Independent Risk Factor For Type 2 Diabetes Mellitus Research Articles

Narrative literature review of antidiabetic drugs' effect on hyperuricemia: elaborating actual data and mechanisms.

To optimize the treatment plan for patients with type 2 diabetes mellitus (T2DM) and hyperuricemia, this narrative literature review summarizes the effect of antidiabetic drugs on serum uric acid (SUA) levels using data from observational studies, prospective clinical trials, post hoc analyses, and meta-analyses. SUA is an independent risk factor for T2DM, and evidence has shown that patients with both gout and T2DM exhibit a mutually interdependent effect on higher incidences. We find that insulin and dipeptidyl peptidase 4 inhibitor (DPP-4i) except linagliptin could increase the SUA and other drugs including metformin, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), linagliptin, sodium-glucose cotransporter 2 inhibitors (SGLT2i), and α-glucosidase inhibitors have a reduction effect on SUA. We explain the mechanisms of different antidiabetic drugs above on SUA and analyze them compared with actual data. For sulfonylureas, meglitinides, and amylin analogs, the underlying mechanism remains unclear. We think the usage of linagliptin and SGLT2i is the most potentially effective treatment of patients with T2DM and hyperuricemia currently. Our review is a comprehensive summary of the effects of antidiabetic drugs on SUA, which includes actual data, the mechanisms of SUA regulation, and the usage rate of drugs.

Apolipoprotein E E3/E4 genotype is associated with an increased risk of type 2 diabetes mellitus complicated with coronary artery disease

ObjectiveDyslipidemia is a co-existing problem in patients with diabetes mellitus (DM) and coronary artery disease (CAD), and apolipoprotein E (APOE) plays an important role in lipid metabolism. However, the relationship between the APOE gene polymorphisms and the risk of developing CAD in type 2 DM (T2DM) patients remains controversial. The aim of this study was to assess this relationship and provide a reference for further risk assessment of CAD in T2DM patients.MethodsThe study included 378 patients with T2DM complicated with CAD (T2DM + CAD) and 431 patients with T2DM alone in the case group, and 351 individuals without DM and CAD were set as controls. The APOE rs429358 and rs7412 polymorphisms were genotyped by polymerase chain reaction (PCR) - microarray. Differences in APOE genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for age, gender, body mass index (BMI), history of smoking, and history of drinking to access the relationship between APOE genotypes and T2DM + CAD risk.ResultsThe frequencies of the APOE ɛ3/ɛ4 genotype and ε4 allele were higher in the T2DM + CAD patients, and the frequencies of the APOE ɛ3/ɛ3 genotype and ε3 allele were lower than those in the controls (all p < 0.05). The T2DM + CAD patients with ɛ4 allele had higher level in low-density lipoprotein cholesterol (LDL-C) than those in patients with ɛ2 and ɛ3 allele (p < 0.05). The results of logistic regression analysis showed that age ≥ 60 years old, and BMI ≥ 24.0 kg/m2 were independent risk factors for T2DM and T2DM + CAD, and APOE ɛ3/ɛ4 genotype (adjusted odds ratio (OR) = 1.93, 95% confidence interval (CI) = 1.18–3.14, p = 0.008) and ɛ4 allele (adjusted OR = 1.97, 95% CI = 1.23–3.17) were independent risk factors for T2DM + CAD. However, the APOE genotypes and alleles were not found to have relationship with the risk of T2DM.ConclusionsAPOE ε3/ε4 genotype and ε4 allele were independent risk factors for T2DM complicated with CAD, but not for T2DM.

Association between type 2 diabetes mellitus and body composition based on MRI fat fraction mapping.

To explore the association between type 2 diabetes mellitus (T2DM) and body composition based on magnetic resonance fat fraction (FF) mapping. A total of 341 subjects, who underwent abdominal MRI examination with FF mapping were enrolled in this study, including 68 T2DM patients and 273 non-T2DM patients. The FFs and areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and abdominal muscle (AM) were measured at the level of the L1-L2 vertebral. The FF of bone marrow adipose tissue (BMAT) was determined by the averaged FF values measured at the level of T12 and L1 vertebral, respectively. The whole hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured based on 3D semi-automatic segmentation on the FF mapping. All data were analyzed by GraphPad Prism and MedCalc. VAT area, VAT FF, HFF, PFF of T2DM group were higher than those of non-T2DM group after adjusting for age and sex (P < 0.05). However, there was no differences in SAT area, SAT FF, BMAT FF, AM area and AM FF between the two groups (P > 0.05). VAT area and PFF were independent risk factors of T2DM (all P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) for VAT area and PFF in differentiating between T2DM and non-T2DM were 0.685 and 0.787, respectively, and the AUC of PFF was higher than VAT area (P < 0.05). Additionally, in seemingly healthy individuals, the SAT area, VAT area, and AM area were found to be significantly associated with being overweight and/or obese (BMI ≥ 25) (all P < 0.05). In this study, it was found that there were significant associations between T2DM and VAT area, VAT FF, HFF and PFF. In addition, VAT area and PFF were the independent risk factors of T2DM. Especially, PFF showed a high diagnostic performance in discrimination between T2DM and non-T2DM. These findings may highlight the crucial role of PFF in the pathophysiology of T2DM, and it might be served as a potential imaging biomarker of the prevention and treatment of T2DM. Additionally, in individuals without diabetes, focusing on SAT area, VAT area and AM area may help identify potential health risks and provide a basis for targeted weight management and prevention measures.

