As cystic fibrosis (CF) patients live longer, more women with CF desire pregnancy. Although several retrospective analyses of pregnancy exist, to date there have been no prospective studies of the metabolic effects of pregnancy in CF women. The investigators hypothesize that pregnancy worsens insulin resistance in CF, including peripheral insulin sensitivity, hepatic insulin resistance and resistance to the anabolic effects of insulin on proteolysis. They believe that these metabolic changes will result in worsened clinical status which will persist post-partum. They propose a longitudinal study of 10 pregnant CF patients. Each patient will be studied before pregnancy (when possible), during the final two weeks of each trimester of pregnancy, and 6 months post-partum. Results from these patients will be compared to results from 10 non-CF pregnant women and 10 non-pregnant CF controls. These two control groups will be matched to the pregnant CF patients for age and pre-pregnancy weight. The following clinical parameters will be measured: 1) clinical status will be measured by a modified NIH scoring system; 2) measurement of pulmonary function including FEV1, FVC, and FEF1-25; 3) glucose tolerance will be measured by a 3-hour OGTT; 4) body composition will be measured by 40K to determine the effect of pregnancy on fat and lean mass. To determine the effects of pregnancy on insulin-regulated metabolism, the PI will measure: 1) peripheral insulin sensitivity using a step-wise hyperinsulinemic euglycemic clamp; 2) protein synthesis and protein breakdown, and insulin effect on these, using the stable isotope 1[13C] leucine; 3) measurement of hepatic glucose production and hepatic insulin sensitivity using the stable isotope 6H6-glucose. Finally, resting energy expenditure will be measured throughout each stage of pregnancy, using indirect calorimetry. The study will provide a comprehensive examination of the metabolic effects of pregnancy. Whether the global hypothesis is accepted or rejected by the data, these studies will provide useful and novel information regarding the effects of pregnancy in cystic fibrosis. To date, all pregnant CF women have developed gestational diabetes during the first trimester of pregnancy.
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