- A healthy kidney cannot excrete large quantities of either glucose or ketones without creating serious dehydration. In a real sense, this sets up the whole diabetic problem resulting from overfeeding.
- In biochemistry, “push-back” reactions become noticeable at a “threshold,” and get stronger the more the threshold is exceeded.
- The push-back reactions may be traceable to fundamental changes in gene expression such as the re-programming of cells to deal with a chronic stress/inflammation response.
- This re-programming of gene expression may be traceable to an infection or a trauma, coupled with chronically insufficient nutrition, which weakens defenses and repair mechanisms.
- The first tie-in with obesity is insufficient whole-foods nutrition (essential and V3 nutrients), which contributes to chronic over-feeding by many different mechanisms, including improper regulation of appetite, too rapid a gastic emptying, a reduced feeling of satiety with each and every meal, poor coping with emotional stressors, a background, unquenchable chronic hunger signal from insufficient nutrition, a secondary hunger signal from partial dehydration and ignored or blunted thirst signals, food cravings traceable in part to certain missing nutrients (e.g. a sugar craving from serious antioxidant deficiency – the brain trying to coax us to eat a sweet fruit: in vain, given man-made much sweeter treats).
- Skeletal muscle can take up only so much glucose because it can store only so much glycogen and only so much fat. It pushes back on the process of forced glucose uptake. Forcing glucose into muscle results in glycolysis and lactate excretion. The liver converts the lactate to glucose. Futile cycle.
- As we age, we lose skeletal muscle and thus the muscles lose even more capacity to take up glucose.
- The brain’s uptake of glucose is more or less constant.
- Adipose tissues are the main reservoir for excess glucose. Adipose tissues store fat until a “personal threshold” that defines “personal obesity” is reached. Mechanistically, this is some kind of push back that begins at the threshold and gets stronger as it is exceeded. This is a second tie-in between diabetes and obesity.
- This personal obesity threshold is highly variable from person to person, and may bear little resemblance to the single criterion that doctors have defined as obesity.
- Beyond that point of push back, adipose tissues more aggressively hydrolyze fats, producing free fatty acids, greatly increasing the circulating level of these.
- Some of the excess free fatty acids from adipose tissue are then taken up by the liver and converted into fat. In this way, the appearance of fatty liver defines the personal threshold, the point of first “glucose refusal” in fat cells.
- As more fat accumulates in the liver, its rejection of fatty acids increases, even as fatty liver slowly degenerates to steatohepatitis, to ever increasing fibrosis, and then to cirrhosis (if the person lives long enough).
- The stressed and inflamed liver is one source of chronic stress/inflammation that may either initiate or augment the chronic stress/inflammation response that characterizes most cases of type 2 diabetes: chronic gluconeogenesis, lipolysis in fat cells, “insulin resistance,” and others.
- At the point at which fat cells are first “refusing” to make and store more fat, and are over-producing free fatty acids from their available fat stores, releasing glycerol into the circulation (which the liver also converts to glucose), the circulating glucose and fat (as free fatty acids and triglycerides) are essentially orphaned. They have nowhere good to go, as they cannot be efficiently excreted, as long as regular feeding and current levels of physical activity continue. They just keep circulating.
- Dosing with insulin temporarily forces glucose uptake into insulin-dependent cells, which is then mostly glycolytically processed, and the products remade into glucose. An obviously futile cycle.
- Any attempt to turn the cellular glucose into fat is met by increasing push back in both fat cells and the liver. An obviously futile cycle ensues.
Note: This model may also apply to some skinny diabetics if they have a defective setting of their “personal threshold” of obesity.
The big question: What are the reactions in adipose and liver cells that establish a “refusal” to store more fat – and thus the refusals to take up more glucose by fat cells and more fatty acids by liver? These are the refusals that ultimately orphan both glucose and fats. One thing is certain: There are no causes (controlling events) anywhere in the process. There are multiple points of regulation/dysregulation and wholesale changes in gene expression.