That is a complex question. It is important to know that not everyone is susceptible to this disease even if they carry extra body fat mass. Several studies look for body factors which might develop into this body dysfunction. Insulin resistance is a major cause of several diseases including Type 2 Diabetes, Polycystic Ovary Disease and Metabolic Syndrome. Insulin resistance is where the normal body process of glucose transport from the blood stream into cells becomes defective. Research suggests varied complex causes. Anything that disrupts this “door” for glucose transport from the blood into the cells is suspect.
Possible causes include:
1) Changes in the microbiome of the gut producing substances could damage the glucose transport system.
2) Increased fatty acid levels in the blood stream may harm the glucose transport systems. (When we ingest high levels of energy (calories) in the form of carbohydrates the unused extra glucose is then synthesized into fatty acids in the liver and stored in our adipose tissues.)
3) Substances produced by certain cells increases inflammation. Resistin is part of a family of hormones and it is increased in both Obesity and Diabetes. As body mass index (BMI) rises so does resistin levels. Resistin is producted by several cells but when macrophages (specialized white blood cells) infiltrate and increase in number in the abdominal white adipose (fat) cells, we have increased weight gain and for many people, increased insulin resistance. The exact nature of how it effects our weight and insulin resistance is unknown.
Even though we have yet to find this exact cause of insulin resistance, we know that over several years, the resistance to the insulin becomes greater. The cells require higher levels of insulin to transport the glucose (open the door) to enter the cells. It becomes much harder to lose weight and easier to gain weight. This forms a negative feedback loop where greater amounts of body fat probably increase insulin resistance in genetically sensitive individuals. When our pancreas beta cells no longer function adequately to produce the needed insulin, we have the disease of Type 2 Diabetes.