scholarly journals Fasting serum total bile acid levels are associated with insulin sensitivity, islet β-cell function and glucagon levels in response to glucose challenge in patients with type 2 diabetes

2020 ◽  
Vol 67 (11) ◽  
pp. 1107-1117
Author(s):  
Xiao-hua Wang ◽  
Feng Xu ◽  
Ming Cheng ◽  
Xing Wang ◽  
Dong-mei Zhang ◽  
...  
Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 970-P
Author(s):  
KRISHNAMOORTHY SATHEESH ◽  
CHAMUKUTTAN SNEHALATHA ◽  
ARUN NANDITHA ◽  
ARUN RAGHAVAN ◽  
RAMACHANDRAN VINITHA ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Marianna Santopaolo ◽  
Niall Sullivan ◽  
Anita Coral Thomas ◽  
Valeria Vincenza Alvino ◽  
Lindsay B. Nicholson ◽  
...  

Background: Chronic low-grade inflammation and alterations in innate and adaptive immunity were reported in Type 2 diabetes (T2D). Here, we investigated the abundance and activation of T cells in the bone marrow (BM) of patients with T2D. We then verified the human data in a murine model and tested if the activation of T cells can be rescued by treating mice with abatacept, an immunomodulatory drug employed for the treatment of rheumatoid arthritis. Clinical evidence indicated abatacept can slow the decline in beta-cell function.Methods: A cohort of 24 patients (12 with T2D) undergoing hip replacement surgery was enrolled in the study. Flow cytometry and cytokine analyses were performed on BM leftovers from surgery. We next compared the immune profile of db/db and control wt/db mice. In an additional study, db/db mice were randomized to receive abatacept or vehicle for 4 weeks, with endpoints being immune cell profile, indices of insulin sensitivity, and heart performance.Results: Patients with T2D showed increased frequencies of BM CD4+ (2.8-fold, p = 0.001) and CD8+ T cells (1.8-fold, p = 0.01), with the upregulation of the activation marker CD69 and the homing receptor CCR7 in CD4+ (1.64-fold, p = 0.003 and 2.27-fold, p = 0.01, respectively) and CD8+ fractions (1.79-fold, p = 0.05 and 1.69-fold, p = 0.02, respectively). These differences were confirmed in a multivariable regression model. CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T-cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and the levels of proinflammatory cytokines and improved cardiac function but not insulin sensitivity.Conclusions: Results provide proof-of-concept evidence for the activation of BM adaptive immunity in T2D. In mice, treatment with abatacept dampens the activation of adaptive immunity and protects from cardiac damage.


Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Wei-Hao Hsu ◽  
Chin-Wei Tseng ◽  
Yu-Ting Huang ◽  
Ching-Chao Liang ◽  
Mei-Yueh Lee ◽  
...  

Prediabetes should be viewed as an increased risk for diabetes and cardiovascular disease. In this study, we investigated its prevalence among the relatives and spouses of patients with type 2 diabetes or risk factors for prediabetes, insulin resistance, and β-cell function. A total of 175 individuals were included and stratified into three groups: controls, and relatives and spouses of type 2 diabetic patients. We compared clinical characteristics consisting of a homeostatic model assessment for insulin resistance (HOMA-IR) and beta cell function (HOMA-β), a quantitative insulin sensitivity check index (QUICKI), and triglyceride glucose (TyG) index. After a multivariable linear regression analysis, the relative group was independently correlated with high fasting glucose, a high TyG index, and low β-cell function; the relatives and spouses were independently associated with a low QUICKI. The relatives and spouses equally had a higher prevalence of prediabetes. These study also indicated that the relatives had multiple factors predicting the development of diabetes mellitus, and that the spouses may share a number of common environmental factors associated with low insulin sensitivity.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xinlei Wang ◽  
Xiaoqin Zhao ◽  
Yunjuan Gu ◽  
Xiaohui Zhu ◽  
Tong Yin ◽  
...  

In China, most normal BMI (body mass index of ≥18.5 to <25 kg/m2) adults with type 2 diabetes (T2DM) exhibit visceral adiposity. This study compared the effects of exenatide and humalog Mix25 on normal BMI patients with T2DM and visceral adiposity. A total of 95 patients were randomized to receive either exenatide or humalog Mix25 treatment for 24 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were quantified by magnetic resonance imaging (MRI) and liver fat content (LFC) by liver proton magnetic resonance spectroscopy (1H MRS). Each patient’s weight, waist circumference, BMI, blood glucose, insulin sensitivity, pancreatic β-cell function, and fibroblast growth factor 21 (FGF-21) levels were measured. Data from 81 patients who completed the study (40 and 41 in the exenatide and humalog Mix25 groups, respectively) were analysed. The change in 2 h plasma blood glucose was greater in the exenatide group (P=0.039). HOMA-IR and MBCI improved significantly after exenatide therapy (P<0.01, P=0.045). VAT and LFC decreased in both groups (P<0.01 for all) but to a greater extent in the exenatide group, while SAT only decreased with exenatide therapy (P<0.01). FGF-21 levels declined more in the exenatide group (P<0.01), but were positively correlated with VAT in the entire cohort before (r=0.244, P=0.043) and after (r=0.290, P=0.016) the intervention. The effects of exenatide on glycaemic metabolism, insulin resistance, pancreatic β-cell function, and fat deposition support its administration to normal BMI patients with T2DM and visceral adiposity.


2015 ◽  
Vol 308 (6) ◽  
pp. E535-E544 ◽  
Author(s):  
Christoffer Martinussen ◽  
Kirstine N. Bojsen-Møller ◽  
Carsten Dirksen ◽  
Siv H. Jacobsen ◽  
Nils B. Jørgensen ◽  
...  

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.


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