scholarly journals Increased Risk for Type 2 Diabetes in Relation to Adiposity in Middle-Aged Black South African Men compared to Women

2021 ◽  
Author(s):  
Clement Kufe ◽  
Lisa Micklesfield ◽  
maphoko Masemola ◽  
Tinashe Chikowore ◽  
Andre-Pascal Kengne ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Beta Cell ◽  
South African ◽  
Beta Cell Function ◽  
Cell Function ◽  
C Peptide ◽  
Black South African ◽  
Regional Adiposity

Aims: Despite a higher prevalence of overweight and obesity in black South African women compared to men, the prevalence of type 2 diabetes does not differ. We explored if this could be due to sex differences in insulin sensitivity, clearance and or beta cell function, and also sex-specific associations with total and regional adiposity. Methods: This cross-sectional study included 804 black South African men (n=388) and women (n=416). Dual-energy x ray absorptiometry was used to measure total and regional adiposity. Insulin sensitivity (Matsuda index), secretion (C peptide index) and clearance (C peptide/insulin ratio) were estimated from an oral glucose tolerance test. Results: After adjusting for sex differences in fat mass index, men were less insulin sensitive and had lower beta cell function than women (p<0.001), with the strength of the associations with measures of total and central adiposity being greater in men than women (p<0.001 for interactions). Further, the association between total adiposity and type 2 diabetes risk was also greater in men than women (relative risk ratio (95% confidence interval): 2.05 (1.42 to 2.96), p<0.001 vs. 1.38 (1.03 to 1.85), p=0.031). Conclusion: With increasing adiposity, particularly increased centralisation of body fat linked to decreased insulin sensitivity and beta cell function, Black African men are at greater risk for type 2 diabetes than their female counterparts.

scholarly journals SAT-667 Partial Beta-Cell Destruction: An Atypical Case of Immune Checkpoint Inhibitor Diabetes Mellitus

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Zoe Quandt ◽  
Katy K Tsai ◽  
Victoria C Hsiao
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Immune Checkpoint ◽  
Beta Cell Function ◽  
Cell Function ◽  
Autoimmune Diabetes ◽  
Insulin Production ◽  
C Peptide

Abstract Background: Autoimmune diabetes mellitus (CPI-DM) caused by immune checkpoint inhibitors (CPIs) is rare- occurring in approximately one percent of patients exposed to this form of cancer immunotherapy. Typically, this immune related adverse event occurs after treatment with PD-1/PD-L1 inhibitors. It is characterized by abrupt insulinopenia leading to acute hyperglycemia. Beta cell autoantibodies are positive in approximately half the cases. DKA is common at the time of diagnosis. Recovery of beta cell function has been reported in only two case reports. In one case, spontaneous resolution occurred following cessation of CPI therapy and in the other the patient was treated with infliximab for concurrent inflammatory arthritis prior to resolution of CPI-DM. Clinical Case: A 50-year-old woman was started on adjuvant pembrolizumab for stage IIIC melanoma following surgery. She had no prior history of diabetes mellitus, thyroid disease, or other autoimmune disease. Pre-infusion random blood glucoses (RBG) were 84 - 105 mg/dL. After 36 weeks, she developed hypothyroidism (TSH 17.5 (0.5-4.1 mIU/L), FT4 6 (10-18 ug/dL)) and started levothyroxine. Pembrolizumab was continued. For nine weeks following her diagnosis with CPI- hypothyroidism, her pre-infusion RBG ranged from 102-133. At 45 weeks (15 cycles) after initiating pembrolizumab, her RBG was 260. She was not on glucocorticoids and had no other signs of inflammation or stress. Pembrolizumab was continued. Just prior to her 17th cycle, 48 weeks after initiating adjuvant pembrolizumab, her RBG was 482 with a normal anion gap and HCO3, and her A1c was 8.9%. Her last dose of pembrolizumab was held. She started metformin and liraglutide. In just three weeks, a random c-peptide was inadequate at 1.7 (0.8-3.5 ng/mL) with a recent RBG of 220 and A1c of 10.3%, showing the acuity and extremity of her hyperglycemia. Over the course of the year, she has achieved excellent glucose control (A1c 6.3-7.1) on this regimen with preservation of insulin production (c-peptides 1.4-1.8 with matched RBG 92-129). She never required insulin. Her beta cell autoantibodies are negative. Clinical Lessons: This is a case of CPI-DM in which the patient did not have complete loss of beta-cell function. The acuity of her hyperglycemia is not consistent with new onset type 2 diabetes. At diagnosis, her c-peptide was inadequate suggesting insufficient insulin production rather than insulin resistance. Therefore, her hyperglycemia is more consistent with CPI-DM than type 2 diabetes. Atypically, she did not progress to fulminant beta cell failure, which could have been due to cessation of pembrolizumab (which is not unique to this case), initiation of liraglutide and metformin, or other unknown immunologic responses that inhibited full beta cell loss. This case raises the possibility of preventing fully insulin dependent CPI-DM if hyperglycemia is caught and treated early.

