Precursors of diabetes - not everyone has the same risk for cardiovascular disease

People with impaired blood sugar metabolism who have pre-diabetes (= prediabetes) have an increased risk of type 2 diabetes, cardiovascular disease, dementia, and cancer. But their individual risk for these diseases differs significantly. New analyzes show that the study of fatty liver, increased abdominal fat and disruption of insulin production and effects can help predict and prevent the risk of cardiovascular disease and type 2 diabetes. These findings were published by DZD scientists in the prestigious journal The Lancet Diabetes & Endocrinology.

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

Precursors of diabetes. Image: Syda Productions - fotolia

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 clinical practice it is difficult to distinguish these mechanisms - which would be very helpful for the personalized prevention and treatment of diabetes. For example, only the fasting blood sugar may be elevated or it may happen that the sugar metabolism derails within a few hours after ingestion. In other patients, both phenomena can be observed. Based on the appearances different "risk phenotypes" can be distinguished.

Phenotypes determine cardiovascular risk
In an analysis of 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 - as measured by magnetic resonance imaging (MRI) - and a disruption of production and effect of insulin crucial for diabetes risk. The three risk phenotypes of fatty liver and a disruption of insulin production and effect also predicted how successful a lifestyle intervention was in normalizing elevated blood glucose levels in people with prediabetes. In addition, especially patients with fatty liver and increased belly fat content thickened the carotid artery and thus an increased risk of cardiovascular disease.

Phenotypes of prediabetes
Based on the increasing awareness of the various metabolic phenotypes that characterize metabolically healthy obese people and those with normal metabolism, scientists have established the prevalence of the four risk phenotypes among the different BMI categories (normal weight, obesity, obesity) People with normal blood sugar levels and in people with prediabetes studied. 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, and the incidence of fatty liver and increased levels of abdominal fat in overweight and obese people increases significantly.

Conclusions for prevention and therapy
Norbert Stefan, first author of the paper, suggests that "after classifying the categories normal glucose metabolism and prediabetes, the fatty liver, the increased belly fat content and a disturbance of production and effect of insulin in the assessment of the risk for cardiovascular disease and type 2 Diabetes should be considered. If this approach turns out to be promising, then it could become part of the medical guidelines for the prevention and treatment of diabetes and the associated diseases. "Hans-Ulrich Haring, the final author of the paper, adds that" the application of precise phenotyping strategies to improve understanding of the development of cardiovascular disease and type 2 diabetes in clinical trials. "

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