Yoram Shenker

Alterations in energy balance following exenatide administration

Exenatide is a medication similar in structure and effect to native glucagon-like peptide-1, an incretin hormone with glucose-lowering properties. The aim of the study was to measure the change in total energy expenditure (TEE) and body composition during exenatide administration and by deduction the relative contributions of energy expenditure and energy intake to exenatide-induced weight loss. Forty-five obese (body mass index, 30-40 kg·m⁻²) subjects were identified. After exclusion criteria application, 28 subjects entered into the study and 18 subjects (12 female, 6 male) completed the study, which consisted of 6 visits over 14 weeks and injection of exenatide for an average of 84 ± 5 days. Respiratory gas analysis and doubly labeled water measurements were performed before initiation of exenatide and after approximately 3 months of exenatide administration. The average weight loss from the beginning of injection period to the end of the study in completed subjects was 2.0 ± 2.8 kg (p = 0.01). Fat mass declined by 1.3 ± 1.8 kg (p = 0.01) while the fat-free mass trended downward but was not significant (0.8 ± 2.2 kg, p = 0.14). There was no change in weight-adjusted TEE (p = 0.20), resting metabolic rate (p = 0.51), or physical activity energy expenditure (p = 0.38) and no change in the unadjusted thermic effect of a meal (p = 0.37). The significant weight loss because of exenatide administration was thus the result of decreasing energy intake. In obese nondiabetic subjects, exenatide administration did not increase TEE and by deduction the significant weight loss and loss of fat mass was due to decreased energy intake.

The Utility of Metaiodobenzylguanidine (MIBG) Scintigraphy in Patients with Pheochromocytoma

BackgroundRadiolabeled metaiodobenzylguanidine scintigraphy (MIBG) can be used to image pheochromocytomas. While cross-sectional imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) usually localize the tumor, MIBG is often obtained to rule out multifocal and metastatic disease, and to corroborate anatomic imaging with functional data. We questioned the utility of MIBG in the diagnosis and management of pheochromocytoma.MethodsAll patients who received MIBG at one academic center from 1999 to 2004 were identified. For the subset of patients who received MIBG in the work-up of possible pheochromocytoma, the following data were reviewed: demographics, symptoms, results of biochemical and imaging studies, histopathological diagnosis, and management.ResultsA total of 60 patients received MIBG, including 27 patients for the evaluation of a possible pheochromocytoma. Biochemical testing was performed in all patients. Fourteen patients received MIBG despite normal biochemistry and an absence of risk factors such as a hereditary syndrome or prior history of pheochromocytoma. None of these 14 low-risk patients with negative biochemistry had a final diagnosis of pheochromocytoma. In the ten patients with pheochromocytoma, all tumors were localized by CT and/or MRI. Importantly, MIBG did not identify any foci of disease not seen on cross sectional imaging, and MIBG did not alter the surgical management of any patient in this series.ConclusionsIn patients with clinical findings suggestive of pheochromocytoma, biochemical testing should be used to confirm the diagnosis, and cross-sectional imaging is sufficient for tumor localization. In the absence of hereditary disease or a past history of pheochromocytoma, MIBG does not alter the treatment plan and therefore should not be routinely performed. Instead, MIBG should be used selectively, such as for the rare patient with a biochemical diagnosis of pheochromocytoma and no tumor seen on exhaustive anatomical imaging.

A Retrospective Study Comparing Neutral Protamine Hagedorn Insulin with Glargine as Basal Therapy in Prednisone-Associated Diabetes Mellitus in Hospitalized Patients

OBJECTIVE To compare glycemic outcomes in hospitalized patients with or without type 2 diabetes mellitus receiving neutral protamine Hagedorn insulin (NPH) vs glargine as basal insulin for management of glucocorticoid-associated hyperglycemia. METHODS We conducted a retrospective review of electronic medical records in prednisone-treated adult patients with hyperglycemia in a university hospital. Consecutive patients were selected in both the NPH and glargine cohorts using inclusion and exclusion criteria. Baseline characteristics were assessed in each cohort. Glycemic outcomes were analyzed by comparing fasting blood glucose, mean daily blood glucose concentration, median daily blood glucose concentration, and the number of hypoglycemic episodes on a prespecified index day. RESULTS One hundred twenty patients were included: 60 patients in the NPH cohort and 60 patients in the glargine cohort. The weight-based insulin requirement was lower in the NPH cohort than in the glargine cohort (0.27 ± 0.2 units/kg vs 0.34 ± 0.2 units/kg [P = .04] for basal insulin and 0.26 ± 0.2 units/kg vs 0.36 ± 0.2 units/kg [P = .03] for bolus insulin). NPH and glargine cohorts were similar regarding age, sex, race, body mass index, hemoglobin A1c, serum creatinine, and prednisone dosage. Glycemic outcomes in the NPH cohort compared with outcomes in the glargine cohort were similar regarding mean fasting blood glucose concentration (134 ± 49 mg/dL vs 139 ± 54 mg/dL [P = .63]), mean daily blood glucose (167 ± 46 mg/dL vs 165 ± 52 mg/dL [P = .79]), median blood glucose (160 ± 49 mg/dL vs 159 ± 57 mg/dL [P = .90]), and number of hypoglycemic episodes per day (0.12 ± 0.3 vs 0.10 ± 0.3 [P = .77]). CONCLUSIONS NPH and glargine appear to be equally effective as basal insulin in the management of hyperglycemia in hospitalized patients receiving prednisone. However, the total daily insulin doses used were lower in the NPH cohort.

Regulation of adrenal atrial natriuretic hormone receptor subtypes

Regulation of atrial natriuretic hormone (ANH) receptor binding and aldosterone suppression was studied in isolated adrenal glomerulosa cells from rats fed a high-salt (HS) or low-salt (LS) diet for 3 days. In plasma of HS rats, aldosterone levels were 5 times lower and immunoreactive ANH two times higher than in LS rats. Competitive binding studies showed the same affinity for human atrial natriuretic hormone (hANH) in both pools of cells, but receptor density was 50% higher on LS cells. A linear ANH analog that binds to non-guanylate-cyclase-coupled receptors did not show increased binding to LS cells. Cyclic GMP production in response to hANH was identical in both groups. The aldosterone-inhibitory effect of hANH on both groups of basal and angiotensin II-stimulated cells was also identical. Thus a short-term high-salt diet causes decreased density of ANH receptors in glomerulosa cells without changing biological activity of ANH. These results suggest that dietary salt content changes the number of ANH receptors and that non-guanylate-cyclase-coupled receptors contain at least two classes of receptors.