Associations of albuminuria in a multi-racial workforce : the Auckland and Tokoroa workforce diabetes study

Abstract

Slight albuminuria (microalbuminuria) is predictive of diabetic nephropathy, increased coronary heart disease morbidity, early overall mortality and increased cardiovascular mortality in patients with diabetes mellitus. There is less information about the associations of slight albuminuria in non-diabetic populations. Previous studies have implicated hypertension, obesity, hyperglycaemia and hypertriglyceridaemia. The association between increased urinary albumin excretion and morbidity and mortality that has been described in non-insulin dependent diabetic patients may also apply to the general population as in creased cardiovascular disease morbidity and early mortality have been reported in elderly non-diabetic subjects. The Workforce Diabetes Study was carried out between May, 1988 and June, 1990 and recruited 5,677 employees (67% response), aged 40 years and over, from 41 work sites in Auckland and 5 work sites in Tokoroa. Early morning urine samples, obtained from 5,670 employees, were cultured for infection and urinary albumin measurements were made using a sensitive immunoturbidimetric assay. Gender-specific reference values were determined in a subgroup of 3,597 people after excluding 2,073 individuals with: (i) Albustix-positive proteinuria; (ii) diabetes mellitus; (iii) bacteriuria; (iv) current hypertension; (v) body mass index > 30 kg/m2; and (vi) serum triglyceride > 2.5 mmol/L. The 97.5 percentile concentrations for urinary albumin was 28 mg/L in men and 29 mg/L in women. In the study group of 5,670 people, urinary albumin concentrations were higher in men than women and showed a significant decline with age in both sexes. In contrast, the albumim:creatinine ratio was higher in women than men due to their lower excretion of urinary creatinine, and declined slightly with age in women, but not men. Log albuminuria showed piecewise linear relationships with diastolic blood pressure and body mass index, linear relationships with hypertriglyceridaemia and hypercholesterolaemia and a negative piecewise linear relationship with high density lipoprotein- cholesterol. Estimates of where a significant increase in slope occurred (and associated 95% confidence intervals) were at points corresponding to a diastolic blood pressure of 76 (69.6,82.3) mm Hg, a body mass index of 25.9 (23.9,26.9) kg/m2 in men, a body mass in dex of 28.4 (23.4,33.4) kg/m2 in women, and a serum high density lipoprotein-cholesterol concentration of 1.40 (1.36,1.44) mmol/L. The relationship between number of cigarettes smoked per day and log urinary albumin concentrations appeared approximately piecewise linear with an estimated change of slope at a point corresponding to 10 (6-14) cigarettes smoked per day, above which the slope appeared to remain constant. Similarly, the relationship between alcohol consumption and log urinary albumin concentrations appeared non-linear with an estimated increase of slope at a point corresponding to an alcohol consumption (95% confidence interval) of 5 (2,8) g/day. After adjusting for age, gender, ethnicity and other lifestyle variables, significant risks (95% confidence interval) for microalbuminuria were found for people reporting alcohol consumption >32 g/day compared with non-drinkers (1.76 (1.07,2.89)), and for current cigarette smokers compared with non-smokers (1.37 (1.01,1.88)). However, there was no significant effect of exercise. Log albuminuria showed linear relationships with dietary protein and cholesterol in takes, a piecewise linear relationship with dietary salt intake, and a negative linear relationship with dietary fibre intake, and a negative piecewise linear relationship with the ratio of polyunsaturated to saturated fat. After adjusting for age, gender, and ethnicity, a significantly increased relative risk (95% confidence interval) for microalbuminuria was found for people reporting dietary cholesterol consumption >226 mg/day compared with people reporting consumption < 226 mg/day (1.32 (1.02,1.70)), and a significantly reduced relative risk for people reporting dietary fibre consumption >26 g/day compared with people reporting consumption <26 g/day (0.74 (0.58,0.95)). However, there was no significant effect of dietary protein, polyunsaturated to saturated fat ratio or salt. The relationship between log albuminuria and plasma glucose was approximately piece- wise linear with significant changes of slope at points corresponding to plasma glucose concentrations (95% confidence interval) 2 hours after a 75 g glucose load of 6.7 (6.4,7.0) mmol/L and 9.2 (8.6,9.8) mmol/L. After adjusting for the effects of gender, obesity, hypertension, hypertriglyceridaemia, cigarette smoking, heavy alcohol consumption, high dietary cholesterol intake and low dietary fibre intake in a multiple logistic regression model, hyperglycaemia was the most significant risk factor associated with urinary albumin concentrations in all three ethnic groups. However, blood glucose concentrations did not completely explain the higher relative risk (95% confidence interval) of microalbuminuria in Maori (5.97; 4.48,7.78) and Pacific Island (5.33; 4.13,6.87) workers compared with Europeans, and it is speculated that other factors such as specific foods and other renal diseases may contribute. These results indicate that elevated urinary albumin concentrations are associated with an adverse pattern of cardiovascular risk factors in the general population, and support the accumulating evidence that microalbuminuria may be a marker for cardiovascular disease. Higher age-standardised prevalences of asymptomatic bacteriuria were observed in Maori women (18.0%) compared with Pacific Island women (9.8%), and European women (8.7%). Similarly, higher prevalences were observed in Maori men (3.2%), compared with Pacific Island men (0.7%) and European men (1.3%). After controlling for age and gender, the relative risk for asymptomatic bacteriuria in Maori people was estimated to be 2.09 times that for non-Maori people (associated 95% confidence interval 1.37 to 3.20). Significant associations of bacteriuria included a past history of myocardial infarction, a past history of kidney disease, absence of tertiary education, and impaired glucose tolerance. The most common pathogens, isolated from a subsample of 1660 participants, were Escherichia coli, 27 cases (50.9%), and Streptococcal sp, 14 cases (26.4%).