Exploring knowledge, attitudes, and risk factors of Type 2 diabetes mellitus among Malaysian undergraduate students

Diabetes and physical activity

To clarify the expression of N6-methyladenosine (m6 A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population. The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6 A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6 A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23-7.47]) in model 4. Seven significantly altered m6 A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6 A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

Background and aimsMen and women have different type 2 diabetes mellitus (T2DM) risks, which have been reported across populations of different ethnicity. Where differences in T2DM risk for sex (biological) have been studied, research on gender (socio-cultural) and T2DM risk is lacking. We explored, in a multi-ethnic population, the association of six gender-related characteristics with incident T2DM over 3 years, and the mediation by known risk factors for T2DM. Methods and resultsWe included 9605 women and 7080 men of the multi-ethnic HELIUS study (Amsterdam, the Netherlands). We studied associations between gender-related characteristics and incident T2DM, using Cox regression. After a median of 3.0 years (IQR 2.0; 4.0), 198 (2.1%) women and 137 (1.9%) men developed T2DM. A lower T2DM risk was observed in those not being the primary earner (HR 0.67; 95% CI 0.47; 0.93) and a higher desired level of social support (HR 0.62; 95% CI 0.44; 0.87). Hours spent on household work, home repairs, type of employment and male- or female-dominated occupation were not associated with T2DM incidence. No evidence for effect modification by biological sex or ethnicity was found. Known risk factors of T2DM did not mediate the observed associations. ConclusionGender-related characteristics, not being the primary earner and a higher desired social support were associated with reduced T2DM risk, and this was not mediated by known risk factors for T2DM.

Type 2 diabetes mellitus (T2DM) is one of the major public health problems worldwide; both genetic and environmental factors are its risk factors. Arsenic, an environmental pollutant, might be a risk factor for T2DM, but the association of low-to-moderate level arsenic exposure with the risk of T2DM is still inconsistent. Single nucleotide polymorphisms (SNPs) can affect the development of T2DM, but the study on KEAP1 rs11545829(G>A) SNP is few. In this paper, we explored the effect of KEAP1 rs11545829(G>A) SNP and low-to-moderate level arsenic exposure on risk of T2DM in a cross-sectional case-control study conducted in Shanxi, China. Total of 938 participants, including 318 T2DM cases and 618 controls, were enrolled. Blood glycosylated haemoglobin (HbA1c) was detected by Automatic Biochemical Analyzer, and participants with HbA1c≧6.5% were diagnosed as T2DM. Urinary total arsenic (tAs, mg/L), as the indicator of arsenic exposure, was detected by liquid chromatography-atomic fluorescence spectrometry (LC-AFS). Genomic DNA was extracted and the genotypes of KEAP1 rs11545829 SNP were examined by multiplex polymerase chain reaction (PCR). The urinary tAs concentration in recruited participants was 0.075(0.03-0.15) mg/L, and was associated with an increased risk of T2DM (OR = 8.45, 95% CI 2.63-27.17); rs11545829 mutation homozygote AA genotype had a protective effect on risk of T2DM (OR = 0.42, 95 % CI 0.25-0.73). Although this protective effect of AA genotype was found in participants with higher urinary tAs level (>0.032mg/L) (OR = 0.48, 95%CI 0.26-0.86), there was no interaction effect for arsenic exposure and rs11545829 SNP on risk of T2DM. In addition, BMI modified the association between rs11545829 SNP and the risk of T2DM (RERI = -1.11, 95% CI -2.18-0.04). The present study suggest that low-to-moderate level arsenic exposure may be a risk factor, while KEAP1 rs11545829 SNP mutation homozygote AA genotype may be a protective factor for risk of T2DM, especially for T2DM patients with urinary tAs level>0.032mg/L.