An early prediction model for type 2 diabetes mellitus based on genetic variants and nongenetic risk factors in a Han Chinese cohort.

We aimed to construct a prediction model of type 2 diabetes mellitus (T2DM) in a Han Chinese cohort using a genetic risk score (GRS) and a nongenetic risk score (NGRS). A total of 297 Han Chinese subjects who were free from type 2 diabetes mellitus were selected from the Tianjin Medical University Chronic Disease Cohort for a prospective cohort study. Clinical characteristics were collected at baseline and subsequently tracked for a duration of 9 years. Genome-wide association studies (GWASs) were performed for T2DM-related phenotypes. The GRS was constructed using 13 T2DM-related quantitative trait single nucleotide polymorphisms (SNPs) loci derived from GWASs, and NGRS was calculated from 4 biochemical indicators of independent risk that screened by multifactorial Cox regressions. We found that HOMA-IR, uric acid, and low HDL were independent risk factors for T2DM (HR >1; P<0.05), and the NGRS model was created using these three nongenetic risk factors, with an area under the ROC curve (AUC) of 0.678; high fasting glucose (FPG >5 mmol/L) was a key risk factor for T2DM (HR = 7.174, P< 0.001), and its addition to the NGRS model caused a significant improvement in AUC (from 0.678 to 0.764). By adding 13 SNPs associated with T2DM to the GRS prediction model, the AUC increased to 0.892. The final combined prediction model was created by taking the arithmetic sum of the two models, which had an AUC of 0.908, a sensitivity of 0.845, and a specificity of 0.839. We constructed a comprehensive prediction model for type 2 diabetes out of a Han Chinese cohort. Along with independent risk factors, GRS is a crucial element to predicting the risk of type 2 diabetes mellitus.

FRI145 Prevalence Of Type 2 Diabetes Mellitus And Risk Factors For Its Development In Patients With Primary Aldosteronism

Abstract Disclosure: M. Araujo-Castro: None. M. Paja Fano: None. M. González Boillos: None. B. Pla Peris: None. E. Pascual-Corrales: None. A. García Cano: None. P. Parra: None. P. Martín Rojas-Marcos: None. J. Ruiz-Sanchez: None. A. Vicente Delgado: None. E. Gómez Hoyos: None. R. Ferreira: None. I. García Sanz: None. M. Recasens Sala: None. R. Barahona San Millan: None. M. Picón César: None. P. Díaz Guardiola: None. J. García González: None. C.M. Perdomo: None. L. Manjón Miguélez: None. R. García Centeno: None. Á. Rebollo Román: None. P. Gracia Gimeno: None. C. Robles Lázaro: None. M. Morales-Ruiz: None. M. Calatayud Gutiérrez: None. S. Simone Andree Furio Collao: None. D. Meneses: None. M. Sampedro Nuñez: None. V. Escudero Quesada: None. E. Mena Ribas: None. A. Sanmartin Sánchez: None. C. Gonzalvo Diaz: None. C. Lamas: None. F. Hanzu: None. Purpose: To evaluate the prevalence of type 2 diabetes mellitus (T2DM) in patients with primary aldosteronism (PA) and the risk factors for its development. Methods: A retrospective multicenter study of PA patients in follow-up in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Adrenal venous sampling (AVS) was informative of laterality in 128 out of 226 patients and adrenalectomy was performed in 201 patients. Unilateral PA was defined as biochemical cure after adrenalectomy or as a lateralization index in AVS &amp;gt; 2 with ACTH or &amp;gt;3 without ACTH stimulation. Results: Overall, 649 patients with PA were included. Median age was 55.5 (range 27.3-81.6) years, 59.1% were female and 58.5% had hypokalemia at diagnosis. A total of 224 patients were classified as unilateral PA (142 based on biochemical cure after adrenalectomy and 82 based also on AVS results) and 49 as bilateral PA. At diagnosis, 21.2% (n=137) had T2DM and 25 of them had microvascular complications, being diabetic kidney disease the most common (n=19). We identified as risk factors of type 2 diabetes: male sex (OR 2.80 [1.81-4.34], P&amp;lt;0.001), older age (OR 1.05 [1.03-1.07], P&amp;lt;0.001), familiar history of T2DM (OR 4.64 [2.39-8.99]), P&amp;lt;0.001), dyslipidemia (OR 4.05 [2.67-6.14], P&amp;lt;0.001), cardiovascular (OR 1.30 [1.14-1.48], P&amp;lt;0.001) and cerebrovascular disease (OR 1.59 [0.92-2.74], P=0.003), sleep apnea syndrome (SAS) (OR 2.21 [1.34-3.63], P=0.003), higher BMI (OR 1.06 per unit [1.03-1.10], &amp;lt;0.001), hypertension duration (OR 1.04 per year [1.02-1.06], P&amp;lt;0.001) and the number of antihypertensive drugs (OR 1.50 [1.29-1.74], P&amp;lt;0.0001). In the multivariant analysis, all these variables were independent risk factors for T2DM except for SAS, hypertension duration, sex, and BMI. No association was observed with plasma aldosterone concentration, potassium levels, unilaterality of PA or other parameters. No significant differences in the evolution of the glycemic control (fasting plasma glucose and HBA1c) were observed between T2DM who underwent surgery and those medically treated (P&amp;gt;0.05). Conclusion: Type 2 diabetes affects about one quarter of patients with PA and risk factors for its development are common than to the general population. Medical and surgical treatment provide a similar benefit in terms of glucose control in patients with PA and T2DM. Presentation: Friday, June 16, 2023

