insulin resistance. The aim of the present study is to discover details of the molecular mechanism of exercise on control or progress of diabetic condition in patients via network analysis. Gene expression profiles of patients with T2D before and after doing exercise are retrieved from Gene Expression Omnibus (GEO) and are pre-evaluated by the GEO2R program. Data are studied based on expression values, regulatory relationships between the differentially expressed genes (DEGs), gene ontology analyses, and protein-protein interaction PPI network analysis. A number of 118 significant DEGs were identified and classified based on fold change (FC) values as most dysregulated genes and dysregulated individuals. Action map analysis revealed that 18 DEGs appeared as the critical genes. Gene ontology analysis showed that 24 DEGs are connected to at least four pathways. JUN, IL6, IL1B, PTGS2, FOS, MYC, ATF3, CXCL8, EGR1, EGR2, NR4A1, PLK3, TTN, and UCP3 were identified as central DEGs. Finally; JUN, IL6, IL1B, PTGS2, FOS, ATF3, CXCL8, EGR1, and EGR2 were introduced as the critical targeted genes by exercise. Since the critical genes after exercise are upregulated and mostly are known as the risk factors of T2D, it can be concluded that unsuitable exercise can develop diabetic conditions in patients. Acute exercise-induced inflammation and immune disturbances seem to be associated with the development of T2D in patients.

The predictive value of plasma uridine for type 2 diabetes and its atherosclerotic complications.

Uridine might be a common link between pathological pathways in diabetes and cardiovascular diseases. This study aimed to investigate the predictive value of plasma uridine for type 2 diabetes (T2D) and T2D with atherosclerosis. Individuals with T2D and healthy controls (n = 218) were randomly enrolled in a cross-sectional study. Patients with T2D were divided into two groups based on carotid ultrasound: patients with carotid atherosclerosis (CA) (group DCA) and patients without CA (group D). Plasma uridine was determined using HPLC-MS/MS. Correlation and logistic regression analyses were used to analyze the results. Fasting and postprandial uridine were significantly increased in patients with T2D compared with healthy individuals. Logistic regression suggested that fasting and postprandial uridine were independent risk factors for T2D. The receiver operating characteristic (ROC) curve showed that fasting uridine had a predictive value on T2D (95% CI, 0.686-0.863, sensitivity 74.3%, specificity 71.8%). Fasting uridine was positively correlated with LDL-c, FBG, and PBG and negatively correlated with fasting C-peptide (CP-0h) and HOMA-IS. The change in postprandial uridine from fasting baseline (Δuridine) was smaller in T2D patients with CA compared with those without (0.80 (0.04-2.46) vs 2.01 (0.49-3.15), P = 0.010). Δuridine was also associated with T2D with CA and negatively correlated with BMI, CP-0h, and HOMA-IR. Fasting uridine has potential as a predictor of diabetes. Δuridine is closely associated with carotid atherosclerosis in patients with T2D.

Association between liver enzymes and type 2 diabetes: a real-world study.

This study aimed to examine the association of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl-transferase (GGT), with type 2 diabetes (T2D) risk, particularly their dose-response relationship. This cross-sectional study enrolled participants aged >20 years old who underwent physical examination at our local hospital from November 2022 to May 2023. A generalized additive model (GAM) was fit to assess the dose-response relationship between liver enzymes and T2D risk. Furthermore, data from the UK Biobank (n=217,533) and National Health and Nutrition Examination Survey (NHANES 2011-2018; n= 15,528) were analyzed to evaluate whether the dose-response relationship between liver enzymes and T2D differed by population differences. A total of 14,100 participants were included (1,155 individuals with T2D and 12,945 individuals without diabetes) in the analysis. GAM revealed a non-linear relationship between liver enzymes and T2D risk (P non-linear < 0.001). Specifically, T2D risk increased with increasing ALT and GGT levels (range, <50 IU/L) and then plateaued when ALT and GGT levels were >50 IU/L. Elevated AST within a certain range (range, <35 IU/L) decreased the risk of T2D, whereas mildly elevated AST (>35 IU/L) became a risk factor for T2D. The UK Biobank and NHANES data analysis also showed a similar non-linear pattern between liver enzymes and T2D incidence. Liver enzymes were non-linearly associated with T2D risk in different populations, including China, the UK, and the US. Elevated ALT and GGT levels, within a certain range, could increase T2D risk. More attention should be given to liver enzyme levels for early lifestyle intervention and early T2D prevention. Further studies are necessary to explore the mechanism of the non-linear association between liver enzymes and T2D risk.

