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Reduced pancreatic insulin release and reduced peripheral insulin sensitivity contribute to hyperglycaemia in cystic fibrosis

  • Endocrinology
  • Original Paper
  • Published:
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Abstract

Traditional opinion holds that patients with cystic fibrosis (CF) develop impaired glucose tolerance or diabetes due to insulinopenia caused by fibrosis of the pancreas. However, studies on the dynamics of insulin secretion and peripheral insulin action have yielded confliciting results. We studied 18 patients with CF (9 ♂, 9 ♀, age 15–29 years) and 17 healthy control subjects (8 ♂, 9 ♀, 20–32 years). Oral glucose tolerance tests and combined i.v.-glucose-tolbutamide-tests were performed on separate days in fasting subjects. Bergman's “Minimal Model” was used to quantitate both peripheral insulin sensitivity (SI) and insulin-independent glucose disposal (glucose effectiveness; SG). Based on National Diabetes Data Group criteria, 4 patients were classified as diabetic 922%; CF-DM), 3 patients (17%) had impaired glucose tolerance (CF-IGT) while glucose metabolism was normal in 11 patients (61%; CF-NGT). Irrespective of the degree of glucose tolerance, the insulin response to oral glucose was not reduced but delayed, up to 60 min in the CF-IGT/DM group. First-phase insulin release (0–10 min) after i.v.-glucose was significantly lower in CF patients (29% of healthy controls;P<0.0001), with no difference between the CF-NGT and CF-IGT/DM groups. Insulin release following tolbutamide injection was only marginally reduced in CF patients (64% of controls). In contrast, SI was significantly reduced in the subgroup of CF patients with abnormal glucose metabolism (CF-IGT/DM: 0.97±0.16·10−4 l/min/pmol; control group: 1.95±0.25;P<0.05).

Conclusion

The early insulin release is reduced in response to i.v.-glucose, while in the oral glucose tolerance test, insulin secretion is quantitatively preserved, but delayed. Reduced peripheral insulin sensitivity is a major factor for impaired glucose tolerance and diabetes mellitus in CF patients.

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Abbreviations

AUC :

area under the curve

CF :

cystic fibrosis

DM :

diabetes mellitus

IGT :

impaired glucose tolerance

IVGTT :

intravenous glucose tolerance test

K G :

coefficient of glucose disposal

NDDG :

National Diabetes Data Group

NGT :

normal glucose tolerance

OGTT :

oral glucose tolerance test

S G :

glucose effectiveness (insulin-independent glucose disposal)

S I :

insulin sensitivity index

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Authors and Affiliations

  1. Department of Paediatrics I, University of Ulm, D-89070, Ulm, Germany

    R. W. Holl, E. Heinze & W. M. Teller

  2. Department of Paediatrics II, University of Ulm, D-89070, Ulm, Germany

    A. Wolf & M. Rank

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  1. R. W. Holl
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  2. E. Heinze
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  3. A. Wolf
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  4. M. Rank
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  5. W. M. Teller
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Holl, R.W., Heinze, E., Wolf, A. et al. Reduced pancreatic insulin release and reduced peripheral insulin sensitivity contribute to hyperglycaemia in cystic fibrosis. Eur J Pediatr 154, 356–361 (1995). https://doi.org/10.1007/BF02072102

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  • DOI: https://doi.org/10.1007/BF02072102

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