Every day a great number of people are getting the news — they have prediabetes. Some 88 million adults in the United States have it, according to the U.S. Centers for Disease Control (CDC), and the vast majority of them don’t know it.
And yet not all of these people are the same, according to a new report from Germany. In fact, the authors say, there are no fewer than six distinct subtypes of prediabetes, and knowing which one a patient has can help medical personnel formulate the best therapy for that person. The study was done by scientists at the Institute for Diabetes Research and Metabolic Diseases of Heimholtz Zentrum München at the University of Tübingen, Tübingen University Hospital, and the German Center for Diabetes Research (DZD) and was published in the journal Nature Medicine.
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According to study author Hans-Ulrich Häring, MD, who began investigating prediabetes 25 years ago, “For people with prediabetes it has not been possible until now to predict whether they would develop diabetes and be at risk for serious complications such as kidney failure or whether they would only have a harmless form with slightly higher blood glucose levels but without significant risk.”
Six types of prediabetes
Over the course of a quarter century, the researchers conducted extensive examinations of 899 people who took part in initiatives called the Tübingen Family Study and the Tübingen Lifestyle Program. The subjects were frequently given various type of clinical examinations, such as lab tests, magnetic resonance imaging (MRIs) and genetic analysis. The researchers also scrutinized such variables as blood sugar levels, body fat and body fat distribution, liver fat, blood lipid levels (especially cholesterol and triglycerides), and genetic factors. The variations that the researchers discovered in the subjects led them to conclude that there was not just one type of prediabetes, but six. According to lead author Robert Wagner, MD, “As in manifest diabetes, there are also different disease types in the preliminary stage of diabetes, which differ in blood glucose levels, insulin action and insulin secretion, body fat distribution, liver fat and genetic risk.”
Different risk levels
The researchers divided the subjects into six groups, or clusters. Cluster 5 was identified as the population at highest risk of type 2 diabetes. These were people who were obese, showed insulin resistance, and had high levels of fatty liver and low insulin secretion. Subjects in cluster 6 represented what the researchers called “an insulin resistant phenotype”— that is, they were people whose body cells don’t respond well to insulin. Their blood sugar levels, however, were lower than those in cluster 5 and “their risk of type 2 diabetes was considered to be moderate,” although the researchers found that with them kidney damage occurred even before their diabetes was diagnosed. Subjects in cluster 3, a group that also showed high rates of diabetes, were found to have “elevated genetic risk” along with “low insulin secretion.” The clusters at lowest risk were 1, 2 and 4. Both 1 and 2 consisted of healthy people, but those in cluster 2 were “slim,” and had “a particularly low risk of developing complications.” Cluster 4 was comprised of people who were overweight, but because their metabolism “is still relatively healthy,” their risk was low.
To test whether their six-cluster classification would apply to another group of patients, the researchers widened their analysis to include some 7,000 subjects included in a British study of the health of middle-aged civil servants known as the Whitehall 11 Study. They found the six clusters to be still identifiable.
The researchers cautioned that their approach was not designed to provide definite subtypes for heathcare providers to use in a clinical setting, but they said that the results suggestion “some potential therapeutic implications.” For example, a person identified as being in cluster 5 would benefit from high-intensity lifestyle and dietary interventions, while another in cluster 3 “might benefit from a standard aerobic exercise and dietary caloric restriction via reduction of visceral fat.” The researchers plan next to find out “to what extent the new findings are applicable for the classification of individual persons into high-risk groups.” This could give healthcare providers much more specific guidelines and practices on how best to help their patients with prediabetes.