scholarly journals A Low Frequency Genetic Variant in the Hepatic Glucokinase Gene is Associated with Type 2 Diabetes and Insulin Resistance in Chinese Population

2020 ◽  
Author(s):  
Ada Admin ◽  
Yumin Ma ◽  
Yingying Luo ◽  
Siqian Gong ◽  
Xianghai Zhou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Chinese Population ◽  
Cell Function ◽  
Low Frequency ◽  
Pooled Analysis ◽  
Cluster Sampling ◽  
Model Assessment ◽  
Two Samples

<a>Glucokinase (GCK) regulates insulin secretion and hepatic glucose metabolism, its inactivating variants could cause diabetes. We aimed to evaluate the association of a low-frequency variant of GCK (rs13306393) with type 2 diabetes (T2DM), prediabetes or both (IGR) in Chinese population. An association study was firstly conducted in a random cluster sampling population (Samples 1, 537 T2DM, 768 prediabetes and 1912 controls), then another independent Samples 2 (3896 T2DM, 2301 prediabetes and 868 controls) was used to confirm the findings in Samples 1. A-allele of rs13306393 was associated with T2DM [OR 3.08 (95%CI 1.77-5.36), p=0.00007] in Samples 1. Rs13306393 was also associated with prediabetes [OR 1.67 (95%CI 1.05-2.65), p=0.03] in Samples 2. In pooled analysis of two samples, A-allele increased the risk of T2DM [OR1.57 (95%CI 1.15-2.15), p=0.005], prediabetes [OR 1.83 (95%CI 1.33-2.54), p=0.0003) or IGR [OR 1.68 (95% CI 1.26-2.25), p=0.0004], insulin resistance estimated by homeostasis model assessment (beta=0.043, p=0.001), HbA1c (beta=0.029, P=0.029) and urinary albumin excretion (beta=0.033, p=0.025) irrespective of age, gender and BMI. Thus, the Chinese specific low-frequency variant increased the risk of T2DM through reducing insulin sensitivity rather than islet beta cell function, which should be considered in clinical use of GCK activators in the future.</a>

scholarly journals A Low Frequency Genetic Variant in the Hepatic Glucokinase Gene is Associated with Type 2 Diabetes and Insulin Resistance in Chinese Population

2020 ◽  
Author(s):  
Ada Admin ◽  
Yumin Ma ◽  
Yingying Luo ◽  
Siqian Gong ◽  
Xianghai Zhou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Chinese Population ◽  
Cell Function ◽  
Low Frequency ◽  
Pooled Analysis ◽  
Cluster Sampling ◽  
Model Assessment ◽  
Two Samples

<a>Glucokinase (GCK) regulates insulin secretion and hepatic glucose metabolism, its inactivating variants could cause diabetes. We aimed to evaluate the association of a low-frequency variant of GCK (rs13306393) with type 2 diabetes (T2DM), prediabetes or both (IGR) in Chinese population. An association study was firstly conducted in a random cluster sampling population (Samples 1, 537 T2DM, 768 prediabetes and 1912 controls), then another independent Samples 2 (3896 T2DM, 2301 prediabetes and 868 controls) was used to confirm the findings in Samples 1. A-allele of rs13306393 was associated with T2DM [OR 3.08 (95%CI 1.77-5.36), p=0.00007] in Samples 1. Rs13306393 was also associated with prediabetes [OR 1.67 (95%CI 1.05-2.65), p=0.03] in Samples 2. In pooled analysis of two samples, A-allele increased the risk of T2DM [OR1.57 (95%CI 1.15-2.15), p=0.005], prediabetes [OR 1.83 (95%CI 1.33-2.54), p=0.0003) or IGR [OR 1.68 (95% CI 1.26-2.25), p=0.0004], insulin resistance estimated by homeostasis model assessment (beta=0.043, p=0.001), HbA1c (beta=0.029, P=0.029) and urinary albumin excretion (beta=0.033, p=0.025) irrespective of age, gender and BMI. Thus, the Chinese specific low-frequency variant increased the risk of T2DM through reducing insulin sensitivity rather than islet beta cell function, which should be considered in clinical use of GCK activators in the future.</a>

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 Association of Serum Ferritin and Inflammatory Biomarkers with Insulin Resistance in Chinese Type 2 Diabetes Mellitus Patients

2020 ◽  
Vol 1 (7) ◽  
pp. 363-371
Author(s):  
Pratiksha Paudel ◽  
Shitian Zhang ◽  
Bei Guo ◽  
Alisha Pannu ◽  
Gajarishiyan Rasalingam ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Ferritin ◽  
Chinese Population ◽  
Inflammatory Biomarkers ◽  
Model Assessment ◽  
Tnf Α

