Precursors of diabetes - not everyone carries the same risk of cardiovascular disease

Precursors of diabetes - not everyone carries the same risk of cardiovascular disease

People with a disturbed blood sugar metabolism who have an early stage of diabetes (= prediabetes) are at increased risk for type 2 diabetes, cardiovascular diseases, dementia and cancer. But their individual risk for these diseases differs significantly. New analyzes show that testing for fatty liver, increased belly fat, and disruption in the production and effects of insulin can help to better predict and prevent the risk of cardiovascular diseases and type 2 diabetes. These results were published by DZD scientists in the renowned journal The Lancet Diabetes & Endocrinology.

Diabetes and its precursors have reached epidemic proportions worldwide. What is worrying is the fact that high blood sugar is associated with an increased risk of type 2 diabetes, cardiovascular disease, dementia and cancer, even in prediabetes. But even at the prediabetes stage, the risk of these diseases differs significantly between people. Scientists from the Department of Internal Medicine IV at the University Hospital in Tübingen and the Institute for Diabetes Research and Metabolic Diseases (IDM) at the Helmholtz Zentrum München, partner of the German Center for Diabetes Research (DZD), took this finding as an opportunity to investigate the factors behind these differences in the risk of disease could explain.

Type 2 diabetes is not the same as type 2 diabetes
Several mechanisms play a role in the development of type 2 diabetes. But in everyday clinical practice it is difficult to distinguish between these mechanisms - which would be very helpful for the personalized prevention and therapy of diabetes. For example, only fasting blood sugar may be increased or the sugar metabolism may derail within a few hours after eating. Both phenomena can be observed in other patients. Different "risk phenotypes" can be distinguished on the basis of their appearances.

Phenotypes determine the cardiovascular risk
In an analysis of the data from 1,003 participants in the Tübingen diabetes family study, in which 405 people had prediabetes, the four risk phenotypes were fatty liver, increased abdominal fat - measured using magnetic resonance imaging (MRI) - and a disruption in production and the effect of insulin on the risk of diabetes. The three risk phenotypes, fatty liver and a disturbance in the production and effects of insulin, also predicted how successful lifestyle intervention for normalizing elevated blood sugar levels in people with prediabetes was. In addition, especially patients with fatty liver and increased abdominal fat content showed a thickening of the carotid artery and thus an increased risk of cardiovascular diseases.

Phenotypes of prediabetes
Based on the increasing knowledge of the existence of the various phenotypes of metabolism, which characterize the obese people with healthy metabolism and the normal weight people with metabolic disorders, the scientists have contributed to the frequency of the four risk phenotypes under the different BMI categories (normal weight, overweight, obesity) People with normal blood sugar levels and in people with prediabetes were examined. They were able to show that there is a different distribution of these phenotypes between the BMI categories (Figure). While e.g. an insulin production defect is by far the most common risk phenotype in normal weight people with prediabetes, the frequency of fatty liver and the increased abdominal fat content in overweight and obese people increases significantly.

Conclusions for prevention and therapy
Norbert Stefan, first author of the work, suggests that "according to the classification of the categories normal sugar metabolism and prediabetes, the fatty liver, the increased abdominal fat content and a disruption in the production and effects of insulin when assessing the risk for cardiovascular diseases and type 2 - Diabetes should be considered. If this approach turns out to be promising, it could find its way into the medical guidelines for the prevention and therapy of diabetes and the associated diseases. "Hans-Ulrich Häring, last author of the work, adds that" the use of precise phenotyping strategies clinical studies will improve understanding of the development of cardiovascular diseases and type 2 diabetes. "

Original publication:
Norbert Stefan, Andreas Fritsche, Fritz Schick, Hans-Ulrich Häring. Phenotypes of prediabetes and stratification of cardiometabolic risk. Lancet Diabetes & Endocrinology 2016 [epub ahead of print] DOI: http://dx.doi.org/10.1016/S2213-8587(16)00082-6

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