Insulin, Cardiovascular Function and Long-Term Diabetic Complications
Pp. 81-113 (33)
Niels Juel Christensen
Patients with long-term diabetes develop angiopathy and neuropathy.
Macroangiopathy refers to myocardial infarction, strokes and ischemic gangrene.
Retinopathy and nephropathy are due to microangiopathy. The development of late
diabetic complications is often assumed to be due to hyperglycemia and production of
reactive oxygen species (ROS) in mitochondria. Despite regulation of blood glucose
and blood pressure many patients still die of diabetic angiopathy. Intensive blood
glucose control did reduce the risk for retinopathy and neuropathy, but had no
significant effect on clinical renal outcomes. Blood pressure lowering in type 2 diabetic
patients leads to a significant reduction in albuminuria, whereas improvement in renal
failure was not significant. Newer therapies are therefore of vital importance. Diabetes
is caused by insulin deficiency. Insulin treatment may induce insulin resistance and
increase body weight. The appearance in plasma after injection is delayed, and patients
may have relative high insulin values during the day. Insulin has a number of specific
effects on the cardiovascular system and the kidney. This review focuses on insulin’s
effects on capillary permeability in muscle endothelial cells and in podocytes in the
kidney. Insulin deficiency and resistance rather than hyperglycemia may be directly
responsible for lack of capillary recruitment in muscles and abnormal function of
podocytes in the glomerulus in the kidney. It is concluded, that it is unlikely that longterm
complications can be eliminated without development of a more physiologic
insulin delivery system or alternatively with development of drugs that temporarily can
activate specific insulin signaling pathways in the cells.
Bariatric surgery, Bilirubin, Blood flow, Calorie restriction,
Capillary recruitment, Cardiovascular disease, Diabetic macroangiopathy, Diabetic microangiopathy, Gangrene, Hyperglycemia, Hypotension, Insulin, Insulin
resistance, Insulin treatment, MSNA, Nephropathy, Neuropathy, NO, Obesity, Plasma
volume, Prevention, Retinopathy, ROS, Sympathetic activity, TER, Tissue recruitment,
Urinary albumin excretion.