Decreased circulating BMP-9 levels in patients with Type 2 diabetes is a signature of insulin resistance

2017 ◽  
Vol 131 (3) ◽  
pp. 239-246 ◽  
Author(s):  
Yong Luo ◽  
Ling Li ◽  
Xiaohui Xu ◽  
Tong Wu ◽  
Mengliu Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Healthy Subjects ◽  
Fasting Blood Glucose ◽  
Oral Glucose ◽  
Model Assessment ◽  
Cross Sectional ◽  
Lipid Infusion ◽  
The Relationship

Bone morphogenetic protein 9 (BMP-9) has been demonstrated to improve glucose homoeostasis in diabetic mice. However, no report has demonstrated the relationship of circulating BMP-9 levels with insulin resistance (IR) or Type 2 diabetes mellitus (T2DM) in humans. The objective of the present study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analysed by ELISA in 280 well-characterized individuals. Two-hour oral glucose tolerance test (OGTT) and euglycaemic–hyperinsulinaemic clamp (EHC) were performed in 20 healthy subjects. Acute IR was induced by lipid infusion for 4 h in 20 healthy volunteers. Real-time (RT)-PCR and Western blotting were used to assess mRNA and protein expression of BMP-9. The effect of a glucagon-like peptide-1 (GLP-1) receptor agonist (PEX168) on circulating BMP-9 was investigated in a 24-week treatment trial. Circulating BMP-9 levels were significantly higher in healthy subjects than in newly diagnosed patients with T2DM. Circulating BMP-9 negatively correlated with HbA1c, fasting blood glucose (FBG), OGTT, the area under the curve for glucose (AUCglucose) and homoeostasis model assessment of insulin resistance (HOMA-IR). Multivariate regression analyses showed that BMP-9 levels were independently associated with non-esterified fatty acid (NEFA) and AUCglucose. Both hyperinsulinaemia and lipid infusion decreased circulating BMP-9 levels. BMP-9 mRNA and protein expressions were significantly decreased in muscle and adipose tissues of T2DM patients. In the placebo treated group, BMP-9 levels continued to decline over time, whereas in the PEX 168 treated groups BMP-9 levels remained stable. Our data suggest that BMP-9 is likely to play an important role in IR in humans.

scholarly journals The relationship between insulin sensitivity and serum antithrombin 3 activity in patients with type 2 diabetes

2021 ◽  
Author(s):  
Hong Wang ◽  
Jie Cao ◽  
Jian-bin Su ◽  
Xueqin Wang ◽  
Dong-mei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Cross Sectional Study ◽  
Oral Glucose ◽  
Model Assessment ◽  
Cross Sectional ◽  
Increased Risk ◽  
The Relationship

Background: Antithrombin 3 (AT3) is a physiological inhibitor of thrombin, and serum AT3 activity was found to be decreased at the status of type 2 diabetes (T2D). T2D was presented with an increased risk of thrombotic complications at the background of impaired insulin sensitivity. The aim of this study was to investigate the relationship between insulin sensitivity indices and serum AT3 activity in patients with T2D. Methods: We conducted a cross-sectional study in patients with T2D who consented to participate in the study at the Endocrinology Department of Affiliated 2 Hospital of Nantong University from January 2015 to June 2018. All patients received serum AT3 activity test and 75-g oral glucose tolerance test (OGTT). Basal and systemic insulin sensitivity were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index (ISIMatsuda), respectively, from the OGTT. And other relevant clinical data were also collected. Results: Total 1612 patients with T2D were enrolled in the study, with a mean age of 58.67±13.09 years and a median diabetes duration of 6 years (interquartile range, 1–10 years). Across ascending quartiles of serum AT3, HOMA-IR progressively decreased, while ISIMatsuda progressively increased (all p for trend <0.001). Moreover, serum AT3 was negatively correlated with HOMA-IR (r= –0.189, p<0.001) and positively correlated with ISIMatsuda (r=0.221, p<0.001). After adjusting for other metabolic risk factors, hemostatic parameters and glucose-lowering therapies by multivariate liner regression analysis, HOMA-IR (β= −0.185, t= −5.960, p<0.001) and ISIMatsuda (β= 0.197, t=6.632, p<0.001) remained independently associated with the serum AT3 activity in patients with T2D, respectively. Conclusions: Reduced basal and systemic insulin sensitivity are associated with decreased serum AT3 activity in patients with T2D.

