Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients.

Objective: Type-2 diabetes is a progressive disease. However, little is known about whether decreased fasting or postprandial pancreatic β-cell responsiveness is more prominent with increased duration of diabetes. The aim of this study was to evaluate the relationship between insulin secretion both during fasting and 2 h postprandial, and the duration of diabetes in type-2 diabetic patients. Design: Cross-sectional clinical investigation. Methods: We conducted a meal tolerance test in 1466 type-2 diabetic patients and calculated fasting (M0) and postprandial (M1) β-cell responsiveness. Results: The fasting C-peptide, postprandial C-peptide, M0, and M1 values were lower, but HbA1c values were higher, in patients with diabetes duration > 10 years than those in other groups. There was no difference in the HbA1c levels according to the tertiles of their fasting C-peptide level. However, in a group of patients with highest postprandial C-peptide tertile, the HbA1c values were significantly lower than those in other groups. After adjustment of age, sex, and body mass index (BMI), the duration of diabetes was found to be negatively correlated with fasting C-peptide (γ = −0.102), postprandial C-peptide (γ = −0.356), M0 (γ = −0.263), and M1 (γ = −0.315; P < 0.01 respectively). After adjustment of age, sex, and BMI, HbA1c was found to be negatively correlated with postprandial C-peptide (γ = −0.264), M0 (γ = −0.379), and M1 (γ = −0.522), however, positively correlated with fasting C-peptide (γ = 0.105; P < 0.01 respectively). In stepwise multiple regression analysis, M0, M1, and homeostasis model assessment for insulin resistance (HOMA-IR) emerged as predictors of HbAlc after adjustment for age, sex, and BMI (R2 = 0.272, 0.080, and 0.056 respectively). Conclusions: With increasing duration of diabetes, the decrease of postprandial insulin secretion is becoming more prominent, and postprandial β-cell responsiveness may be a more important determinant for glycemic control than fasting β-cell responsiveness.

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Effect of Glucagon-Like Peptide-1 on α- and β-Cell Function in C-Peptide-Negative Type 1 Diabetic Patients

Molecular Endocrinology ◽

10.1210/mend.24.4.9999 ◽

2010 ◽

Vol 24 (4) ◽

pp. 875-875

Author(s):

Urd Kielgast ◽

Meena Asmar ◽

Sten Madsbad ◽

Jens J. Holst

Keyword(s):

Insulin Secretion ◽

Cell Function ◽

Glucagon Secretion ◽

Diabetic Patients ◽

Β Cell ◽

C Peptide ◽

Endogenous Insulin Secretion ◽

Endogenous Insulin ◽

Type 1 Diabetic Patients

Abstract Context: The mechanism by which glucagon-like peptide-1 (GLP-1) suppresses glucagon secretion is uncertain, and it is not determined whether endogenous insulin is a necessary factor for this effect. Objective: Our objective was to characterize the α- and β-cell responses to GLP-1 in type 1 diabetic patients without residual β-cell function. Methods: Nine type 1 diabetic patients, classified as C-peptide negative by a glucagon test, were clamped at plasma glucose of 20 mmol/liter for 90 min with arginine infusion at time 45 min and concomitant infusion of GLP-1 (1.2 pmol/kg · min) or saline. Results: Infusion with GLP-1 increased C-peptide concentration just above the detection limit of 33 pmol/liter in one patient, but C-peptide remained immeasurable in all other patients. In the eight remaining patients, total area under the curve of glucagon was significantly decreased with GLP-1 compared with saline: 485 ± 72 vs. 760 ± 97 pmol/liter · min (P < 0.001). In addition, GLP-1 decreased the arginine-stimulated glucagon release (incremental AUC of 103 ± 21 and 137 ± 16 pmol/liter · min, with GLP-1 and saline, respectively, P < 0.05). Conclusions: In type 1 diabetic patients without endogenous insulin secretion, GLP-1 decreases the glucagon secretion as well as the arginine-induced glucagon response during hyperglycemia. GLP-1 induced endogenous insulin secretion in one of nine type 1 diabetic patients previously classified as being without endogenous insulin secretion.

