In CF, early insulin secretion defect but also IR contribute to glucose intolerance. Early in the course of the disease, increased glucose AUC and reduced early insulin secretion are more closely associated with a worse clinical status than conventional glucose tolerance categories.
In a context of significantly reduced insulin secretion, variations of insulin sensitivity are associated with variations of glucose tolerance in adult patients with CF.
Since the OGTT is required on a regular basis in CF patients to screen for CFRD, OGTT-derived indices appear to be suitable for evaluating insulin secretion.
CF is associated with abnormal glucose excursion in the presence of relatively normal lipid excursion. The rapid normalization of glucose values after a mixed meal should be further explored and, if confirmed, might have significant implications for CFRD diagnostic.
Validation of insulin secretion indices in cystic fibrosisDear Editor, Recently, our group published a paper in the Journal validating, in cystic fibrosis (CF) patients, surrogate insulin secretion indices against the gold standard method, the Intravenous Glucose Tolerance Test (IVGTT) [1]. In this study, we compared dynamic measures of insulin secretion during the IVGTT and surrogate indices using data from an oral glucose tolerance test (OGTT) in healthy control subjects as well as CF patients with various glucose tolerances. We found that early insulin secretion indices derived from the OGTT such as the one proposed by Stumvoll et al. (1.283 + 1.829 × Ins 30 (pmol/L) − 138.7 × Glyc 30 (mmol/L) + 3.772 × Ins 0 (pmol/L)) [2] or the Insulin Secretion Rate (ISR, (Ins 30 − Ins 0 ) (mU/L)/(Gly 30 − Gly 0 ) (mg/dL)) [3] can evaluate early insulin secretion in CF subjects.However, when using these OGTT-derived indices in a large database of 204 CF subjects, it appears that in 7% of cases, essentially in patients with de novo diabetes, these formulas provide negative values. In CF patients, because of significant alteration in early insulin secretion [4], some patients demonstrate in the first 30 min of the OGTT, a rapid glucose rise without a concomitant significant insulin increase. In this situation, these formulas will provide negative values which are obviously without physiological significance and including them into an analysis raises significant methodological problems. To overpass this limitation, we reanalyzed previously published data to determine if the Area Under the Curve (AUC) obtained during time 0 to 30 min (AUC 0-30 ) of the OGTT is also a surrogate index of early insulin secretion in CF subjects [1]. This measure correlates significantly with early insulin secretion quantified with the IVGTT (AUC 0-10 ) (r = 0.59, p = 0.021 for healthy controls subjects, r = 0.50, p = 0.041 for CF subjects). Therefore, this easily calculated value (AUC 0-30 ) obtained during the OGTT can be used as a proxy of insulin secretion in CF patients. Its accuracy at various stages of the disease should however be confirmed in futures studies.
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