The epidemiological attempt to study the natural history and pathogenesis of diabetes as a whole can only rely on one common and stable factor, high blood glucose, despite the wide variation in clinical manifestations and various contributing factors. However, high blood glucose alone does not answer all the questions. Over the past 30 years, evidence has accumulated that numerous and etiologically different mechanisms (genetic, environmental or immunologic processes) may play an important role in the pathogenesis, the clinical course and the emergence of complications of the 'diabetic state' (9,14). Does correction of hyperglycemia prevent all of the various pathologic changes observed with diabetes? There is some evidence that people with diabetes who are not treated develop more complications than well-controlled patients (9,15,16). However, there are few instances in which characteristic complications of diabetes have been described before hyper-glycemia was observed. This indicates the vast heterogeneity of diabetes and illustrates the fact that it is not yet clear to what extent the long-term classical diabetic complications are the result of hyperglycemia, the generally accepted and fundamental factor for diabetes, or related factors such as, for instance, insulin deficiency, plasma or tissues osmolality changes, glycated proteins and lipid abnormalities. Despite these questions, hyperglycemia remains the most important factor required for the diagnosis of diabetes.
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