13: LOW BODY MASS INDEX DIABETES IS CHARACTERIZED BY IMPAIRED INSULIN SECRETION

Purpose of StudyFibrocalculous Pancreatic Diabetes (FCPD) and Lean Diabetes (LD) are unique forms of diabetes affecting millions of people in developing countries, characterized by the presence or absence of pancreatic calcifications on ultrasound and insulin-requiring but ketosis-resistant diabetes. To optimize therapeutic strategies for FCPD and lean diabetes patients, it is imperative to conclusively assess their insulin secretion using gold-standard methodologies.Methods UsedComprehensive tests were undertaken in n=22 Indian males with FCPD (age 30±2 y, BMI 19.7±0.6 kg/m2, HbA1c 9.0±0.3%) and n=6 with LD (age 36±4 y, BMI 18.3±0.1 kg/m2, HbA1c 11.6±1.3%), and compared with n=12 age, BMI matched ND, n=16 T1D (HbA1c 9.1±0.3%) and n=12 T2D subjects (age 36±2 y, BMI 26.0±0.3 kg/m2, HbA1c 9.7±0.6%). Following correction of hyperglycemia for over two weeks, mixed-meal tolerance tests (MMTT) and C-peptide deconvolution analysis was performed to assess beta-cell function.Summary of ResultsGlucose and C-peptide responses to MMTT suggest subjects with FCPD (14.5±2.2 pmol/kg/min) and LD (15.0±2.9 pmol/kg/min) have markedly impaired insulin secretion relative to both ND and T2D (p<0.001), and not statistically different from T1D (figure 1).ConclusionsThus, we report the first studies showing that patients with low BMI diabetes have impaired insulin secretion despite correction of hyperglycemia, consistent with nutritional effects on beta cell development or function.Abstract 13 Figure 1

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Glycemia, Beta-Cell Function and Sensitivity to Insulin in Mildly to Critically Ill Covid-19 Patients

Medicina ◽

10.3390/medicina57010068 ◽

2021 ◽

Vol 57 (1) ◽

pp. 68 ◽

Cited By ~ 1

Author(s):

Ioannis Ilias ◽

Aristidis Diamantopoulos ◽

Maria Pratikaki ◽

Efthymia Botoula ◽

Edison Jahaj ◽

...

Keyword(s):

Insulin Secretion ◽

Beta Cell ◽

Critically Ill ◽

Beta Cell Function ◽

Cell Function ◽

Model Assessment ◽

Secondary Diabetes ◽

C Peptide ◽

Number Of Patients ◽

Patients With Diabetes

Background and objectives: Critically and non-critically ill patients with SARS-CoV-2 infection (Covid-19) may present with higher-than-expected glycemia, even in the absence of diabetes. With this study we aimed to assess glucose, glycemic gap (GlyG) and insulin secretion/sensitivity measures in patients with Covid-19. Materials and Methods: We studied, upon admission, 157 patients with Covid-19 (84: in wards and 73: in intensive care units; ICU); 135 had no history of diabetes. We measured blood glucose upon admission as well as glycated hemoglobin (A1c), plasma insulin and C-peptide. We calculated the GlyG and the Homeostasis Model Assessment 2 (HOMA2) estimates of steady state beta cell function (HOMA2%B) and insulin sensitivity (HOMA2%S). Statistical assessment was done with analysis or the Kruskal-Wallis test. Results: Compared to patients in the wards without diabetes, patients with diabetes in the wards, as well as patients in the ICU (without or with diabetes) had higher admission glycemia. The GlyG was significantly higher in patients without diabetes in the ICU compared to patients without diabetes in the wards, while HOMA2%B based on glucose and insulin was significantly higher in the ICU patients compared to patients in the wards. Of all the parameters, HOMA2%S based on C-peptide/glucose was higher in survivors (n = 133). Conclusions: In our series of patients with Covid-19, a substantial number of patients with and without diabetes had admission hyperglycemia and those who were critically ill may have had compromised insulin secretion and lowered sensitivity to insulin. These findings lend credence to reports of association between Covid-19 and hyperglycemia/secondary diabetes.

