Citations

In vitro studies indicate that glucagon-like peptide-1(7-36)-amide (GLP-1) can enhance hepatic glucose uptake. To determine whether GLP-1 increases splanchnic glucose uptake in humans, we studied seven subjects with type 1 diabetes on two occasions. On both occasions, glucose was maintained at ∼5.5 mmol/l during the night using a variable insulin infusion. On the morning of the study, a somatostatin, glucagon, and growth hormone infusion was started to maintain basal hormone levels. Glucose (containing [3H]glucose) was infused via an intraduodenal tube at a rate of 20 μmol · kg−1 · min−1. Insulin concentrations were increased to ∼500 pmol/l while glucose was clamped at ∼8.8 mmol/l for the next 4 h by means of a variable intravenous glucose infusion labeled with [6,6-2H2]glucose. Surprisingly, the systemic appearance of intraduodenally infused glucose was higher (P = 0.01) during GLP-1 infusion than saline infusion, indicating a lower (P < 0.05) rate of initial splanchnic glucose uptake (1.4 ± 1.5 vs. 4.8 ± 0.8 μmol · kg−1 · min−1). On the other hand, flux through the hepatic uridine-diphosphate–glucose pool did not differ between study days (14.2 ± 5.5 vs. 13.0 ± 4.2 μmol · kg−1 · min−1), implying equivalent rates of glycogen synthesis. GLP-1 also impaired (P < 0.05) insulin-induced suppression of endogenous glucose production (6.9 ± 2.9 vs. 1.3 ± 1.4 μmol · kg−1 · min−1), but caused a time-dependent increase (P < 0.01) in glucose disappearance (93.7 ± 10.0 vs. 69.3 ± 6.3 μmol · kg−1 · min−1; P < 0.01) that was evident only during the final hour of study. We conclude that in the presence of hyperglycemia, hyperinsulinemia, and enterally delivered glucose, GLP-1 increases total body but not splanchnic glucose uptake in humans with type 1 diabetes.

Although it is well established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 pmol x kg(-1) x min(-1)) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed after a carbohydrate meal. Insulin concentrations were either kept constant at basal levels (n = 6) or varied so as to create a prandial insulin profile (n = 6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during both the basal (1.21 +/- 0.15 vs. 1.32 +/- 0.19 mol/l per 6 h) and prandial (0.56 +/- 0.14 vs. 0.56 +/- 0.10 mol/l per 6 h) insulin infusions. During both the basal and prandial insulin infusions, glucose disappearance promptly increased after initiation of the glucose infusion to rates that did not differ on the GLP-1 and saline study days. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during both the basal (-2.7 +/- 0.3 vs. -3.1 +/- 0.2 micromol/kg) and prandial (-3.1 +/- 0.4 vs. -3.0 +/- 0.6 pmol/kg) insulin infusions. We conclude that when insulin and glucagon concentrations are matched, GLP-1 has negligible effects on either insulin action or glucose effectiveness in people with type 2 diabetes. These data strongly support the concept that GLP-1 improves glycemic control in people with type 2 diabetes by increasing insulin secretion, by inhibiting glucagon secretion, and by delaying gastric emptying rather than by altering extrapancreatic glucose metabolism.

Despite numerous advances in interventional radiology and vascular surgery, the clinician continues to be confronted with inoperable vascular disease. Previous studies have shown that ulceration associated with a transcutaneous oxygen pressure (tcPO 2 )of,20 mmHg is refractory to all attempts at healing. External pneumatic compression for the treatment of peripheral vascular disease has been available for several years, although there is a relative paucity of data regarding its role in clinical practice as well as its efficacy. The objective of this study was to examine the experience with circulator boot therapy in the treatment of ischemic ulcers in the absence of osteomyelitis, and specifically to determine whether such therapy can be of benefit in ischemic limb ulceration associated with a tcPO 2 of,20 mmHg. A retrospective chart review was undertaken of all patients with a lower limb ulcer who, in the absence of osteomyelitis, underwent circulator boot therapy at the Gonda Vascular Center. A total of 98 patients was identified. Two patients died within 1 month of commencing therapy and were not included in further analysis. The tcPO 2 data were unavailable in five patients. Outcome in the patient population was classified as favorable if (1) healing was achieved, (2) the ulcer decreased in size, or (3) the affected limb improved sufficiently to allow successful revascularization. An unfavorable outcome was one where a major amputation was performed or where the ulcer increased in size. Out of a total of 29 patients with a tcPO 2 ,20 mmHg at the area of ulceration, 19 had a favorable outcome following circulator boot therapy. Of the remaining 62 patients with a tcPO 2 .20 mmHg, 54 had a favorable outcome. Circulator boot therapy is associated with improved outcomes in limb ulceration due to peripheral vascular disease. Complete ulcer healing as well as preservation of the affected limb can be achieved in most cases.