PhD ceremony Mr. N. Li: Novel mechanisms for prevention and treatment of type 2 diabetes

PhD ceremony: Mr. N. Li

Dissertation: Novel mechanisms for prevention and treatment of type 2 diabetes

Promotor(s): prof. M. Hofker, prof. C. Wijmenga

Faculty: Medical Sciences

Type 2 diabetes(T2D) has become one of the most common chronic diseases worldwide in the past 20-30 years. Although the discovery of insulin was an epoch-making achievement in the history of treating diabetes, we still face problems that insulin and treatments to improving insulin signaling cannot solve. The focus of this thesis is mechanisms for preventing and treating T2D. 50 putative genes associated with T2D were reviewed and classified based on current knowledge of their presumed molecular functions; these genes, mainly discovered by recent genome-wide association studies, will be potential targets for anti-diabetic drugs in the future. We also discussed whether hypertriglyceridemia and low-HDL cholesterol can be causal factors in the development of insulin resistance. If this is true, we could prevent T2D by intervening in the hypertriglyceridemia and low-HDL cholesterol. Furthermore, we tested association of 95 lipid loci collectively and individually with glucose-related traits in two independent cohorts (LifeLines, 10,995 subjects and PREVEND, 2,438 subjects). And there are other, new, problems arising as side-effects from the use of insulin, which also need to be treated. We introduced an improved regimen for treating insulin allergy, which indicates novel mechanism of T2D related to immune tolerance. Anti-insulin antibody induced dysglycemia was also described, and we suggest a new classification for insulin-related-antibody-induced dysglycemia based on the pathophysiological mechanisms involved. There is still much to do before T2D is defeated and we have shown that the current genetics approaches are excellent for the urgently needed insight into the mechanisms.