Diabetes

diabetes mellitus is a chronic metabolic disease of impaired glucose regulation, defined by persistent hyperglycemia arising from defects in insulin secretion, insulin action, or both. Diagnosis rests on threshold values of fasting or post-load glucose or of glycated hemoglobin (HbA1c), the same measure used to judge control thereafter. In type 1 diabetes, autoimmune destruction of pancreatic β-cells produces absolute insulin deficiency and an absolute requirement for replacement; type 2 diabetes, which accounts for the large majority of cases, combines insulin resistance with progressive β-cell failure, so hyperglycemia appears only once secretion can no longer compensate. Other forms include gestational diabetes, monogenic diabetes of the young, and diabetes secondary to pancreatic disease or drugs. Hypoglycemia is largely a hazard of treatment rather than of the disease, which is why regimens that raise insulin levels independently of glucose demand more monitoring than those that do not.

The disease matters clinically because of what sustained hyperglycemia does to vessels and nerves. Microvascular complications — diabetic nephropathy, diabetic retinopathy and neuropathy — arise from small-vessel and neural injury, while macrovascular disease brings coronary artery disease, myocardial infarction, stroke and peripheral artery disease. Diabetic foot ulceration sits at the junction of the two, following from neuropathy that removes protective sensation together with impaired perfusion, and is the leading cause of non-traumatic amputation. Diabetes also affects pregnancy outcomes, bone healing, liver and kidney function, and quality of life.

Management combines glycemic control with organ protection, and the two aims no longer coincide automatically. The biguanide metformin remains the usual first agent in type 2 disease, but sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists are now chosen for demonstrated cardiovascular and renal benefit that exceeds what their glucose lowering alone would predict, which has shifted treatment selection from a purely glucose-centered logic toward the complications being prevented.