The majority of cystic fibrosis (CF) patients now survive beyond childhood, and CF related diabetes (CFRD), due to insulin deficiency, is common. CFRD without fasting hyperglycemia (FH) is found in 25 percent of CF adults and is associated with increased morbidity and mortality. BMI and pulmonary function deteriorate much more rapidly in these patients than in CF patients with normal glucose tolerance. Insulin deficiency alters protein and fat metabolism resulting in loss of weight and lean body mass and contributing to pulmonary disease and clinical decline. Preliminary isotopic data have shown that insulin and, to a lesser extent, the oral diabetes agent repaglinide acutely improve protein synthesis in patients with CFRD without FH. The objective of this research is to recruit 150 adult patients with CFRD without fasting hyperglycemia for a multi-center, twelve month, placebo- controlled intervention trial testing the ability of insulin or repaglinide to improve BMI and stabilize pulmonary function. It will test the hypotheses that: 1. Participants receiving either insulin or repaglinide will increase their BMI compared to control participants. 2. Insulin will be more effective than repaglinide at increasing BMI. 3. The increase in BMI will be primarily due to increased muscle mass. 4. The increase in BMI will be accomplished without significant changes in dietary macronutrient or calorie composition. 5. Insulin or repaglinide therapy will prevent pulmonary function decline compared to both control subjects and to their own baseline as measured the previous year. This will be associated with improvement in NIH clinical score and will be directly related to weight gain and increase in thigh muscle volume. 6. Participants receiving insulin or repaglinide will improve hand grip strength, and this will be directly related to weight gain and increase in thigh muscle volume. If it can be shown that insulin or repaglinide also improves body mass and pulmonary function, it would have a major impact on the current therapy and prognosis for adult CF patients. The question of whether these patients should receive diabetes therapy was given the highest priority for future research funding at a national consensus conference on CFRD
| Moran, Antoinette; Pekow, Penelope; Grover, Patricia et al. (2009) Insulin therapy to improve BMI in cystic fibrosis-related diabetes without fasting hyperglycemia: results of the cystic fibrosis related diabetes therapy trial. Diabetes Care 32:1783-8 |
| Schwarzenberg, Sarah Jane; Thomas, William; Olsen, Timothy W et al. (2007) Microvascular complications in cystic fibrosis-related diabetes. Diabetes Care 30:1056-61 |
