1800-P: Cotadutide, a GLP-1/GCG Receptor Co-Agonist, Improves Insulin Sensitivity and Restores Normal Insulin Secretory Capacity in DIO Mice

Hyperproinsulinemia is commonly present in subjects with impaired glucose tolerance. The present study was undertaken to investigate the proinsulin level in Bangladeshi IGT subjects and to explore its association with insulin resistance. This observational study was conducted under a case-control design with IGT subjects (n=50) and controls (n=44). IGT was diagnosed following the WHO Study Group Criteria. Serum glucose was measured by glucose-oxidase method, serum lipid profile by enzymatic method and serum insulin and serum proinsulin were measured by ELISA method. Insulin secretory capacity (HOMA%B) and insulin sensitivity (HOMA%S) were calculated from fasting serum glucose and fasting serum insulin by homeostasis model assessment. The study subjects were age- and BMI- matched. Mean (±SD) age (yrs) of the control and IGT subjects were 40±6 and 40±5 respectively (p=0.853). Mean (±SD) BMI of the control and IGT subjects were 23±3 and 22±2 respectively (p=0.123). Fasting glucose was not significantly higher in IGT subjects, but serum glucose 2 hours after 75 gm glucose load was significantly higher in IGT subjects. Median (Range) value of fasting serum glucose (mmol/l) of control and IGT subjects were 5.3 (3.8-6) and 5.2 (4-12) respectively; (p=0.297). Median (Range) value of serum glucose (mmol/l) 2 hours after 75 gm glucose load of control and IGT subjects were 6.1 (3-7.8) and 7.9 (5- 21) respectively; (p=0.001). Fasting TG was significantly higher in IGT subjects and LDL-c was significantly lower in IGT subjects. Serum Total cholesterol and HDL-c were not significantly different between the IGT and control subjects. Median (Range) value of fasting serum TG (mg/dl) of control and IGT subjects were 119 (51-474) and 178 (82-540) respectively; (p=0.001). Median (Range) value of fasting serum T chol (mg/dl) of control and IGT subjects were 180 (65-272) and 186 (140-400) respectively; (p=0.191). Median (Range) value of fasting serum HDL-C (mg/dl) of control and IGT subjects were 29 (19-45) and 31 (15-78) respectively; (p=0.914). Median (Range) value of fasting serum LDL-C (mg/dl) of control and IGT subjects were 117(29-201) and 111(41- 320) respectively; (p=0.001). Fasting serum proinsulin was significantly higher in IGT subjects. Median (Range) value of fasting serum proinsulin (pmol/l) of control and IGT subjects were 9.2(1.8-156) and 17(3-51) respectively; (p=0.001). Insulin secretory capacity (HOMA%B) was higher but insulin sensitivity (HOMA%S) was significantly lower in case of IGT subjects. Median (Range) value of HOMA%B of control and IGT subjects were 97(46-498) and 164(17-300) respectively; (p=0.001). Median (Range) value of HOMA%S of control and IGT subjects were 68(19-270) and 39(15-110) respectively (p=0.001). In multiple regression analysis a significant negative association was found between fasting proinsulin and insulin sensitivity (p=0.037). The data led to the following conclusions: a) Insulin resistance is the predominant defect in Bangladeshi IGT subjects. b) Basal proinsulin level is significantly increased in IGT subjects. c) Insulin resistance is negatively associated with serum proinsulin in IGT subjects. DOI: http://dx.doi.org/10.3329/bjmb.v7i2.22411 Bangladesh J Med Biochem 2014; 7(2): 41-46

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Leptin and Other Factors as Determinants of Insulin Secretion and Sensitivity in Bangladeshi Type 2 Diabetic Subjects

Journal of Bangladesh Society of Physiologist ◽

10.3329/jbsp.v3i0.1786 ◽

1970 ◽

Vol 3 ◽

pp. 1-7

Author(s):

