Clinical Significance of the Maximum Body Mass Index Before Onset of Type 2 Diabetes for Predicting Beta-Cell Function

Abstract Objective This study aimed to clarify the clinical significance of the maximum body mass index (BMI) before the onset of type 2 diabetes (MBBO) for predicting pancreatic beta-cell function. Methods This was a cross-sectional observational study. Of 1304 consecutively admitted patients with type 2 diabetes, we enrolled 410 patients satisfying the criteria in this study. The correlations between the C-peptide index (CPI), which is one of the parameters that reflects beta-cell function, and various clinical parameters, including MBBO and duration of diabetes, were analyzed in multiple linear regression analyses. Results The analyses revealed that MBBO was correlated with CPI independently after adjustment for age, sex, HbA1c, and duration of diabetes. When we divided the subjects into three subgroups by MBBO (MBBO < 25 kg/m2; 25 kg/m2 ≤ MBBO < 30 kg/m2; MBBO ≥ 30 kg/m2), CPI was negatively correlated with duration of diabetes in each subgroup, while the rates of CPI based on the duration of diabetes were not different among the three MBBO subgroups. In contrast, the declining rates of CPI were higher in the BMI ≥ 25 kg/m2 group on admission than in the BMI < 25 kg/m2 group on admission. Conclusions MBBO may be an independent factor correlating with beta-cell function and may predict insulin secretion capacity at diagnosis, but it does not seem to affect the rate of decline in insulin secretion capacity after diagnosis. It is important to preserve beta-cell function by decreasing a patient’s BMI during treatment after diagnosis regardless of MBBO.

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ER stress increases store-operated Ca2+ entry (SOCE) and augments basal insulin secretion in pancreatic beta cells

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.012721 ◽

2020 ◽

Vol 295 (17) ◽

pp. 5685-5700

Author(s):

Irina X. Zhang ◽

Jianhua Ren ◽

Suryakiran Vadrevu ◽

Malini Raghavan ◽

Leslie S. Satin

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Beta Cell ◽

Er Stress ◽

Beta Cells ◽

Beta Cell Function ◽

Cell Function ◽

Critical Role ◽

Beta Cell Apoptosis

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.

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Association between small intestinal bacterial overgrowth and beta-cell function of type 2 diabetes

Journal of International Medical Research ◽

10.1177/0300060520937866 ◽

2020 ◽

Vol 48 (7) ◽

pp. 030006052093786

Author(s):

Li-hui Yan ◽

Biao Mu ◽

Da Pan ◽

Ya-nan Shi ◽

Ji-hong Yuan ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Beta Cell ◽

Early Phase ◽

Beta Cell Function ◽

Cell Function ◽

Bacterial Overgrowth ◽

Small Intestinal Bacterial Overgrowth ◽

Total Phase

Aims Previous studies suggest that small intestinal bacterial overgrowth (SIBO) is associated with type 2 diabetes. However, few studies have evaluated the association between SIBO and beta-cell function in type 2 diabetes. The aim of this study was to evaluate whether beta-cell function was associated with SIBO. Materials and methods One hundred four patients with type 2 diabetes were included in this study. Based on the presence of SIBO, the patients were divided into SIBO-positive and SIBO-negative groups. Oral glucose tolerance tests were performed. Insulin sensitivity was measured using 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and the insulin sensitivity index (ISIM). Insulin release was calculated by HOMA-β, early-phase insulin secretion index InsAUC30/GluAUC30, and total-phase insulin secretion index InsAUC120/GluAUC120. Results Compared with the SIBO-negative group, patients in the SIBO-positive group showed a higher glucose level at 120 minutes, HbA1c, 1/HOMA-IR, and ISIM and a lower HOMA-β level, early-phase InsAUC30/GluAUC30, and total-phase InsAUC120/GluAUC120. Multiple linear regression analysis showed that body mass index, glucose at 0 minutes, and SIBO were independently associated with the early-phase and total-phase insulin secretion. Conclusion SIBO may be involved in lower levels of insulin release and worse glycemic control.

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Liraglutide improves the beta-cell function without increasing insulin secretion during a mixed meal in patients, who exhibit well-controlled type 2 diabetes and coronary artery disease

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-019-0438-6 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Christian Anholm ◽

Preman Kumarathurai ◽

Anders Jürs ◽

Lene Rørholm Pedersen ◽

Olav Wendelboe Nielsen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Insulin Secretion ◽

Coronary Artery ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Mixed Meal ◽

Artery Disease

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A Plant-Based Meal Stimulates Incretin and Insulin Secretion More Than an Energy- and Macronutrient-Matched Standard Meal in Type 2 Diabetes: A Randomized Crossover Study

Nutrients ◽

10.3390/nu11030486 ◽

2019 ◽

Vol 11 (3) ◽

pp. 486 ◽

Cited By ~ 3

Author(s):

