Macroalbuminuria And Cardiovascular Disease

Although the prevalence of microalbuminuria is similar in type 1 and type 2 diabetes,64 the rate of progression to overt DN is slower in elderly Caucasian patients with type 2 diabetes, being of the order of 20% over a decade, compared with approximately 80% within a decade for patients with type 1 diabetes in the original studies published in the early 1980s.87 The cumulative risk of ESRD is also less in patients with type 2 diabetes, with one early study showing a cumulative risk of ESRD of 11%.88 The main reason for this disparity is that most Caucasian patients with type 2 diabetes die from cardiovascular disease before developing DN,89,90 therefore leading to survivor bias in published studies (Figure 3.3). Microalbuminuria has been identified as a predictor of increased mortality from cardiovascular disease in both type 191 and type 2 diabetes13,35,92 and also in non-diabetic subjects.37 In some but not all of these studies, microalbuminuria predicted mortality independently of other conventional cardiovascular risk factors such as dyslipidaemia, hypertension and smoking.

Two studies from the Steno Diabetes Centre in Denmark have described predictors of total mortality in patients with type 1 and type 2 diabetes. In the first study of 328 patients with type 2 diabetes over 5 years, the median AER at baseline was 8 mg/24 hr, and subjects with AER above the median value had a relative risk of all-cause mortality of 2.7. After 5 years of follow-up, 8% of patients with normoalbuminuria, 20% with microalbuminuria and 35% with macroalbuminuria had died (predominantly from cardiovascular causes). Predictors of all-cause mortality when examined by multivariate regression were pre-existing coronary heart disease (relative risk [RR] 2.9, 95% CI 1.6-5.1), AER (RR 1.9, 95% CI 1.4-2.6), HbA1c (RR

Type 1

Elderly type 2

Young, non-Caucasian type 2

Hyperglycaemia Hypertension Dyslipidaemia




Microvascular disease (retinopathy, nephropathy)

ยป Macrovascular disease

Figure 3.3 Differing relationships of microalbuminuria to vascular disease in patients with type 1 diabetes and non-Caucasian type 2 diabetes compared with elderly patients with type 2 diabetes (modified from Jerums and Chattington207).

1.2, 95% CI 1.0-1.4) and age (RR 1.08, 95% CI 1.03-1.13). Predictors of cardiovascular mortality were preexisting coronary heart disease (RR 6.1, 95% CI 2.8-13.5), macroalbuminuria (RR 2.5, 95% CI 1.1-5.8), 1% increase in HbA1c (RR 1.3, 95% CI 1.1-1.6) and a 10 mmHg rise in systolic blood pressure (RR 1.2, 95% CI 1.0-1.4).93

The second study from the Steno Diabetes Centre involved a 10-year follow-up in 1984-94 of 939 patients with 5 or more years' duration of type 1 diabetes.94 Total mortality increased according to baseline level of AER. Ten-year total mortality was 15% in patients with normoalbuminuria, 25% in patients with microalbuminuria and 44% in macroalbuminuric patients. The median survival after onset of overt DN was 17.2 years. Multivariate regression analysis showed that the relative risk of all-cause mortality was 2.03 for male sex, 1.07 for age, 0.96 for height, 1.51 for smoking, 1.70 for lower social class, 1.45 for AER category, 1.63 for hypertension, 8.96 for serum creatinine and 1.11 for HbA1c. Age, smoking, AER category and hypertension were also significant predictors of cardiovascular mortality. These results indicate that similar risk factors predict mortality in type 1 and type 2 diabetes.

The relationship of DN and cardiovascular mortality in patients with type 1 diabetes has been studied extensively by Borch-Johnsen in Denmark. Studies between 1933 and 1981 in a cohort of 1030 patients with type 1 diabetes showed a markedly increased relative risk of death in patients with overt DN compared to patients without DN.95-97 Recent studies in some ethnic groups have suggested that the prognostic importance of proteinuria for cardiovascular disease in type 2 diabetes is considerably less than in type 1 diabetes. For instance, in studies in Pima Indians, proteinuria was shown to entail a 3.5-fold higher risk of death, and proteinuria combined with hypertension was associated with a sevenfold higher risk of death.98

This compares with a 40-fold increase in risk of death entailed by proteinuria in patients with type 1 diabetes studied before 1952.95

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