Contribution of endogenous glucagon-like peptide 1 to glucose metabolism after Roux-en-Y gastric bypass.

The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of uncertainty. We used exendin-9,39, a competitive antagonist of GLP-1, to examine glucose metabolism, islet hormone secretion, and gastrointestinal transit in subjects after RYGB and in matched control subjects. Subjects were studied in the presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39 resulted in an increase in integrated postprandial glucose concentrations post-RYGB (3.6 ± 0.5 vs. 2.0 ± 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased insulin concentrations (12.3 ± 2.2 vs. 18.1 ± 3.1 nmol/6 h, P = 0.002) and the ß-cell response to glucose (Total, 13 ± 1 vs. 11 ± 1 × 10(-9) min(-1), P = 0.01) but did not alter the disposition index (DI). In control subjects, exendin-9,39 also increased glucose (2.2 ± 0.4 vs. 1.7 ± 0.3 mol/6 h, P = 0.03) without accompanying changes in insulin concentrations, resulting in an impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min by exendin-9,39 did not alter meal appearance, and similarly, suppression of glucose production and stimulation of glucose disappearance were unaltered in RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose metabolism and on gastrointestinal motility years after RYGB. However, it remains uncertain whether this explains all of the changes after RYGB.

Symptomatic amyloid goiters: report of five cases.

BACKGROUND: Massive amyloid deposition in the thyroid to the point of goiter formation is rare. Here we describe the clinical presentation and outcomes of five patients with amyloid goiter (radiographically confirmed goiter in the context of tissue-proven thyroid amyloidosis) encountered in the past 23 years at our institution. METHODS: Mayo Clinic archives were searched between 1987 and 2010 for a diagnosis of "thyroid amyloidosis," "amyloid deposits," "amyloid deposition," or "liquid chromatography consistent with amyloid." Inclusion criteria were symptomatic thyromegaly; tissue confirmation of thyroid enlarged by amyloid deposits; and radiologic confirmation of thyroid enlargement. RESULTS: Five patients were identified who met all inclusion criteria. Amyloid goiter etiology included both primary and secondary amyloidosis, and the goiters ranged in weight from 50 to 130 g each. Diagnosis was made by fine-needle aspiration biopsy with Congo red staining and, if needed, spectrophotometry. All five patients had histories of persistent hoarseness for several years before presentation with compressive symptoms referable to their enlarging thyroids, and all had some degree of thyroid dysfunction (both hypothyroidism and hyperthyroidism) by the end of our follow-up period, which ranged from 5 months to 13 years. Two patients underwent surgical interventions, two were managed conservatively, and in one, the goiter shrank after systemic therapy for amyloidosis. CONCLUSIONS: Our clinical observations suggest slower goiter progression and a higher prevalence of thyroid dysfunction than previously thought.

The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes.

We designed an experiment to examine the effect of bile acid sequestration with Colesevelam on fasting and postprandial glucose metabolism in type 2 diabetes. To do so, we tested the hypothesis that Colesevelam increases the disposition index (DI), and this increase is associated with increased glucagon-like peptide-1 (GLP-1) concentrations. Thirty-eight subjects on metformin monotherapy were studied using a double-blind, placebo-controlled, parallel-group design. Subjects were studied before and after 12 weeks of Colesevelam or placebo using a labeled triple-tracer mixed meal to measure the rate of meal appearance (Meal Ra), endogenous glucose production (EGP), and glucose disappearance (Rd). Insulin sensitivity and ß-cell responsivity indices were estimated using the oral minimal model and then used to calculate DI. Therapy with Colesevelam was associated with a decrease in fasting (7.0 ± 0.2 vs. 6.6 ± 0.2 mmol/L; P = 0.004) and postprandial glucose concentrations (3,145 ± 138 vs. 2,896 ± 127 mmol/6 h; P = 0.01) in the absence of a change in insulin concentrations. Minimal model-derived indices of insulin secretion and action were unchanged. Postprandial GLP-1 concentrations were not altered by Colesevelam. Although EGP and Rd were unchanged, integrated Meal Ra was decreased by Colesevelam (5,191 ± 204 vs. 5,817 ± 204 µmol/kg/6 h; P = 0.04), suggesting increased splanchnic sequestration of meal-derived glucose.