Original article:
Different risk factors of microangiopathy in patients with Type I diabetes mellitus of short versus long duration. The EURODIAB IDDM Complications Study. Karamanos B, Porta M, Songini M et al., and the EURODIAB IDDM Complications Study Group. Diabetologia 2000; 43: 348–55.

Summary
The aim of the study was to identify factors associated with early onset of and late protection from microangiopathy in Type 1 diabetes using the cross-sectional data of the EURODIAB IDDM project.
In this sample, 25% (75/300) of those with a duration of Type 1 diabetes of <5 years presented some degree of microangiopathy. These individuals, compared with those who did not develop early-onset microangiopathy, had a higher prevalence of current smoking and a more frequent family history of hypertension. Most (55) of these 75 individuals had microalbuminuria, 12 had retinopathy and eight had both.
Among individuals with a duration of diabetes >14 years, 18% (190/1062) did not present any clinical sign of microangiopathy. Comparing those with and those without microangiopathy, the former had both higher BMI and a more central fat distribution, and had higher HbA1c, blood pressure, fibrinogen, LDL cholesterol and triglyceride levels. Similar trends, although not statistically significant (perhaps because of smaller numbers), were also seen for most of these factors among patients with <5 years of disease (Table I).
Table I: Comparison of age- and duration-adjusted means of continuous variables between groups with and without microangiopathy in Type 1 diabetic patients with short (< years) and long (>14 years) duration of diabetes.

Comparing extreme groups — those who developed microangiopathy within the first 5 years of disease with those who did not, even after 14 years — the former had a higher prevalence of hypertension, a worse lipid profile, and higher levels of blood pressure, von Willebrand factor and HbA1c (Table I). They had a lower frequency of severe hypoglycemia but a higher frequency of smoking and cardiovascular disease.
Based on these findings the authors recommend early initiation of long-term interventions aimed at controlling many of the risk factors for microvascular complications.

Comment
That one out of four patients with Type 1 diabetes shows some degree of microangiopathy during the first 5 years of disease, is by itself of great clinical importance. Of note, however, is the overwhelming predominance of microalbuminuria over retinopathy: 21% (63/300) vs. 7% (20/300). A previous study reported a much lower (6%) prevalence of microalbuminuria in the first 3 years of Type 1 diabetes; probably, at least in part, because of differences in methodology and age structure of the samples [1]. Although microalbuminuria remains the best available marker for diabetic nephropathy risk, this assessment, particularly when based on a single determination, is far from perfect. Additionally, a recent study demonstrated that the rate of progression from microalbuminuria to proteinuria is lower than that initially reported, and that some patients with microalbuminuria may in fact revert to normoalbuminuria [2]. Nevertheless, although we may be able to improve risk assessment of renal disease in the future, these results support current screening strategies early in the course of Type 1 diabetes. In this regard, early detection and treatment of Type 1 diabetes complications have been recently favorably evaluated by cost-effectiveness analyses [3].
Additionally, these cross-sectional data suggest the presence of a set of interrelated risk factors for microangiopathy. Although highlighting the importance of glucose control, the study indicates a possible role for various cardiovascular risk factors in the course of Type 1 diabetes.
The fact that those who did not have microangiopathy after at least 14 years of disease had a greater frequency of severe episodes of hypoglycemia in the preceding year, illustrates the current dilemma of intensive insulin treatment schemes. The fact that those who had microangiopathy had a worse lipid profile, a higher BMI, a more central fat distribution, a higher systolic blood pressure, higher levels of hemostatic factors, and a more frequent family history of hypertension and personal history of smoking, suggests that a metabolic syndrome may underlie the development of microangiopathy in individuals with Type 1 diabetes. Although the authors highlighted differences in risk factors in the early vs. the later stages of the disease, the small sample size for those in the early stages could explain most of these differences. Yet, higher levels of von Willebrand factor and a worse lipid profile in early developers than in those free of microangiopathy after at least 14 years of disease suggest that endothelial dysfunction may underlie the development of these complications.
A metabolic syndrome appears to lie at the root of the development of Type 2 diabetes and its macrovascular complications. Additionally, insulin resistance is associated with the development of microangiopathy in both Type 2 [4] and Type 1 diabetes [5]. Inflammatory markers have been related to cardiovascular disease [6] and microangiopathy [7]. Endothelial dysfunction is related to vasculopathy in Type 2 diabetes [8] and is perhaps present in Type 1 disease [9]. Unraveling these connections may offer better preventive options to diabetic patients.
In short, data from the present study highlight the importance of early preventive interventions in Type 1 diabetes. As correctly pointed out by the authors, we require prospective studies to assess the long-term clinical significance of their findings. Furthermore, better identification of those at higher risk, perhaps through genetic markers, may provide more effective intervention strategies for the future. In the meantime, in addition to glucose control, smoking cessation [10] and hypertension control are two interventions that appear to offer much to the Type 1 diabetic patient.

References
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Summary and Comment:
Maria Inκs Schmidt, Porto Alegre, Brazil