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Pancreatic beta-cell function and glucose metabolism in human segmental pancreas and kidney transplantation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.264.3.e441 ◽

1993 ◽

Vol 264 (3) ◽

pp. E441-E449 ◽

Cited By ~ 2

Author(s):

E. Christiansen ◽

H. B. Andersen ◽

K. Rasmussen ◽

N. J. Christensen ◽

K. Olgaard ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Metabolism ◽

Beta Cell ◽

Kidney Transplant ◽

Beta Cell Function ◽

Cell Function ◽

Pancreatic Beta Cell ◽

Secretion Rate ◽

C Peptide ◽

Insulin Secretion Rate

beta-Cell function and glucose metabolism were studied in eight insulin-dependent diabetic recipients of combined segmental pancreas and kidney transplant with peripheral insulin delivery (Px), in eight nondiabetic kidney-transplant individuals (Kx), and in eight normal subjects (Ns) after three consecutive mixed meals. All subjects had normal fasting plasma glucose, but increased basal levels of C-peptide were demonstrated in the transplant groups (P < 0.05 relative to Ns). Postprandial hyperglycemia was increased 14% in Kx and 32% in Px (P < 0.05), whereas compared with Ns postprandial C-peptide levels were increased three- and twofold, respectively, in Kx and Px (P < 0.05). Compared with Ns basal insulin secretion rate (combined model) was increased 2-fold in Kx and 1.4-fold in Px (P < 0.05). Maximal insulin secretion rate was reduced 25% in Px compared with Kx (P < 0.05) but not different from that of Ns (P NS). Also, maximal insulin secretion rate occurred later in Px than in controls (Tmax: Px 50 min, Kx 30 min, and Ns 32 min; P < 0.05). The total integrated insulin secretion was increased 1.4-fold in Px compared with Ns (P < 0.05) but decreased 1.4-fold compared with Kx (P < 0.05). Fasting and postprandial proinsulin-to-C-peptide molar ratios were inappropriately increased in Px compared with Kx and Ns. Basal hepatic glucose production was increased 43% in Px and 33% in Kx compared with Ns (P < 0.05). Postprandial total systemic glucose appearance was similar in all three groups, whereas peripheral glucose disposal was 15% reduced in Px (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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059. POOR GROWTH BEFORE BIRTH IMPAIRS INSULIN SECRETION - WHAT WE HAVE LEARNT ABOUT THE MECHANISMS FROM THE PLACENTALLY-RESTRICTED SHEEP

Reproduction Fertility and Development ◽

10.1071/srb09abs059 ◽

2009 ◽

Vol 21 (9) ◽

pp. 14

Author(s):

K. L. Gatford

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

Beta Cell ◽

Insulin Action ◽

Cell Function ◽

Cell Mass ◽

Beta Cell Mass ◽

Poor Growth ◽

Impaired Insulin ◽

Impaired Insulin Action

Diabetes occurs when insulin secretion fails to increase sufficiently to compensate for developing insulin resistance. This implies that the increased risk of diabetes in adults who were small at birth reflects impaired insulin secretion as well as their well-known insulin resistance. More recently, direct evidence has been obtained that adults and children who were growth-restricted before birth secrete less insulin than they should, given their level of insulin resistance. Our research group is using the placentally-restricted (PR) sheep to investigate the mechanisms underlying impaired insulin action (sensitivity and secretion) induced by poor growth before birth. Like the intra-uterine growth-restricted (IUGR) human, the PR sheep develops impaired insulin action by adulthood, but has enhanced insulin sensitivity in infancy, associated with neonatal catch-up growth1, 2. Impaired insulin action begins to develop in early postnatal life, where although basal insulin action is high due to enhanced insulin sensitivity, maximal glucose-stimulated insulin action is already impaired in males3. Our cellular and molecular studies have identified impaired beta-cell function rather than mass as the likely cause of impaired insulin secretion, and we have reported a novel molecular defect in the calcium channels involved in the insulin secretion pathway in the pancreas of these lambs3. Upregulation of IGF-II and insulin receptor are implicated as key molecular regulators of beta-cell mass in the PR lamb3. By adulthood, both basal and maximal insulin action are profoundly impaired in the male lamb who was growth-restricted at birth2. These studies suggest therapies to prevent diabetes in the individual who grew poorly before birth should target beta-cell function, possibly in addition to further increasing beta-cell mass, to improve insulin secretion capacity, and its ability to increase in response to development of insulin resistance. We are now using the PR sheep to test potential therapies, since the timing of pancreatic development and hence exposure to a growth-restricting environment, is similar to that of the human.

