Insulin resistance lets blood sugar look normal while the pancreas works overtime
Insulin resistance means the body's cells stop answering insulin's signal to pull sugar out of the blood. For a while the pancreas compensates by pumping out more, keeping glucose normal. When that extra effort finally falters, blood sugar climbs, and the result is often type 2 diabetes, of which this resistance is a major cause.
Normally, rising blood glucose prompts beta cells in the pancreatic islets of Langerhans to release insulin. Skeletal muscle, fat and the liver respond by taking up sugar, and as levels drop the beta cells ease off, so glucose settles around 5 mmol/L, or 90 mg/dL. In a resistant body the same dose of insulin moves less sugar. Muscle is thought to matter most, and the liver, which should throttle back its own glucose output when insulin is present, may keep releasing it.
The pancreas answers by producing extra insulin, a state called hyperinsulinemia, and during this compensated phase blood sugar can stay normal. If the beta cells cannot keep up, fasting or after-meal glucose begins to rise, and eventually type 2 diabetes sets in. Fat tissue adds a vicious twist: resistant fat cells leak more free fatty acids into the blood, which deepens the resistance, yet fat cells tend to stay sensitive to insulin's storage signal, so the surplus hormone encourages new fat and faster weight gain. The condition often clusters with belly fat, high blood pressure, high triglycerides and low HDL cholesterol, and resistance in brain cells has been implicated in neurodegenerative disease.
Obesity, inactivity and a family history of diabetes top the risk list, along with polycystic ovary syndrome and fatty liver disease; people with hepatitis C face three to four times the usual odds. Epidemiological studies link more than 90 minutes of daily activity with a 28% lower diabetes risk. Short sleep can cause resistance, and sensitivity naturally runs higher in the morning than the evening, so meals out of step with the body clock may worsen it. Corticosteroids, SSRIs, some HIV drugs and atypical antipsychotics are implicated, and cortisol blunts insulin by reducing how many GLUT4 glucose transporters reach the cell surface. Diet surely plays a part, but nutrition research struggles to pin down which foods are responsible.
Puzzles remain. Insulin sensitivity improves sharply after bariatric surgery, and in rats whose duodenum is removed, prompting speculation about an undiscovered gut signal that tells cells to resist; nobody has found it. Known genetic variants, near genes such as NAT2 and GCKR, explain only 25–44% of the inherited component. The most rigorous measurement methods, such as the hyperinsulinemic euglycemic clamp, are seldom used in everyday clinics.
Source: Insulin resistance