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Plasma C-Peptide Levels and Clinical Remissions in Recent-Onset Type I Diabetic Patients Treated With Cyclosporin A and Insulin

Diabetes ◽

10.2337/diab.39.7.768 ◽

1990 ◽

Vol 39 (7) ◽

pp. 768-774 ◽

Cited By ~ 29

Author(s):

R. Assan ◽

G. Feutren ◽

J. Sirmai ◽

C. Laborie ◽

C. Boitard ◽

...

Keyword(s):

Cyclosporin A ◽

Diabetic Patients ◽

Type I ◽

C Peptide ◽

Recent Onset ◽

Onset Type

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Plasma C-peptide levels and clinical remissions in recent-onset type I diabetic patients treated with cyclosporin A and insulin

Diabetes ◽

10.2337/diabetes.39.7.768 ◽

1990 ◽

Vol 39 (7) ◽

pp. 768-774 ◽

Cited By ~ 11

Author(s):

R. Assan ◽

G. Feutren ◽

J. Sirmai ◽

C. Laborie ◽

C. Boitard ◽

...

Keyword(s):

Cyclosporin A ◽

Diabetic Patients ◽

Type I ◽

C Peptide ◽

Recent Onset ◽

Onset Type

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Effect of Glucagon-Like Peptide-1 on α- and β-Cell Function in C-Peptide-Negative Type 1 Diabetic Patients

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-2440 ◽

2010 ◽

Vol 95 (5) ◽

pp. 2492-2496 ◽

Cited By ~ 37

Author(s):

Urd Kielgast ◽

Meena Asmar ◽

Sten Madsbad ◽

Jens J. Holst

Keyword(s):

Insulin Secretion ◽

Cell Function ◽

Glucagon Secretion ◽

Diabetic Patients ◽

Β Cell ◽

C Peptide ◽

Endogenous Insulin Secretion ◽

Endogenous Insulin ◽

Type 1 Diabetic Patients

Abstract Context: The mechanism by which glucagon-like peptide-1 (GLP-1) suppresses glucagon secretion is uncertain, and it is not determined whether endogenous insulin is a necessary factor for this effect. Objective: To characterize the α- and β-cell responses to GLP-1 in type 1 diabetic patients without residual β-cell function. Methods: Nine type 1 diabetic patients, classified as C-peptide negative by a glucagon test, were clamped at plasma glucose of 20 mmol/liter for 90 min with arginine infusion at time 45 min and concomitant infusion of GLP-1 (1.2 pmol/kg · min) or saline. Results: Infusion with GLP-1 increased C-peptide concentration just above the detection limit of 33 pmol/liter in one patient, but C-peptide remained immeasurable in all other patients. In the eight remaining patients, total area under the curve of glucagon was significantly decreased with GLP-1 compared with saline: 485 ± 72 vs. 760 ± 97 pmol/liter · min (P < 0.001). In addition, GLP-1 decreased the arginine-stimulated glucagon release (incremental AUC of 103 ± 21 and 137 ± 16 pmol/liter · min, with GLP-1 and saline, respectively, P < 0.05). Conclusions: In type 1 diabetic patients without endogenous insulin secretion, GLP-1 decreases the glucagon secretion as well as the arginine-induced glucagon response during hyperglycemia. GLP-1 induced endogenous insulin secretion in one of nine type 1 diabetic patients previously classified as being without endogenous insulin secretion.

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Potentiation of the early-phase insulin response by a prior meal contributes to the second-meal phenomenon in type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00244.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. E984-E990 ◽

Cited By ~ 17

Author(s):

Seung-Hwan Lee ◽

Andrea Tura ◽

Andrea Mari ◽

Seung-Hyun Ko ◽

Hyuk-Sang Kwon ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Early Phase ◽

