Profiling of plasma extracellular vesicle miRNA reveals the association of miR-3120-5p with type 2 diabetes mellitus.

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.

Dyslipidemia is strongly associated with the development of prediabetes and type 2 diabetes mellitus (T2DM). The atherogenic index of plasma (AIP), as a comprehensive index for assessing lipid metabolism, has received extensive attention from researchers in recent years. However, there are relatively few studies exploring the relationships between AIP and the risk of prediabetes and T2DM in the Chinese population. This study focuses on exploring the relationships of AIP with the risk of prediabetes and T2DM in the Chinese population. We conducted an analysis of the public data from the China Health and Retirement Longitudinal Study (CHARLS), involving a total of 12,060 participants aged 45 years and above in China. The study explored the relationships of AIP with prediabetes and T2DM risk through multivariate logistic regression, subgroup analysis, smooth curve fitting, and threshold effect analysis. After adjusting for potential confounding factors, we observed positive associations between AIP and the risk of prediabetes [odds ratio (OR) = 1.75, 95% confidence interval (CI): 1.49-2.06] and T2DM (OR = 2.91, 95% CI: 2.38-3.57). Participants with higher AIP levels demonstrated a significantly elevated risk of prediabetes (OR = 1.52, 95% CI: 1.33-1.74) and T2DM (OR = 2.28, 95% CI: 1.92-2.71) compared to those with lower AIP levels. AIP showed consistent correlations with prediabetes and T2DM risk in different subgroups. The results showed the non-linear relationships between AIP and risk of prediabetes and T2DM, with inflection points at 0.29 and -0.04, respectively. When AIP > 0.29, there was a positive association between AIP and the risk of prediabetes (OR = 2.24, 95% CI: 1.67-3.00, p < 0.0001). Similarly, when AIP > -0.04, AIP was positively associated with the risk of T2DM (OR = 3.33, 95% CI: 2.67-4.16, p < 0.0001). This study demonstrated non-linear positive associations of AIP with the risk of prediabetes and T2DM among participants ≥ 45 years of age in China.

A multi-platform assessment of extracellular vesicles from the plasma and urine of women with preeclampsia.

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.

BackgroundRisk of type 2 diabetes mellitus (T2DM) is increased in metabolically obese but normal-weight people. However, we have limited knowledge of how to prevent T2DM in normal-weight people. We aimed to evaluate the association between triglyceride glucose (TyG) index and incident T2DM among normal-weight people in rural China.MethodsWe included data from 5706 people with normal body mass index (BMI) (18.5–23.9 kg/m2) without baseline T2DM in a rural Chinese cohort followed for a median of 6.0 years. A Cox proportional-hazard model was used to assess the risk of incident T2DM by quartiles of TyG index and difference in TyG index between follow-up and baseline (TyG-D), estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A generalized additive plot was used to show the nonparametric smoothed exposure–response association between risk of T2DM and TyG index as a continuous variable. TyG was calculated as ln [fasting triglyceride level (mg/dl) × fasting plasma glucose level (mg/dl)/2].ResultsRisk of incident T2DM was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG index (adjusted HR [aHR] 2.48 [95% CI 1.20–5.11], 3.77 [1.83–7.79], and 5.30 [2.21–12.71], Ptrend < 0.001 across quartiles of TyG index). Risk of incident T2DM was increased with quartile 4 versus quartile 1 of TyG-D (aHR 3.91 [2.22–6.87]). The results were consistent when analyses were restricted to participants without baseline metabolic syndrome and impaired fasting glucose level. The generalized additive plot showed cumulative increased risk of T2DM with increasing TyG index.ConclusionsRisk of incident T2DM is increased with increasing TyG index among rural Chinese people, so the index might be an important indicator for identifying people at high risk of T2DM.

