Associations of betatrophin levels with irisin in Chinese women with normal glucose tolerance.

Objective To study change of insulin resistance and beta-cell function of the patients in hyper-tension with normal glucose tolerance(NGT) to phthogonesis of type 2 diabetes mellitus(T2DM). Methods 84 pa-tients with hypertension were divided into NGT group,and groups of impaired glucose tolerance(IGT) with groups of T2DM. The blood pressure, height, weight, waist circumference, hip circumference, high-density lipoproteins (HDL-C)and total cholesterol(TC) ,fasting plasma glucose(FPG) and fasting plasma insulin(FINS) were measured to deter-mine the body mass index(BMI) ,waist/hip ratio(WHR) ,insulin secretion function[ including Homa β-cell function index(HBCI) and fasting β-cell function index(FBCI)] and insulin resistance level [ including Homa model insulin resistance index(IR) and insulin action index(IAI)] ,statistic comparison were measured between the groups of dif-ferent glucose tolerances. Results The BMI, WHR, diastolic blood pressure ( DBP), TC in IGT group and T2DM group were bigger or higher than those in NGT group ( P<0.05, P<0.01 ), the IAI, HOMA-IS and FBCI in T2DM group were lower than those in NGT group with these in NGT group were lower than those in NGT group( P<0.05 ,P<0.01 ). The HOMA-IR in IGT group and T2DM group were higher than those in NGT group with these in T2DM group were higher than those in NGT group. Conclusion T2DM group and IGT group had more insulin resistance level,sensitivity of insulin and islet β-cell function decrease than those in IGT group,the IGT group and T2DM group are analogous at the body weight is heavier, with waist/hips ratio, triglyceride level and DBP are higher than those in the NGT group in clinic. Key words: Insulin resistance; Islets of langerhuns; Hypertension; Impaired glucose tolerance

ObjectTo detect the levels of plasma High-Mobility Group Box-1(HMGB1) in Chinese subject with obesity and type 2 diabetes mellitus (T2DM), and to investigate the correlations between plasma HMGB1 concentration and parameters of body fat, insulin resistance (IR) metabolism and inflammation.MethodsThis study recruited 79 normal glucose tolerance (NGT) subjects and 76 newly diagnosed T2DM patients. NGT and T2DM groups were divided into normal weight (NW) and obese (OB)subgroups respectively. Anthropometric parameters such as height, weight, waist circumference, hip circumference and blood pressure were measured. Plasma concentrations of HMGB1, IL-6, fasting plasma glucose (FPG), 2 hours post challenge plasma glucose (2hPG), serum lipid, glycated hemoglobin (HbA1C) and fasting insulin (FINS) were examined. The homeostasis model assessment (HOMA) was performed to assess IR status.ResultsPlasma HMGB1 levels were higher in T2DM group than that in NGT group. The concentrations of serum HMGB1 were also higher in subjects with OB than those in subjects with NW both in NGT and T2DM groups. Plasma levels of HMGB1 were positively correlated with waist hip ratio (WHR), blood pressure, FPG, FINS, HOMA-IR, TG, IL-6 and negatively correlated with HOMA-βand high-density lipoprotein-cholesterol (HDL-c) independent of age, gender and BMI. Plasma levels of HMGB1 were significantly correlated with diabetes in fully adjusted models.ConclusionPlasma HMGB1 levels were increased in Chinese subjects with pure T2DM, which might be caused by IR. Serum HMGB1 participated in the pathological process of obesity and T2DM via its proinflammatory effect.