Population attributable fractions of fatty liver disease for type 2 diabetes Mellitus

PurposeTo determine the population attributable fraction (PAF) of fatty liver disease (FLD) for type 2 diabetes mellitus (T2DM) and compare it to the PAFs of other metabolic abnormalities.MethodsWe conducted a 10-year retrospective cohort study of 33,346 individuals in Karamay Central Hospital of Xinjiang. Individuals were followed up for T2DM occurrence based on FBS. The PAFs of FLD were calculated generally and respectively in different sex and age groups. A comparison of the PAF of FLD and that of other metabolic abnormalities, as well as the PAFs of FLD in different groups classified based on age and sex, was performed using Cox regression.ResultsDuring an average follow-up period of 3.71 years, 1486 T2DM were diagnosed. The incidence density of T2DM was 1.2/100 person-years, and cumulative incidence rate was 4456.31/100,000 person-years. Partial PAF (PAFp) of FLD in the entire population was 23.11%. In the male population, PAFp was higher at 30–40 years old. In the female population, it was higher when age ≥ 60 years old. In multivariable Cox regression model, FLD, male sex, age ≥ 45 years old, overweight, hypertriglyceridaemia, and systolic hypertension were independent risk factors for T2DM, with corresponding PAFp of 25.00%, 24.99%, 36.47%, 24.96%, 5.71%, and 6.76%, respectively. Age ≥ 45 years old showed the highest PAFp and adjusted hazard ratio, followed by FLD.ConclusionsFLD contributes more to T2DM incidence than other metabolic disorders. Particular attention should be given to male populations of 30–40 and female populations above 60 for FLD prevention and treatment.

Dietary intakes of methionine, threonine, lysine, arginine and histidine increased risk of type 2 diabetes in Chinese population: does the mediation effect of obesity exist?

BackgroundPublished studies have shown positive associations of branched chain and aromatic amino acids with type 2 diabetes mellitus (T2DM), and the findings remain consistent. However, the associations of other essential and semi-essential amino acids, i.e., methionine (Met), threonine (Thr), lysine (Lys), arginine (Arg) and histidine (His), with T2DM remain unknown. Obesity is an important independent risk factor for T2DM, and excessive amino acids can convert into glucose and lipids, which might underlie the associations of amino acids with obesity. Therefore, we aimed to estimate the associations between dietary intakes of these 5 amino acids and T2DM risk, as well as the mediation effects of obesity on these associations, in a Chinese population.MethodsA total of 10,920 participants (57,293 person-years) were included, and dietary intakes of 5 amino acids were investigated using 24-h dietary recalls. Anthropometric obesity indices were measured at both baseline and the follow-up endpoints. Associations of amino acids with T2DM were estimated using COX regression models, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were shown. The mediation effects of obesity indices were analyzed, and the proportion of the mediation effect was estimated.ResultsHigher intakes of the 5 amino acids were associated with increasing T2DM risk, while significant HRs were only shown in men after adjustments. No interaction by gender was found. Regression analyses using quintiles of amino acids intakes showed that T2DM risk was positively associated with amino acids intakes only when comparing participants with the highest intake levels of amino acids to those with the lowest intake levels. Adjusted correlation coefficients between amino acid intakes and obesity indices measured at follow-up endpoints were significantly positive. Mediation analyses showed that mediation effects of obesity indices existed on associations between amino acids intakes and T2DM risk, and the mediation effect of waist circumference remained strongest for each amino acid.ConclusionsWe found positive associations of dietary intakes of Met, Thr, Lys, Arg and His with increasing T2DM risk in general Chinese residents, on which the mediation effect of obesity existed. These findings could be helpful for developing more constructive guidance in the primary prevention of T2DM based on dietary interventions.

