Decreased Serum Growth Differentiation Factor 15 Levels After Lifestyle Intervention in Patients With Newly Diagnosed Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Xingxing He ◽  
Jiaorong Su ◽  
Xiaojing Ma ◽  
Jingyi Lu ◽  
Yufei Wang ◽  
...  

Abstract Background: Recent studies noted that circulating growth differentiation factor 15 (GDF15) were closely related to metabolic states. The study aimed to explore the changes of GDF15 levels and their influencing factors after 4 weeks of lifestyle intervention (LI) or LI combined with breakfast meal replacement (LI+MR) in newly diagnosed type 2 diabetes patients. Methods: A total of 84 patients with available serum samples at both baseline and Week 4 were enrolled in this biomarker substudy. All subjects underwent a 2-hour 75g oral glucose tolerance test at baseline and Week 4. Serum GDF15 levels were determined by a sandwich enzyme-linked immunosorbent assay. Results: After 4-weeks of LI, GDF15 levels overall significantly decreased compared with baseline (P<0.05). ∆GDF15 levels were significantly and negatively associated with baseline GDF15 levels (r=–0.450, P<0.001). The optimal cut-off point of baseline GDF15 levels for predicting a GDF15 decrease after 4-weeks of LI was 904.57 pg/ml, with an area under curve of 0.699. Based on the cut-off point of 900 pg/ml, patients with baseline GDF15 ≥900 pg/ml had significantly decreased GDF15 levels after LI, while those <900 pg/ml had no significant changes. Regression models showed that baseline GDF15 level was an independent positive factor for the improvement of fasting plasma glucose and homeostasis model assessment for insulin resistance only in patients with baseline GDF15 levels ≥900 pg/ml. Conclusions: LI led to significantly decreased GDF15 levels among patients with newly diagnosed type 2 diabetes and its effect was more significant among patients with baseline GDF15 levels ≥900 pg/ml.Trial registration: ClinicalTrials.gov, NCT02248714. Registered 25 September 2014 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02248714?term=NCT02248714&draw=2&rank=1

2016 ◽  
Vol 174 (2) ◽  
pp. 147-155 ◽  
Author(s):  
Mingyuan Tian ◽  
Zerong Liang ◽  
Rui Liu ◽  
Ke Li ◽  
Xinrong Tan ◽  
...  

ObjectiveZinc-α2-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients.Design and methodsA subset of 141 subjects with nT2DM were assigned to receive placebo (n=47) or sitagliptin (n=94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations.ResultsCirculating ZAG levels were lower in nT2DM than in control individuals (P<0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P<0.05 orP<0.01), whereas the glucose infusion rate during the stable period of the clamp (Mvalues) during EHC were significantly increased (P<0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (bothP<0.01) and the change of ZAG (ΔZAG) was positively associated with ΔADI, ΔHOMA-IR, ΔBMI, Δfasting insulin and negatively associated with Δ tumor necrosis factor-α (TNF-α). Furthermore, sitagliptin treatment resulted in significantly lowered plasma TNF-α level (P<0.05).ConclusionA low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent.


Author(s):  
Yangyang Cheng ◽  
Xiaohui Du ◽  
Bilin Zhang ◽  
Junxia Zhang

Abstract Background Serum wnt1-induced signaling pathway protein 1 (WISP1) levels are increased with obesity, which is a common complication associated with lower extremity atherosclerotic disease (LEAD). However, to date, the relationship between elevated WISP1 levels and the incidence of lower extremity atherosclerotic disease (LEAD) in type 2 diabetes mellitus (T2DM) remains unclear. Methods 174 newly diagnosed type 2 diabetic patients were enrolled in our study. Patients were divided into two groups, LEAD group (n=100) and control group (n=74). Anthropometric parameters, blood pressure and some biochemical parameters were obtained. Body composition was detected by bioelectrical impedance analysis (BIA). Levels of serum insulin were determined by radioimmunoassay. Serum WISP1 and interleukin 6 (IL-6) levels were determined using an enzyme-linked immunosorbent assay. Results It was shown that serum WISP1 levels in diabetic patients with LEAD were higher than those without LEAD (P<0.001). Serum WISP1 levels were positively related with waist circumference (r=0.237, P=0.003), waist-hip ratio (r=0.22, P=0.006), visceral fat area (r=0.354, P<0.001), serum creatinine (r=0.192, P=0.012), interleukin 6 (r=0.182, P=0.032), c-reactive protein (r=0.681, P<0.001), triglycerides (r=0.119, P<0.001), fasting glucose (r=0.196, P=0.011), glycated hemoglobin (r=0.284, P<0.001), and HOMA-IR (r=0.285, P<0.026). Compared with the lowest tertile, the odds ratio of the middle tertile for LEAD incidence was 3.27 (95% CI, 1.24–8.64) and 4.46 (95% CI, 1.62–12.29) for the highest tertile after adjusting confounding factors. Conclusion The results suggest that increased serum WISP1 levels independently contribute to the incidence of LEAD in patients with newly diagnosed T2DM.


