Paediatric cystic fibrosis related diabetes

Journal of Diabetes Nursing, June, 2004 by Judith Campbell, Mark Bone

Introduction

Cystic fibrosis related diabetes (CFRD) develops in 10-15% of people with cystic fibrosis. Prevalence increases with age, and is an expected complication of CF as survival rates increase. Early identification of CFRD has been shown to impact positively on health status. Treatment is aimed at achieving optimal nutritional and clinical status, avoiding metabolic derangement through maintenance of normoglycaemia. This article presents guidelines for the management of children and adolescents with CFRD, and discusses problems that may arise.

KEY WORDS

* CFRD

* Screening

* Oral glucose tolerance test

* Treatment

* Diabetes complications

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Cystic fibrosis related diabetes (CFRD) develops in individuals with cystic fibrosis (CF) as a consequence of pancreatic pathology. The prevalence of CFRD increases with age; the average age of onset is between 18 and 21 years (Finklestein et al, 1988). CFRD rarely develops in children less than 10 years of age (Lanng et al, 1991).

There is clear evidence that early identification of CFRD has a positive impact on health status (Lanng et al, 1992; Nousia-Arvanitakis et al, 2001; Rolan et al, 2001). Delaying the diagnosis can result in unnecessary deterioration in both lung function and clinical status. Several studies have shown that long-standing deterioration in glucose tolerance and an insidious decline in clinical status frequently occur in CF several years before a diagnosis of diabetes is made (Lanng et al, 1992; Milla et al, 2000; Koch et al, 2001).

Correct screening, early diagnosis and appropriate treatment are therefore crucial to the health outcomes of children and adolescents with CF. The diabetes and CF teams at Booth Hall Children's Hospital, Manchester, began a screening and treatment programme in 2003, in order to address these concerns.

Screening for CFRD

The classic symptoms of diabetes are not sufficiently sensitive alone to be used as a screening test. Only a third of patients with CFRD have symptoms of polyuria and polydipsia at the time of diagnosis. Patients who develop overt symptoms of hyperglycaemia on presentation have been found to have a relatively greater decline in pulmonary function and weight loss than those identified on screening. It is therefore important that glucose intolerance is diagnosed early to identify those individuals at high risk of developing a decline in lung function, a fall in nutritional status or a new diagnosis of CFRD.

A fasting venous plasma glucose of >7 mmol/l indicates diabetes in the non-CF population, but fasting plasma glucose levels may not be reliable in identifying early CFRD. According to the World Health Organization (WHO, 1999), only 16% of patients with CFRD would be identified using this criterion. Children and adolescents with CF can have transient elevation of random and fasting glucose levels with a normal oral glucose tolerance test (OGTT). Thus fasting glucose and random glucose measurements, which are routinely used for the diagnosis of type 1 and type 2 diabetes, in conjunction with patient history, have reduced sensitivity and specificity in CF. Glucose tolerance and insulin resistance often vary in CF, being influenced by factors such as nutritional status and infection.

The published consensus is that the routine use of OGTT and serial glucose home blood glucose monitoring (HBGM) appears to be the most specific and sensitive tool currently available for the diagnosis of CFRD (Lanng et al, 1995); Cucinotta et al, 1999; Yung et al, 1999).

The North American CF Consensus Committee recognises four glucose tolerance categories in CF, based on the OGTT results (1.5 g/kg; max 75g) (Table 1). These represent a spectrum of deteriorating glucose intolerance progressing from impaired glucose tolerance (IGT) through to CFRD with fasting hyperglycaemia.

The OGTT may be used for the diagnosis of diabetes mellitus and is also the accepted screening test for CFRD. However, in a person with CF, a 'diabetic' OGTT does not mean that the individual has diabetes, but has, at that time, abnormal glucose tolerance. In a proportion of patients, a 'diabetic' OGTT will revert to normal with time and will require ongoing assessment, especially during periods of physical stress. It is therefore recommended that the OGTT should be performed annually in children and adolescents with CF over the age of 10 years.

Symptoms of CFRD

* Unexplained polyuria or polydipsia

* Failure to maintain or gain weight despite nutritional intervention

* Poor growth velocity

* Delayed progression of puberty

* Unexplained chronic decline in pulmonary function.

CFRD may be chronic or intermittent. Patients with intermittent CFRD repeatedly require insulin therapy to control hyperglycaemia when they are physically stressed, with infection, intensive nutritional intervention or treatment with steroids for pulmonary disease. Blood glucose levels can normalise between periods of stress and thus require suspension of insulin therapy.