Associations of blood glucose, helper T cells and cytokine levels with degree of periodontal lesion in type 2 diabetes mellitus patients accompanied by chronic periodontitis.

To explore the associations of blood glucose with degree of periodontal lesions in patients with type 2 diabetes mellitus (T2DM) accompanied by chronic periodontitis (CP). Sixty-five eligible patients were included as a T2DM+CP group, another 65 patients with T2DM alone were included as a T2DM group, and another 65 patients with CP alone were included as a CP group. Their blood glucose, insulin, Th cells and cytokine levels and periodontal indices were compared. The correlations between each index and periodontal indices were analysed. The influencing factors for T2DM accompanied by CP were explored. The levels of fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR) of T2DM+CP, T2DM and CP groups followed a descending order (P<0.05). FPG, HbA1c, FINS, CD4+ Th1 cell, CD4+ Th17 cell, interferon-gamma (IFN-γ) and interleukin-17 (IL-17) all had positive correlations with gingival index, bleeding index, probing depth and attachment loss in T2DM patients accompanied by CP (P<0.05). Periodontal lesions were more severe in T2DM patients accompanied by CP, and the severity was positively correlated with the levels of FPG, HbA1c, Th1, Th17, IFN-γ and IL-17. High levels of FPG, HbA1c, IFN-γ and IL-17 are independent risk factors for T2DM accompanied by CP.

1263-P: Gender Differences in the Impact of Low Muscle Mass on Type 2 Diabetes Incidence—Eighteen-Year Follow-up Data from the Prospective Korean Genome and Epidemiology Study

Background: Current evidence suggests that diminished muscle mass is associated with an increased risk of diabetes. This study aimed to investigate whether the effect of low muscle mass (LMM) on incident diabetes varied depending on the tracking period using a prospective, longitudinal design. Methods: We recruited 6968 subjects without diabetes, aged 40 to 69 years, from the Korean Genomes and Epidemiology study and followed them to monitor the development of type 2 diabetes mellitus (T2DM). A standard 75-g oral glucose tolerance test was conducted at every 2-year follow-up visit. Skeletal muscle mass was assessed using bioelectrical impedance analysis, and a weight-adjusted skeletal muscle mass was defined as muscle mass index (MMI). We assessed the relationship between LMM, the sex-specific lowest tertile of MMI, and the risk of developing T2DM using Cox regression models. Results: Of 6968 (47.4% men), 1846 progressed diabetes during the 18-year follow-up. LMM was associated with an increased risk of T2DM at 10 years and 10-18 years of follow-up in both genders after adjustment for confoundings. After additional adjustment for waist circumference, men with LMM were at significant risk of incident diabetes during the 10-year follow-up (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.28-1.86) but lost significance in 10-18 years., whereas women with LMM were at significantly increased risk (HR 1.32, 95% CI 1.03-1.69) only in 10-18 years. Over 18 years, LMM in men was consistently associated with an increased risk of diabetes from the initial period (at 2-year follow-up), whereas LMM in women has been shown to increase risk in the late period (from 12-year follow-up). Conclusion: This study showed that LMM is an independent risk factor for T2DM with gender differences over time. LMM was a constant risk factor for diabetes in men, whereas it affected the later onset of diabetes in women. Disclosure E.Kim: None. Y.Cho: None. O.Hong: None. S.Moon: None. J.Han: None. S.Yoo: None. N.H.Cho: None.

U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population.

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.