scholarly journals The relationship between insulin sensitivity and serum AT3 activity in patients with type 2 diabetes

2021 ◽  
Author(s):  
Hong Wang ◽  
Jie Cao ◽  
Jian-bin Su ◽  
Xue-qin Wang ◽  
Dong-mei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Cross Sectional Study ◽  
Oral Glucose ◽  
Model Assessment ◽  
Cross Sectional ◽  
Increased Risk ◽  
The Relationship

Abstract Background: Serum antithrombin 3 (AT3) is a physiological inhibitor of thrombin, and AT3 activity was found to be decreased at the status of type 2 diabetes (T2D). T2D was presented with an increased risk of thrombotic complications at the background of impaired insulin sensitivity. The aim of this study was to investigate the relationship between insulin sensitivity and serum AT3 activity in patients with T2D. Methods: We recruited 1612 patients with T2D for this cross-sectional study from the Second Affiliated Hospital of Nantong University. All patients performed 75-g oral glucose tolerance test (OGTT), and basal and systemic insulin sensitivity were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index (ISI Matsuda ), respectively. Serum AT3, one of the hemostatic parameters, and the relevant clinical data were collected, as well as other laboratory indicators. Results: It is showed that HOMA-IR decreased, while ISI Matsuda notably increased, across ascending quartiles of serum AT3. Moreover, serum AT3 were was negatively correlated with (r = –0.189, p < 0.001) and positively correlated with ISI Matsuda (r = 0.221, p < 0.001). After adjusted for metabolic risk factors, hemostatic parameters and glucose-lowering therapies by multivariate liner regression analysis, HOMA-IR (β = −0.179, t = −5.823, p < 0.001) and ISI Matsuda (β = 0.191, t = 6.395, p < 0.001) was remained independently associated with the serum AT3 activity patients with T2D, respectively. Conclusions: Reduced basal and systemic insulin sensitivity are associated with decreased AT3 activity in patients with T2D.

scholarly journals Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

2018 ◽  
Vol 315 (6) ◽  
pp. E1242-E1250 ◽  
Author(s):  
Donghua Hu ◽  
Ryan D. Russell ◽  
Devika Remash ◽  
Timothy Greenaway ◽  
Stephen Rattigan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Flow ◽  
Adipose Tissue ◽  
Resistance Training ◽  
Blood Volume ◽  
Fasting Blood Glucose ◽  
Microvascular Blood Flow ◽  
Oral Glucose ◽  
Model Assessment

The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC; 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P < 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT; however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = −0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses; however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.

scholarly journals Cigarette Smoking Is Negatively Associated with the Prevalence of Type 2 Diabetes in Middle-Aged Men with Normal Weight but Positively Associated with Stroke in Men

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Su Wang ◽  
Jie Chen ◽  
Yuzhong Wang ◽  
Yu Yang ◽  
Danyu Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cigarette Smoking ◽  
Normal Weight ◽  
Anthropometric Measurement ◽  
Oral Glucose ◽  
Model Assessment ◽  
Family History Of Diabetes ◽  
Negatively Associated ◽  
The Relationship

