Exp Clin Endocrinol Diabetes 2006; 114 - P03_035
DOI: 10.1055/s-2006-932921

Effect of meglitinide on postprandial ghrelin secretion patterns in type 2 diabetes mellitus

N Rudovich 1, M Möhlig 1, B Otto 2, MO Weickert 1, J Spranger 1, HJ Rochlitz 1, M Ristow 1, M Osterhoff 1, AFH Pfeiffer 1
  • 1DIFE, KLE, Nuthetal, Germany
  • 2Innenstadt University Hospital, Munich, Germany

Aims: Ghrelin has been implicated in the regulation of feeding behaviour and energy balance. Circulating ghrelin rises before and decreases postprandially. Ghrelin levels were found to be reciprocal to those of glucose and insulin. The mechanism of the progressive weight gain in type 2 diabetic patients (T2DM) remains unknown. We investigated relationship between drug-stimulated insulin secretion and pattern of the ghrelin secretion in individuals with T2DM.

Methods: This single-blind randomised three period crossover study was conducted in 20 patients with T2DM (m12/8f; 58.2±2.1 years; BMI 28.6±1.1kg/m2; mean±SEM). After 2-wk run-in period (metformin (MET) 2000mg/d), repaglinide (REP) (1mg tds) plus MET, or nateglinide (NAT) (60mg tds) plus MET were given for two 1-wk treatment periods, separated by 1-wk placebo (PL) plus MET. Liquid meal tests with single preprandial doses of REP (2mg), NAT (120mg) or PL were performed at the end of each treatment period. The non-diabetic control-group (m 8/2 f; 55.7±2.4 years; BMI 31.7±0.6kg/m2) was untreated. Glucose, insulin and ghrelin levels were measured at 0, 30, 60, 120, 240min postprandially.

Results: Fasting glucose concentration was reduced by REP (p=0.025). Post-challenge insulin concentrations at 30 and 60min were elevated with both meglitinides, and at 120min with REP compared to PL (p<0.05). Fasting and postprandial ghrelin concentrations were not different between all treatments and between diabetic and control subjects. After administration of meglitinide a nadir of serum ghrelin was observed at 60min with a subsequent increase to maximal levels at 240min (p=0.006 for REP; p=0.004 for NAT), which was similar to the pattern seen in control subjects.

Conclusion: Short –term treatment with meglitinides has no effect on basal and postprandial ghrelin concentrations in patients with T2DM. Treatment with meglitinide reconstructed postprandial ghrelin secretion patterns those of non-diabetic controls. This may help to improve the control of feeding behaviour in diabetic patients.