Hypothalamic astrocytes that produce Fatty Acid Binding Protein 7 (FABP7) are targets of FGF1; these cells are also in close contact with leptin-sensitive neurons, influence their function, and regulate leptin sensitivity. An abnormal function of FABP7+ astrocytes thus may contribute to the resistance to leptin and insulin that appear during aging and during exposure to high-fat diets. During aging, FABP7+ astrocytes develop cytoplasmic granules derived from degenerating mitochondria. This mitochondrial degeneration is partly due to the oxidative stress of the heightened amounts of fatty acids that are taken up by these cells and oxidized within mitochondria. A pathological degeneration of mitochondria in these cells may compromise their normal functions and contribute to abnormalities in the control of blood glucose by the hypothalamus. Diagnosis
The World Health Organization definition of diabetes (both type 1 and type 2) is for a single raised glucose reading with symptoms, otherwise raised values on two occasions, of either:
fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl)orwith a glucose tolerance test, two hours after the oral dose a plasma glucose ≥ 11.1 mmol/l (200 mg/dl)A random blood sugar of greater than 11.1 mmol/l (200 mg/dl) in association with typical symptoms or a glycated hemoglobin (HbA1c) of ≥ 48 mmol/mol (≥ 6.5 DCCT %) is another method of diagnosing diabetes.
In the liver, insulin normally suppresses glucose release. However, in the setting of insulin resistance, the liver inappropriately releases glucose into the blood. The proportion of insulin resistance versus beta cell dysfunction differs among individuals, with some having primarily insulin resistance and only a minor defect in insulin secretion and others with slight insulin resistance and primarily a lack of insulin secretion.Other potentially important mechanisms associated with type 2 diabetes and insulin resistance include: increased breakdown of lipids within fat cells, resistance to and lack of incretin, high glucagon levels in the blood, increased retention of salt and water by the kidneys, and inappropriate regulation of metabolism by the central nervous system. However, not all people with insulin resistance develop diabetes since an impairment of insulin secretion by pancreatic beta cells is also required.In the early stages of insulin resistance, the mass of beta cells expands, increasing the output of insulin to compensate for the insulin insensitivity. But when type 2 diabetes has become manifest, a type 2 diabetic will have lost about half of their beta cells.Fatty acids in the beta cells activate FOXO1, resulting in apoptosis of the beta cells.The causes of the aging-related insulin resistance seen in obesity and in type 2 diabetes are uncertain. Effects of intracellular lipid metabolism and ATP production in liver and muscle cells may contribute to insulin resistance. New evidence also points to a role of a brain region called the hypothalamus in the development of insulin resistance.