Purpose To determine whether hypertriglyceridemic waist (HTGW) and high lipid accumulation product (LAP) preceded the incidence of type 2 diabetes mellitus (T2DM), and to investigate the interactions of HTGW and LAP with other components of metabolic syndrome on the risk of T2DM. Methods A total of 15,717 eligible participants without baseline T2DM and aged 35 and over were included from a Chinese rural cohort. Cox proportional hazards regression models were used to estimate the association of HTGW and LAP with the incidence of T2DM, and the restricted cubic spline model was used to evaluate the dose-response association. Results Overall, 867 new T2DM cases were diagnosed after 7.77 years of follow-up. Participants with HTGW had a higher hazard ratio for T2DM (hazard ratio (HR): 6.249, 95% confidence interval (CI): 5.199-7.511) after adjustment for potential confounders. The risk of incident T2DM was increased with quartiles 3 and 4 versus quartile 1 of LAP, and the adjusted HRs (95% CIs) were 2.903 (2.226-3.784) and 6.298 (4.911-8.077), respectively. There were additive interactions of HTGW (synergy index (SI): 1.678, 95% CI: 1.358-2.072) and high LAP (SI: 1.701, 95% CI: 1.406-2.059) with increased fasting plasma glucose (FPG) on the risk of T2DM. Additionally, a nonlinear (P nonlinear < 0.001) dose-response association was found between LAP and T2DM. Conclusion The subjects with HTGW and high LAP were at high risk of developing T2DM, and the association between LAP and the risk of T2DM may be nonlinear. Our study further demonstrates additive interactions of HTGW and high LAP with increased FPG on the risk of T2DM.

BackgroundObesity is a well-known risk factor for type 2 diabetes mellitus (T2DM). Studies have shown that the Chinese visceral adiposity index (CVAI), a novel visceral adiposity indicator, is positive associated with the risk of T2DM in the Chinese population. This study aimed to investigate the correlation between CVAI and incident T2DM in a Japanese population.MethodsWe performed a secondary analysis of open-access data from a retrospective cohort study. This study included 15,464 participants who received regular medical examinations at Murakami Memorial Hospital. All participants underwent a questionnaire survey, physical examination, and blood biochemical testing at baseline. The main outcome was new-onset T2DM during follow-up. Cox regression analysis and Kaplan–Meier analysis were used to analyze the risk of CVAI on T2DM, and we conducted smooth curve fitting. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of CVAI, body mass index (BMI), and waist circumference (WC) for incident T2DM.ResultsDuring a median follow-up time of 5.39 years, 373 new-onset T2DM events were observed. Kaplan–Meier curves showed that the incidence of T2DM increased as the CVAI increased (log-rank χ2 = 187.1076 and 129.6067 in males and females, respectively, both P <0.001). After adjustment for covariates, per 1 increase of CVAI was associated with a 1.0133-fold and 1.0246-fold higher risk of incident T2DM in males and females, respectively (both P <0.001). Those individuals in the top CVAI quartile group had the highest risk of new-onset T2DM (HR = 3.1568 and 5.8415 in males and females, respectively, both P <0.05). A nonlinear relationship was identified by the smooth fitting curve between CVAI and T2DM events in both genders. ROC analysis indicated that CVAI had better predictive power than BMI and WC in both genders.ConclusionOur results demonstrate that CVAI was significantly associated with an increased risk of new-onset T2DM in Japanese adults.

PurposeCreatinine to body weight (Cre/BW) ratio is considered the independent risk factor for incident type 2 diabetes mellitus (T2DM), but research on this relationship is limited. The relationship between the Cre/BW ratio and T2DM among Chinse individuals is still ambiguous. This study aimed to evaluate the correlation between the Cre/BW ratio and the risk of T2DM in the Chinese population.MethodsThis is a retrospective cohort study from a prospectively collected database. We included a total of 200,658 adults free of T2DM at baseline. The risk of incident T2DM according to Cre/BW ratio was estimated using multivariable Cox proportional hazards models, and a two-piece wise linear regression model was developed to find out the threshold effect.ResultsWith a median follow-up of 3.13 ± 0.94 years, a total of 4001 (1.99%) participants developed T2DM. Overall, there was an L-shaped relation of Cre/BW ratio with the risk of incident T2DM (P for non-linearity < 0.001). When the Cre/BW ratio (× 100) was less than 0.86, the risk of T2DM decreased significantly as the Cre/BW ratio increased [0.01 (0.00, 0.10), P < 0.001]. When the Cre/BW ratio (× 100) was between 0.86 and 1.36, the reduction in the risk of developing T2DM was not as significant as before [0.22 (0.12, 0.38), P < 0.001]. In contrast, when the Cre/BW ratio (× 100) was greater than 1.36, the reduction in T2DM incidence became significantly flatter than before [0.73 (0.29,1.8), P = 0.49].ConclusionThere was an L-shaped relation of Cre/BW ratio with incidence of T2DM in general Chinese adults. A negative curvilinear association between Cre/BW ratio and incident T2DM was present, with a saturation effect predicted at 0.86 and 1.36 of Cre/BW ratio (× 100).

To investigate the impact of dynamic change of waist circumference or body mass index (BMI) on type 2 diabetes mellitus (T2DM) populations in a cohort study. We not only obtained the baseline survey data from program 'Prevention of Multiple Metabolic Disorders and metabolic syndrome (MS) in Jiangsu Province'(PMMJS) which started in 1994, and we conducted twice follow-ups from January 2002 to August 2003, and March 2006 to November 2007. After excluding subjects who were found to have T2DM at baseline, cardiovascular disease(CVD), and BMI<18.5 kg/m(2) , and loss to follow up because of relocation, death or other reasons, a total of 3 461 subjects were included in this analysis. They received investigation including questionnaires investigation, measurement and laboratory examination. The differences of gender, smoking, alcohol drinking and T2DM family history in different groups were examined using χ(2)-test, median and inter-quartile range were calculated for TG, and they were examined by rank test. Four equal parts of the differences of waist circumference and BMI were carried out in the COX regression model, to investigate the association between 2 years change of waist circumference or BMI and incidence of T2DM. We also examined the association between BMI and waist circumference modification and incident risk of T2DM in subjects with normal baseline BMI, baseline obese subjects, subjects with normal baseline waist circumference and baseline abdominal obese subjects. A total of 3 461 participants (1 406 males, 2 055 females) were investigated, including 160 new T2DM cases (60 males, 100 females) who were from between baseline and the second following up. The accumulative incidence was 4.6% (60/3 461). Multivariate COX regression model analysis results showed that the T2DM risk was relatively high in the highest quartile of waist circumference D-value group(HR=2.06, 95% CI: 1.27-3.16), the T2DM risk was also high in the highest quartile of BMI D-value group (HR=1.30, 95% CI: 0.86-1.95). In subjects with abdominal obesity and normal waist circumference at baseline, the incidence rate of T2DM in non-control group was 7.1% (40/565) , 6.3% (45/645), higher than that in control group (3.4%(71/2 096), 4.5%(4/155)) (χ(2) values were 3.98 and 15.18, P values were 0.043 and <0.001). In subjects with normal waist circumference, T2DM risk was higher in non-control group than that in control group (HR=2.12, 95% CI: 1.40-3.22). In abdominal obese subjects, T2DM risk was also higher in non-control group than that in control group (HR=1.14, 95% CI: 1.04-1.92). If waist circumference was not controlled, T2DM risk was high, no matter BMI controlled or not (HR(95% CI) were 1.73(1.17-2.54), 2.45(1.63-3.69) respectively). Controlling the waistline could reduce the risk of diabetes, and once waist circumference was not controlled, T2DM risk would be increased no matter BMI was controlled or not.

Objective To explore the relationship between advancing age and the risk of developing coronary artery disease(CAD), type 2 diabetes mellitus(T2DM), and both coronary artery disease and type 2 diabetes mellitus(CAD+ T2DM). Methods A case-control study was conducted to investigate the relationship between advancing age and the risk of CAD, T2DM, and CAD+ T2DM in middle-aged and elderly patients. Results Aging was independently associated with increased risk of T2DM and CAD + T2DM(P<0.05). Compared with patients aged below 60, the risk of T2DM was higher in patients aged 70 or over(OR=3.80, 95% CI: 2.39-6.04, P=0.000); The risk of CAD+ T2DM was lower in patients aged below 60 than in patients aged 60 to 69(OR=4.14, 95%CI: 2.60-6.60, P=0.000)and in patients aged 70 or over(OR=11.50, 95%CI: 7.18-18.42, P=0.000). Patients of older ages had a 2.78 times higher risk of developing CAD+ T2DM. Conclusions The onset of T2DM, and CAD+ T2DM is associated with age. Key words: Aging; Coronary disease; Comorbidity

