Smoking and Microalbuminuria: A case-control study in African-Americans with type 2 diabetes

African-Americans are at increased risk of diabetic nephropathy (1,2). Cigarette smoking has been shown to increase the risk of microalbuminuria in Caucasian populations with type 1 and type 2 diabetes (3,4,5,6). In contrast, despite their high risk of nephropathy, the association between cigarette smoking and microalbuminuria in African-Americans with diabetes has not previously been assessed. We conducted a case-control study to examine the association between lifetime cigarette smoking history and risk of prevalent microalbuminuria in patients with recently diagnosed type 2 diabetes. Our study population was African-American patients with type 2 diabetes duration ≤2 years who had an initial visit to the Grady Diabetes Clinic in Atlanta, Georgia, between January 1994 and December 1996. The present study is partially based on secondary data from a cross-sectional analysis of this study population, which has been previously described in detail (7). We excluded patients missing urine albumin and/or urine creatinine measurements and patients with clinical nephropathy (urine albumin-to-creatine [Alb/Cr] ratio >250 μg/mg). Serum and urine creatinine were measured in a random morning urine specimen at the first clinic visit. Patients were divided into two groups based on Alb/Cr ratios: normoalbuminuria (Alb/Cr <25 μg/mg) or microalbuminuria (Alb/Cr from 25 to 250 μg/mg) (8). All 246 microalbuminuric patients were case subjects; based on a priori power calculations, 506 control subjects were randomly sampled from the 766 normoalbuminuric patients.

Lifetime smoking history was obtained via telephone interview by three trained and blinded interviewers. Patients were classified as smokers if they had smoked at least 100 cigarettes in their lifetime and had ever smoked on a regular basis for at least 6 months, and number of pack-years smoked was estimated. Before the interview, informed consent was obtained from all participants, and the Emory University Human Investigations Committee approved the study. Multiple logistic regression was done to assess the relation between microalbuminuria status (yes or no) and pack-years of cigarettes smoked before diabetes diagnosis while controlling for other clinical variables.

The Alb/Cr ratio was calculated for 1,055 (90.4%) of the 1,167 initially eligible patients; 43 (4.1%) with evidence of clinical nephropathy (Alb/Cr >250 μg/mg) were excluded. Of the remaining 1,012 patients, 246 (23.3%) had microalbuminuria (case subjects), and 766 (72.6%) had normoalbuminuria (control subjects). We interviewed 138 (56.1%) of the case subjects and 297 (58.7%) of the control subjects. Patients interviewed were older than patients not interviewed (mean age 53.5 vs. 48.4 years, P < 0.0001), had slightly shorter diabetes duration (mean 0.37 vs. 0.44 years, P = 0.04), and had higher HDL cholesterol levels (mean 44.7 vs. 42.6 mg/dl, P = 0.04). The proportion of women was statistically significantly higher in the interviewed group (71.5 vs. 60.9%). There were no differences in mean arterial blood pressure or HbA_1c. Among the 435 case and control subjects who completed the interview, the mean diabetes duration was just under 5 months, the mean age was 53.5 ± 13 years, the mean BMI was 33.7 ± 8.9 kg/m², and the mean number of years of school completed was 10.7 ± 2.9. Case subjects had significantly higher mean arterial blood pressures (P = 0.002) and triglycerides (P = 0.03) as well as trends toward fewer years of education (P = 0.06) and higher BMI (P = 0.06) than control subjects.

Pack-years of cigarette smoking was higher among case than control subjects (mean pack-years 15.1 ± 23.0 for case subjects vs. 11.1 ± 18.8 for control subjects), but this difference was not statistically significant (P = 0.17). Among current smokers, mean pack-years was significantly higher for case than for control subjects (34.3 ± 20.9 vs. 22.7 ± 17.7, P = 0.007) and was also significantly higher among case than control subjects when only looking at ever smokers (30.2 ± 24.6 for case subjects vs. 23.9 ± 21.4 for control subjects, P = 0.03). Forty-eight percent of our population either currently smoked or were ex-smokers.

After excluding patients with estimated creatinine clearance >250 ml/min (n = 12) from the multiple logistic regression analysis, the number of reported pack-years of smoking was independently associated with increased risk of prevalent microalbuminuria, controlling for HbA_1c, mean arterial blood pressure, age, self-reported hypertension, and diabetes duration. Estimates from the final model showed that each increase of 10 pack-years of smoking corresponded to a 14% increase in microalbuminuria risk (odds ratio [OR] = 1.14, 95% CI 1.03–1.26). An increase of 40 pack-years of smoking corresponded to an OR of 1.69 (95% CI 1.12–2.56). There was evidence of a linear dose-response, with microalbuminuria risk increasing as pack-years increased (Table 1).

This case-control study is the first to examine the relation between lifetime cigarette smoking, measured in pack-years, and microalbuminuria prevalence in African-Americans with recent-onset type 2 diabetes. Pack-years of cigarettes smoked until diabetes diagnosis was independently related to prevalence of microalbuminuria in these patients while controlling for HbA_1c, age, mean arterial blood pressure, hypertension, and diabetes duration.

Several limitations should be noted when interpreting our results. First, there is the potential for misclassification of both exposure and outcome. We relied on self-reported lifetime smoking histories to calculate the main exposure, pack-years. Our use of a single Alb/Cr ratio may have misclassified the microalbuminuria status of some patients. Misclassification of normo- and microalbuminura in our study is likely to be random and independent of the main exposures, biasing our ORs toward the null. Blood pressure was only measured once, so we could not assess patients’ long-term blood pressure patterns. Data on the use of antihypertensive medications was incomplete in the database, and thus we relied on self-reported hypertensive status from the telephone interview. In particular, we did not have complete data on ACE inhibitor use in this population; ACE inhibitors are known to reverse the nephrotoxic effects of smoking (9). Selection bias is also a concern due to low interview response rates. It is possible that nonparticipants had on average smoked more than subjects who completed our interview.

Although response rates were low (56.1% of case subjects and 58.7% of control subjects), we feel that these data offer preliminary evidence that smoking is an independent risk factor for microalbuminuria in African-Americans with type 2 diabetes. Given the high risk for end-state renal disease in this group, clinicians should increase efforts to encourage patients with microalbuminuria to stop smoking. Further, in view of the difficulty that many smokers have in quitting, patients with type 2 diabetes and microalbuminuria who continue to smoke should be more closely monitored for progressive renal disease, and renoprotective therapies should be aggressively applied in these patients.