Associations of Lifestyle Patterns with Glucose and Lipid Metabolism in Finnish Adults at Increased Risk of Type 2 Diabetes.

Various lifestyle and sociodemographic factors have been associated with risk factors for type 2 diabetes (T2D). However, their combined associations with T2D risk factors have been studied much less. This study investigates cross-sectional associations of lifestyle patterns with T2D risk factors among 2925 adults at increased risk participating in the Stop Diabetes study. Lifestyle patterns are determined using principal component analysis (PCA) with several lifestyle and sociodemographic factors. The associations of lifestyle patterns with measures of glucose and lipid metabolism and serum metabolites analyzed by nuclear magnetic resonance (NMR) spectroscopy are studied using linear regression analysis. "Healthy eating" pattern is associated with better glucose and insulin metabolism, more favorable lipoprotein and fatty acid profiles and lower serum concentrations of metabolites related to inflammation, insulin resistance, and T2D. "High socioeconomic status and low physical activity" pattern is associated with increased serum concentrations of branched-chain amino acids, as are "Meat and poultry" and "Sleeping hours" patterns. "Snacks" pattern is associated with lower serum concentrations of ketone bodies. Our results show, in large scale primary care setting, that healthy eating is associated with better glucose and lipid metabolism and reveal novel associations of lifestyle patterns with metabolites related to glucose metabolism.

The Potential of the Adzuki Bean (Vigna angularis) and Its Bioactive Compounds in Managing Type 2 Diabetes and Glucose Metabolism: A Narrative Review.

Type 2 diabetes (T2D) is a common noncommunicable disease. In the United States alone, 37 million Americans had diabetes in 2017. The adzuki bean (Vigna angularis), a legume, has been reported to possess antidiabetic benefits. However, the extent and specific mechanisms through which adzuki bean consumption may contribute to T2D prevention and management remain unclear. Therefore, the aim of this narrative review is to analyze current evidence supporting the utilization of adzuki beans in the diet as a strategy for preventing and managing T2D. Animal studies have demonstrated a positive impact of adzuki beans on managing T2D. However, supporting data from humans are limited. Conversely, the potential of adzuki bean consumption in preventing T2D via modulating two T2D risk factors (obesity and dyslipidemia) also lacks conclusive evidence. Animal studies have suggested an inconsistent and even contradictory relationship between adzuki bean consumption and the management of obesity and dyslipidemia, in which both positive and negative relationships are reported. In sum, based on the existing scientific literature, this review found that the effects of adzuki bean consumption on preventing and managing T2D in humans remain undetermined. Consequently, human randomized controlled trials are needed to elucidate the potential benefits of the adzuki bean and its bioactive components in the prevention and management of T2D.

Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis.

Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

Depression and type 2 diabetes risk: a Mendelian randomization study.