Relationship between serum betatrophin levels and the first-phase of glucose-stimulated insulin secretion

SummaryBackground Fractalkine (FKN) is an inflammatory cytokine that has been shown with increased serum levels in diabetic patients and is considered to contribute to the adipose tissue inflammation by supporting monocyte adhesion to adipocytes which has an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). Our aim was to evaluate the effects of glucose ingestion on the serum fractal - kine levels in healthy subjects with normal glucose tolerance (NGT) and newly diagnosed T2DM patients.MethodsA total of 67 patients were included in this study, and they were divided into NGT (n=34) and T2DM (n=33) groups according to their oral glucose tolerance test (OGTT) results. The serum FKN and C-reactive protein (CRP) levels were measured at 0 and 120 minutes during an OGTT following overnight fasting.ResultsThe 0-minute (basal) and 120-minute OGTT FKN levels were found to be significantly higher in the T2DM group when compared to the NGT group (p=0.012 and p=0.001, respectively). However, no significant differences were observed in terms of the changes in the basal and 120-minute OGTT FKN levels in the T2DM and NGT groups (p=0.433 and p=0.06, respectively). A significant positive correlation was observed between the 120-minute OGTT FKN and glucose levels in the study group consisting of all of the patients (r=0.331, p=0.006).ConclusionsIn this study, basal and post-glycemic load FKN levels were found to be higher in newly diagnosed T2DM patients than those with NGT; however, there was no additional change in FKN levels by glycemic load.

Objectives:To assess glucagon-like peptide 1 (GLP-1) secretion after oral glucose tolerance tests (OGTTs) in subjects with newly diagnosed type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) to clarify changes in GLP-1 secretion during the course of T2DM.Methods:In this cross sectional study, 80 subjects were divided into the NGT, IGT, and T2DM groups after undergoing a 75 g OGTT from March to December 2014 at the School of Medicine, First Affiliated Hospital, Shihezi University, Xinjiang, China. Plasma total GLP-1 was measured at 0, 30, 60, 120, and 180 minutes. Homeostasis model assessment of insulin resistance (HOMA-IR), islet β-cell function (HOMA-β), Gutt index, Matsuda index, incremental GLP-1 (ΔGLP-1), and areas under the curves of GLP-1 (AUCglp-1), glucose (AUCg), and insulin (AUCins) were calculated.Results:Plasma total GLP-1 at 30-120 minutes and ΔGLP-1 at 30-120 minutes were lower in the T2DM group than in the IGT and NGT groups (p<0.05). Peak GLP-1 levels were 35% lower in the T2DM group than in the NGT group. Plasma total GLP-1, ΔGLP-1, and AUCglp-1 correlated negatively with HOMA-IR and AUCg, and positively with HOMA-β, Gutt index, Matsuda index, and AUCins (p<0.05).Conclusion:The GLP-1 secretion after 75 g OGTT was impaired in newly diagnosed T2DM patients, inversely proportional to IR and hyperglycemia, and positively correlated with β-cell function and insulin sensitivity.

Circulating endothelial progenitor cells (EPCs) contribute to vascular homeostasis and are fewer in those with type 2 diabetes mellitus (T2DM) compared with normal glucose tolerance (NGT), suggesting a link between EPCs and T2DM-associated vasculopathies. The purpose of this study was to assess EPC number and mobilization by acute submaximal exercise in older adults with NGT, impaired glucose tolerance (IGT) or T2DM. We tested the hypothesis that EPC mobilization is lower in IGT compared with NGT and further reduced in older adults with T2DM. Forty-five older (50-75 yr of age) men and women with NGT (n = 18), IGT (n = 10), or T2DM (n = 17) were characterized and underwent submaximal aerobic exercise tests with blood sampling for enumeration of vascular endothelial growth factor receptor 2+ (VEGFR2+) cells, CD34+ hematopoetic progenitor cells, and CD34+/VEGFR2+ EPCs by flow cytometry before and after exercise. Basal EPC number was 65 and 61% lower in the IGT and T2DM groups, respectively, compared with the NGT group (P < 0.05). EPC number increased 23% after acute exercise in the NGT group (P < 0.01), but did not change in the IGT or T2DM groups. Before and after exercise, VEGFR2+ cell number was lower in a stepwise manner across the NGT, IGT, and T2DM groups (P < 0.05). Basal CD34+ cell number was lower in the IGT group compared with NGT (P < 0.05), but did not change after exercise in any group. These findings suggest a CD34+/VEGFR2+ EPC mobilization defect in IGT and T2DM that could play a role in the cardiovascular diseases and capillary rarefaction associated with insulin resistance.