Study on nomograph predicting the risk of type 2 diabetes mellitus in Beijing community adults

Objective: Development and validation of a nomogram for predicting the 4-year incidence of type-2 diabetes mellitus (T2DM) in a Chinese population was attempted. Methods: This prospective cohort study was conducted in Shijingshan District Pingguoyuan Community (Beijing, China) from December 2011 to April 2012 among adults aged≥40 years not suffering from T2DM. Finally, 8 058 adults free of T2DM were included with a median duration of follow-up of 4 years. Participants were divided into a modeling group and verification group using simple random sampling at a ratio of 7∶3. Univariate and multivariate Cox proportional risk models were applied to identify the independent risk predictors in the modeling group. A nomogram was constructed to predict the 4-year incidence of T2DM based on the results of multivariate analysis. The Concordance Index and calibration plots were used to evaluate the differentiation and calibration of the nomogram in both groups. Results: A total of 5 641 individuals were in the modeling group and 2 417 people were in the validation group, of which 265 and 106 had T2DM, respectively, at 4-year follow-up. In the modeling group, age (HR=1.349, 95%CI 1.011-1.800), body mass index (HR=1.347, 95%CI 1.038-1.746), hyperlipidemia (HR=1.504, 95%CI 1.133-1.996), fasting blood glucose (HR=4.189, 95%CI 3.010-5.830), 2-h blood glucose level according to the oral glucose tolerance test (HR=3.005, 95%CI 2.129-4.241), level of glycosylated hemoglobin (HR=3.162, 95%CI 2.283-4.380), and level of γ-glutamyl transferase (HR=1.920, 95%CI 1.385-2.661) were independent risk factors for T2DM. Validation of the nomogram revealed the Concordance Index of the modeling group and validation group to be 0.906 (95%CI 0.888-0.925) and 0.844 (95%CI 0.796-0.892), respectively. Calibration plots showed good calibration in both groups. Conclusion: These data suggest that our nomogram could be a simple and reliable tool for predicting the 4-year risk of developing T2DM in a high-risk Chinese population.

Circulating Bone Morphogenetic Protein-9 is Decreased in Patients with Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease.

We aimed to examine the association between bone morphogenetic protein-9 (BMP-9) and type 2 diabetes mellitus (T2DM) in conjunction with non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR) and to identify evidence supporting the potential role of BMP-9 in the clinical prevention and treatment of T2DM in conjunction with NAFLD. One hundred and twenty subjects were included in this study. We sorted all of the subjects into four groups of equal size (n=30 each). A trained expert assessed the height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the subjects and computed the body mass index (BMI). All subjects had their fasting blood glucose (FBG), fasting insulin (FINS), serum BMP-9, and biochemical indices assessed. Significant variations were observed in BMI, SBP, DBP, ALT, TC, TG, HDL-C, LDL-C, ApoB, FBG, FINS, HOMA-IR, and serum BMP-9 among the four groups (P<0.05). The level of serum BMP-9 was positively correlated with HDL-C, while the level of serum BMP-9 was negatively correlated with BMI, SBP, DBP, ALT, TC, TG, LDL-C, FBG, FINS, and HOMA-IR. Multiple stepwise regression analyses revealed that FINS, LDL-C, HDL-C, and BMI were independent factors impacting serum BMP-9 levels (P<0.05). Logistic regression analyses revealed that BMP-9 was a protective factor for T2DM paired with NAFLD, while HOMA-IR was a risk factor. Serum BMP-9 levels are significantly lower in the T2DM+NAFLD group when compared to other groups, and BMP-9 is an independent risk factor for T2DM paired with NAFLD.

Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio: A valuable predictor of type 2 diabetes mellitus incidence.

BackgroundGamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) have been proven to be valuable predictors of type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the association between GGT/HDL-C ratio and incident T2DM.MethodsThe study retrospectively analyzed 15453 participants from 2004 to 2015. Cox proportional hazards regression models and Kaplan-Meier curves were used to elucidate the effect of GGT/HDL-C ratio on T2DM. Restricted cubic spline (RCS) analysis was performed to explore any non-linear correlation between GGT/HDL-C ratio and the risk of T2DM. The predictive performance of GGT, HDL-C and GGT/HDL-C ratio for T2DM was evaluated utilizing receiver-operating-characteristic (ROC) curves.ResultsDuring a median follow-up of 5.39 years, 373 cases of incident T2DM were observed. Kaplan-Meier curves showed that the cumulative probabilities of T2DM increased in the participants with higher GGT/HDL-C ratio significantly (P < 0.001). Cox models further clarified that high GGT/HDL-C ratio was an independent risk factor for T2DM (HR = 1.01, 95% CI = 1.00-1.01, P = 0.011). Linear positive correlation between GGT/HDL-C ratio and the risk of T2DM was demonstrated through RCS analysis. In the ROC analysis, GGT/HDL-C ratio (AUC = 0.75, 95% CI = 0.73-0.77) showed competitive role in the prediction of T2DM compared with single GGT and HDL-C.ConclusionsThe GGT/HDL-C ratio could serve as a valuable predictor of T2DM, and the risk of T2DM increases in the condition of higher GGT/HDL-C ratio.

The possible correlation between serum GRB2 levels and carotid atherosclerosis in patients with type 2 diabetes mellitus.

