Brive1987 wrote: ↑
After reading up I tried to summarise IR and eventual T2D into Brive-speak. Less technical but is it accurate?
So insulin normally tells cells to ‘open’ and accept necessary energy/cell fuel from blood glucose.
But, the onset of insulin resistance makes the cells resistant to insulin’s efforts and they don’t accept enough glucose. This then requires higher insulin doses to achieve a partial brute-force outcome. This dynamic in turn raises insulin levels and keeps resting or fasting blood sugar high with more glucose getting stored as fat rather than expended as energy. The cells, however, think they are starving and demand more food - you eat and the cycle repeats.
Eventually the brute force secretion of excess insulin wears the pancreas out. Insulin production fails and you are fucked with T2D.
Yes, insulin is required to allow glucose in the blood enter cells. Resistance simply means you need more insulin to have the same effect. As resistance develops, more insulin is needed, while at the same time the higher glucose levels are slowly killing off the pancreatic cells that make insulin. We know insulin resistance is heritable, and that it is expressed when one becomes overweight; you can come from a family of Type 2 diabetics and avoid it by staying thin and exercising a lot. It's obvious from the mechanism above that type 2 DM is a condition that progresses (diet-control, then diet + metformin, then diet + metformin + sulfonylurea, then diet + insulin), but the important thing to understand is that good control slows the progression as you keep your beta cells alive for longer if they aren't exposed to high blood sugars. Making the effort to do it right when the disease is mild is therefore very important, as it will do you more good in the long run than being obsessional about it at a later stage.
Metformin is interesting, as it has several mechanisms of action, and they aren't well understood. It does not squeeze out extra insulin from the pancreas (like sulfonylureas and their descendants) so it rarely causes hypoglycemia when used alone. The main effect seems to be on the liver's control of the short term storage and dispensation of glucose. Glucose is stored as glycogen in the liver, as a ready-use locker - a few molecules can be snipped off the chain and secreted into the blood when needed to keep the blood sugar at adequate levels when exercising or between meals. This is called gluconeogenesis. Metformin was felt to increase uptake of sugar into the liver, and to slow it's release later on. If, through insulin resistance, you have higher blood sugars the flip side of the coin is that sugar is stuff that ought to be intracellular. So the cells are short on glucose for energy and they don't like it. They signal the liver to release more glucose, raising the blood sugar but not doing them much good because that sugar still can't enter the cells. Type 2 diabetics have a lot more gluconeogenesis going on than non-diabetics as a result, and metformin interferes with this. It is also felt to interfere with the signalling by inhibiting production of glucagon, a hormone that raises blood glucose, and to reverse the insulin-insensitivity of some tissues to a small degree. An old, cheap, safe drug (more so than phenformin, which I'm old enough to remember). Should be in the water supply of fat western countries.