Testosterone is a metabolically active hormone in males for metabolic homeostasis. Although the coexistence of low testosterone levels and type 2 diabetes mellitus (T2DM) have been associated, there are no reports that evaluate alterations in total testosterone (TT) levels and the risk of newly diagnosed T2DM. This review evaluates this question in adult men with high or low levels of total testosterone (TT), as well as the role played by other hormones such as free testosterone (FT), sex hormone binding globulin (SHBG), dihydrotestosterone (DHT), estrogens and testosterone bioavailable (bT). We searched for studies published up to July 30, 2023, in five databases, following a PECO strategy. We found twenty-two studies for quantitative analysis and meta-analyzed the same quantity of studies. This first meta-analysis incorporates the assessment of the risk of low TT and T2DM in longitudinal studies. 43,038 adult men are included. Our meta-analysis shows that there is an association between low TT levels and the risk of newly diagnosed T2DM (OR 1.52; 95% CI 1.10-2.10; p < 0.05; I²: 79%). It is also evident that SHBG in low TT studies behaves as a risk factor for T2DM in the same way as FT, although without statistical significance. bT behaves as a protective factor. There is no association between estrogen, DHT and T2DM. In adult men with low TT values, there is a greater risk of developing a newly diagnosed of T2DM. SHBG values in low TT patients also present a higher risk of T2DM as the same FT but without statistical significance. bT behaves as a protective factor We have not found an association between risk of T2DM and the levels of estrogen, DHT although there are very few studies that report these hormones.

Prospective observational studies uniformly link vitamin D deficiency with the incidence of type 2 diabetes mellitus (T2DM), yet trials supplementing participants at risk of T2DM with vitamin D to reduce progression to T2DM have yielded inconsistent results. Inconsistencies between supplementation trials may be due to insufficient dosing or small sample sizes. Observational studies may also have reported spurious associations due to uncontrolled confounding by lifestyle or genetic factors. Alternatively, observational and intervention studies may not be entirely comparable. Observational studies show an association between higher vitamin D status, which is predominantly derived from sun exposure, and decreased incidence of T2DM. Trials intervene with vitamin D supplementation, and therefore may be missing alternate causes of the effect of sun exposure, as seen in observational studies. We propose that sun exposure may be the driving force behind the associations seen in observational studies; sun exposure may have additional benefits beyond increasing serum 25-hydroxyvitamin D (25OHD) levels. We performed an electronic literature search to identify articles that examined associations between sun exposure and T2DM and/or glucose metabolism. A best evidence synthesis was then conducted using outcomes from analyses deemed to have high methodological quality. Ten eligible full-text articles were identified, yielding 19 T2DM-related outcomes. The best evidence analysis considered 11 outcomes which were grouped into six outcome types: T2DM, fasting glucose, glucose tolerance, fasting insulin, insulin secretion and insulin sensitivity. There was moderate evidence to support a role of recreational sun exposure in reducing odds of T2DM incidence. High-level evidence was lacking; evidence presented for other outcomes was of low or insufficient level. This review highlights significant gaps in research pertaining to sun exposure and T2DM-related outcomes. Further research is encouraged as we aim to identify novel preventative strategies for T2DM.

ABSTRACT&#x0D; &#x0D; Background: Type 2 diabetes mellitus (T2DM) is a multifactorial disease involving genetic and environmental factors. The E23K KCNJ11 gene polymorphism causes KATP canal overactivity, decreases cell membrane depolarization potential, and decreases insulin secretion. E23K polymorphism of the KCNJ11 gene as a risk factor for T2DM.&#x0D; Research Objective: This study aimed to analyze the E23K polymorphism of the KCNJ11 gene as a risk factor for T2DM in the Bengkulu Serawai.&#x0D; Method: This study is a case-control study. The subjects of the study were 100 people with T2DM patients as a case group (50 people) and Non-DM subjects with families who did not have a history of T2DM as a control group (50 people). Fasting blood glucose (GDP) was analyzed by spectrophotometry and E23K KCNJ11 gene by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Data were analyzed by statistics.&#x0D; Results: The frequency of AA genotypes in cases was higher than the controls (12% and 8%) (p = 0.001). The frequency of A allele in the case was higher than the control (32% and 18%) (p = 0.017). The risk of T2DM on AA / GA genotypes was 4.75 times higher in cases than controls (p = 0,000, OR 4.75 95% CI 2.01-11.24). The risk of T2DM in A allele was 2.14 times higher in cases than in controls (p = 0.017, OR 2.14, 95% CI 1.11-4.15).&#x0D; Conclusion: E23K polymorphism of the KCNJ11 gene as a risk factor for T2DM in Bengkulu Serawai Tribe.&#x0D; &#x0D; Keywords: E23K gene KCNJ11, DMT2, Non-DMT2.&#x0D;