Extensive observational evidence has suggested an association between depression and type 2 diabetes (T2D). However, the causal relationships between these two diseases require further investigation. This study aimed to evaluate the bidirectional causal effect between two types of depression and T2D using two-sample Mendelian randomization (MR). We applied two-step MR techniques, using single-nucleotide polymorphisms (SNPs) as the genetic instruments for analysis. We utilized summary data from genome-wide association studies (GWASs) for major depression (MD), depressive status (frequency of depressed mood in the last two weeks), T2D, and other known T2D risk factors such as obesity, sedentary behavior (time spent watching television), and blood pressure. The analysis utilized inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, MR pleiotropy residual sum, and outlier methods to determine potential causal relationships. The study found that MD was positively associated with T2D, with an odds ratio (OR) of 1.26 (95% CI: 1.10-1.43, p = 5.6×10-4) using the IVW method and an OR of 1.21 (95% CI: 1.04-1.41, p = 0.01) using the weighted median method. Depressive status was also positively associated with T2D, with an OR of 2.26 (95% CI: 1.03-4.94, p = 0.04) and an OR of 3.62 (95% CI: 1.33-9.90, p = 0.01) using the IVW and weighted median methods, respectively. No causal effects of MD and depressive status on T2D risk factors were observed, and T2D did not influence these factors. Our study demonstrates a causal relationship between depression and an increased risk of developing T2D, with both major depression and depressive status being positively associated with T2D.

Genetics causal analysis of oral microbiome on type 2 diabetes in East Asian populations: a bidirectional two-sample Mendelian randomized study.

The dysbiosis of the oral microbiome is associated with the progression of various systemic diseases, including diabetes. However, the precise causal relationships remain elusive. This study aims to investigate the potential causal associations between oral microbiome and type 2 diabetes (T2D) using Mendelian randomization (MR) analyses. We conducted bidirectional two-sample MR analyses to investigate the impact of oral microbiome from saliva and the tongue T2D. This analysis was based on metagenome-genome-wide association studies (mgGWAS) summary statistics of the oral microbiome and a large meta-analysis of GWAS of T2D in East Asian populations. Additionally, we utilized the T2D GWAS summary statistics from the Biobank Japan (BBJ) project for replication. The MR methods employed included Wald ratio, inverse variance weighting (IVW), weighted median, MR-Egger, contamination mixture (ConMix), and robust adjusted profile score (RAPS). Our MR analyses revealed genetic associations between specific bacterial species in the oral microbiome of saliva and tongue with T2D in East Asian populations. The MR results indicated that nine genera were shared by both saliva and tongue. Among these, the genera Aggregatibacter, Pauljensenia, and Prevotella were identified as risk factors for T2D. Conversely, the genera Granulicatella and Haemophilus D were found to be protective elements against T2D. However, different species within the genera Catonella, Lachnoanaerobaculum, Streptococcus, and Saccharimonadaceae TM7x exhibited multifaceted influences; some species were positively correlated with the risk of developing T2D, while others were negatively correlated. This study utilized genetic variation tools to confirm the causal effect of specific oral microbiomes on T2D in East Asian populations. These findings provide valuable insights for the treatment and early screening of T2D, potentially informing more targeted and effective therapeutic strategies.

Association of Protein Tyrosine Phosphatase Receptor Type D and Serine Racemase Genetic Variants with Type 2 Diabetes in Malaysian Indians.

Type 2 diabetes (T2D) candidate genes, protein tyrosine phosphatase receptor type D (PTPRD), and serine racemase (SRR) were suggested by a genome-wide association study (GWAS) in the Chinese population. Association studies have been replicated among East Asian populations. The association of PTPRD and SRR genetic variants with T2D in Southeast Asian populations still needs to be studied. This study aimed to investigate the association of PTPRD and SSR genetic variants with T2D in Malaysian Indian subjects. The single nucleotide polymorphisms (SNPs) of PTPRD (rs649891 and rs17584499) and SRR (rs4523957, rs391300, and rs8081273) were genotyped in 397 T2D and 285 normal Malaysian Indian subjects. The homozygous dominant genotype of rs17584499 is frequent in diabetic patients (56.5%) compared to normal subjects (47.3%). In contrast, the homozygous recessive genotype of rs8081273 is more frequent among normal subjects (12.5%) than diabetic patients (5.6%). The dominant genetic model showed that PTPRD rs17584499 (CC) is a risk factor for T2D (OR = 1.42, P = 0.029), whereas the recessive genetic model showed that SRS SNP rs8081273 was protective for T2D (OR = 0.42, P = 0.003). This study confirmed the association of PTPRD rs17584499 genetic variations with T2D in Malaysian Indians. While the SRR rs8081273 (TT) genotype showed protection against T2D, more investigation in different populations is required to confirm this protection.