BackgroundThe oral minimal model is a simple, useful tool for the assessment of β-cell function and insulin sensitivity across the spectrum of glucose tolerance, including normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) in humans.MethodsPlasma glucose, insulin, and C-peptide levels were measured during a 180-minute, 75-g oral glucose tolerance test in 24 Korean subjects with NGT (n=10) and T2DM (n=14). The parameters in the computational model were estimated, and the indexes for insulin sensitivity and β-cell function were compared between the NGT and T2DM groups.ResultsThe insulin sensitivity index was lower in the T2DM group than the NGT group. The basal index of β-cell responsivity, basal hepatic insulin extraction ratio, and post-glucose challenge hepatic insulin extraction ratio were not different between the NGT and T2DM groups. The dynamic, static, and total β-cell responsivity indexes were significantly lower in the T2DM group than the NGT group. The dynamic, static, and total disposition indexes were also significantly lower in the T2DM group than the NGT group.ConclusionThe oral minimal model can be reproducibly applied to evaluate β-cell function and insulin sensitivity in Koreans.

Aim. To evaluate the differences in insulin resistance (IR) among subjects with normal glucose tolerance (NGT), hyperinsulinemia with NGT (HINS), impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM). Methods. 5 NGT, 25 HINS, 25 IGT, and 25 T2DM subjects participated in this research. The hyperinsulinemic-euglycemic clamp technique (HECT) was performed in all of them to evaluate IR levels. The relative factors influencing IR were evaluated. The simple insulin sensitivity indices were calculated, and the correlation between each index and the M value was analyzed. Results. The M values of NGT, HINS, IGT, and T2DM groups were 11.88 ± 2.93 mg·kg−1·min−1, 6.23 ± 1.73 mg·kg−1·min−1, 6.37 ± 2.12 mg·kg−1·min−1, and 6.19 ± 1.89 mg·kg−1·min−1, respectively. M values in HINS, IGT, and T2DM groups were lower than those in the NGT group (P = 0.005); however, the differences among the HINS, IGT, and T2DM groups were not statistically significant (P = 0.835). The independent factors influencing the M value were waistline and fasting insulin level (FINS). The simple insulin sensitivity indices, especially Matsuda and Gutt index, were significantly associated with the M value (P < 0.01). Conclusion. IR existed in the HINS, IGT, and T2DM groups, and IR levels were consistent in the three groups. The independent factors influencing IR were waistline and FINS.

We hypothesized that the serum from individuals with type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) would reduce in vitro capillary-like network formation compared with normal glucose tolerance (NGT) serum and that this would occur along with higher serum concentrations of inflammatory cytokines and lower concentrations of angiogenic growth factors. Subjects were sedentary, older (55-65 yr) adults with NGT, IGT, or T2DM (n = 10/group) matched for body mass index. Human retroviral telomerized endothelial cells (HRVT-ECs) or coronary artery endothelial cells (CECs) were used in a capillary-like network formation assay using endothelial basal medium supplemented with 7.5% serum. Quantification of HRVT-EC network length indicated that serum from the T2DM group resulted in 32 and 35% lower network formation than when using serum from the NGT and IGT groups, respectively (P < 0.05). Serum from T2DM subjects resulted in CEC network formation that was 11 and 8% lower than when using serum from NGT and IGT subjects, respectively (P < 0.05). Analysis of serum cytokines indicated that IL-6 was 41% and 49% higher in the IGT and T2DM groups, respectively, compared with the NGT group (P < 0.05) and there was a trend for higher soluble interleukin-6 receptor (sIL-6R; P = 0.06) and IL-8 (P = 0.08) in the T2DM serum compared with NGT. The use of recombinant IL-6 and sIL-6R at concentrations detected in the T2DM serum also reduced capillary network formation compared with NGT concentrations (P < 0.05). These results suggest that IL-6 and sIL-6R present in the serum of T2DM individuals impair in vitro endothelial cell function across different cell lines. Our findings may have implications for the microvascular complications associated with T2DM.NEW & NOTEWORTHY Higher concentrations of serum factors, specifically Interleukin-6 and its soluble receptor found in individuals with type 2 diabetes (T2DM) appear to impair endothelial cell capillary-like network formation compared with those present in serum from individuals with impaired glucose tolerance and normal glucose tolerance. This may have implications for the vascular complications associated with T2DM.

