Patients with type 2 diabetes mellitus account for 95% of those with diabetes. On average, the cost of care for diabetes is now at least four times that of any other diseases. Blindness and renal failure are caused primarily by type 2 diabetes; thus, appropriate treatment of type 2 diabetes is an urgent need for the improvement of human health and the reduction of medical costs. 

It is obvious that investigative approaches with too great an emphasis on insulin and blood glucose levels, which represent the mainstream of modern medicine, are insufficient in obtaining the full picture of type 2 diabetes. In general, advances in research for a certain disease and the development of drugs should reduce the incidence of the disease. Researchers who discovered and developed insulin were awarded the Nobel Prize in the 20th century. In addition, several different types of oral hypoglycemic agents were developed. Still, the number of patients with type 2 diabetes has increased.  Now, 10% to 20% of adults have diabetes or are at risk for the disease, and the incidence of diabetes among young people has increased sharply. These phenomena suggest that current knowledge about the management of diabetes may be inadequate.

Western and Chinese Medicine

Comparative and comprehensive understanding of the disease may be achieved by integrating Western medicine, which emphasizes local analysis and data, and Chinese medicine, which considers overall analysis, balance, and observations as highly important. I learned traditional Chinese medicine and Western medicine in China. In Japan, under the guidance of my three mentors, Professor Akira Takada, Professor Nobuhiro Sato, and Professor Sumio Watanabe, I studied the liver from the viewpoint of Western medicine, which increased my understanding of the association between type 2 diabetes and the liver. The integration of Chinese medicine and Western medicine helped me understand that association.

Liver Responsibility and Functioning

I would say that type 1 diabetes is a pancreatic disease and that type 2 diabetes is a liver disease. In traditional Chinese medicine, the liver is considered an organ for digestion, absorption, and metabolism as well as an important organ regulating the functions of the whole body, in particular, the emotions, reproductive organs, eyes, fascia, and tendons. The liver is responsible for the free coursing of blood throughout the body. In other words, smooth material transport in the liver leads to efficient functioning of qi and blood throughout the body, as well as digestion, absorption, metabolism, and the emotions.  Around 219, Zhang Zhong-jing described liver disease-related wasting thirst (equivalent to type 2 diabetes). His view is relevant from the viewpoint of modern medicine. In most cases, tissue circulation is basically maintained by the arteriovenous system. In addition, the portal vein and biliary systems are present in the liver, suggesting that the liver serves as a material transport control center regulating the flow of substances throughout the body.

Moreover, the liver has a variety of physiological functions:  detoxification, bile production, cholesterol synthesis, albumin secretion, and it serves as the metabolic center for nutrients. Insulin secreted by the pancreas and nutrients absorbed in the small intestine (excluding long-chain fatty acids) first flow into the liver via the portal vein. Approximately 50% of insulin and approximately 50% of postprandial glucose are taken up by hepatocytes, and the remaining substances flow through the liver and circulate throughout the whole body. Storage of sugar in the liver reduces the postprandial surge in blood glucose levels, and stored sugar is released into the blood during fasting to prevent hypoglycemia. The liver is the sole organ producing glucose from metabolites of fat and protein (gluconeogenesis) and replenishes blood glucose between meals, particularly during fasting. Thus, the liver's material transport and metabolic functions maintain the blood glucose level within the normal range.

Importance Qi in Proper Health

In light of traditional Chinese medicine, a lifestyle characterized by overeating, lack of exercise, and mental depression induces material stagnation in the liver and causes internal inflammation called internal heat. As conditions worsen, a constitution susceptible to metabolic and circulatory impairments (qi deficiency with blood stasis) develops, resulting in systemic disorders. In traditional Chinese medicine, qi and blood are considered the basic materials of life, which originate from the spleen and the stomach, that is, the digestive system. The integrated function of digestion, absorption, and metabolism is called spleen qi (PIQI), and the function is regulated primarily by the liver.

Qi indicates a minute but important substance that is present like air but not visible macroscopically. Qi deficiency in diabetes corresponds to ATP (energy substance) deficiency caused by an energy metabolism disorder, and blood stasis indicates a blood circulation disorder. Complications of diabetes result from a qi deficiency with blood stasis or metabolic and circulatory impairments affecting individual tissue cells. This can be likened to the fact that, in modern life, traffic and energy disturbance affect society as a whole. Thus, a constitution susceptible to metabolic and circulatory impairments is closely related to a variety of diabetes complications. 

