Insulin secretion and anti-GAD65 antibodies in subjects with impaired glucose tolerance

To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subjects, 531 nondiabetic subjects with NGT ( n = 293) and IGT ( n = 238; 310 Japanese and 232 Mexican Americans) received an oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, and C-peptide every 30 min. The insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda index) was measured from plasma insulin and glucose concentrations. The insulin secretion/insulin resistance (IS/IR) or disposition index was calculated as ΔISR/ΔG ÷ IR. As FPG increased in NGT subjects, the IS/IR index declined exponentially over the range of FPG from 70 to 125 mg/dl. The relationship between the IS/IR index and FPG was best fit with the equation: 28.8 exp(−0.036 FPG). For every 28 mg/dl increase in FPG, the IS/IR index declined by 63%. A similar relationship between IS/IR index and FPG was observed in IGT. However, the decay constant was lower than in NGT. The IS/IR index for early-phase insulin secretion (0–30 min) was correlated with the increase in FPG in both NGT and IGT ( r = −0.43, P < 0.0001 and r = −0.20, P = 0.001, respectively). However, the correlation between late-phase insulin secretion (60–120 min) and FPG was not significant. In conclusion, small increments in FPG, within the “normal” range, are associated with a marked decline in glucose-stimulated insulin secretion and the decrease in insulin secretion with increasing FPG is greater in subjects with NGT than IGT and primarily is due to a decline in early-phase insulin secretion.

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Impact of incretin hormones on β-cell function in subjects with normal or impaired glucose tolerance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00571.2005 ◽

2006 ◽

Vol 291 (6) ◽

pp. E1144-E1150 ◽

Cited By ~ 60

Author(s):

Elza Muscelli ◽

Andrea Mari ◽

Andrea Natali ◽

Brenno D. Astiarraga ◽

Stefania Camastra ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Cell Function ◽

Oral Glucose ◽

Incretin Effect ◽

Β Cell ◽

Β Cell Function ◽

Glucose Sensitivity ◽

Cell Glucose

The mechanisms by which the enteroinsular axis influences β-cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT; n = 11) or impaired glucose tolerance (IGT; n = 10), using C-peptide deconvolution to calculate insulin secretion rates and mathematical modeling to quantitate β-cell function. The incretin effect was taken to be the ratio of oral to IV responses. In NGT, incretin-mediated insulin release [oral glucose tolerance test (OGTT)/IV ratio = 1.59 ± 0.18, P = 0.004] amounted to 18 ± 2 nmol/m2 (32 ± 4% of oral response), and its time course matched that of total insulin secretion. The β-cell glucose sensitivity (OGTT/IV ratio = 1.52 ± 0.26, P = 0.02), rate sensitivity (response to glucose rate of change, OGTT/IV ratio = 2.22 ± 0.37, P = 0.06), and glucose-independent potentiation were markedly higher with oral than IV glucose. In IGT, β-cell glucose sensitivity (75 ± 14 vs. 156 ± 28 pmol·min−1·m−2·mM−1 of NGT, P = 0.01) and potentiation were impaired on the OGTT. The incretin effect was not significantly different from NGT in terms of plasma glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide responses, total insulin secretion, and enhancement of β-cell glucose sensitivity (OGTT/IV ratio = 1.73 ± 0.24, P = NS vs. NGT). However, the time courses of incretin-mediated insulin secretion and potentiation were altered, with a predominance of glucose-induced vs. incretin-mediated stimulation. We conclude that, under physiological circumstances, incretin-mediated stimulation of insulin secretion results from an enhancement of all dynamic aspects of β-cell function, particularly β-cell glucose sensitivity. In IGT, β-cell function is inherently impaired, whereas the incretin effect is only partially affected.

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Effect of Artemisia dracunculus Administration on Glycemic Control, Insulin Sensitivity, and Insulin Secretion in Patients with Impaired Glucose Tolerance

Journal of Medicinal Food ◽

10.1089/jmf.2016.0005 ◽

2016 ◽

Vol 19 (5) ◽

pp. 481-485 ◽

Cited By ~ 6

Author(s):

Miriam Méndez-del Villar ◽

Ana M. Puebla-Pérez ◽

María J. Sánchez-Peña ◽

Luis J. González-Ortiz ◽

Esperanza Martínez-Abundis ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Glycemic Control ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Artemisia Dracunculus

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Insulin secretion and impaired glucose tolerance. Reply to Mari A, Ferrannini E [letter]

Diabetologia ◽

10.1007/s00125-010-1859-9 ◽

2010 ◽

Vol 53 (10) ◽

pp. 2271-2272

Author(s):

A. B. Jenkins ◽

L. V. Campbell

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance

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Uncoupling Protein 2 and Peroxisome Proliferator-Activated Receptor γ Gene Polymorphisms in Association with Diabetes Susceptibility in Chinese Han Population with Variant Glucose Tolerance

International Journal of Endocrinology ◽

10.1155/2018/4636783 ◽

2018 ◽

Vol 2018 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

Meicen Zhou ◽

Shuli He ◽

Fan Ping ◽

Wei Li ◽

Lixin Zhu ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Peroxisome Proliferator ◽

Chinese Han ◽

Peroxisome Proliferator Activated Receptor ◽

Han Population ◽

Increased Risk

Objective. To investigate the association of polymorphisms in uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor (PPARγ) with glucolipid metabolism in Chinese Han population. Methods. Five hundred eighty-nine subjects were divided into normal glucose tolerance (NGT) group (n=198) and abnormal glucose tolerance group (n=358). HbA1c, blood lipid profile, plasma glucose, and insulin were determined. Insulin sensitivity (HOMA-IR and Matsuda index (ISIM)) and insulin secretion indexes (HOMA-β, early and total phase disposition index) were evaluated. Eight potential functional SNPs in UCP2 and 7 in PPARγ were selected. SNPs were genotyped on Sequenom MassARRAY platform. Results. The GG genotype of rs2920502 in PPARγ was associated with decreased risk of impaired glucose tolerance (G allele: OR: 0.818, 95%CI: 0.526–0.969, P=0.042; GG: OR: 0.715, 95%CI: 0.527–0.97, P=0.031). The TT genotype of rs3856806 in PPARγ was associated with increased risk of impaired glucose tolerance (T allele: OR: 1.46, 95%CI: 1.055–2.017, P=0.022; TT: OR: 1.58, 95%CI: 1.104–2.761, P=0.032). The GG genotype of rs2920502 in PPARγ had better blood glucose and increased insulin secretion and had lower HOMA-IR than GC/CC genotypes. Conclusion. It probably could prevent insulin resistance in early stage by classifying the genotype of rs649446 and rs7109266 in UCP2. The GG genotype of rs2920502 in PPARγ had a decreased risk for diabetes. The TT genotype of rs3856806 in PPARγ had an increased risk for diabetes.

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