This study aimed to investigate the relationship between asthma and the risk of Type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) data from 2009 to 2016. Weighted t-tests and weighted chi-square tests were used to compare the baseline characteristics between patients with T2DM and individuals without T2DM. Weighted multivariate logistic regression models were used to determine the association between asthma and the risk of T2DM. Two-sample univariate Mendelian randomization (MR) was performed to analyze asthma and the risk of T2DM. Among the 2348 participants included, the prevalence of asthma was 70.9% in T2DM patients. The results of the weighted multivariate logistic regression models revealed that asthma was significantly positively linked to T2DM risk, with odds ratios of 2.24, 2.26, and 1.92 in Models 1, 2, and 3, respectively. The fitting curve analysis demonstrated that asthma was positively correlated with the risk of T2DM. The MR results revealed a marked causal effect of asthma on T2DM, identifying asthma as a risk factor for T2DM. Sensitivity analysis confirmed the robustness of MR findings. Asthma was significantly and positively associated with T2DM risk, indicating that it serves as a risk factor for the onset of this condition.

Mitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50–59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.

Menopause and diabetes: EMAS clinical guide

Association of FTO gene methylation with incident type 2 diabetes mellitus: A nested case-control study.

BackgroundSocio-economic position (SEP) and ethnicity influence type 2 diabetes mellitus (T2DM) risk in adults. However, the influence of SEP on emerging T2DM risks in different ethnic groups and the contribution of SEP to ethnic differences in T2DM risk in young people have been little studied. We examined the relationships between SEP and T2DM risk factors in UK children of South Asian, black African-Caribbean and white European origin, using the official UK National Statistics Socio-economic Classification (NS-SEC) and assessed the extent to which NS-SEC explained ethnic differences in T2DM risk factors.Methods and FindingsCross-sectional school-based study of 4,804 UK children aged 9–10 years, including anthropometry and fasting blood analytes (response rates 70%, 68% and 58% for schools, individuals and blood measurements). Assessment of SEP was based on parental occupation defined using NS-SEC and ethnicity on parental self-report. Associations between NS-SEC and adiposity, insulin resistance (IR) and triglyceride differed between ethnic groups. In white Europeans, lower NS-SEC status was related to higher ponderal index (PI), fat mass index, IR and triglyceride (increases per NS-SEC decrement [95%CI] were 1.71% [0.75, 2.68], 4.32% [1.24, 7.48], 5.69% [2.01, 9.51] and 3.17% [0.96, 5.42], respectively). In black African-Caribbeans, lower NS-SEC was associated with lower PI (−1.12%; [−2.01, −0.21]), IR and triglyceride, while in South Asians there were no consistent associations between NS-SEC and T2DM risk factors. Adjustment for NS-SEC did not appear to explain ethnic differences in T2DM risk factors, which were particularly marked in high NS-SEC groups.ConclusionsSEP is associated with T2DM risk factors in children but patterns of association differ by ethnic groups. Consequently, ethnic differences (which tend to be largest in affluent socio-economic groups) are not explained by NS-SEC. This suggests that strategies aimed at reducing social inequalities in T2DM risk are unlikely to reduce emerging ethnic differences in T2DM risk.

