The Effects of Anti-Inflammatory Treatment on Insulin Resistance in Healthy Volunteers

INCLUSION CRITERIA: Age: Greater than 18 and less than 45 years. Number: 44 completed studies (22 placebo, 22 Salsalate). Sex: 22 Males and 22 Females. BMI: Greater than or equal to 30 kg.m(2) EXCLUSION CRITERIA: Age below 18 or above 45 years to minimize the risk of glucose clamp. Diabetes mellitus (as per 75 g OGTT, WHO 1999 criteria) Cardiovascular disease including: abnormal EKG, personal history of coronary heart disease;symptomatic angina pectoris or cardiac insufficiency as defined by NYHA; classification as functional class III or IV. Systolic blood pressure greater than 160mmHG and/or diastolic blood pressure greater than 100 mmHg and/or on antihypertensive therapy or resting heart rate greater than 90 bpm. Hematological disorder, including prolonged prothrombin time (normal range 10.9-12.9 sec) and partial thromboplastin time (24-36 sec) and thrombocytopenia (less than 150,000 mm(3)). Respiratory disease (including influenza, asthma) Allergies (including hay fever) Gastrointestinal (including peptic ulcer), hepatic or renal disease (ALT and AST greater than 3-fold above upper limit of normal range, creatinine greater than 1.3 mg/dl). Alcoholism, alcohol-induced autonomic neuropathy. Any endocrinological disorder, including hypopituitarism/pituitary dysfunctions or lesions, hypo/hyperthyroidism, insulinoma. CNS disease Psychosis or personal history of any psychiatric disorder. Taking medications within one month prior to beginning the study, including medications known to have pharmacological interactions with salicylates or that may affect insulin sensitivity and secretion (including salicylates, COX 1 and COX 2 inhibitors, warfarin, Beta-Blockers, phenothiazines, antidepressants, antiarrhythmic drugs, antimuscarinic drugs). Acute inflammation as assessed by history, physical and laboratory examination (subjects with C-reactive protein 2 standard deviations above the population mean will not be admitted). The population mean was calculated from subjects admitted at our research unit. Pregnant or lactating females or females on hormonal contraceptives. History of metabolic acidosis. Allergy to aspirin, other salicylates, or bleeding diathesis or currently on oral anticoagulants. Any current viral illness. Active cancer within 5 years prior to screening for the study. Positive urine drug screening test. Inability to provide informed consent. Smokers