BackgroundA simple and readily available biomarker can provide an effective approach for the surveillance of type 2 diabetes mellitus (T2DM) in the elderly. In this research, we aim to evaluate the role of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as an indicator for new-onset T2DM in an elderly Chinese population aged over 75 years.MethodsThis longitudinal retrospective cohort study was conducted using a free database from a health check screening project in China. Participants with baseline TG and HDL measurements were enrolled, and the data of T2DM development were collected. The cumulative incident T2DM rates in different quintile groups of TG/HDL-C ratio (Q1 to Q5) were calculated and plotted. The independent effect of baseline TG/HDL-C ratio on T2DM risk during the follow-up period was tested by the Cox proportional hazard model. Subgroup analysis was also conducted to clarify the role of TG/HDL-C ratio in specific populations.ResultsA total of 231 individuals developed T2DM among 2,571 subjects aged over 75 years during follow-up. Regardless of adjustment for potential confounding variables, elevated TG/HDL-C ratio independently indicated a higher risk of incident T2DM [hazard ratio (HR) = 1.29; 95% confidence interval (CI), 1.14–1.47; P < 0.01. As compared with the lowest quintile (Q1), elevated TG/HDL-C ratio quintiles (Q2 to Q5) were associated with larger HR estimates of incident T2DM [HR (95% CI), 1.35 (0.85–2.17), 1.31 (0.83–2.06), 1.85 (1.20–2.85), and 2.10 (1.38–3.20), respectively]. In addition, a non-linear correlation was found between TG/HDL-C ratio and the risk of T2DM, and the slope of the curve decreased after the cutoff point of 2.54. Subgroup analysis revealed a stronger positive correlation among male individuals and those with body mass index <24 kg/m2.ConclusionsIncreased TG/HDL-C ratio indicates a greater risk of new-onset T2DM regardless of confounding variables. TG/HDL-C ratio is a simple but effective indicator in predicting T2DM in older adults. More future investigations are warranted to further promote the clinical application of TG/HDL-C ratio.

Double trouble: T2DM genetic risk factors play a causal role in CAD.

The Effect of Vitamin D Supplementation on Glycemic Control and Body Mass Index in the Obese, Vitamin D Deficient Adult with Type 2 Diabetes Mellitus: A Systematic Review Protocol

Low skeletal muscle is known to be associated with insulin resistance and suggested as a potential risk factor for type 2 diabetes mellitus (T2DM). Serum creatinine is the primary metabolite of creatine in the skeletal muscle and used as a surrogate of muscle mass. Therefore, low serum creatinine levels may be associated with the risk of T2DM. However, there were few studies about the association between serum creatinine levels and the risk of T2DM in Korea. We aimed to evaluate the association between serum creatinine levels and the risk of T2DM in Korea. We analyzed a total of 264,832 nondiabetic adults older than 30 years of age who had undergone a national health examination from 2002 to 2012 in the Korean National Health Insurance Service Cohort. The serum creatinine was divided into four categories (&amp;lt;0.70, 0.70∼0.89, 0.90∼1.19, ≥1.20 mg/dl for men, &amp;lt;0.60, 0.60∼0.79, 0.80∼1.09, ≥1.10 mg/dl for women). Hazard ratios for T2DM were calculated using Cox proportional hazards models. In men, serum creatinine levels and the risk for T2DM showed an inverse J-shaped association, with the lowest risk among men with serum creatinine between 0.90 and 1.19 mg/dl. This inverse J-shaped association between serum creatinine level and the risk for T2DM was confirmed after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose. In women, subjects with highest serum creatinine level had the highest risk of T2DM. However, serum creatinine was not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. Lower serum creatinine was significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl even after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. Highest creatinine level was significantly associated with an increased risk of T2DM in women, however, this association disappeared after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. Disclosure D. Song: None. H. Lee: None. Y. Hong: None. Y. Sung: None.

Triglyceride-glucose index (TyG index) is associated with type 2 diabetes mellitus (T2DM), but research on this relationship is limited in Japan. The purpose of this study was to evaluate the correlation between TyG index and the risk of T2DM in the Japanese population. Here, 12732 participants were selected from the NAGALA study (NAfld in the Gifu Area, Longitudinal Analysis) conducted between 2004 and 2015 for a retrospective cohort analysis. The association between TyG index and T2DM was assessed using the Cox proportional-hazard model. Subgroup analyses were conducted according to age, sex, smoking status, alcohol consumption, waist circumference, BMI, and follow-up duration. The formula for TyG index was expressed as ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. After follow-up, 150 (1.18%) patients developed T2DM. After adjusting for potential confounders, a linear relationship was observed between TyG and the risk of T2DM. After adjusting for age, sex, BMI, waist circumference, HDL-cholesterol, total cholesterol, systolic blood pressure, regular exercise, smoking status, and alcohol consumption, TyG index, as a continuous variable, was associated with an increased risk of T2DM (adjusted hazard ratio (aHR), 1.79; 95% confidence interval (95% CI), 1.25-2.57). Compared with the first quartile of TyG index, subjects in the fourth quartile were 2.33-fold more likely to develop T2DM (aHR 2.33, 95% CI 1.09-4.96; P for trend 0.0224). Subgroup analyses showed that the association between TyG index and incident T2DM stably existed in different subgroups according to the variables tested. Therefore, TyG index was linearly related to the risk of incident T2DM in the Japanese population and may be used as a monitoring tool.