Cell Function ◽

Insulin Response ◽

Free Fatty Acid Level ◽

Diabetic Patients ◽

Insulinogenic Index ◽

C Peptide

Improved glucose tolerance following a sequential meal is known as the second-meal phenomenon. We aimed to investigate its extent and underlying mechanisms in patients with type 2 diabetes. Metabolic responses after lunch in 12 diabetic patients were compared on two separate days: one with (Day BL) and another without (Day FL) breakfast. The responses of hormones were calculated by the incremental area under the curve (iAUC) values for 180 min after each meal. Indexes of early-phase insulin secretion were assessed, and β-cell function was estimated by mathematical modeling. [iAUCglucose(180–360 min)] was significantly lower on Day BL than on Day FL (181 ± 43 vs. 472 ± 29 mmol·liter−1·min, P = 0.0005). The magnitude of the The second-meal phenomenon [iAUCglucose(180–360 min) on Day BL/Day FL] was 35 ± 9%. The peak levels of insulin and C-peptide were attained 45 min earlier after the second meal than after the first meal. iAUCglucose(180–360 min) correlated negatively with iAUCinsulin(180–210 min) ( r = −0.443, P = 0.0300), insulinogenic index ( r = −0.769, P < 0.0001), acute C-peptide response ( r = −0.596, P = 0.0021), and potentiation factor [i.e., potentiation effect on insulin secretion] ratio (180–360)/(0–20) ( r = −0.559, P = 0.0045), while correlated positively with free fatty acid level before lunch ( r = 0.679, P = 0.0003). The second-meal phenomenon was evident in patients with type 2 diabetes. Potentiation of the early-phase insulin response by a prior meal contributes to this phenomenon in type 2 diabetes.

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Relationship Between First-Phase Insulin Secretion and Age, HLA, Islet Cell Antibody Status, and Development of Type I Diabetes in 220 Juvenile First-Degree Relatives of Diabetic Patients

Diabetes Care ◽

10.2337/diacare.14.8.718 ◽

1991 ◽

Vol 14 (8) ◽

pp. 718-723 ◽

Cited By ~ 24

Author(s):

J.-J. Robert ◽

I. Deschamps ◽

D. Chevenne ◽

M. Roger ◽

A. Mogenet ◽

...

Keyword(s):

Insulin Secretion ◽

Islet Cell ◽

Type I Diabetes ◽

Islet Cell Antibody ◽

Diabetic Patients ◽

Type I ◽

First Degree Relatives ◽

Cell Antibody ◽

First Phase Insulin Secretion

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Role of gastric inhibitory polypeptide in postprandial hyperinsulinemia of obesity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.254.6.e767 ◽

1988 ◽

Vol 254 (6) ◽

pp. E767-E774 ◽

Cited By ~ 3

Author(s):

L. R. Roust ◽

M. Stesin ◽

V. L. Go ◽

P. C. O'Brien ◽

R. A. Rizza ◽

...

Keyword(s):

Insulin Secretion ◽

Kinetic Model ◽

Healthy Subjects ◽

Gastric Inhibitory Polypeptide ◽

Volume Of Distribution ◽

Insulin Clearance ◽

C Peptide ◽

Obese Subjects ◽

Secretion Rates

To assess the contribution of gastric inhibitory polypeptide (GIP) to the postprandial hyperinsulinemia of obesity, secretion rates of GIP (generated from kinetic analyses from infusions of porcine GIP) and insulin (from C-peptide applied to a validated kinetic model) to meals of 3 sizes were determined in 10 obese (5 male and 5 female) and 10 lean, sex- and age-matched healthy subjects. Although the postprandial secretion rates of GIP were greater in obese subjects (P = 0.03), postprandial concentrations of GIP were not. The latter may be explained by the greater volume of distribution of GIP in obese subjects (P = 0.036). Secretion rates and volume of distribution of GIP were correlated (r = 0.652, P less than 0.01). Despite excessive integrated postprandial (P = 0.010) insulin concentrations, insulin secretion was not significantly different between obese and lean subjects. We conclude that 1) although postprandial plasma GIP concentrations are normal, GIP secretion is increased in obesity, 2) the postprandial hyperinsulinemia of obesity is not due to excessive insulin secretion but is likely secondary to altered insulin clearance, and 3) GIP cannot account for the hyperinsulinemia of obesity through its insulinotropic action.

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