Dendritic cells and macrophages in insulin dependent diabetes mellitus

The onset of diabetes mellitus is characterized by various symptoms, all the result of a disturbed glucose metabolism. The main symptoms are thirst and polydypsia, polyuria, glucosuria, and weight loss. The faster the onset of diabetes, the more prominent these symptoms will be. The disturbed glucose metabolism underlying these symptoms, is due to an absolute deficiency of insulin secretion, a reduction in its biologic effectiveness or both. Diabetes mellitus is nowadays classified in two major types: Type 1, or insulin-dependent diabetes mellitus (100M), occurs most commonly in juveniles. It is a catabolic disorder in which circulating insulin is virtually absent, since the pancreatic p-cells, due to their absence, cannot respond to any insulinogenic stimulus. Administration of exogenous insulin is therefore required to reverse the catabolic state, to prevent ketosis and to bring the elevated blood glucose level down. Type 2, or non-insulin·dependent diabetes mellitus (NIDDM). represents a group of milder forms of diabetes that occur predominantly in adults. Circulating endogenous insulin is almost always sufficient to prevent ketoacidosis, but is often either subnormal or relatively inadequate in the face of the increased needs owing to tissue insensitivity. The longer diabetes mellitus exists, the greater the chance of developing the characteristic complications: micro- and macroangiopathy, and neuropathy. Microangiopathy may cause retinopathy and nephropathy, while macroangiopathy gives rise to an elevated incidence of coronary heart disease, cerebro-vascular accidents, and ischemic complications in the legs. The quality of life of diabetic patients can be profoundly reduced by these complications, while also the life-expectancy is considerably shorter for diabetic patients. Therefore, prevention of late complications, and prevention of the disease itself, are major goals in diabetes research. Prevention of the disease can only be expected if the mechanisms leading to the disease will be better understood. Though some studies have indicated that some type 2 patients show characteristics of type 1 disease, and that the boundaries between type 1 and type 2 diabetes might be not as absolute, it is nevertheless generally assumed that the mechanisms leading to either type 1 or type 2 diabetes are different. This thesis considers aspects of the mechanism leading to IDDM or type 1 diabetes mellitus.

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