Background. The prevalence of diabetes and potentially related complications, including stroke, is rapidly increasing in China. The long-term effects of lifestyle may affect glucose metabolism in the general population. Although some studies have shown an association between smoking and the risk of type 2 diabetes mellitus (T2DM), the relationship remains unclear. Furthermore, the relationship between smoking and stroke in patients with T2DM has not been fully elucidated. Objective. We investigated the influence of cigarette smoking on T2DM and stroke in China. Detailed questionnaires about smoking status and anthropometric measurement were completed by participants, and oral glucose tolerance testing (OGTT), hemoglobin A1c (HbA1c), homeostasis model assessment of IR (HOMA-IR), and blood lipids were measured. Results. In total, 8196 adults aged 40 years or older were included. We found a reduced risk of impaired glucose regulation (IGR) and T2DM in male smokers with normal weight (body mass index BMI<25 kg/m2 or waist circumference WC<90 cm) compared with nonsmokers after adjusting for age, alcohol intake, physical activity, educational level, family history of diabetes, SBP, DBP, TG, TC, HDL-C, and LDL-C. However, no significant association was detected in male current smokers with overweight/obesity or female smokers. In addition, compared with nonsmokers without T2DM, current smokers with T2DM had a significantly higher risk of stroke (odds ratio: 2.64, 95% confidence interval: 1.25–5.57; P=0.011) after adjusting for confounders. Conclusions. Smoking was negatively associated with T2DM in Chinese men of normal body weight, but no significant association was found for men with overweight/obesity or women. In addition, smoking was positively associated with nonfatal stroke, especially in patients with T2DM. Further prospective studies are needed to examine the association between smoking, diabetes, and stroke in different ethnic groups.

scholarly journals Nutrient intakes and dysglycaemia in populations of West African origin

2011 ◽  
Vol 105 (2) ◽  
pp. 297-306 ◽  
Author(s):  
Simon G. Anderson ◽  
Novie Younger ◽  
Adrian H. Heald ◽  
Marshall K. Tulloch-Reid ◽  
Wiyumile P. Simukonda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dietary Intake ◽  
Tolerance Test ◽  
Cross Sectional Study ◽  
Dietary Factors ◽  
Oral Glucose ◽  
African Origin ◽  
Cross Sectional ◽  
The Relationship

Examining the relationship between glucose intolerance and dietary intake in genetically similar populations with different dietary patterns and rates of type 2 diabetes may provide important insights into the role of diet in the pathogenesis of this disease. The objective of the present study was to assess the relationship between dietary variables and dysglycaemia/type 2 diabetes among three populations of African origin. The study design consists of a cross-sectional study of men and women of African descent aged 24–74 years from Cameroon (n 1790), Jamaica (n 857) and Manchester, UK (n 258) who were not known to have diabetes. Each participant had anthropometric measurements and underwent a 2 h 75 g oral glucose tolerance test. Habitual dietary intake was estimated with quantitative FFQ, developed specifically for each country. The age-adjusted prevalence of undiagnosed type 2 diabetes in Cameroon was low (1·1 %), but it was higher in Jamaica (11·6 %) and the UK (12·6 %). Adjusted generalised linear and latent mixed models used to obtain OR indicated that each 1·0 % increment in energy from protein, total fat and saturated fats significantly increased the odds of type 2 diabetes by 9 (95 % CI 1·02, 1·16) %, 5 (95 % CI, 1·01, 1·08) % and 16 (95 % CI 1·08, 1·25) %, respectively. A 1 % increase in energy from carbohydrates and a 0·1 unit increment in the PUFA:SFA ratio were associated with significantly reduced odds of type 2 diabetes. The results show independent effects of dietary factors on hyperglycaemia in African origin populations. Whether modifying intake of specific macronutrients helps diabetes prevention needs testing in randomised trials.

scholarly journals Correlation between Blood Activin Levels and Clinical Parameters of Type 2 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hui Wu ◽  
Michael Wu ◽  
Yi Chen ◽  
Carolyn A. Allan ◽  
David J. Phillips ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Fasting Glucose ◽  
Serum Levels ◽  
Activin A ◽  
Oral Glucose ◽  
Clinical Parameters ◽  
Model Assessment

Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined.Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein.Results. Serum levels of activin A (93.3 ± 27.0 pg/mL, mean ± SD), B (81.8 ± 30.8 pg/mL), or follistatin (6.52 ± 3.15 ng/mL) were not different (P>0.05) between subjects with normal OGTT (n=39), impaired glucose tolerance and/or fasting glucose (n=17), or T2D (n=36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P<0.001), fasting insulin (P=0.02), glycated hemoglobin (P=0.003), and homeostasis model assessment of insulin resistance (HOMA-IR;P<0.001). Follistatin was positively correlated with HOMA-IR alone (P=0.01).Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease.

