Diazoxide-Mediated Insulin Suppression in Hyperinsulinemic Obese Men

The purpose of this study is to explore diazoxide efficacy in treatment of obese men and assessment of maximal insulin suppression in obese men without hyperglycaemia. Obesity is associated with markedly elevated plasma insulin levels throughout the day. The concept is that obese subjects predominantly develop lean tissue resistance against the glucoregulatory actions of insulin, but remain relatively sensitive to the lipogenic and antilipolytic effects of insulin in adipose tissue. According to this theory, suppression of hyperinsulinism by diazoxide, a well known inhibitor of glucose stimulated insulin secretion, might be useful to treat obesity because it will help to reverse the process of lipid storage.

The purpose of this study is to explore diazoxide efficacy in treatment of obese men and assessment of maximal insulin suppression in obese men without hyperglycaemia. Study design: This study is an open-labelled, non-randomized, phase IIa study. Treatment: During a 6 month period, the dosage of Diazoxide will be raised gradually until a maximum of 900 mg/day, under control of bloodpressure and glucose levels. Endpoints, monthly determined: body weight abdominal circumference body composition measured by Dual Energy X-ray Absorptiometry glucose tolerance

Inclusion Criteria: fasting glucose < 7.0 mmol/L fasting C-peptide plasma level > 1.0 nmol/L HbA1c of 6.0% or lower Absence of comorbidity Absence of medication use Exclusion Criteria: Plasma Creatinine > 120 micromol/L Liverenzymes > 2 times the upper normal limit Gout Alcohol use > 2 units/day Illicit drug use Quit smoking less than 6 months ago

Schreuder T, Karreman M, Rennings A, Ruinemans-Koerts J, Jansen M, de Boer H. Diazoxide-mediated insulin suppression in obese men: a dose-response study. Diabetes Obes Metab. 2005 May;7(3):239-45. doi: 10.1111/j.1463-1326.2004.00449.x.