Introduction An impaired glucose tolerance later in the day may be an early sign of diabetes1,2, suggesting that there is diurnal variation in pancreatic endocrine function. This may be important in CF, where glucose handling is deficient even in those without established CF-related diabetes (CFRD). To look at this further, we assessed the response to a glucose challenge throughout the day in CF patients and compared it with healthy controls.
Method We compared 20 CF patients (17 pancreatic insufficient) without known CFRD with 6 healthy age and BMI matched controls. Following an overnight fast subjects consumed a standardised mixed meal (the gold standard measure of endogenous insulin secretion3, providing an equivalent glucose load to a standard OGTT) at 0800, 1300 and 1800 hours on the same day. Blood glucose and insulin were measured over 120 minutes for each test meal and the area under the curve (AUC) calculated for the entire duration of each test. β-cell indices [β-cell function (%B), insulin sensitivity (%S), insulin resistance (IR)] were measured using the HOMA method4.
Results See Table (mean±SEM). CF subjects had greater overall glucose levels throughout the day when compared to controls for all 3 tests (p<0.005). β-cell function was highest in the afternoon in the CF group in keeping with a lower AUCglucose at this time and there was a decrease in %S and an increase (p=0.03) in IR with progression of the day.
Conclusions This study demonstrates insulinopoenia and reduced insulin sensitivity in the CF population resulting in glucose intolerance. Although not the primary defect in CF, there is an increase in insulin resistance as the day progresses. The clinical implications of this study are important not only for the diagnosis of CFRD but also its management in terms of the timing and profiling of exogenous insulin administration.
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