Global burden of type 2 diabetes in adolescents from 1990 to 2019.

To evaluate the burden of type 2 diabetes (T2D) among adolescents (15-24 years old) from 1990 to 2019. The age-standardized incidence rate (ASIR) and disability-adjusted life years (DALYs) rate of adolescents were analyzed according to age, sex, geographical location, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) was estimated to quantify the trends. From 1990 to 2019, the ASIR (EAPC = 1.07) and age-standardized DALY rate (EAPC = 2.01) of T2D in adolescents showed an increasing trend. The ASIR was higher in males than in females. The burden was greater in the 20-24-year age group. Of the five SDI regions, the highest ASIR and age-standardized DALY rate were found in low-middle-SDI regions, while the greatest increase in these rates was observed in high-SDI regions (EAPC = 3.28 and 3.55, respectively). Of the 21 regions analyzed, the highest ASIR and age-standardized DALY rate were found in Oceania. Of the 204 countries analyzed, the Marshall Islands (651.16) and Kiribati (277.42) had the highest ASIR and DALYs, respectively. The regions with the greatest increase in the ASIR from 1990 to 2019 were Western Europe (EAPC = 4.15), high-income North America (EAPC = 4.72). The global burden of T2D in adolescents showed an overall upward trend from 1990 to 2019. It is necessary to strengthen prevention measures related to risk factors for T2D among young people, especially in areas with a low-to-medium SDI.

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.

Sleep and insulin sensitivity in adolescents at risk of type 2 diabetes: the Sleep Manipulation in Adolescents at Risk of Type 2 Diabetes randomized crossover study.

To investigate the effect of increasing sleep duration for 1 week, compared to a week of habitual and decreased sleep, on insulin sensitivity (IS) in adolescents at risk for type 2 diabetes (T2D). Adolescents, 13-18 years old, at risk for T2D, with obesity and other risk factors, were recruited for a randomized (1:1), open-label, sex-stratified crossover study, that manipulated time-in-bed to modify sleep duration (measured by actigraphy). Following a week of habitual (HB) sleep, time-in-bed was increased (IN) and decreased (DE) by 1 hour 30 min/night for 1 week, counterbalanced across participants (HBINDE or HBDEIN), and separated by a week of washout sleep. The main outcome measure was IS, obtained via 2-hour oral-glucose-tolerance-test conducted after each sleep week. Of the 43 participants recruited, 36 (84%) completed all sleep interventions (52.8% female, age = 15.1 years, body mass index = 99.9th percentile, order: HBINDE = 18 and HBDEIN = 18). On average, during the HB week, participants slept 7 hours 31 min/night; sleep duration was 1 hour 02 min/night higher during the IN week and 1 hour 19 min/night lower during the DE week. We found a significant effect of sleep week on IS with a large effect size. Following the IN sleep week, IS was 20% higher compared to after the HB and DE sleep weeks, but there was no significant difference in IS following HB versus DE sleep weeks. Whenever possible, clinicians should empower youth at risk of T2D to improve their sleep duration, since even a modest increase in sleep duration of 1 h/night for 1 week can have a positive impact on IS in this population. Sleep Extension and IS in Adolescents, https://clinicaltrials.gov/study/NCT03754036, November 23rd, 2018. ClinicalTrials.gov (ID:NCT03754036).

Sick individuals, sick populations revisited: a test of the Rose hypothesis for type 2 diabetes disparities

IntroductionThe Rose hypothesis predicts that since genetic variation is greater within than between populations, genetic risk factors will be associated with individuals’ risk of disease but not population disparities, and...