Manindra Nath Roy ◽

Salima Akter ◽

Mohammad Jafarulla ◽

Forhadul Hoque Mollah ◽

Ajanta Rani Saha ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

B Cell ◽

Plasma Glucose ◽

Key Words Leptin ◽

Type 2 Diabetic ◽

Insulin Secretory Capacity ◽

Secretory Capacity

Background: The relative contribution of insulin secretion and sensitivity in the development of Type 2 diabetes mellitus (T2DM) vary from population to population due to the heterogeneous nature of the disease. The study was undertaken to evaluate insulin secretory capacity and sensitivity in a Bangladeshi Type 2 diabetic population and to explore the association of some of the anthropometric and biochemical factors known to modulate B-cell function and insulin action. Methods: Ninety one T2DM subjects and 32 age-matched controls were studied for their fasting plasma glucose (FPG), lipids, HbA1c (by HPLC), leptin and C-peptide (ELISA). Insulin secretion (HOMA B) and insulin sensitivity (HOMA S) were calculated by homeostasis model assessment (HOMA). Results: Both insulin secretion and sensitivity were significantly reduced in diabetic as compared to control (HOMA B%, geometric meanÂ±SD, 35.65Â±1.75 vs. 96.29Â±1.50, p < 0.001; HOMA S%, 68.66Â±1.71 vs. 104.951.63, p < 0.001). However, B-cell dysfunction was predominant than insulin resistance in predicting T2DM as the discriminate function coefficient for HOMA B (1.098) was greater than that for HOMA S (0.821). In T2DM, HOMA B had positive correlation with BMI (r=0.368, p < 0.001) and HOMA S was inversely correlated to BMI (r=-0.261, p < 0.01), WHR (r=-0.258, p < 0.01) and plasma TG (r=-0.233, p < 0.001). On multiple regression analysis HOMA B and HOMA S were found to be inversely associated to FPG (p < 0.001) and leptin (p < 0.05) in T2DM. Conclusions: Both insulin secretory dysfunction and insulin resistance are present in Bangladeshi T2DM subjects, but B-cell failure seems to be the predominant abnormality. BMI, plasma glucose, insulin and leptin are the major determinants of insulin secretory capacity and generalized as well as central obesity, plasma glucose, triglycerides, insulin and leptin are among the major determinants of insulin sensitivity in this population. Key Words: Leptin, Insulin, Diabetes Â doi: 10.3329/jbsp.v3i0.1786 J Bangladesh Soc Physiol. 2008 Dec;(3):1-7.

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Increased insulin secretory capacity but decreased insulin sensitivity after correction of iron overload by phlebotomy in hereditary haemochromatosis

Diabetologia ◽

10.1007/s00125-006-0445-7 ◽

2006 ◽

Vol 49 (11) ◽

pp. 2546-2551 ◽

Cited By ~ 37

Author(s):

D. Abraham ◽

J. Rogers ◽

P. Gault ◽

J. P. Kushner ◽

D. A. McClain

Keyword(s):

Insulin Sensitivity ◽

Iron Overload ◽

Hereditary Haemochromatosis ◽

Insulin Secretory Capacity ◽

Secretory Capacity

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62 A MOUSE MODEL OF HEMOCHROMATOSIS EXHIBITS DECREASED INSULIN SECRETORY CAPACITY COMPENSATED BY INCREASED INSULIN SENSITIVITY, AND RESISTANCE TO DIET-INDUCED OBESITY

Journal of Investigative Medicine ◽

10.2310/6650.2005.00005.61 ◽

2005 ◽

Vol 53 (1) ◽

pp. S88.4-S88

Author(s):

M. Sanderson ◽

D. Jones ◽

H. Jouihan ◽

R. Ajioka ◽

R. Cooksey ◽

...

Keyword(s):

Insulin Sensitivity ◽

Mouse Model ◽

Insulin Sensitivity And Resistance ◽

Diet Induced Obesity ◽

Insulin Secretory Capacity ◽

Secretory Capacity

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Central Obesity Plays an Important Role for the Development of Type 2 Diabetes in Bangladeshi Women

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v13i3.19149 ◽

2014 ◽

Vol 13 (3) ◽

pp. 278-284

Author(s):

M O Faruque ◽

N Sultana ◽

A Mannan ◽

L Ali

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Regression Analysis ◽

Insulin Sensitivity ◽

Waist Circumference ◽

Central Obesity ◽

Control Subjects ◽

Insulin Secretory Capacity ◽

Secretory Capacity

Background: Diabetes mellitus coexists at a greater frequency with hypertension, obesity, central obesity, and dyslipidemia. Obesity has been identified as the most important modifiable risk factor in the aetiology of type-2 diabetes mellitus. Central obesity has been shown to be the most pathogenically important in the causation of metabolic disorders including type-2 diabetes. Aims: To determine the association of central obesity with type 2 diabetes in Bangladeshi women. Subjects and Methods: A total of 60 type 2 diabetic female subjects along with 60 healthy female subjects were recruited in this study. Anthropometric indices were measured using standard techniques. Serum glucose was measured using glucose-oxidase method, insulin was measured using ELISA and thyroid hormones were measured using chemiluminescence based automated Immulite Auto analyzer (DPC, USA). Insulin secretory capacity and insulin sensitivity were estimated using fasting glucose and fasting insulin by HOMA-CIGMA software. Results: Waist circumference of the control (89±8) subjects was significantly (p=0.046) lower than the diabetic (94±11) subjects. Waist-hip ratio of the control subjects was significantly lower compared to diabetic subjects. Fasting plasma insulin level in control subjects (7.6±2.2) was significantly (p=0.009) lower compared to diabetic subjects (11.8±9.8). Plasma lipid profile and thyroid hormone status in control and diabetic subjects were not found significantly different. Insulin secretory capacity (HOMA %B) and insulin sensitivity (HOMA%S) in control subjects (93±21, 95±39 respectively) were found to be significantly higher com-pared to diabetic subjects (45±32, 67±42 respectively). In age-adjusted binary logistic regression analysis, waist circumference was found to be significantly associated with diabetes. In multiple linear regression analysis TSH was found to be significantly associated with waist circumference. Conclusion: Waist circumference may be an independent indicator for the development type 2 diabetes in Bangladeshi women which may have influenced by thyroid stimulating hormone (TSH). DOI: http://dx.doi.org/10.3329/bjms.v13i3.19149 Bangladesh Journal of Medical Science Vol.13(3) 2014 p.278-284

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