Objective: Obesity-induced Insulin Resistance (IR) is one of the main causes of Type 2 Diabetes Mellitus (T2DM) and accompanies the progression of T2DM. Serum Ferritin has been shown to be associated with IR. Inflammation is also suggested to be involved in IR and pancreatic β-cell dysfunction. However, there is lack of enough evidence concerning the interrelationship between serum Ferritin, inflammation, and IR in the Chinese population with T2DM. In this study, the relationships between serum Ferritin and inflammatory biomarkers with IR in Chinese population were investigated. Methods: This cross-sectional study was conducted with 207 Chinese participants, aged 40-60 years in Tianjin, China. Serum Ferritin, transferrin, and folate were measured by immuno-assay analyzer. The levels of TNF-α, IL-1β, and IL-6 were detected by ELISA. IR was evaluated by Homeostasis model assessment (HOMA) of IR. Correlations were examined by regression analyses. Results: Serum Ferritin level was higher in non-diabetic obese and diabetic group than the non-diabetic lean group. The levels of TNF-α and CRP were significantly higher in the diabetic obese group than non-diabetic and diabetic lean subjects. Serum Ferritin, TNF-α, and CRP were all correlated with BMI. TNF-α correlated with IR and FPI. TNF-α, IL-6, IL-1β, and CRP were all correlated with FPG and HbA1c. Conclusion: In Chinese population, IR had a significant association with TNF-α but not with serum Ferritin. Serum Ferritin, TNF-α, and CRP were all correlated with BMI. Inflammation and glucose metabolism factors (FPG, HbA1c) showed a strong correlation with each other as well as with adiposity.

scholarly journals SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Kunrong Wu ◽  
Xiaoli Li ◽  
Yuedong Xu ◽  
Xiaoqian Zhang ◽  
Ziwan Guan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Cross Sectional Study ◽  
Model Assessment ◽  
Sectional Study ◽  
Cross Sectional

Background. Metformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively. Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control. The aim of this study was to evaluate if the genetic variants in SLC22A1 rs622342 and ATM rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment. Methods. This cross-sectional study included 111 patients with T2DM treated with metformin. Genotyping was performed by the dideoxy chain-termination method. The homeostatic indexes of IR (HOMA-IR) and beta-cell function (HOMA-BCF) were determined according to the homeostasis model assessment. Results. Fasting plasma glucose (FPG) levels, HbA1c levels, and HOMA-IR were significantly higher in patients with the rs622342 AA genotype than in those with C allele (P<0.05). However, these significant differences were not observed between rs11212617 genotype groups. Further data analysis revealed that the association between the rs622342 polymorphism and HOMA-IR was gender related, and so was rs11212617 polymorphism and HOMA-BCF. HOMA-IR was significantly higher in males with rs622342 AA genotype than in those with C allele (P=0.021), and HOMA-BCF value was significantly higher in females carrying rs11212617 CC genotype than in those with A allele (P=0.038). The common logarithm (Lg10) of HOMA-BCF was positively correlated with the reciprocal of HbA1c (r = 0.629, P<0.001) and negatively associated with Lg10 FPG (r = −0.708, P<0.001). Conclusions. The variant of rs622342 could be a predictor of insulin sensitivity in patients with T2DM treated with metformin. The association between the rs622342 polymorphism and HOMA-IR and the association between the rs11212617 polymorphism and HOMA-BCF were both gender related.

scholarly journals Relationship of Hemoglobin A1c withβCell Function and Insulin Resistance in Newly Diagnosed and Drug Naive Type 2 Diabetes Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Xinguo Hou ◽  
Jinbo Liu ◽  
Jun Song ◽  
Chuan Wang ◽  
Kai Liang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hemoglobin A1c ◽  
Cell Function ◽  
Binary Logistic Regression Analysis ◽  
Model Assessment ◽  
Newly Diagnosed ◽  
Drug Naïve ◽  
Diabetes Patients

Objective. To investigate changes in the glycated hemoglobin A1c (A1c) level and those inβcell function and insulin resistance in newly diagnosed and drug naive type 2 diabetes patients and to evaluate the relationship between them.Design and Methods. A total of 818 newly diagnosed diabetic individuals who were ≥40 years of age were recruited. The subjects were grouped by A1c values (<6.5%, 6.5–7%, 7-8%, 8-9%, and ≥9%). The homeostasis model assessment (HOMA) was used to evaluate pancreaticβcell function (HOMA-β) and insulin resistance (HOMA-IR). ANOVA,t-tests, and binary logistic regression analysis were used for data analysis.Results. Compared with subjects with A1c values <6.5%, individuals with an A1c of 6.5–7% exhibited an increased HOMA-βindex. However, the HOMA-βindex was significantly decreased at A1c values ≥7% and further decreased by 9.3% and by 23.7%, respectively, at A1c values of 7-8% and 8-9%. As A1c increased to ≥9%, a 62% reduction inβcell function was observed, independently of age, gender, body mass index (BMI), blood pressure (BP), blood lipids, and hepatic enzyme levels. Meanwhile, insulin resistance was significantly increased with an increase in A1c values.Conclusions. Elevated A1c values (≥7%) were associated with substantial reductions inβcell function.

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