scholarly journals Serum concentrations of asprosin in new-onset type 2 diabetes

2020 ◽  
Author(s):  
Shakiba Naiemian ◽  
Mohsen naeemipour ◽  
Mehdi Zarei ◽  
Ali Gohari ◽  
Mohammad Reza Behroozikhah ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Model Assessment ◽  
Serum Concentrations ◽  
Atherosclerotic Risk Factor

Abstract Background: Asprosin, a newly identified adipokine, is pathologically increased in individuals with insulin resistance. However, the available evidence on the association of asprosin and type 2 diabetes mellitus (T2DM) status is still scarce. Therefore, this study aimed to determine the relationship between serum concentrations of asprosin and T2DM status . Methods: This observational study was performed based on 194 adults (97 newly diagnosed T2DM and 97 healthy individuals). Anthropometric and biochemical variables were determined in all participants . Serum concentrations of asprosin were measured using enzyme-linked immunosorbent assay (ELISA). Results: In patients with T2DM, the serum concentrations of asprosin were significantly higher than the healthy controls (4.18 [IQR: 4.4] vs. 3.5 [IQR: 1.85], P< 0.001). The concentrations of asprosin were significantly correlated with body mass index (BMI) and fasting blood glucose (FBG) in healthy subjects and with BMI, FBG, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin check index (QUICKI), triacylglycerol (TAG) and total cholesterol/ high-density lipoprotein cholesterol (TC/HDL-C) ratio in the T2DM group. In fully adjusted model, the odds ratio (OR) of T2DM with serum concentrations of asprosin was approximately 1.547 (95% CI 1.293-1.850, P< 0.001) compared to the control group . Multiple stepwise regression analysis indicated that FBG and HOMA-IR were independently associated with asprosin in T2DM. Conclusion : Our findings indicated that serum concentrations of asprosin are increased in patients with T2DM. Also, asprosin is correlated with insulin resistance and TC/HDL-C ratio (atherosclerotic risk factor of cardiovascular diseases) in patients with T2DM.

scholarly journals Dipeptidyl-Peptidase-IV Inhibitors, Imigliptin and Alogliptin, Improve Beta-Cell Function in Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Xu Liu ◽  
Yang Liu ◽  
Hongzhong Liu ◽  
Haiyan Li ◽  
Jianhong Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Dipeptidyl Peptidase ◽  
Chinese Patients ◽  
Oral Glucose ◽  
Model Assessment

ObjectsImigliptin is a novel dipeptidyl peptidase-4 inhibitor. In the present study, we aimed to evaluate the effects of imigliptin and alogliptin on insulin resistance and beta-cell function in Chinese patients with type-2 diabetes mellitus (T2DM).MethodsA total of 37 Chinese T2DM patients were randomized to receive 25 mg imigliptin, 50 mg imigliptin, placebo, and 25 mg alogliptin (positive drug) for 13 days. Oral glucose tolerance tests were conducted at baseline and on day 13, followed by the oral minimal model (OMM).ResultsImigliptin or alogliptin treatment, compared with their baseline or placebo, was associated with higher beta-cell function parameters (φs and φtot) and lower glucose area under the curve (AUC) and postprandial glucose levels. The changes in the AUC for the glucose appearance rate between 0 and 120 min also showed a decrease in imigliptin or alogliptin groups. However, the insulin resistance parameter, fasting glucose, was not changed. For the homeostatic model assessment (HOMA-β and HOMA-IR) parameters or secretory units of islets in transplantation index (SUIT), no statistically significant changes were found both within treatments and between treatments.ConclusionsAfter 13 days of treatment, imigliptin and alogliptin could decrease glycemic levels by improving beta-cell function. By comparing OMM with HOMA or SUIT results, glucose stimulation might be more sensitive for detecting changes in beta-cell function.

scholarly journals Endothelial dysfunction and inflammatory biomarkers as a response factor of concurrent coenzyme Q10 add-on metformin in patients with type 2 diabetes mellitus