The relationship between type 1 diabetes mellitus (T1DM) and periodontal disease may exhibit by the alteration of bone metabolism. However, evidence for this relationship is scarce and inconclusive. Thus, the aims of the present study were to investigate salivary receptor activator of nuclear factor kappa-β (RANK), receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG) gene expression and the RANKL:OPG ratio in T1DM and non-T1DM. Secondary objective was to determine the relationships of RANK, RANKL and OPG gene expression to clinical parameters of T1DM and periodontal disease. Twenty patients with T1DM and twenty age-matched non-T1DM were recruited. Clinical periodontal parameters were measured. Total RNA was isolated from non-stimulated saliva, and the relative gene expressions of RANK, RANKL, OPG and RANKL:OPG ratio were determined by quantitative real-time polymerase chain reaction. The T1DM group had significantly higher mean periodontal parameters than the non-T1DM group, while the mean plaque scores of both groups were not significantly different. There was a trend of higher relative gene expression of RANK, RANKL, and the RANKL:OPG ratio and lower expression of OPG in T1DM group but no statistic significant different when compared to non-T1DM. In the T1DM group, RANKL:OPG correlated with the percentage of bleeding sites, whereas RANK, RANKL, and HbA1c levels correlated with pocket depth. Bone metabolisms demonstrating by decreased OPG gene expression and upregulated of RANK, RANKL, RANKL:OPG with higher pocket depth and bleeding in T1DM may play an important role in periodontal destruction in T1DM.

Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder characterized by defects in insulin secretion and action and obesity plays an important role in the deterioration of glucose metabolism. In the present study we evaluated the degree of insulin resistance and first-phase insulin secretion of beta-cell in obese subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM in Chinese. A total of 220 subjects underwent standard 75 g oral glucose tolerance test (OGTT) and insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity index (S I) was assessed by the reduced sample number (n = 12) of Bergman's minimal model method with FSIGT. Insulin secretion capacities were determined by the insulinogenic index (I 30 min - I 0 min)/(G 30 min - G 0 min) in OGTT and the acute insulin response to glucose (AIR) in FSIGT. The disposition index (DI), the product of AIR and S I was used to determine whether AIR was adequate to compensate for insulin resistance. The S I in healthy lean control group was significantly higher than that in NGT, IGT, and T2DM group, but there was no significant difference among NGT, IGT, and T2DM group. The AIR in NGT group was significantly greater than that in control group, but then it was progressively decreased in IGT and T2DM group. The value of DI in control group was significantly higher than that in those three abnormal groups, and was decreased from NGT to IGT and T2DM group with significant difference. It indicates that obese subjects with different glucose tolerances have a similar degree of insulin resistance but differ in insulin secretion in Chinese Han population.

