Pilot Double-Blind Randomised Controlled Trial: Effects of Jejunal Nutrition on Postprandial Distress in Diabetic Gastropathy (J4G Trial).

Nausea, vomiting and abdominal pain in diabetic patients are often attributed to diabetic gastropathy (DG). Post-pyloric ("jejunal") enteral nutrition (JN) may improve nutrition and glycaemia in difficult cases. The acute effects of JN on postprandial symptoms and gastric function in DG patients has not been studied. DG patients with moderate to severe symptoms (gastroparesis cardinal symptom index (GCSI) > 27), diabetic controls without symptoms (DC; GCSI < 14) and healthy controls (HV) were entered into a randomized, double blind controlled trial. JN with liquid nutrient (2 kcal/min) or water was infused for 60 min prior to ingestion of a standardized mixed solid/liquid test meal. Outcomes included postprandial symptoms and effects on gastrointestinal (GI)−peptide hormones and gastric emptying (GE) assessed by magnetic resonance imaging (MRI). Nine DG, nine DC and twelve HV were recruited. DG patients reported more symptoms after meals than other groups (p < 0.05). Post-prandial symptoms were reduced after JN in DG patients (p < 0.01). GE was more rapid after JN in DG and DC patients (p < 0.05). JN induced a GI−peptide response in all subjects; however, this was less pronounced in diabetic groups. JN has beneficial effects on DG patients' symptoms after a meal. The mechanism is not primarily mediated by effects on GE, but appears to involve other aspects of GI function, including visceral sensitivity.

The role of endogenous incretin secretion as amplifier of glucose-stimulated insulin secretion in healthy subjects and patients with type 2 diabetes.

In order to quantify the role of incretins in first- and second-phase insulin secretion (ISR) in type 2 diabetes mellitus (T2DM), a double-blind, randomized study with 12 T2DM subjects and 12 healthy subjects (HS) was conducted using the hyperglycemic clamp technique together with duodenal nutrition perfusion and intravenous infusion of the glucagon-like peptide 1 (GLP-1) receptor antagonist exendin(9-39). Intravenous glucose alone resulted in a significantly greater first- and second-phase ISR in HS compared with T2DM subjects. Duodenal nutrition perfusion augmented both first- and second-phase ISR but first-phase ISR more in T2DM subjects (approximately eight- vs. twofold). Glucose-related stimulation of ISR contributed only 20% to overall ISR. Infusion with exendin(9-39) significantly reduced first- and second-phase ISR in both HS and T2DM subjects. Thus, both GLP-1 and non-GLP-1 incretins contribute to the incretin effect. In conclusion, both phases of ISR are impaired in T2DM. In particular, the responsiveness to glucose in first-phase ISR is blunted. GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretions are unaltered. The absolute incretin effect is reduced in T2DM; its relative importance, however, appears to be increased, highlighting its role as an important amplifier of first-phase ISR in T2DM.