Hana Kahleova ◽

Andrea Tura ◽

Marta Klementova ◽

Lenka Thieme ◽

Martin Haluzik ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Beta Cell ◽

Repeated Measures ◽

Beta Cell Function ◽

Cell Function ◽

Therapeutic Potential ◽

Plasma Concentrations ◽

C Peptide

Diminished postprandial secretion of incretins and insulin represents one of the key pathophysiological mechanisms behind type 2 diabetes (T2D). We tested the effects of two energy- and macronutrient-matched meals: A standard meat (M-meal) and a vegan (V-meal) on postprandial incretin and insulin secretion in participants with T2D. A randomized crossover design was used in 20 participants with T2D. Plasma concentrations of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), amylin, and gastric inhibitory peptide (GIP) were determined at 0, 30, 60, 120, and 180 min. Beta-cell function was assessed with a mathematical model, using C-peptide deconvolution. Repeated-measures ANOVA was used for statistical analysis. Postprandial plasma glucose responses were similar after both test meals (p = 0.64). An increase in the stimulated secretion of insulin (by 30.5%; 95% CI 21.2 to 40.7%; p < 0.001), C-peptide (by 7.1%; 95% CI 4.1 to 9.9%; p < 0.001), and amylin (by 15.7%; 95% CI 11.8 to 19.7%; p < 0.001) was observed following consumption of the V-meal. An increase in stimulated secretion of GLP-1 (by 19.2%; 95% CI 12.4 to 26.7%; p < 0.001) and a decrease in GIP (by −9.4%; 95% CI −17.3 to −0.7%; p = 0.02) were observed after the V-meal. Several parameters of beta-cell function increased after the V-meal, particularly insulin secretion at a fixed glucose value 5 mmol/L, rate sensitivity, and the potentiation factor. Our results showed an increase in postprandial incretin and insulin secretion, after consumption of a V-meal, suggesting a therapeutic potential of plant-based meals for improving beta-cell function in T2D.

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Recovery of human type 2 diabetes beta cell function associates with transcriptomic signatures that point to novel therapeutic targets

10.21203/rs.3.rs-871924/v1 ◽

2021 ◽

Author(s):

Mara Suleiman ◽

Xiaoyan Yi ◽

Emanuele Bosi ◽

Frederic Burdet ◽

Carmela De Luca ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Beta Cell ◽

Beta Cell Function ◽

Molecular Mechanisms ◽

Cell Function ◽

Therapeutic Targets ◽

Glucose Stimulated Insulin Secretion ◽

Novel Therapeutic

Abstract Remission of type 2 diabetes (T2D) may occur after very low-calorie diets or bariatric surgery, and is associated with improved pancreatic beta cell function. Here, we evaluated if T2D beta cell dysfunction can be rescued ex-vivo and which are the molecular mechanisms involved. Islets from 19 T2D donors were studied after isolation (“basal”) and following culture at 5.5 or 11.1 mmol/l glucose (“cultured”). We evaluated glucose-stimulated insulin secretion (GSIS) and transcriptomes by RNA sequencing, correlated insulin secretion changes (“cultured” vs “basal”) to global gene expression, and searched for potential therapeutic gene targets and compounds that mimic gene signatures of recovered beta cell function in T2D islets. GSIS improved in 12 out of 19 islet preparations from T2D donors after culture at 5.5 mmol/l glucose (insulin stimulation index increased from 1.4±0.1 to 2.3±0.2, p<0.01), mainly due to greater insulin response to high glucose. No improvement was seen in islets cultured at 11.1 mmol/l glucose. Functional improvement was accompanied by changes in expression of 438 genes, many of which involved in functional and inflammatory processes. Of them, 123 were significantly correlated with changes in glucose-stimulated insulin secretion. Drug repurposing and target identification analyses for beta cell functional recovery predicted several chemical (including Src inhibitors and anti-inflammatory drugs) and genetic hits in pathways such as chemokine, MAPK, ERBB signaling, and autophagy. In conclusion, defective insulin secretion in T2D can be rescued, at least in part, by a “non-diabetic” milieu, demonstrating important T2D beta cell functional plasticity. This recovery associates with specific transcriptomic traits, pointing to known as well as novel therapeutic targets to induce T2D remission.

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Inverse relationship between serum adenosine deaminase levels and islet beta cell function in patients with type 2 diabetes

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00671-2 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Jie Cao ◽

Hong Wang ◽

Jian-bin Su ◽

Xue-qin Wang ◽

Dong-mei Zhang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Sensitivity Index ◽

Clinical Parameters ◽

C Peptide ◽

Islet Beta Cell

Abstract Objective Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease, which characterized by islet beta cell dysfunction. Serum adenosine deaminase (ADA) is an important enzyme that regulates the biological activity of insulin, and its levels are greatly increased in inflammatory diseases with insulin resistance. The present study was designed to explore the relationship between serum ADA levels and islet beta cell function in patients with T2D. Methods This cross-sectional study recruited 1573 patients with T2D from the Endocrinology Department of the Affiliated Hospital 2 of Nantong University between 2015 and 2018. All participants were received serum ADA test and oral glucose tolerance test (OGTT). Insulin sensitivity index (assessed by Matsuda index using C-peptide, ISIM-cp), insulin secretion index (assessed by ratio of area under the C-peptide curve to glucose curve, AUCcp/glu) and islet beta cell function (assessed by insulin secretion-sensitivity index 2 using C-peptide, ISSI2cp) were derived from OGTT. And other clinical parameters, such as HbA1c, were also collected. Results It was showed that HbA1c was significantly increased, while ISIM-cp, AUCcp/glu and ISSI2cp significantly decreased, across ascending quartiles of serum ADA levels. Moreover, serum ADA levels were negatively correlated with ISSI2cp (r = − 0.267, p < 0.001). Furthermore, after adjusting for other clinical parameters by multiple linear regression analysis, serum ADA levels were still independently associated with ISSI2cp (β = − 0.125, t = − 5.397, p < 0.001, adjusted R2 = 0.459). Conclusions Serum ADA levels are independently associated with islet beta cell function in patients with T2D.

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