2019 ◽  
Vol 11 (04) ◽  
pp. 317-322
Author(s):  
Hayder M. Al-Kuraishy ◽  
Ali I. Al-Gareeb ◽  
Hala A. Shams ◽  
Farah Al-Mamorri
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Coenzyme Q10 ◽  
Healthy Subjects ◽  
Model Assessment ◽  
Inflammatory Changes

Abstract OBJECTIVES: The objective of the study was to evaluate the effect of metformin alone or in combination with coenzyme Q10 (CoQ10) on inflammatory changes and endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A total numbers of 54 patients with T2DM compared to 30 healthy subjects were divided into three groups: Group A (n = 30): healthy subjects without any medications; Group B (n = 24): T2DM patients treated with metformin 1 g/day; and Group C (n = 30): T2DM patients treated with metformin 1 g/day plus CoQ10, 300 mg/day. The duration of the study was 8 weeks. Fasting blood glucose, glycated hemoglobin, lipid profile, blood pressure variables, fasting insulin, insulin resistance, homeostatic model assessment of insulin resistance, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured before and after therapy. RESULTS: Metformin and/or CoQ10 therapy illustrated an insignificant effect on the fody mass index. This combination produced a significant improvement of metabolic changes in patients with T2DM (P < 0.01). sVCAM-1 serum level was decreased significantly after the initiation of metformin and/or CoQ10 therapy compared to the baseline P < 0.05. E-selectin was declined significantly following metformin monotherapy and after metformin plus CoQ10 therapy (P = 0.0001). CONCLUSION: CoQ10 add-on metformin therapy improves endothelial dysfunction and inflammatory changes in patients with T2DM alongside with amelioration of metabolic profile.

Associations of Plasma BACE1 Level and BACE1 C786G Gene Polymorphism with Cognitive Functions in Patients with Type 2 Diabetes: A Cross- Sectional Study

2020 ◽  
Vol 17 (4) ◽  
pp. 355-364 ◽  
Author(s):  
Sai Tian ◽  
Rong Huang ◽  
Dan Guo ◽  
Hongyan Lin ◽  
Jiaqi Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gene Polymorphism ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Multivariable Logistic Regression Analysis ◽  
Model Assessment ◽  
Cross Sectional ◽  
Logical Memory ◽  
Bace1 Level

Background: β-Site APP-cleaving enzyme 1 (BACE1) is a key enzyme involved in the pathophysiology of Type 2 Diabetes Mellitus (T2DM) and Mild Cognitive Impairment (MCI). We aimed to investigate the potential associations of plasma BACE1 levels and BACE1 gene polymorphism with different cognitive performances in T2DM patients with MCI. Methods: The recruited 186 T2DM subjects were divided into 92 MCI group and 94 healthy-cognition controls, according to the Montreal Cognitive Assessment (MoCA) scores. Sociodemographic characteristics, clinical parameters and neuropsychological tests were assessed. BACE1 C786G gene polymorphism and plasma BACE1 level were determined. Results: Compared to controls, MCI patients exhibited higher plasma BACE1 levels. Plasma BACE1 levels were negatively associated with MoCA, Clock Drawing Test and Logical Memory Test scores, whereas positively associated with Trail Making Test-B time in the MCI group (all p<0.05), after adjusting fasting blood glucose, glycosylated hemoglobin, and homeostasis model assessment of insulin resistance by C-peptide. Multivariable logistic regression analysis showed a significant trend towards increased MCI risk with high plasma BACE1 level in T2DM patients (OR = 1.492, p = 0.027). The plasma BACE1 levels of GG and GC genotypes were obviously higher than that of CC genotype in T2DM-MCI patients (p = 0.035; p = 0.026, respectively). Conclusion: Increased plasma BACE1 levels were associated with poor overall cognition functions, especially visuospatial abilities, visual/logical memory and executive functions in T2DM-MCI patients. Additionally, elevated plasma BACE1 level was a risk factor for MCI in T2DM patients, and might be influenced by BACE1 C786G gene mutations.

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