Biochemical mechanism of diabetes prevention

The core biochemical logic of diabetes prevention is essentially to intervene in the key regulatory nodes of glucose and lipid metabolism to maintain the homeostasis of the secretory function of pancreatic islet β cells, improve the insulin sensitivity of peripheral tissues, alleviate the body's chronic low-grade inflammatory state, interrupt the vicious cycle of "metabolic overload - tissue damage - decompensation", and fundamentally reduce the risk of type 2 diabetes.

When I was doing a metabolic screening in the community last month, I met a young man who works as a game developer. He was 32 years old, normal weight, and his fasting blood sugar of 6.1mmol/L was just on the red line of impaired glucose tolerance. He was so frightened that he directly replaced all drinks with sugar-free sparkling water, ate brown rice, boiled vegetables, and only dared to eat tomatoes. As a result, the glycosylated hemoglobin increased from 5.7% to 6.0% during the follow-up test two months later. He squatted at the triage table with the report for a long time and could not recover. The pitfall he stepped on was actually the misunderstanding that most ordinary people have about diabetes prevention: they think that just eating less sugar is enough, but they don't know that metabolic regulation is an interlocking network, which affects the whole body. It is far from being covered by "quit sugar".

At present, there are two mainstream directions in the nutrition field regarding sugar control. Each has its own biochemical evidence and is suitable for different groups of people. It is impossible to say who is right and who is wrong. The core basis for supporters of a low-carb diet is that reducing carbohydrate intake directly reduces the load of gluconeogenesis in the liver, and there will be no large blood sugar fluctuations after meals. This means that pancreatic beta cells do not need to secrete insulin in frequent pulses, which is equivalent to giving the pancreatic islets a "long vacation." I myself have encountered several patients with abdominal obesity and impaired glucose tolerance. After adhering to a reasonable low-carb diet for three months, fasting insulin levels dropped by half, and insulin sensitivity returned directly to the normal range. But on the other hand, scholars who support high-fiber whole grain diets also have solid cohort data. Their logic is that there is no need to completely cut off carbohydrates. As long as refined rice noodles are replaced with low-GI whole grains and beans, dietary fiber can slow down the decomposition of carbohydrates by intestinal α-glucosidase, and the postprandial blood sugar peak can be reduced by 30%. Above, short-chain fatty acids produced by intestinal flora fermenting dietary fiber can also act on G-protein-coupled receptors in adipose tissue to reduce the release of inflammatory factors. Last year, a cohort of 100,000 people at the Peking University School of Public Health showed that people who eat more than 50g of whole grains every day can reduce the risk of diabetes by 23%. Both paths are valid, but for people with disordered lipid metabolism and high triglycerides, rashly taking the extremely low-carbon path may aggravate insulin resistance, which is not worth the gain.

What many people don’t know is that our pancreatic beta cells are actually a delicate organ, and its compensatory capacity is not unlimited. To use an inappropriate analogy, it is like an old salesman in the unit. It is okay to work overtime occasionally to meet the performance. If he is forced to work continuously every day, no matter how capable he is, he will collapse. I once met a lady who runs a milk tea shop. She tried to drink 3 or 4 cups of full-sugar milk tea formula every day. She was diagnosed with impaired glucose tolerance at the age of 30. Her fasting insulin level was twice that of normal people, indicating that the beta cells were already desperately secreting insulin to suppress blood sugar. If the burden on the beta cells was not reduced at this time, it is likely to develop into irreversible diabetes in two or three years. There are now studies that have confirmed that even occasional postprandial hyperglycemia, as long as the peak value exceeds 11.1mmol/L, will cause oxidative damage to beta cells. This damage accumulates to a certain level and cannot be reversed.

There is also a deeper mechanism, which is chronic low-grade inflammation that many people don’t take seriously. The swimming ring on your belly is not a motionless "dead fat". It is full of activated macrophages, which will continuously secrete inflammatory factors such as TNF-α and IL-6. These factors will interfere with the phosphorylation process of the insulin receptor - just like insulin is originally the key to the door, but the inflammatory factors block the keyhole. The key cannot be inserted and turned, and blood sugar cannot enter the cells to be used. This is what we often call insulin resistance. I used to have a salesman who was 175cm tall and weighed only 130kg. He looked quite thin, but his waist circumference was 96cm. His fasting blood sugar was 6.8. I told him not to rush to take medicine first, but to run for 20 minutes every day and drink less cold beer. In 3 months, his waist circumference was reduced to 88. When he checked his blood sugar, it returned directly to 5.4. This is because the inflammatory factors have dropped after the visceral fat has been reduced, the "keyhole" of insulin has been cleared, and the blood sugar has naturally stabilized.

Intermittent fasting, which has been particularly controversial recently, is also a typical controversial method. Some people say it is a magic way to prevent sugar, while others say it can damage the stomach and induce gastric diseases. From a biochemical mechanism, intermittent fasting can indeed activate the AMPK pathway, which is equivalent to pressing an "energy-saving switch" for cells. It can not only enhance the sensitivity of peripheral tissues to insulin, but also induce autophagy, clean up damaged proteins in β cells, and delay the aging of β cells. But I have also met patients with gastric ulcers who followed the 16+8 fast online and were so hungry that their stomachs bleed. There is also an old man who has developed hypofunction of the pancreatic islets. After fasting, his blood sugar goes up and down, almost inducing ketoacidosis. So this method itself is fine, but you have to select people and you can’t blindly follow the trend.

In fact, after doing science popularization on metabolic health for so many years, my deepest feeling is that the biochemical mechanism of diabetes prevention is full of professional terms and seems far away from ordinary people, but in practice it is nothing more than following the body's metabolic laws and not putting unnecessary burden on various organs. You don’t have to eat boiled vegetables all the time, and you don’t have to give up milk tea completely. Occasionally, you can drink a cup if you are craving for it, and walk for half an hour after drinking to let your muscles consume the excess blood sugar. On the contrary, it is easier to stick to it than extreme taboos, and it is more in line with the body’s operating logic. After all, metabolic regulation is a dynamic network, and there is never a standard answer that is universally applicable. The most effective one is the one that suits you.