Daniel Peckham, Alison Morton and Helen White. Jan, 2001. Diabetes Mellitus [online]. Seacroft and St James's University Hospitals, Leeds, UK. Available from http://www.cysticfibrosismedicine.com

Diabetes mellitus and glucose intolerance are common in adolescent and adult patients with cystic fibrosis (Lanng et al, 1995). Diabetes occurs in up to 30% of individuals by the age of 25 and is invariably associated with pancreatic exocrine dysfunction (malabsorption). The prevalence in patients over 20 years of age may be as high as 53% (Laang et al, 1995). CF related diabetes (CFRD) is distinct from type 1 or type 2 diabetes but has features of each of these. It is associated with insulinopenia and insulin resistance. Ketoacidosis is unusual but can occur, especially if there has been a long period of symptomatic hyperglycaemia before diagnosis (Moran et al, 1998). There is enough insulin production to suppress ketogenesis as in type 2 diabetes and glucagon deficiency may also protect from ketone formation.

Histologically: The pancreas shows fatty replacement, fibrosis and a reduction in the number and function of secretory cells. These include the ß-cells within the islets of Langerhans which produce insulin. These changes are likely to result from obstruction of pancreatic ducts by abnormal, thick secretions. Autopsy studies, however, have not shown that fibrotic islet changes are significantly greater in patients with CFRD than in patients with CF without diabetes. Such studies suggest that CFRD is more than merely severe fibrosis induced islet damage. Islet amyloid polypeptide is co-secreted with insulin in normal health but does not accumulate within the islet. Amyloid deposition is not seen in type 1 diabetes or in chronic pancreatitis but is seen in type 2 diabetes. Autopsy studies did not find islet amyloid in any of the patients with cystic fibrosis without CFRD but this deposition was found in 17% of the borderline diabetic cases and in 69% of the cases with full CFRD. There is thus a suggested similarity between CFRD and type 2 diabetes. This has led to the speculation that impaired glucose tolerance is very common in adults with CF because of fibrotic damage to the islet, but may only progress to full CFRD in patients with a genetic defect in insulin secretion similar to that found in type 2 diabetes (Moran et al, 1998).

Physiology: Diabetes mellitus and impaired glucose tolerance in cystic fibrosis is associated with a delay and reduction in peak insulin production following a carbohydrate load. In cystic fibrosis there also appears to be an element of insulin resistance and the normal anabolic effect of insulin is reduced (Holl et al, 1995; Holl et al, 1997; Hardin et al, 1998) The use of oral corticosteroids will increase the tendency to develop diabetes. The insulin deficient state leads to worse pulmonary outcome (Milla & Moran, 1999).

Early diagnosis: The early diagnosis of, and intervention in, diabetes mellitus can have a profound impact on patient well being, protecting against weight loss and deterioration in lung function (Laang et al, 1992). Patients over about 10 years of age should have an annual oral glucose tolerance test (OGTT) as it is the only sure way of detecting CF related diabetes mellitus. An OGTT should also be part of an investigative screen for unexplained weight loss or deterioration in lung function. Fasting glucose and HbA1C levels remain poor tools for the early diagnosis of CF related diabetes (Laang, 1997; Baker & DuBois, 1999). Impaired glucose tolerance is common and may progress to full diabetes or revert to normal (Laang et al, 1995). In Leeds a repeat OGTT is recommend in such patients after a six month interval. In large adult clinics there are obvious practical problems in performing an annual OGTT on all non diabetic patients. The Brompton group suggest selective OGTT screening in patients with abnormal HbAlC or random blood glucose results, symptoms of hyperglycaemia or weight loss (Yung et al, 1997). The OGTT is the only reliable tool for early diagnosis.

Treatment: Some patients can be controlled for some time on oral hypoglycaemic agents (Culler et al, 1994), although most patients are best treated with insulin. Some patients may only show significant hyperglycaemia after meals. Thrice daily rapid acting insulin may be useful in such cases. Treatment with insulin during meals may also protect against endogenous protein breakdown and favour protein synthesis in the fed state (Moran et al, 1999). All patients with CF related diabetes mellitus should maintain a high energy dietary intake with the insulin dose tailored to their individual requirements. They should not decrease their carbohydrate intake but should be encouraged to eat regular meals with similar carbohydrate content each day. In view of the increased longevity in CF we now aim for tight blood sugar control. Diabetic related complications, e.g. retinopathy, have been reported in patients with CF (Laang et al, 1994; Yung et al, 1998).

1) Blood sugars high (treat with insulin)

2) Blood sugars normal (repeat GTT in 3 months /BM chart)

References

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Milla CE, Moran AM. Insulin production at baseline influences, the rate of decline in FEV1 in CF patients without fasing hyperglycaemia. Pediatr Pulmonol 1999; Suppl 19: 489

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Moran A, Milla C, Ducret R, Nair KS. Protein metabolism in clinically stable, well-nourished adult CF patients with abnormal glucose tolerance. Pediatr Pulmonol 1999; Suppl 19: 305

Yung B, Kemp M, Hooper J, Hodson ME. Diagnosis of cystic fibrosis related diabetes: a selective approach in performing the oral glucose tolerance test based on a combination of clinical and biochemical criteria. Thorax 1997; 54: 40-43

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