Reduced Insulinotropic Effect of Gastric Inhibitory Polypeptide in First-Degree Relatives of Patients With Type 2 Diabetes

Meier, Juris J.; Hücking, Katrin; Holst, Jens J.; Deacon, Carolyn F.; Schmiegel, Wolff; Nauck, Michael A.

doi:10.2337/diabetes.50.11.2497

Cited by 212 publications

(166 citation statements)

References 63 publications

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“…Measurements Glucose was measured as described [18,19] using a glucose oxidase method with a Glucose Analyzer 2 (Beckman Instruments, Munich, Germany).…”

Section: Methodsmentioning

confidence: 99%

Metabolic consequences of a 50% partial pancreatectomy in humans

et al. 2008

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Aims/hypothesis Partial pancreatectomy is frequently performed in patients with pancreatic tumours or chronic pancreatitis, but little is known about the metabolic impact of this intervention. We examined the effects of approximately 50% partial pancreatectomy on glucose homeostasis and insulin secretion. Methods Fourteen patients with chronic pancreatitis, ten patients with pancreatic carcinoma and 13 patients with benign pancreatic tumours or extra-pancreatic masses (control group) underwent 240 min oral glucose tolerance tests before and after pancreatic tail-resection (n=12), duodenopancreatectomy (n=19) or duodenum-preserving pancreatic-head resection (n=6). Results Partial pancreatectomy led to a reduction in postchallenge insulin excursions by 49% in chronic pancreatitis patients, 52% in carcinoma patients and 55% in controls (p<0.05). Nevertheless, post-challenge glucose concentrations were transiently ameliorated after surgery (p<0.001). In the control participants, pancreatic-head resection caused a transient reduction of post-challenge glycaemia, whereas pancreatic-tail resection increased both fasting and postchallenge glycaemia (p<0.05). Insulin sensitivity was highest in chronic pancreatitis patients before surgery (p<0.01), but remained unchanged by the partial pancreatectomy. High pre-operative body weight and elevated fasting glucose levels were associated with poor glycaemic control after surgery. Conclusions/interpretation Insulin secretion is diminished after pancreatic-head and -tail resection, but post-challenge glucose concentrations can be ameliorated after pancreatichead resection. These data highlight the unequal impact of different surgical procedures on glucose control and suggest that obesity and high pre-operative glucose levels should be considered as risk factors for the development of hyperglycaemia after pancreatic surgery.

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“…Measurements Glucose was measured as described [18,19] using a glucose oxidase method with a Glucose Analyzer 2 (Beckman Instruments, Munich, Germany).…”

Section: Methodsmentioning

confidence: 99%

Metabolic consequences of a 50% partial pancreatectomy in humans

et al. 2008

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“…Glucose was infused alone for the first 30 min to estimate glucose-stimulated insulin secretion. From 30 to 90 min, GIP was administered intravenously at an infusion rate of 2.0 pmol kg −1 min −1 , as previously described [11].…”

Section: Methodsmentioning

confidence: 99%

“…Synthetic GIP was purchased from PolyPeptide Laboratories (Wolfenbüttel, Germany) and processed for infusion as described previously [11].…”

Section: Peptidesmentioning

confidence: 99%

“…Secondly, the secretion of GLP-1 is impaired in patients with type 2 diabetes [9,10], while GIP secretion appears to be more or less normal [10]. To clarify whether the loss of GIP effect in type 2 diabetes is a result of a primary, possibly genetically determined, defect or whether it develops later in the pathogenesis of type 2 diabetes, we previously studied the insulinotropic effects of GIP in a cohort of first-degree relatives of type 2 diabetes patients during a hyperglycaemic clamp [11]. Under these conditions, around 50% of the relatives showed defects in GIP-induced insulin secretion, reminiscent of the secretion pattern observed in patients with type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…Under these conditions, around 50% of the relatives showed defects in GIP-induced insulin secretion, reminiscent of the secretion pattern observed in patients with type 2 diabetes. These results led to the assumption of a primary, possibly genetically determined, defect in GIP action that confers the risk of developing type 2 diabetes [11,12]. However, the first-degree relatives included in the study were also characterised by an impairment in glucose-induced insulin secretion [11], meaning that it was difficult to distinguish between an impairment in glucose-stimulated insulin secretion and a specific defect in GIP action.…”

Section: Introductionmentioning

confidence: 99%

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Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

et al. 2005

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Aims/hypothesis: The insulinotropic effect of gastric inhibitory polypeptide (GIP) is reduced in patients with type 2 diabetes and around 50% of their first-degree relatives under hyperglycaemic conditions. It is unknown whether this is a result of a specific defect in GIP action or of a general reduction in beta cell function. Moreover, impaired secretion of glucagon-like peptide 1 (GLP-1) has been described in patients with type 2 diabetes. Therefore, we studied the insulinotropic effect of GIP in women with previous gestational diabetes (pGDM) under euglycaemic fasting conditions and during a hyperglycaemic clamp experiment. The secretion of GIP and GLP-1 was assessed following oral glucose ingestion. Materials and methods:On separate occasions we performed an OGTT and administered an i.v. bolus of 20 pmol GIP/kg body weight in 20 women with pGDM and 20 control women. An additional hyperglycaemic clamp experiment (140 mg/dl [7.8 mmol/l] over 120 min) with i.v. infusion of GIP (2 pmol kg −1 min −1 ; 30-90 min) was performed in 14 women in each group. Capillary and venous blood samples were drawn for the measurement of glucose (glucose oxidase), insulin, C-peptide, GIP and GLP-1 (specific immunoassays). Indices of insulin sensitivity and beta cell function were calculated. Statistical analyses were carried out using repeated measures ANOVA. Results: Following oral glucose ingestion, plasma glucose, insulin and C-peptide concentrations increased to higher levels in the women with pGDM than in the control women (p<0.05). The women with pGDM were characterised by a higher degree of insulin resistance than the control women (p=0.007 for the Matsuda index), but showed no overt defects in glucosestimulated insulin secretion (p=0.40 for the insulinogenic index following i.v. glucose). The secretion of GLP-1 and GIP was not different between the groups (p=0.87 and p=0.57, respectively). The insulin secretory response to GIP administration was similar in the two groups both after GIP bolus administration and during the hyperglycaemic clamp experiment (p=0.99 and p=0.88, respectively). A hyperbola-like relationship was found between the degree of insulin sensitivity (Matsuda index) and the insulin secretory response to GIP and i.v. glucose administration. Conclusions/interpretation: These results do not support the hypothesis of an early defect in GIP action as a risk factor for subsequent development of diabetes in women with previous gestational diabetes. The inverse relationship between insulin resistance and the insulin secretory response to glucose or GIP suggests that beta cell secretory function in response to different stimuli increases adaptively when insulin sensitivity is diminished.

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