Insulin Clearance in the Liver May Predict Metabolic Syndrome Risk

Metabolic syndrome is characterized by obesity, high blood pressure, disturbed lipid metabolism and insulin resistance of body cells. People who suffer from this lethal quartet are at greater risk for developing diabetes, cardiovascular diseases and specific cancer diseases. As scientists in the research group of Natalia Rudovich and Andreas F. H. Pfeiffer of the German Institute for Human Nutrition, a partner in the DZD, show in a current study, the rate at which the liver clears insulin may predict the risk for metabolic syndrome at a very early stage – independently of other factors. The researchers have now published their results in the journal Diabetes Care*.

To learn more about the metabolic processes that underlie the metabolic syndrome and its most important health complication, type 2 diabetes, the Potsdam scientists conducted a large population-based study ** in the Berlin/Potsdam region. The researchers examined the insulin sensitivity of body cells, the rate of insulin clearance in the liver and the insulin secretion of the subjects.
In addition, they collected data on the age, gender, waist circumference, blood pressure, blood glucose level and lipid metabolism.
Consistent with previous studies, the study results show that decreased insulin clearance in the liver is closely associated with various components of the metabolic syndrome, such as insulin secretion. As the Potsdam researchers also show, decreased insulin clearance in the liver – independent of excess weight and age of the subjects – is a very early indication of incipient metabolic syndrome and impaired glucose metabolism.
"In the future, an insulin clearance test may be indicated to identify high-risk individuals very early on, prior to the onset of type 2 diabetes", said Natalia Rudovich, who led the scientific study. "Targeted preventive and therapeutic measures could then be initiated before the disease becomes manifest."
"The metabolic data we collected also give us insight into the mechanisms that are involved in the pathogenesis of type 2 diabetes," Professor Pfeiffer added. "As we observed in our study, the greater the insulin secretion, the less insulin is degraded by the liver. This suggests that insulin secretion directly regulates insulin degradation and that high insulin secretion causes the insulin level in the liver to increase even more through an inhibition of the insulin degradation. Such a mechanism could explain, for example, why a high consumption of sugary drinks, which is associated with a strong release of insulin, favors the development of non-alcoholic fatty liver disease and thus type 2 diabetes. Among other things, insulin stimulates lipid synthesis in the liver."

Background information:
*Pivovarova, O., Wolfgang Bernigau et al.; Diabetes Care 36:1–7, 2013; doi: 10.2337/dc12-1203

Type 2 diabetes (formerly known as adult-onset diabetes) is characterized not only by high blood glucose levels, but also by insulin resistance of the cells of the body, elevated insulin levels in the blood and decreased insulin clearance in the liver. Type 2 diabetes develops slowly over years, whereas damage to the vascular system and the eyes can occur already at an early stage of the disease. Serious health complications are cardiovascular disease, blindness or kidney failure.

**The trial participants were recruited from the Metabolic Syndrome Berlin-Potsdam Study (MESYBEPO), in which 2,500 residents of Berlin and Potsdam participated. At the beginning of the study, 325 of the 800 recruited study participants showed a metabolic syndrome but had not yet developed diabetes. After an average follow-up observation period of five years the researchers examined 189 of the study participants once again. Of these, 47 participants developed a metabolic syndrome for the first time during the follow-up observation period, whereas 33 of the trial participants developed a disorder of the glucose metabolism for the first time.