Glucose tolerance in patients with narcolepsy

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Objectives: Increased body weight is a common feature of narcolepsy. In addition, an increased occurrence of non-insulin dependent diabetes has been reported. So far, it is not known whether glucose metabolism in narcolepsy is disturbed due to, or independently of obesity. Methods: We studied 17 patients with narcolepsy/cataplexy and 17 healthy controls matched for age, sex and body mass index (BMI) in a case-control design. A 75g oral glucose tolerance test was performed in all. We assessed glucose tolerance by means of the glucose curve during oral glucose challenge from 0 to 240minutes; insulin sensitivity and insulin secretion by homeostasis model assessment and minimal model analysis; basal HbA1c, TSH, and cholesterol levels. Analyses were undertaken for the complete group and for a subgroup of eight patients and controls that were individually matched for BMI with the aim to identify a narcolepsy specific risk that is independent of overweight. Results: For the complete group standard endocrine measures and indices of the oral glucose tolerance test did not differ between and controls. However, when comparing the subgroup of eight patients and controls that were individually matched for BMI mean glucose level at 120minutes and area under curve were significantly lower in patients (P=0.01 and P=0.02, respectively). Conclusions: On a group level and controlling for BMI, we found no difference in glucose metabolism between narcoleptic patients and controls. However, in a subgroup of BMI-equivalent cases and controls we observed a flattening of glucose clearance in patients which suggest subtle weight-independent abnormalities of glucose metabolism. Nevertheless our results draw the focus of interest back to the narcolepsy inherent overweight and point to weight management as the most promising clinical route to improve glucose metabolism in narcolepsy patients.