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Creation and characterization of a mitochondrial DNA-depleted pancreatic beta-cell line: impaired insulin secretion induced by glucose, leucine, and sulfonylureas

Diabetes ◽

10.2337/diabetes.47.4.621 ◽

1998 ◽

Vol 47 (4) ◽

pp. 621-631 ◽

Cited By ~ 53

Author(s):

K. Tsuruzoe ◽

E. Araki ◽

N. Furukawa ◽

T. Shirotani ◽

K. Matsumoto ◽

...

Keyword(s):

Mitochondrial Dna ◽

Insulin Secretion ◽

Beta Cell ◽

Cell Line ◽

Pancreatic Beta Cell ◽

Impaired Insulin Secretion ◽

Beta Cell Line ◽

Impaired Insulin

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The Incretin Effect in Female Mice With Double Deletion of GLP-1 and GIP Receptors

Journal of the Endocrine Society ◽

10.1210/jendso/bvz036 ◽

2019 ◽

Vol 4 (2) ◽

Author(s):

Bo Ahrén ◽

Yuichiro Yamada ◽

Yutaka Seino

Keyword(s):

Insulin Secretion ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Insulin Response ◽

Oral Glucose ◽

Incretin Effect ◽

Intravenous Glucose ◽

C Peptide ◽

Female Mice

Abstract To establish the contribution of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) for the incretin effect after oral glucose, studies were undertaken in female mice with genetic deletion of receptors for GIP and GLP-1 (double incretin receptor knockout [DIRKO] mice) and their wild-type (WT) counterparts. Insulin secretion was explored after oral glucose (doses ranging from 0 to 100 mg), after intravenous glucose (doses ranging from 0 to 0.75 g/kg), and after oral and intravenous glucose at matching circulating glucose. DIRKO mice had glucose intolerance after oral glucose challenges in association with impaired beta-cell function. Suprabasal area under the curve for C-peptide (AUCC-peptide) correlated linearly with suprabasal AUCglucose both in WT (r = 0.942, P = .017) and DIRKO mice (r = 0.972, P = .006). The slope of this regression was lower in DIRKO than in WT mice (0.012 ± 0.006 vs 0.031 ± 0.006 nmol C-peptide/mmol glucose, P = .042). In contrast, there was no difference in the insulin response to intravenous glucose between WT and DIRKO mice. Furthermore, oral and intravenous glucose administration at matching glucose levels showed that the augmentation of insulin secretion after oral glucose (the incretin effect) in WT mice (11.8 ± 2.3 nmol/L min) was entirely absent in DIRKO mice (3.3 ± 1.2 nmol/L min). We conclude that GIP and GLP-1 are required for normal glucose tolerance and beta-cell function after oral glucose in mice, that they are the sole incretin hormones after oral glucose at higher dose levels, and that they contribute by 65% to insulin secretion after oral glucose.

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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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CART knock out mice have impaired insulin secretion and glucose intolerance, altered beta cell morphology and increased body weight

Regulatory Peptides ◽

10.1016/j.regpep.2005.02.016 ◽

2005 ◽

Vol 129 (1-3) ◽

pp. 203-211 ◽

Cited By ~ 76

Author(s):

N. Wierup ◽

W.G. Richards ◽

A.W. Bannon ◽

M.J. Kuhar ◽

B. Ahrén ◽

...

Keyword(s):

Body Weight ◽

Insulin Secretion ◽

Beta Cell ◽

Glucose Intolerance ◽

Cell Morphology ◽

Knock Out ◽

Impaired Insulin Secretion ◽

Impaired Insulin ◽

Knock Out Mice

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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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