Bacterial endotoxins and type 1 diabetes

Mariann Lassenius joined Medaffcon’s Medical Affairs team in June 2016. Right before her transition to Medaffcon Mariann finalized her doctoral dissertation researching diabetes and the long-term complications related to it. Read through a short summary of her research below.

Bacterial endotoxins and type 1 diabetes

In Finland, approximately 7 % of the population has diabetes, a sixth of them type 1 diabetes (juvenile diabetes), and the incidence of the disease in Finland is the highest in the world. Both genetic and environmental factors have an effect on the disease onset of type 1 diabetes. A long disease-duration and a poor glycaemic control significantly increase the risk for co-morbidities such as diabetic nephropathy, retinopathy, and neuropathy as well as cardiovascular diseases.

Low-grade inflammation is a typical feature of many chronic diseases. Different bacteria with both beneficial and harmful influences on our body inhabit our environment. The high blood glucose levels associated with diabetes increase the risk of bacterial infections. Bacterial endotoxins/lipopolysaccharides (LPS) are components of the cell-membrane of gram-negative bacteria, causing a strong inflammatory response when interacting with our body. Following bacterial infections, the risk for kidney damage also increases.

My clinical doctoral thesis (www.finndiane.fi) demonstrated that in persons with type 1 diabetes, elevated LPS activities were connected to the progression of nephropathy, inflammation, lipid metabolism and obesity. Compared to healthy control subjects, patients were also more frequently diagnosed with adverse changes in markers associated with intestinal inflammation.

The human intestine, containing ten times the amount of bacterial cells than the number of cells in our body, is a potential source of bacterial endotoxins. Food-derived lipids have been demonstrated to increase the absorption of endotoxins from the intestine to the blood circulation. In our follow-up studies, we analysed the short-term effects of fat- and energy-rich meals on LPS activity, metabolism and inflammatory factors. Our trials did not find a significant connection between the short-term fat challenge and the LPS activity in the circulation. Compared to healthy control subjects, persons with type 1 diabetes, however, presented adverse changes in their lipid metabolism, possibly increasing the risk for cardiovascular diseases.

Clinically, the study emphasises the adverse effects of gram-negative bacterial infections contributing to the disease-process of diabetic kidney damage. Considering potential sources of bacterial infections as an integrated part of a comprehensive clinical treatment, may decrease the patients’ risk of developing long-term diabetic complications.

Mariann Lassenius, PhD

Scientific Advisor

Medaffcon Oy

+358 50 3452 393

mariann.lassenius@medaffcon.fi