Aims/hypothesis: Long-term trials in insulintreated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA 1 c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide's effect on satiety and food intake in humans has not yet been assessed. Methods: In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60±9 years, BMI 28.9±4.8 kg/m 2 ) and 15 nondiabetic obese men (age 41±21 years, BMI 34.4±4.5 kg/m 2 ) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 μg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time. Results: Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Δ−202±64 kcal, −23±8%, p<0.01) and obese (Δ−170±68 kcal, −16±6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides. Conclusions/interpretation: The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.

The factors influencing appetite in humans are poorly understood. There is a weak relation between appetite and gastric emptying in normal subjects. Recent studies have shown that fasting and postprandial antral areas increase in patients with functional dyspepsia compared with normal subjects. We evaluated the hypothesis that antral area, and hence antral distention, is a significant determinant of postprandial fullness. Fourteen normal subjects had simultaneous measurements of gastric emptying by scintigraphy and antral area by ultrasound after ingestion of 350 mL 20% glucose. Fullness and hunger were assessed by visual analog scales. Measurements of the gastric-emptying half time (t1/2) by scintigraphy and ultrasound were not significantly different (129.6 +/- 11.8 min compared with 115.6 +/- 11.4 min). Fullness increased (P < 0.001) and hunger decreased (P < 0.001) after the drink. Both fullness and the magnitude of the increase in fullness after the drink were related to antral area (r > 0.56, P < 0.05), the increase in antral area (r > 0.59, P < 0.05), and the scintigraphic content of the distal stomach (r > 0.57, P < 0.05), but not to the ultrasound or scintigraphic t1/2 values. In contrast, hunger and the magnitude of the decrease in hunger after the drink were not related to either antral area, the increase in antral area, or the rate of gastric emptying. We conclude that postprandial fullness, but not hunger, was closely related to antral distention in normal subjects.

A chronic vegetarian diet has no major effect on fasting SI motility; but acute dietary change may alter the cycle length and component phases of the IDMC.

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