Obesity is the most common chronic disease in the U.S. Patients with obesity are at high risk for type 2 diabetes mellitus (T2DM); however, many of their risk factors for T2DM are modifiable. It is important to identify patients with obesity at high risk for T2DM to appropriately direct treatment and resources. We conducted an observational study of EMR data of 399,711 adults with BMI ≥ 25 kg/m2 and without baseline T2DM between 2000 and 2019. We first identified a literature-based pool of risk factors for T2DM onset and conducted variable selection by applying LASSO penalized Cox regression with ten-fold cross-validation on an 80% training dataset. We estimated a regular Cox model on the training dataset with selected variables and evaluated model performance on the remaining 20% dataset. Over a mean of 7.4 years of follow-up, 38,898 (9.8%) study patients developed T2DM. The predictive model achieved a Harrell’s C-statistic of 0.81. The greatest risk of T2DM was associated with gestational diabetes (HR 2.53; 95% CI 2.12-3.01), Asian and Hispanic race/ethnicity (HRs 2.38 and 1.94; 95% CIs 2.24-2.53 and 1.86-2.02, respectively), family history of DM (HR 2.00; 95% CI 1.95-2.04) and PCOS (HR 1.84; 95% CI 1.63-2.07). Female sex (HR 0.77; 95% CI 0.75-0.79), having a partner (HR 0.90; 95% CI 0.88-0.92) or commercial insurance (HR 0.86; 95% CI 0.84-0.88) were associated with a lower risk of T2DM. Characteristics found in &amp;gt;5% of patients that carried additional risk included proteinuria (5.0% of patients; HR 1.53; 95% CI 1.47-1.59), hypertension (23.9%; HR 1.21; 95% CI 1.18-1.25), high cholesterol (11.9%; HR 1.19; 95% CI 1.15-1.23), and history of smoking (40.5%; HR 1.18; 95% CI 1.15-1.21). Each standard deviation increase in BMI (5.2 kg/m2) was associated with a 1.51-fold (95% CI 1.49-1.52) increase in T2DM onset. It is feasible to use predictive modeling to identify patients with overweight and obesity at high risk of T2DM. This approach could be utilized to guide population management and clinical treatment decisions. Disclosure A. Turchin: Consultant; Self; Proteomics International, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi, Stock/Shareholder; Self; Brio Systems. F. J. Morrison: None. M. Shubina: None. S. Shinde: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. N. Ahmad: Employee; Self; Eli Lilly and Company. H. Kan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Bristol-Myers Squibb Company, GlaxoSmithKline plc. Funding Eli Lilly and Company

Background Genome-wide association studies have linked several single nucleotide polymorphisms with type 2 diabetes mellitus (T2DM). The present case–control study explored the probable association between the rs10811661 CDKN2A/B gene polymorphism and the risk of T2DM in a Saudi Arabian population. Patients and methods The study included 526 T2DM patients and 567 healthy control participants. The CDKN2A/B (rs10811661) polymorphism was genotyped using the TaqMan allelic discrimination method. Results The results identified single nucleotide polymorphism rs10811661 of CDKN2A/B as a risk factor for T2DM (odds ratio = 1.9; 95% confidence interval: 1.57–2.30; P= 0.0001). Levels of fasting plasma glucose and 2-h postprandial plasma glucose were significantly higher in patients with normal glucose tolerance but carrying the rs10811661 (C/T) risk allele compared with noncarriers. Conclusion A significant association was observed between CDKN2A/B rs10811661 (C/T) and susceptibility to T2DM in the Saudi Arabian population. Furthermore, the T allele is associated with an increased risk in patients with T2DM. The findings show that T2DM may interact with CDKN2A/B rs10811661 (C/T), which increases the risk of T2DM.

Cardiovascular risk factors in Mexican-American children at risk for type 2 diabetes mellitus (T2DM)