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Insulin Resistance and Microalbuminuria

A Cross-Sectional, Case-Control Study of 158 Patients With Type 2 Diabetes and Different Degrees of Urinary Albumin Excretion

¹ Clinical Research Centre for Rare Diseases "Aldo e Cele Daccò," Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica (Bergamo), Italy
² Department of Clinical and Experimental Medicine, University of Padova, Italy
³ Unit of Diabetology, Azienda Ospedaliera, Ospedali Riuniti, Bergamo, Italy
⁴ Unit of Nephrology, Azienda Ospedaliera, Ospedali Riuniti, Bergamo, Italy

Address correspondence and reprint requests to Giuseppe Remuzzi, MD, FRCP, "Mario Negri" Institute for Pharmacological Research, Negri Bergamo Laboratories, Via Gavazzeni, 11-24125 Bergamo, Italy. E-mail: gremuzzi{at}marionegri.it

Abbreviations: AER, albumin excretion rate; GDR, glucose disposal rate; GFR, glomerular filtration rate

Microalbuminuria is a risk factor for renal and cardiovascular disease. A role for insulin resistance in the pathogenesis of microalbuminuria has been suggested but is still unproven. In this case-control, cross-sectional study, we compared glucose disposal rate (GDR), measured by hyperinsulinemic-euglycemic clamp, in 50 pairs of matched type 2 diabetic patients with micro- or normoalbuminuria (main study) and in 29 matched pairs of diabetic patients with macro- or microalbuminuria (substudy). In the main study, GDR was 25% lower in micro- than in normoalbuminuric patients (5.20 ± 1.91 vs. 6.86 ± 2.88 mg · kg^–1 · min^–1, P < 0.05) and was independently associated with microalbuminuria (P = 0.002), with each 1 mg · kg^–1 · min^–1 decrease predicting 40% increased prevalence (odds ratio 1.37 [95% CI 1.14–1.70]). Microalbuminuria was threefold more frequent in patients with GDR 7.50 ± 2.56 mg · kg^–1 · min^–1 than in those with higher GDR (60% vs. 20%, P < 0.005). In the substudy, GDR in macro- and microalbuminuric patients was comparable (5.52 ± 2.56 vs. 5.16 ± 1.61 mg · kg^–1 · min^–1) and independent of macroalbuminuria. GDR was significantly correlated with urinary albumin excretion rate in the main study (P = 0.004) but not in the substudy (P = 0.60). In type 2 diabetes, more severe insulin resistance is independently associated with microalbuminuria. Longitudinal studies are needed to clarify the role of insulin resistance in the pathogenesis of microalbuminuria and related complications.

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