scholarly journals Beta cell function and insulin sensitivity in obese youth with maturity onset diabetes of youth mutations vs type 2 diabetes in TODAY: Longitudinal observations and glycemic failure

2020 ◽  
Vol 21 (4) ◽  
pp. 575-585
Author(s):  
Silva Arslanian ◽  
Laure El ghormli ◽  
Morey H. Haymond ◽  
Christine L. Chan ◽  
Steven D. Chernausek ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes ◽  
Obese Youth

scholarly journals Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

2016 ◽  
Vol 175 (5) ◽  
pp. 367-377 ◽  
Author(s):  
Christian Herder ◽  
Kristine Færch ◽  
Maren Carstensen-Kirberg ◽  
Gordon D Lowe ◽  
Rita Haapakoski ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Fasting Insulin ◽  
Subclinical Inflammation ◽  
Increased Risk

Objective Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional. Design and methods We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers. Results Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin. Conclusions Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammation-related processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function.

scholarly journals 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 ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 486 ◽  
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.

scholarly journals Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes

2020 ◽  
Author(s):  
Melissa K Thomas ◽  
Amir Nikooienejad ◽  
Ross Bray ◽  
Xuewei Cui ◽  
Jonathan Wilson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Regression Analysis ◽  
Insulin Sensitivity ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Receptor Agonist ◽  
Cell Function ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis

Abstract Context Novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide. Objective Explore mechanisms of glucose control by tirzepatide. Design Post hoc analyses of fasting biomarkers and multiple linear regression analysis. Setting Forty-seven sites in 4 countries. Patients or other Participants Three hundred and sixteen subjects with type 2 diabetes. Interventions Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), placebo. Main Outcome Measures Analyze biomarkers of beta-cell function and insulin resistance (IR) and evaluate WL contributions to IR improvements at 26 weeks. Results Homeostatic model assessment (HOMA) 2-B significantly increased with dulaglutide and tirzepatide 5, 10, and 15 mg compared with placebo (P ≤ .02). Proinsulin/insulin and proinsulin/C-peptide ratios significantly decreased with tirzepatide 10 and 15 mg compared with placebo and dulaglutide (P ≤ .007). Tirzepatide 10 and 15 mg significantly decreased fasting insulin (P ≤ .033) and tirzepatide 10 mg significantly decreased HOMA2-IR (P = .004) compared with placebo and dulaglutide. Markers of improved insulin sensitivity (IS) adiponectin, IGFBP-1, and IGFBP-2 significantly increased by 1 or more doses of tirzepatide (P &lt; .05). To determine whether improvements in IR were directly attributable to WL, multiple linear regression analysis with potential confounding variables age, sex, metformin, triglycerides, and glycated hemoglobin A1c was conducted. WL significantly (P ≤ .028) explained only 13% and 21% of improvement in HOMA2-IR with tirzepatide 10 and 15 mg, respectively. Conclusions Tirzepatide improved markers of IS and beta-cell function to a greater extent than dulaglutide. IS effects of tirzepatide were only partly attributable to WL, suggesting dual receptor agonism confers distinct mechanisms of glycemic control.

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