Association between insulin resistance and development of microalbuminuria in type 2 diabetes: a prospective cohort study

Abstract

Objective: An association between insulin resistance and microalbuminuria in type 2 diabetes has often been found in cross-sectional studies. We aimed to reassess this relationship in a prospective Taiwanese cohort of type 2 diabetic subjects.

Research design and methods: We enrolled 738 normoalbuminuric type 2 diabetic subjects, aged 56.6 ± 9.0 years, between 2003 and 2005 and followed them through the end of 2009. Average follow-up time was 5.2 ± 0.8 years. We used urine albumin-to-creatinine ratio to define microalbuminuria and the homeostasis model assessment of insulin resistance (HOMA-IR) to assess insulin resistance. The incidence rate ratio and Cox proportional hazards model were used to evaluate the association between HOMA-IR and development of microalbuminuria.

Results: We found incidences of microalbuminuria of 64.8, 83.5, 93.3, and 99.0 per 1,000 person-years for the lowest to highest quartiles of HOMA-IR. Compared with those in the lowest quartile of HOMA-IR, the incidence rate ratios for those in the 2nd, 3rd, and highest quartiles were 1.28 (95% CI 0.88-1.87), 1.44 (0.99-2.08), and 1.52 (1.06-2.20), respectively (trend test: P < 0.001). By comparison with those in the lowest quartile, the adjusted hazard ratios were 1.37 (0.93-2.02), 1.66 (1.12-2.47), and 1.76 (1.20-2.59) for those in the 2nd, 3rd, and highest HOMA-IR quartiles, respectively.

Conclusions: According to the dose-response effects of HOMA-IR shown in this prospective study, we conclude that insulin resistance could significantly predict development of microalbuminuria in type 2 diabetic patients.

Figure 1

Kaplan-Meier estimates of probability of normoalbuminuria according to 4 quartiles of HOMA-IR at baseline.

Figure 2

Adjusted HR of microalbuminuria development in type 2 diabetic patients for overall subjects and those with good metabolic profiles at baseline. Type 2 diabetic patients with good metabolic profiles were those who had no ACEI/ARB use, BMI <24 kg/m², triglycerides <150 mg/dL, waist circumference <80 cm (female) or <90 cm (male), HDL cholesterol >40 mg/dL (male) or >50 mg/dL (female), and blood pressure <130/80 mmHg. The controlled covariates in the survival analyses included demographics (baseline age, sex, education, smoking status, and diabetes duration) and baseline biomedical profiles (waist circumference, BMI, triglycerides, ACR, HDL cholesterol, HbA_1c, and mean arterial pressure). The reference group for each model was those who were in the lowest quartile of the corresponding HOMA-IR index. The mean arterial pressure (MAP) was calculated by the formula: mean arterial pressure = diastolic blood pressure + 1/3 (systolic blood pressure – diastolic blood pressure). T2DM, type 2 diabetes. †Test for trend. *P < 0.05 in multivariable Cox proportional hazards model.