New classification of prediabetes

Not every person who at some point has an elevated blood sugar or HbA1C level or is very overweight will later develop type 2 diabetes. With a new classification into six clusters, an attempt is now being made to better assess the individual risk.

Three out of six clusters are associated with a significantly increased risk

Not every person who at some point has an elevated blood sugar or HbA1C level or is very overweight will later develop type 2 diabetes. With a new classification into six clusters, an attempt is now being made to better assess the individual risk.

According to the previous definition, prediabetes is a pathological oral glucose tolerance test (2-hour value 140–199 mg / dl), increased fasting blood sugar (100–126 mg / dl) or an HbA1C value between 5.7 and 6.4 % in front. The annual conversion rate to manifest type 2 diabetes is 5–10%, and prediabetic complications can develop even if the metabolism is prediabetic. So far, however, there have been no parameters with which the individual prognosis can be better predicted.

In order to achieve a better assessment here, Robert Wagner from the University of Tübingen and his working group used the results of the TUEF / TULIP study (Tübingen Family Study / Tübingen Lifestyle Intervention Program). Since 2003, this study has tracked 899 people who have an increased risk of diabetes due to abnormal blood sugar levels, a positive family history, an increased BMI or a history of gestational diabetes. All participants had an oral glucose load test, an MRI-based determination of body fat and proton MR spectroscopy of the fat content of the liver.

In the cluster analysis, six clusters could then be identified, of which three subtypes (3, 5 and 6) are associated with an increased risk.

Cluster 1: Low risk:

Although these people are overweight, they have average insulin sensitivity and adequate insulin secretion. Glucose tolerance is normal.

Cluster 2: Very low risk

These people are of normal weight and have normal glucose metabolism with good insulin sensitivity.

Cluster 3: High risk

These people are overweight to obese, with moderately reduced insulin sensitivity and already reduced insulin secretion and a prediabetic metabolic situation. There is also an increased genetic risk for type 2 diabetes. There is (compared to cluster 1) a three-fold increased risk of type 2 diabetes and a significantly increased cardiovascular risk.

Cluster 4: Low Risk

The patient is (predominantly subcutaneous) obesity – with good insulin sensitivity, adequate insulin secretion and normal glucose tolerance. One also speaks of “metabolically healthy obesity”.

Cluster 5: Very high risk

These patients are not only obese, the liver fat is also greatly increased. There is an insulin-resistant fatty liver, decreased insulin secretion and prediabetes. The risk of manifest diabetes is increased by a factor of 5 and there is a high cardiovascular risk.

Cluster 6: High risk

These patients are also obese with a high percentage of visceral fat. Increased kidney hilum fat is noticeable. There is insulin resistance, normal insulin secretion and normal glucose tolerance. The risk of manifest type 2 diabetes is comparatively low – but the patients have a significantly higher risk of diabetic nephropathy even before the onset of type 2 diabetes.

The classification of the clusters was confirmed for the 6,810 participants of the British Whitehall 2 cohort with an observation period of more than 16 years.

Belonging to the various clusters could also have an impact on the choice of preventive measures in the future. In people with subtype 3, endurance exercise and a reduction in calories to break down visceral adipose tissue might prevent the manifestation of type 2 diabetes – in subtype 5, intensified diet and lifestyle intervention is indicated. In people with subtype 6, early therapy could be indicated even if blood sugar levels are still normal.

Those:
Wagner, R et al; Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes



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