2018 ◽  
Vol 315 (6) ◽  
pp. E1242-E1250 ◽  
Author(s):  
Donghua Hu ◽  
Ryan D. Russell ◽  
Devika Remash ◽  
Timothy Greenaway ◽  
Stephen Rattigan ◽  
...  

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.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2979 ◽  
Author(s):  
Wilrike J. Pasman ◽  
Robert G. Memelink ◽  
Johan de Vogel-Van den Bosch ◽  
Mark P. V. Begieneman ◽  
Willem J. van den Brink ◽  
...  

(1) Background: Recent research showed that subtypes of patients with type 2 diabetes may differ in response to lifestyle interventions based on their organ-specific insulin resistance (IR). (2) Methods: 123 Subjects with type 2 diabetes were randomized into 13-week lifestyle intervention, receiving either an enriched protein drink (protein+) or an isocaloric control drink (control). Before and after the intervention, anthropometrical and physiological data was collected. An oral glucose tolerance test was used to calculate indices representing organ insulin resistance (muscle, liver, and adipose tissue) and β-cell functioning. In 82 study-compliant subjects (per-protocol), we retrospectively examined the intervention effect in patients with muscle IR (MIR, n = 42) and without MIR (no-MIR, n = 40). (3) Results: Only in patients from the MIR subgroup that received protein+ drink, fasting plasma glucose and insulin, whole body, liver and adipose IR, and appendicular skeletal muscle mass improved versus control. Lifestyle intervention improved body weight and fat mass in both subgroups. Furthermore, for the MIR subgroup decreased systolic blood pressure and increased VO2peak and for the no-MIR subgroup, a decreased 2-h glucose concentration was found. (4) Conclusions: Enriched protein drink during combined lifestyle intervention seems to be especially effective on increasing muscle mass and improving insulin resistance in obese older, type 2 diabetes patients with muscle IR.


Author(s):  
Zhu Li ◽  
Yan-Ling Yang ◽  
Yan-Juan Zhu ◽  
Chen-Guang Li ◽  
Yun-Zhao Tang ◽  
...  

Abstract Objective Myonectin is one of the myokines and has gained interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes mellitus (T2DM).The objective of this study was to investigate circulating serum myonectin levels in nondiabetes and T2DM and elucidate possible relationships between serum myonectin levels and metabolic parameters in patients with T2DM. Design A total of 362 Chinese patients with T2DM and 100 age- and sex-matched healthy controls were recruited in this study. Clinical characteristics, blood biochemistry, and circulating myonectin levels were measured by enzyme-linked immunosorbent assay. Results Circulating myonectin levels were significantly decreased in T2DM compared with controls. Obese nondiabetic controls had significantly lower serum myonectin levels compared with lean nondiabetic controls. In diabetic patients, serum myonectin concentrations were significantly negatively correlated with body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), hemoglobin A1c (HbA1c), fasting insulin (Fins), the homeostatic model assessment of insulin resistance (HOMA-IR), visceral fat area, and subcutaneous fat area. After adjusting for covariates, multivariate stepwise regression analysis demonstrated that BMI, LDL-C, TG, HOMA-IR, and visceral fat were the main independent predictors of low serum myonectin concentrations. Conclusions Circulating myonectin levels were decreased in T2DM patients and in obese subjects. Moreover, serum myonectin levels were correlated with metabolic markers of T2DM. These data suggest that myonectin may be a useful marker in predicting the development of obesity and T2DM.


2020 ◽  
Vol 8 (1) ◽  
pp. e001500
Author(s):  
Nobuo Sasaki ◽  
Ryoji Ozono ◽  
Ryo Maeda ◽  
Yukihito Higashi

IntroductionLittle is known about the risk of hypertension in patients with the early stage of type 2 diabetes. We investigated the risk of hypertension in participants with newly diagnosed type 2 diabetes and prediabetes.Research design and methodsThis is a retrospective cohort study consisting of 2136 middle-aged participants (1022 with normal fasting glucose/normal glucose tolerance (NFG/NGT), 418 with impaired fasting glucose (IFG), 466 with impaired glucose tolerance (IGT) and 230 with diabetes) and 3426 elderly participants (1762 with NFG/NGT, 599 with IFG, 781 with IGT, and 284 with diabetes). All participants underwent 75 g oral glucose tolerance tests at baseline.ResultsOver a median 59-month follow-up period, 459 middle-aged and 1170 elderly participants developed hypertension. In middle-aged participants, the odds of incident hypertension were significantly higher in those with IFG (OR 1.40; p=0.019), IGT (OR 1.49; p=0.004), and diabetes (OR 1.55; p=0.013) than those with NFG/NGT, which was no longer significant after adjustment for body mass index. Subgroup analysis showed that the risk of hypertension was significantly higher in diabetes than NFG/NGT only in participants without obesity. Conversely, obesity was a risk factor of hypertension only in those with IFG and NFG/NGT. In elderly participants, there was no difference in the risk of hypertension among the NFG/NGT, IFG, IGT and diabetes groups.ConclusionsThe risk of hypertension is modest in participants with newly diagnosed type 2 diabetes and prediabetes. Our findings suggest that the early stages of type 2 diabetes and prediabetes may be a key period for reducing hypertension, given the pronounced risk of hypertension in patients with diabetes reported in previous studies. In terms of reducing the risk for hypertension, obesity treatment might be advantageous in the early stages rather than the advanced stages of impaired glucose metabolism.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Su Wang ◽  
Jie Chen ◽  
Yuzhong Wang ◽  
Yu Yang ◽  
Danyu Zhang ◽  
...  

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.


2011 ◽  
Vol 165 (4) ◽  
pp. 597-601 ◽  
Author(s):  
Dandong Wu ◽  
Ling Li ◽  
Mengliu Yang ◽  
Hua Liu ◽  
Gangyi Yang

ObjectiveSecreted protein acidic and rich in cysteine (SPARC) also known as BM-40 which has been studied in various pathological conditions, has recently been suggested as a key player in the pathology of obesity and type 2 diabetes mellitus (T2DM). However, there are few studies on putative pathophysiologic roles of SPARC in glucose metabolism. The aim of this study was to determine whether plasma SPARC concentrations were altered in subjects with different glucose metabolic conditions and to investigate the affecting factors.Design and methodsIn this study, 54 newly diagnosed T2DM subjects, 53 subjects with impaired glucose regulation (IGR), and 53 normal subjects (body mass index (BMI): 24.98±3.75 vs 24.70±2.78 and 24.53±3.66 kg/m2, P>0.05) were enrolled. Plasma SPARC levels were measured with an ELISA under overnight fasting conditions. The relationships between plasma SPARC and several metabolic factors, such as BMI, blood lipids, blood glucose, plasma insulin levels, and other factors were also assessed.ResultsSPARC levels were higher in subjects with T2DM compared with IGR and control subjects (16.74±6.99 vs 14.04±8.03 μg/l, P<0.05 and 16.74±6.99 vs 11.72±4.47 μg/l, P<0.01). However, there was no difference in plasma SPARC levels between IGR subjects and the controls. Plasma SPARC levels correlated positively with BMI, the percentage of fat, triglyceride, fasting plasma insulin, 2 h plasma insulin after a glucose load, and the homeostasis model assessment of insulin resistance in simple regression analysis.ConclusionThe present work indicates a potential link between SPARC and the pathogenesis of T2DM.


Sign in / Sign up

Export Citation Format

Share Document