Background and purposeGrowth factor receptor-bound protein 2(GRB2), a bridging protein. An animal study showed that downregulation of GRB2 inhibited the activation of PI3K/AKT/NF-kB pathway which improved lipid accumulation and inflammatory infiltration in rats with atherosclerosis (AS), resulting in an anti-AS effect. This was the first study to investigate blood GRB2 levels in type 2 diabetes mellitus(T2DM) patients with carotid atherosclerosis (CAS), exploring its relationship with various metabolic indicators, and further, examining whether GRB2 has an AS effect in patients with T2DM.MethodsA total of 203 participants were recruited in the study, including 69 T2DM patients without CAS (T2DM group), 67 T2DM patients with CAS (CAS group), and 67 in the age-sex-matched healthy subjects (Control group). Serum GRB2 levels were measured using enzyme-linked immunosorbent assay (ELISA) in 203 subjects who had received carotid ultrasonography. In addition, cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), glycosylated hemoglobin (HBA1c), fasting insulin (FINS), hypersensitive C-reactive protein (Hs-CRP), and Interleukin 6 (IL-6) were also tested. The correlation between serum GRB2 levels and other indexes was analyzed. Finally, we analyzed the risk factors affecting carotid intima-media thickness (CIMT) in T2DM patients.ResultsSerum GRB2 levels were increased in the T2DM group than in the control group, and further elevated in the CAS group (median 3.05 vs 4.40 vs 7.09 ng/ml, P<0.001). Spearman correlation analysis showed that GRB2 concentrations were negatively correlated with HDL-C, and positively associated with duration of diabetes, waist-to-hip ratio (WHR), TC, HBA1c, FPG, FINS, homeostasis model assessment-insulin resistance index (HOMA-IR), Hs-CRP, IL-6 and CIMT (P<0.01). Furthermore, serum GRB2 levels (P<0.001) remained independently related to CIMT after adjusting for the age, sex, duration of diabetes, and Body Mass Index (BMI) variables. Stepwise multiple linear regression analysis showed that IL-6, HDL-C, HBA1c, and CIMT are independent correlation factors of serum GRB2 (P<0.01). Univariate logistic regression suggested that disease duration, WHR, systolic blood pressure (SBP), TG, HDL-C, HBA1c, FPG, HOMA-IR, IL-6, Hs-CRP, and GRB2 independently associated with T2DM is combined with CAS(P<0.05). And multivariate logistic regression analysis showed that duration of diabetes, IL-6, and serum GRB2 levels were independent risk factors for T2DM combined with CAS (P<0.05), and serum GRB2 levels were a highly sensitive indicator of early AS (OR=1.405, 95% CI: 1.192-1.658 P<0.001). Moreover, the ROC curve AUC area of serum GRB2 expression levels was 0.80 (95%CI: 0.7291-0.8613, P < 0.001), with a sensitivity of 83.58% and specificity of 70.59%. The risk of CAS was substantially higher in patients with T2DM whose serum GRB2 concentration was >4.59 ng/ml.ConclusionsSerum GRB2 concentrations were significantly increased in T2DM combined with CAS, and serum GRB2 levels were linearly correlated with CIMT, suggesting that GRB2 may be involved in the occurrence and development of T2DM with CAS, which can be used as a predictor of whether T2DM is combined with CAS.

Characteristics of pregnancy with gestational diabetes mellitus and the consecutive pregnancy as predictors for future diabetes mellitus type 2

AimTo explore possible obstetrical history-related, modifiable risk factors of future type 2 diabetes mellitus (T2DM), with focus on characteristics of the index gestational diabetes mellitus (GDM) pregnancy and the consecutive pregnancy. MethodsThis retrospective, population-based, cohort study included 788 women with GDM, who had consecutive deliveries at Emek Medical Center during 1991–2012. Women with pre-existing diabetes were excluded. Factors associated with T2DM development were examined using stepwise multiple Cox regression model. ResultsOverall 178 women developed T2DM (23%). Multivariable analysis demonstrated that the most significant independent risk factors for T2DM development were birth weight ≥ 4000 g (HRadj1.7 95% CI [1.001–2.8]), fasting oral glucose tolerance test value (OGTT, HRadj1.03 95% CI [1.01–1.04], 1-hour post-OGTT glucose value (HRadj1.01 95% CI [1.006–1.02]), earlier gestational week in which GDM was diagnosed (HRadj 0.96 95% CI [0.93–0.99]), higher parity (HRadj 1.15 95% CI [1.06–1.25] and GDM recurrence in the consecutive delivery (HRadj2.4 95% CI [1.6–3.7]). Kaplan Meier survival curve of the time from the consecutive pregnancy until T2DM development showed a statistically significant effect of GDM recurrence and the risk for T2DM. Body mass index (BMI) gain between pregnancies and inter-pregnancy interval were not independent risk factors for T2DM. ConclusionsObstetric characteristics of women with GDM and particularly GDM recurrence are associated with increased risk for T2DM. Strategies to prevent those factors and especially GDM recurrence might reduce the risk of future T2DM.

