Not everyone who is noticed at some time or other for having high blood glucose or HbA1C levels, or who is very overweight, will go on to develop type 2 diabetes. With a new classification in six clusters, an attempt is now being made to better assess the individual risk.
According to the previous definition, prediabetes is present when there is a pathological oral glucose tolerance test (2-h value 140-199 mg/dl), an elevated fasting blood sugar (100-126 mg/dl) or an HbA1C value between 5.7 and 6.4 %. The annual conversion rate to manifest type 2 diabetes is 5-10 % and even with a prediabetic metabolic state, prediabetic secondary diseases can already develop. Until now, however, there have been no parameters with which the individual prognosis can be better predicted.
In order to achieve a better assessment, Robert Wagner from the University of Tübingen (Universität Tübingen) and his working group used the results of the TUEF/TULIP study (Tübingen Family Study/Tübingen Lifestyle Intervention Programme). In this study, 899 people have been followed up since 2003 who have an increased risk of diabetes due to conspicuous blood glucose values, a positive family history, an increased BMI or a history of gestational diabetes. All participants had undergone an oral glucose load test, MRI-based determination of body fat and proton MR spectroscopy for liver fat content at baseline.
These people are overweight but have average insulin sensitivity and adequate insulin secretion. Glucose tolerance is normal.
These individuals are of normal weight and have normal glucose metabolism with good insulin sensitivity.
These people are overweight to obese, with moderately reduced insulin sensitivity and already reduced insulin secretion and pre-diabetic metabolic status. In addition, there is an increased genetic risk for type 2 diabetes. There is a threefold increased risk of type 2 diabetes (compared to cluster 1) and a significantly increased cardiovascular risk.
There is (predominantly subcutaneous) obesity - with good insulin sensitivity, adequate insulin secretion and normal glucose tolerance. This is also referred to as "metabolically healthy obesity".
These patients are not only obese, but their liver fat is also highly elevated. They have an insulin-resistant fatty liver, reduced insulin secretion and prediabetes. The risk of manifest diabetes is increased by a factor of 5 and there is a high cardiovascular risk.
These patients are also obese with a high proportion of visceral fat. Increased renal hilum fat is conspicuous. There is insulin resistance, still normal insulin secretion and normal glucose tolerance. The risk for manifest type 2 diabetes is comparatively low - but the patients have a significantly increased risk for diabetic nephropathy even before the manifestation of type 2 diabetes.
The classification of the clusters could be confirmed in the 6,810 participants of the British Whitehall 2 cohort with an observation period of more than 16 years.
Belonging to the different clusters could also have an impact on the choice of preventive measures in the future. For people with subtype 3, endurance exercise and calorie reduction to reduce visceral adipose tissue would possibly prevent the manifestation of type 2 diabetes - for subtype 5, intensified diet and lifestyle intervention is indicated. In people with subtype 6, early therapy might be indicated even if blood glucose levels are still normal.
Reference:
Wagner, R et al; Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes.