Cystic fibrosis related diabetes (CFRD)--the end stage of progressive insulin deficiency.

In cystic fibrosis, gradual pancreatic destruction causes progressive insulin deficiency, culminating in cystic fibrosis related diabetes (CFRD). As a consequence of insulin deficiency, elevated glucose levels can be detected (well before the diagnosis of CFRD), by continuous ambulatory subcutaneous interstitial fluid glucose monitoring or 30-min sampled oral glucose tolerance test (OGTT). Current diagnostic criteria for CFRD (based on 0 and 120-min OGTT blood glucose levels) were originally designed to forecast microvascular disease in type 2 diabetes, rather than CF-specific outcomes such as declining weight or lung function. In CF, decline in either weight or lung function predicts early mortality. Both may precede the diagnosis of CFRD by several years. Insulin, a potent anabolic hormone, is recommended treatment for CFRD, but use in earlier stages of insulin deficiency is not established. Conventional dosing (with four or more insulin injections per day) is burdensome and carries substantial risk of hypoglycemia. However, recent uncontrolled trials suggest that once-daily injection of intermediate or long-acting insulin improves weight and lung function, with minimal hypoglycemia risk, in CFRD and also in early insulin deficiency. It is plausible that insulin may be of greater benefit to respiratory function when given prior to the diagnosis of CFRD, after which structural lung disease may be irreversible. It is also plausible that early insulin treatment may prolong the lifespan of the remaining insulin-secreting β-cells. Randomized controlled trials are now needed to determine whether or not current clinical practice should be altered toward the earlier commencement of insulin in CF.