Olfactory dysfunction is a risk factor for the comorbidity of mild cognitive impairment and Type 2 diabetes mellitus.

Diabetes can accelerate cognitive decline and hence affect the prognosis of patients with Type 2 diabetes mellitus (T2DM). Olfactory assessment can facilitate the early identification of cognitive impairment among T2DM patients. This study aims to evaluate the effects of olfactory function on mild cognitive impairment (MCI) in patients with T2DM. A total of 472 T2DM patients who were hospitalized in a first-class hospital in Changsha City from June 2018 to June 2019 were enrolled for this study. Olfactory function and cognitive function were assessed by the alcohol sniff test and the Montreal Cognitive Assessment (MoCA) scale, respectively. Participants were categorized into a comorbidity of MCI and T2DM group and a T2DM group. General information was collected and some biochemical indices were tested. Difference in the alcohol sniff test score between the 2 groups was assessed by 2-sample t-test. Difference in the presence of olfactory dysfunction between the 2 groups was assessed by χ2 test, and multivariable logistic regression was used to determine the relevant factors contributing to the comorbidity of MCI and T2DM. Of the 472 participants, 162 were identified with MCI, making the comorbidity rate at 34.3%. Values of isopropyl alcohol sniff test were significantly different between the 2 groups [(9.15±3.22) cm vs (21.03±4.36) cm, P<0.05]. The number of patients with olfactory dysfunction also differed significantly between the 2 groups (120 vs 50). After adjustment for age, educational level, T2DM duration, fasting insulin, and glycosylated hemoglobin (HbA1c), multivariate logistic regression analysis showed older age (OR=1.14, 95% CI 1.09 to 1.20), longer course of diabetes (OR=1.21, 95% CI 1.12 to 1.31), and olfactory-impaired (OR=4.61, 95% CI 3.04 to 6.18) were independent risk factors for T2DM combined with MCI, and the high education level (OR=0.26, 95% CI 0.15 to 0.38) was an independent protective factor for T2DM combined with MCI. Olfactory dysfunction is an independent risk factor for the comorbidity of MCI and T2DM. Special attention should be paid to those with olfactory dysfunction when carrying out cognitive interventions in T2DM patients.

The causal association between body mass index and type 2 diabetes mellitus-evidence based on regression discontinuity design.

This study aimed to investigate and determine the precise causal association between body mass index (BMI) and type 2 diabetes mellitus (T2DM) using a regression discontinuity design (RDD). The cross-sectional data of 8550 participants were from the China Health and Nutrition Survey (CHNS) in 2015. Influencing factors with statistically significant were selected with logistic regression analysis, and a risk prediction model was established to obtain the risk of individuals suffering from T2DM. RDD was performed with BMI as the grouping variable and the risk of individuals suffering from T2DM as the outcome variable. The predictive factors in the T2DM risk prediction model were age, gender, BMI, habitation, education, physical activity level, preference for sugary beverages, walking, self-evaluation health status and history of hypertension. The AUC (area under receiver operating characteristic curve) of the T2DM risk prediction model was 0.849 (95% CI: 0.833, 0.866). BMI was an independent risk factor for T2DM (OR=1.109, p<0.001); at BMI=31 kg/m2 , the risk of T2DM increased sharply by 5.03% (p=0.006). There was a positive causal association between BMI and T2DM; when BMI=31 kg/m2 , the risk of individuals suffering from T2DM was sharply increased.

Interaction between the rs9356744 polymorphism and metabolic risk factors in relation to type 2 diabetes mellitus: The Cardiometabolic Risk in Chinese (CRC) Study.

