How Can We Prevent Multisystem Complications of Cystic Fibrosis?

J. Stuart Elborn, M.D.

Disclosures

Semin Respir Crit Care Med. 2007;28(3):303-311. 

In This Article

Cystic Fibrosis–Related Diabetes Mellitus

CF-related diabetes mellitus (CFRD) is an increasingly common systemic complication of CF.[50] It is rare in children under 10 years but increases with age, occurring in up to 24% of patients aged 20 years and 74% of those over 30 years.[50] CFRD is defined according to World Health Organization (WHO) criteria ( Table 2 ).[51] The cause of CFRD is multifactorial. Pancreatic fibrosis due to inflammation secondary to obstruction of pancreatic ducts eventually involves pancreatic islet cells. There may also be an intrinsic functional abnormality in CF islet cells.[52,53] Insulinopenia is a key feature of CFRD and results from the destruction of islet cells.[54] There are, however, other changes in intermediary metabolism that increase insulin resistance.[54] Their may be some intrinsic metabolic adaptations that cause this, but systemic inflammation, again, plays a role in increasing insulin resistance (Fig. 2).[55] This is not fully understood in CFRD but the counterregulatory mechanisms of increased sympathetic nervous system activity and cytokine release are almost certainly driven by the sustained inflammatory processes occurring in the lung.[54]

Contributors to the development of cystic fibrosis– related diabetes mellitus (from Harden D, NACFC 2004).

There are currently no strategies known to prevent the development of CFRD. Reducing lung inflammation will decrease insulin resistance and could be a useful intervention to delay the onset of CFRD. It is important to screen for this condition in all adults with CF. There has been considerable debate as to the best method for such screening; annual glucose tolerance testing seems to be the most sensitive and specific.[54,56] Fasting blood glucose and HbA1c have too many false-negatives to be sufficiently reliable. There are some data to suggest that pulmonary function may decline in the few years prior to the development of CFRD.[57] Any patient whose lung function becomes unstable, even in the absence of any symptoms of diabetes mellitus, should also have a glucose tolerance test. Diabetes has been associated with poorer outcome in people with CF, but it is not clear if correction of the insulinopenia and the successful achievement of good diabetes control alter prognosis.[58] Females with CF seem to be particularly vulnerable to the impact of diabetes, with an even greater impact on prognosis.[59] Home monitoring has been reported to be valuable in the diagnosis of diabetes and glucose intolerance in non-CF and CF diabetes. These studies indicate that glucose intolerance is more common than suspected in CF (Fig. 3).[60]

Forced expiratory volume in 1 second (FEV1) before and after the commencement of insulin therapy.

Treatment of CFRD in general should aim to maintain nutrition with a high-energy diet and matching the insulin required to sustain normal blood glucose control.[54] This is usually best achieved using a combination of long- and short-acting insulin analogs. It is very important that high energy is not restricted but that the insulin dose is matched to energy requirements. It is important that the management of diabetes is considered in people with CF who are having large energy intakes. This particularly applies to those who are feeding using a percutaneous gastrostomy tube. In this situation, blood glucose should be monitored closely when tube feeding is initiated and checked regularly subsequently.

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