Objective To investigate the correlation between plasma 25-hydroxyvitamin D(25-OHVD)levels and the CD4+ /CD8+ ratio in elderly men in different states of glucose metabolism. Methods Clinical data of 206 elderly male patients at the geriatrics department of our hospital from April 2011 to August 2017 were collected and retrospectively analyzed.There were 85 patients with type 2 diabetes mellitus(T2DM), 39 patients with impaired glucose tolerance(IGT)and 82 patients with normal glucose tolerance(NGT). Locally weighted regression and multivariate generalized linear regression models were used to analyze the correlation between plasma 25-OHVD levels and the CD4+ /CD8+ ratio. Results There were significant differences in two-hour postprandial blood glucose and homeostasis model assessment of insulin resistance(HOMA-IR)between the NGT, IGT and T2DM groups(6.5 mmol/L, 9.2 mmol/L vs.11.0 mmol/L, 11.92±10.57, 16.46±10.89 vs.32.67±7.39, respectively, P 0.05). The CD4+ /CD8+ ratios in the T2DM and IGT groups were not significantly different from each other(1.4 vs.1.6, P>0.05), but were lower than that in the NGT group(2.7, P<0.01). After adjusting for the influence of related confounders, CD4+ /CD8+ increased by 0.4 on average with each standard deviation(7.62 μg/L)increase of 25-OHVD.Compared with 25-OHVD patients in the first quartile, CD4+ /CD8+ in the second, third and fourth quartile increased by 0.7, 0.9 and 1.1 respectively on average, showing a significant positive correlation and a significant linear trend in the level of 25-OHVD and the CD4+ /CD8+ ratio(P<0.01). Conclusions With the aggravation of glucose tolerance, plasma 25-OHVD levels and the CD4+ /CD8+ ratio decrease by varying degrees in elderly men.The deficiency of plasma 25-OHVD may be an independent risk factor for a low CD4+ /CD8+ ratio. Key words: Diabetes mellitus, type 2; 25-hydroxyvitamin D2; CD4-CD8 ratio

Plasma SFRP5 levels are decreased in Chinese subjects with obesity and type 2 diabetes and negatively correlated with parameters of insulin resistance

Background:The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM.Methods:We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated.Results:In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in “disturbances of pigmentation” and “neurological and psychogenic dermatoses”. The duration of T2DM also significantly associated with the prevalence of “disturbances of pigmentation” and “neurological and psychogenic dermatoses”. Subsequently, the prevalence of “disturbances of pigmentation” was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of “disturbances of pigmentation” was also significant in NGT and T2DM groups (P < 0.01).Conclusions:There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.

PurposeThe pancreatic islet specific microRNA-375 (miR-375) is overexpressed in type 2 diabetes mellitus (T2DM) patients suppressing the glucose-induced insulin secretion. Thus, miR-375 may serve as a biomarker for the early prediction of T2DM among high-risk individuals. We conducted this clinical study to assess the significance of miR-375 among type 2 diabetes mellitus (T2DM) patients and their first-degree relatives.Patients and MethodsWe included 56 Han Chinese individuals (N: NGT = 21, T2DM = 10, FD-NGT =13 and FD-T2DM = 12) who received medical health check-ups from January 2018 to September 2018 at The Third Hospital of Yunnan Province, China. They were categorized as normal glucose tolerance (NGT), T2DM, first-degree relatives with normal glucose tolerance (FD-NGT) and first-degree relatives with T2DM (FD-T2DM). OGTT, C-peptide and Insulin tests were performed to confirm the diagnosis. The miR-375 levels were determined by Quantitative real-time RT-PCR (qRT-PCR).ResultsThe OGTT test showed a significant difference in T2DM and FD-T2DM groups compared with NGT and FD-NGT (p< 0.05). Similar results were observed during C-peptide and insulin tests. Interestingly, the 2-hour insulin test showed FD-NGT group having a significantly higher mean ± standard error of (64.240 ± 12.775) compared to NGT (28.836 ± 10.875). Assessment of miR-375 expression levels in 4 groups showed a significant up-regulation in T2DM and FD-T2DM compared with NGT and FD-NGT groups. A slight increase in miRNA expression was observed in FD-NGT compared with NGT group but was not statistically significant.ConclusionThe OGTT, C-peptide and insulin tests revealed a statistically significant difference in T2DM and FD-T2DM compared with NGT and FD-NGT groups. A significantly higher miR-375 expression was also observed in T2DM and FD-T2DM groups compared with NGT and FD-NGT and thus, miR-375 may serve as a stable biomarker for the early prediction of T2DM among high-risk individuals.