The understanding of the genetic basis of type 2 diabetes mellitus (T2DM) has progressed rapidly, but the interactions among common genetic variants and metabolic risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and metabolic environments on the risk of T2DM. Obesity is emerging as an independent risk factor for T2DM and arterial stiffness. Here, we examined the effect of the rs9356744 polymorphism in the body mass index (BMI) gene CDKAL1 on the risk of T2DM in East Asians and particularly assessed the interactions between this polymorphism and other metabolic risk factors. A total of 1975 subjects in whom the rs9356744 polymorphism had been detected in the CDKAL1 gene were enrolled in this study. The height, weight, blood pressure and relevant markers, including glucose, lipids, liver and renal function, of the participants were successfully measured. Pulse wave velocity (PWV) was measured using an automatic wave form analyzer. At baseline, we found a significant association between BMI and rs9356744 genotypes (CC, CT, TT) (P = 0.048). After adjusting for confounding factors, including sex, age and BMI, participants carrying the T allele of rs9356744 showed a lower incidence of T2DM. Further adjustment for blood pressure and lipids did not appreciably change the results (P = 0.019, 0.009, 0.015, respectively). We found significant interactions between the rs9356744 polymorphism and high-density lipoprotein (HDL), serum uric acid (SUA) and carotid-femoral pulse wave velocity (cf-PWV) in relation to T2DM incidence (P for interaction = 0.007, 0.002, 0.004, respectively), especially in the group with the lowest SUA level and the group with the highest HDL and cf-PWV levels (P for trend = 0.006, 0.008, 0.018, respectively). Furthermore, we found a significant interaction between the rs9356744 polymorphism and cf-PWV in relation to the level of 2-h plasma glucose in the oral glucose tolerance test (OGTT) (P for interaction = 0.0341). In summary, the T allele of rs9356744 was an independent protective factor for T2DM. There were significant interactions between rs9356744 and HDL, SUA, and cf-PWV in relation to T2DM risk.

Development and Validation of a Nomogram to Predict Type 2 Diabetes Mellitus in Overweight and Obese Adults: A Prospective Cohort Study from 82938 Adults in China.

Background The twin epidemic of overweight/obesity and type 2 diabetes mellitus (T2DM) is a major public health problem globally, especially in China. Overweight/obese adults commonly coexist with T2DM, which is closely related to adverse health outcomes. Therefore, this study aimed to develop risk nomogram of T2DM in Chinese adults with overweight/obesity. Methods We used prospective cohort study data for 82938 individuals aged ≥20 years free of T2DM collected between 2010 and 2016 and divided them into a training (n = 58056) and a validation set (n = 24882). Using the least absolute shrinkage and selection operator (LASSO) regression model in training set, we identified optimized risk factors of T2DM, followed by the establishment of T2DM prediction nomogram. The discriminative ability, calibration, and clinical usefulness of nomogram were assessed. The results were assessed by internal validation in validation set. Results Six independent risk factors of T2DM were identified and entered into the nomogram including age, body mass index, fasting plasma glucose, total cholesterol, triglycerides, and family history. The nomogram incorporating these six risk factors showed good discrimination regarding the training set, with a Harrell's concordance index (C-index) of 0.859 [95% confidence interval (CI): 0.850–0.868] and an area under the receiver operating characteristic curve of 0.862 (95% CI: 0.853–0.871). The calibration curves indicated well agreement between the probability as predicted by the nomogram and the actual probability. Decision curve analysis demonstrated that the prediction nomogram was clinically useful. The consistent of findings was confirmed using the validation set. Conclusions The nomogram showed accurate prediction for T2DM among Chinese population with overweight and obese and might aid in assessment risk of T2DM.

One elevated oral glucose tolerance test value in pregnancy increases the risk for future diabetes mellitus type 2.

Women with only one elevated 100g OGTT value are not considered as having gestational diabetes mellitus (GDM) and therefore there are no recommendations to address this population as a risk group for type 2 diabetes mellitus (T2DM). We aimed to elucidate whether one elevated OGTT value increases the risk for T2DM. A retrospective population-based cohort study of women with a first diagnosis of GDM who delivered between 1991 and 2011 was conducted. Women were divided according to GDM diagnosis criteria into three groups: (1) at least two elevated values of Carpenter and Coustan criteria (C&C; N = 209), (2) At least two elevated values of the National Diabetes Data Group (NDDG) criteria (NDDG2; N = 290) and (3) only one elevated value of the NDDG criteria (NDDG1; N = 226). A fourth group comprising women without GDM was included (control; N = 352). The primary outcome was the development of T2DM. The mean follow-up was 12.4 ± 5.3years and the mean age at follow-up was 43.0 ± 5.7years. The rate of T2DM in the control, C&C, NDDG1 and NDDG2 groups were 5%, 18%, 19% and 31%, respectively. All GDM diagnoses were independent risk factors for T2DM in multivariable Cox regression when compared to controls, adjusted hazard ratio and 95% CI: C&C 7.8 [95% CI 3.7-16.4], NDDG1 5.5 [2.6-11.6], and NDDG2 10.5 [5.2-21.4]. Additional independent risk factors were parity, fasting and 1-h post-glucose load of the OGTT and insulin use. Women with one elevated OGTT value using the NDDG criteria are at increased risk for T2DM. Further studies are needed to decide whether those women should be considered a focus group for long-term surveillance and T2DM prevention interventions.