Central Obesity Increases Risk for Microalbuminuria in ...

Central Obesity Increases Risk for Microalbuminuria in Type 1 Diabetes CME

Central Obesity Increases Risk for Microalbuminuria in Type 1 Diabetes CME
News Author: Laurie Barclay, MD
CME Author: D»sir»e Lie, MD, MSEd


December 11, 2006 Û Central obesity is an independent risk factor for incident microalbuminuria in individuals with type 1 diabetes, according to the results of a randomized study reported in the January 2007 issue of the Journal of the American Society of Nephrology.

"Weight gain and central obesity are associated with insulin resistance, hypertension, and dyslipidemia in type 1 diabetes," write Ian H. de Boer, MD, of the University of Washington in Seattle, and colleagues from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group. "These metabolic abnormalities are risk factors for kidney disease in the general population, but data addressing the relationship of central obesity with kidney disease in type 1 diabetes are limited."

To determine whether waist circumference is associated with incident microalbuminuria and change in creatinine clearance, the investigators evaluated 1279 participants with type 1 diabetes who were enrolled in the Epidemiology of Diabetes Interventions and Complications Study, the observational extension of the Diabetes Control and Complications Trial (DCCT).

During 5.8 years of follow-up, 93 of 1105 participants with normal albumin excretion rate (AER) at DCCT closeout developed incident microalbuminuria. After adjustment for DCCT closeout age, sex, duration of diabetes, treatment group, smoking status, glycated hemoglobin (HbA1c), and AER, the hazard ratio (HR) for incident microalbuminuria that was associated with each 10-cm greater waist circumference at DCCT closeout was 1.34 (95% confidence interval [CI], 1.07 - 1.68).

After additional adjustment for levels of blood pressure and serum lipids, this increased risk was modestly attenuated. Creatinine clearance decreased by an average of 0.34 mL/minute per 1.73 m2 per year during 8 years of follow-up. Faster rate of decrease in creatinine clearance was associated with increased age, conventional insulin therapy during the DCCT, smoking, and greater HbA1c level and AER at DCCT closeout, but not with waist circumference.

Study limitations include inability to exclude an effect of central obesity on glomerular filtration rate delayed beyond 8 years of follow-up, lack of radiographic quantification of body fat distribution, less than optimal measurement method for creatinine clearance, and lack of generalizability from a clinical trial setting to the broader population with type 1 diabetes.

"Waist circumference predicts the subsequent development of microalbuminuria in type 1 diabetes," the authors write. "In contrast, no association was observed between waist circumference and change in creatinine clearance over time, further suggesting that microalbuminuria and loss of excretory kidney function may have different risk factors and pathogenic mechanisms in this population."

The National Institutes of Health and the Endocrine Fellows Foundation supported this study. The authors have disclosed no relevant financial relationship.

J Am Soc Nephrol. 2007;18:235-243.

Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Describe the association between waist circumference and risk for microalbuminuria in type 1 diabetes.

List factors affecting creatinine clearance decline in type 1 diabetes.

Clinical Context
Diabetic nephropathy is the leading cause of end-stage renal disease in the United States, particularly in patients with type 1 diabetes, and central obesity, insulin resistance, and hypertension may all be associated with kidney disease and microalbuminuria. According to the current authors, studies examining the association between central obesity and microalbuminuria have been cross-sectional and limited in design and none have addressed the association between central obesity and other renal measures.

This is an extension observational study of participants in the DCCT who were all given intensive treatment of type 1 diabetes at closeout for the DCCT. The DCCT originally recruited 1441 participants aged 13 to 39 years at baseline who were randomly assigned to conventional or intensive insulin therapy and who were followed up for a mean of 6.5 years. Of the DCCT participants, 96% joined this observational extension study.

Study Highlights
DCCT participants who completed the trial were invited to participate in this extension study.

Excluded were those who were pregnant, did not have waist circumference measurements, had fewer than 2 urine follow-ups, and had an AER of 30 mg/24 hours or more at DCCT closeout.

Waist circumference, waist-to-hip ratio, and body mass index were measured.
Waist circumference was chosen over body mass index and waist-to-hip ratio as the primary exposure because of greater correlation with visceral adipose tissue and AER in cross-sectional studies.

Creatinine clearance and AER were measured by timed 4-hour urine collection with each expressed per 24 hours.

Creatinine clearance was evaluated both adjusted and unadjusted for body surface area.

Incident microalbuminuria was defined as an AER 30 mg/24 hours or more on 2 consecutive measurements consistent with American Diabetes Association guidelines.
Waist circumference was divided into quartiles by sex.

Mean age was 33 years, duration of diabetes was 12 years, 96% were white, 45% received intensive therapy during the DCCT, 25% were active smokers, mean body mass index was 25 kg/m2, and mean blood pressure was 116/75 mm Hg.

Median follow-up duration was 5.8 years.

At DCCT closeout, greater waist circumference was associated with greater age in men, greater duration of diabetes in women, intensive insulin therapy during DCCT, greater body mass index, higher blood pressure, and unfavorable lipid profile, but not HbA1c level or AER.

93 (8.4%) of 1105 at-risk individuals developed incident microalbuminuria during the study period.

The cumulative incidence of microalbuminuria was higher in men than in women (10.7 vs 5.8%; P = .001) and in those who had been assigned to conventional vs intensive insulin therapy (12.8% vs 4.5%; P < .001).

The HR for incident microalbuminuria that was associated with each 10-cm increase in waist circumference was 1.34 (95% CI, 1.07 - 1.68), adjusting for sex, race, duration of diabetes, treatment group, HbA1c level, and AER.

The HR was 1.23 when adjusted for cholesterol and lipid profile.
Greater waist circumference was associated with an increased risk for incident microalbuminuria in each sex (HR, 1.65 among women and 1.23 among men).

Waist circumference was highly correlated with body mass index and waist-to-hip ratio.

Incident microalbuminuria was positively correlated with body mass index (HR, 1.46; 95% CI, 1.17 - 1.80) and waist-to-hip ratio (HR, 1.33; 95% CI, 0.97 - 1.81).
88% of participants had 5 creatinine clearance measurements available for analysis.

Median follow-up was 8.0 years.

Mean change in creatinine clearance was -0.34 mL/minute per 1.73 m?.

Waist circumference was not associated with change in creatinine clearance over time in adjusted or unadjusted analyses.

Creatinine clearance decline was associated with greater age, conventional insulin treatment during the DCCT, active smoking, greater HbA1c level, and greater AER.
Pearls for Practice

Central obesity as measured by waist circumference is associated with increased risk for incident microalbuminuria in type 1 diabetes.

Greater age, conventional insulin treatment, active smoking, greater HbA1c level, and greater AER, but not higher waist circumference, are associated with increased decline in creatinine clearance in type 1 diabetes.