1728 DIABETES CARE, VOLUME 22, NUMBER 10, OCTOBER 1999 O besity is an insulin-resistant condi- tion associated with an increased risk for cardiovascular disease and type 2 diabetes (1–3). Individuals who predomi- nantly store fat in the abdominal area (par- ticularly in the visceral area) often present with a cardiovascular risk factor pattern resembling type 2 diabetes (i.e., hyperinsu- linemia, glucose intolerance, hypertension, and dyslipidemia). Studies have suggested that obesity (4–7) and hyperinsulinemia (8–13) are associated with an increased uri- nary albumin excretion (UAE) rate and that increased albuminuria may be a feature of the prediabetic state (7–11,14). However, it is not clear whether the hyperinsulinemia alone or the presence of competing risk fac- tors, such as hypertension or hypergly- cemia/impaired glucose tolerance, is deter- mining the increased albuminuria. In both nondiabetic and type 2 diabetic subjects, even slightly increased UAE in the microalbuminuric range (20–200 μg/min) predicts increased cardiovascular morbidity and mortality (15–19). The cardiovascular risk factor pattern typically associated with hyperinsulinemia/insulin resistance is more pronounced in patients with concomitant abnormal albuminuria (8,20–23); however, the series of events leading to abnormal albuminuria are not clear. The present studies were undertaken to determine if UAE is increased in obe- sity-associated hyperinsulinemia/insulin resistance without hypertension or im- paired glucose tolerance. We examined UAE in lean and obese, normotensive, normal glucose-tolerant Caucasian sub- jects, with special attention directed toward the impact of body fat distribution and cardiovascular risk factors of the insulin resistance syndrome. RESEARCH DESIGN AND METHODS Subjects The study was approved by the Mayo Clinic Institutional Review Board and informed written consent was obtained from all participants. There were 25 men and 25 women volunteers who participated in the study. All were healthy Caucasians with normal blood pressure, and none took any kind of med- ication except women using birth control pills. The age and BMI range was 19–48 years and 18.9–36.0 kg/m 2 . All were non- smokers except one man and one woman who refrained from smoking 4 weeks before the study, and all had been weight stable for at least 3 months before inclusion. All sub- jects had a normal liver and kidney function test, electrolytes, and fasting lipids meas- ured before participation. From the Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota. Address correspondence and reprint requests to Søren Nielsen, MD, Medical Department M (Endocrinol- ogy and Diabetes), Århus Kommunehospital, DK-8000 Århus C, Denmark. Received for publication 6 November 1998 and accepted in revised form 2 July 1999. Abbreviations: DXA, dual-energy X-ray absorptiometry; GCRC, General Clinical Research Center; OGTT, oral glucose tolerance test; UAE, urinary albumin excretion; WHR, waist-to-hip ratio. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Relationship Between Urinary Albumin Excretion, Body Composition, and Hyperinsulinemia in Normotensive Glucose-Tolerant Adults O R I G I N A L A R T I C L E OBJECTIVE — Elevated urinary albumin excretion (UAE) has been associated with insulin resistance and is suggested to be elevated in prediabetic individuals. Upper body obesity, espe- cially visceral obesity, predicts insulin resistance and development of type 2 diabetes. We exam- ined whether UAE clusters with obesity-associated insulin resistance traits in healthy glucose-tolerant normotensive subjects. RESEARCH DESIGN AND METHODS — There were 49 volunteers with a wide range of body fat and body fat distribution studied. All had normal blood pressure and glucose tol- erance and were maintained on a controlled diet for 2 weeks. UAE was assessed from three overnight urine collections, and body composition was assessed by whole-body dual-energy X-ray absorptiometry scanning and abdominal computed tomography scanning. RESULTS — Fasting insulin and insulin responses to oral glucose were significantly increased in obese subjects, who also tended to have more dyslipidemia, greater blood pres- sure, and more visceral fat than lean subjects. These differences were more apparent in upper body obese subjects. UAE was normal in obese and upper body obese subjects and not differ- ent from that of lean subjects. UAE ranged from 0.3 to 8.3 μg/min in lean subjects and from 0.2 to 7.2 μg/min in obese subjects. UAE was not significantly correlated with body composi- tion, plasma insulin, glucose, or lipids. CONCLUSIONS — Obese subjects (even upper body obese subjects) with increased vis- ceral and total body fat, high plasma insulin and triglycerides, and low HDL cholesterol con- centrations do not have elevated UAE. This suggests that UAE is not closely associated with these characteristics and implies a later onset of abnormal albuminuria in the course of the insulin resistance syndrome. Diabetes Care 22:1728–1733, 1999 SØREN NIELSEN, MD MICHAEL D. JENSEN, MD P a t h o p h y s i o l o g y / C o m p l i c a t i o n s