[New findings on the pathogenesis of diabetes mellitus]

Diabetes mellitus is a heterogeneous syndrome. Insulin-dependent type 1 diabetes is characterized by progressive deterioration of B-cells in the islets of Langerhans resulting in a fall in insulin secretion. According to recent studies, autoimmune mechanisms are the reason for the B-cell destruction. These mechanisms can be triggered by viral infections which result in expression of HLA-DR antigens in macrophages and possibly in B-cells of the islets. B-cells are destroyed by cytotoxic T-lymphocytes; plasma cells form islet cell antibodies. The autoimmune process probably starts months to years before clinical manifestation of the disease. A viral infection immediately before clinical manifestation may reactivate the autoimmune process and lead to overt diabetes. T-lymphocytes reject pancreatic B-cells in type 1 diabetics throughout life. Pilot studies using cyclosporin as immunosuppressive agent in newly diagnosed type 1 diabetics have demonstrated that after discontinuation of this treatment diabetics again became insulin-dependent. Type 2 diabetics are usually elderly and non-insulin-dependent; there is a predominant defect in insulin action on peripheral tissues but also a concomitant impairment of B-cell secretion. Fasting plasma insulin levels are normal or increased; fasting C-peptide concentrations may be used to distinguish this type of diabetes from type 1 diabetes. Plasma fasting C-peptide concentrations less than 300 pmol/l usually indicate type 1 diabetes and levels above 300 pmol/l type 2 diabetes. Classification of diabetics according to pathogenesis is important, since different therapeutic and preventive measures are necessary.