Objective: A gain in body weight is a common adverse effect of glucose-lowering therapies in patients with type 2 diabetes, the mechanisms of which are not completely understood. Blood glucose is considered to play a crucial role in the regulation of food intake. On this background, we hypothesized that a short-term reduction of blood glucose concentration to normal values acutely increases food intake in type 2 diabetic patients.
Research design and methods: To test this hypothesis, 12 patients with type 2 diabetes were examined twice, once during a euglycemic (5.0 mmol/l) clamp experiment and another time during a hyperglycemic (10.5 mmol/l) clamp. The experiments were performed in a single-blind fashion with the order of conditions balanced across patients. On both clamp conditions, insulin was infused at a constant rate of 2.5 mU/kg per min for 125 min. Simultaneously, a glucose solution was infused at a variable rate to achieve target glycemic levels. During the final 30 min of the clamps, the patients were allowed to eat as much as they liked from a standard breakfast buffet.
Results: Compared with the hyperglycemic condition, the patients ingested on average 25 +/- 10% more energy during euglycemia (645 +/- 75 vs. 483 +/- 37 kcal; P = 0.029). The increased energy intake during euglycemia was equally distributed across macronutrient components, i.e., during euglycemia the patients ate more carbohydrates (+27.1 +/- 11.4%; P = 0.037), fat (+22.5 +/- 10.0%; P = 0.046), and proteins (+25.2 +/- 11.2%; P = 0.046) than during hyperglycemia. Circulating levels of insulin, amylin, leptin, ghrelin, and glucagon-like peptide-1 did not differ between the euglycemic and hyperglycemia clamp, excluding a major contribution of these hormones to the difference in food intake. Summing up the glucose administered intravenously and the food ingested yielded a remarkably similar total energy influx in both conditions (794 +/- 64 vs. 790 +/- 53 kcal; P = 0.961).
Conclusions: Together our data suggest that total energy supply to the organism is tightly regulated on a short-term basis independent of the route of influx. Alternatively, it can be hypothesized that euglycemia stimulated or that hyperglycemia suppressed food intake at the subsequent buffet meal in our type 2 diabetic patients. Regardless of these different interpretations, our data indicate an important regulatory role of glucose for food intake in type 2 diabetic patients that is of considerable clinical relevance.