Onset of Type 2 Diabetes

Integrated medicine appears to reveal some concepts. Although some genes are involved in the onset of type 2 diabetes, a sharp increase in the incidence of the disease is attributed primarily to lifestyle. A poor lifestyle of overeating, mental depression, and tension and an unhealthy lifestyle of lack of exercise induce a stagnant flow in the liver and disturb the metabolism. 

Type 2 diabetes does not occur acutely but results from gradually worsening conditions. In general, diabetes is viewed on the basis of high and low levels of blood glucose. However, formation of a diabetic constitution precedes abnormal increases in blood glucose levels. Diabetes may be prevented by improving the constitution before worrying about whether blood glucose levels exceed the threshold.

Related Diseases of Type 2 Diabetes

As you may know, the related diseases of type 2 diabetes - obesity, hyperinsulinemia, hypertension, fatty liver, hyperuricemia, arteriosclerotic cardiovascular (cerebrovascular) disease, and lipid metabolism abnormalities - are called metabolic syndrome. Type 2 diabetes represents a relatively severe metabolic syndrome. It should be noted that, as in the case of hyperlipidemia and hyperuricemia, hyperglycemia is not a cause but a consequence of metabolic disorder. Importantly, insulin resistance underlies the pathogenesis of these metabolic disorders. Then, what is insulin resistance like? 

Insulin Resistance

Absorbed glucose is utilized together with oxygen to produce energy (ATP) primarily in the mitochondria of the cells. Insulin promotes the uptake of glucose into the cells of the liver, muscle, and adipose tissues. The lack or decreased activity of insulin leads to low glucose levels in cells and high glucose levels in blood vessels. 

Type 1 diabetes is caused by insulin deficiency, whereas type 2 diabetes primarily results from decreased insulin activity. The decreased activity is caused by insulin resistance in the liver and other tissues, and to overcome the condition, more insulin is secreted in patients with diabetes than in healthy individuals. Insulin secretion may be decreased when pancreatic circulation is impaired or when cells are exhausted after prolonged excess secretion. In either case, a constitution characterized by resistance to the direction of insulin rather than the amount of insulin plays a greater role in type 2 diabetes. This is called insulin resistance.

Decreased Liver Function

Insulin resistance results from decreased liver function. The invasion of biological or chemicaltoxins and the excessive accumulation of physiological substances are harmful to the body. The liver serves as the detoxification center of the body, and fewer toxins accumulate as long as the liver functions properly. Impairment of the detoxification function, however, results in an accumulation of insulin resistance-inducing substances in the body. Free fatty acids (FFA) and tumor necrosis factor (TNF-á) are known as insulin resistance-inducing substances. Free fatty acids released from adipose tissue are usually consumed as fuel in the liver or used as raw material for the synthesis of lipoproteins.  Most hormones and cellular factors (cytokines) are inactivated and disposed of in the liver. TNF-á and unknown insulin resistance-inducing substances also appear to be inactivated and disposed of in the liver.

Metabolic Inflammation

Insulin resistance is associated with metabolic inflammation. TNF-á is more of an inflammatory substance than an insulin resistance-inducing molecule. An increase in inflammatory factors, such as TNF-á, may be attributed to the production in hypertrophic or inflamed adipose tissue or the decreased function of detoxification in the liver. In traditional Chinese medicine, this type of metabolic inflammation is called internal heat. Moreover, inflammation worsens metabolic disorders and angiopathy.

Complications of Type 2 Diabetes

Type 2 diabetes is a serious disease not because of hyperglycemia but because of the complications.  Complications occur more frequently with diabetes than with any other disease. In addition to the three major complications of nephropathy, retinopathy, and neuropathy, a variety of disorders may occur throughout the body. Intracellular low-glucose, hypoxic conditions inevitably lead to dysfunctions in a range of tissue cells including blood vessels. Thus, complications are a consequence of a qi deficiency with blood stasis (constitution characterized by poor conversion of glucose to energy and circulatory disorders), rather than glucose toxicity. For improvement of the constitution characterized by these disorders, proven methods of traditional Chinese medicine are effective, such as tonifying qi (promotion of metabolism), activating the blood (improvement of circulatory disorders), and soothing the liver (revival of stagnant material transport in the liver).

Treatment of Type 2 Diabetes

As described above, treatment of type 2 diabetes definitely requires a combination of three pillars of symptomatic therapy: hypoglycemic treatment, correction of a poor lifestyle, and therapy to improve the constitution characterized by metabolic and circulatory impairment in each tissue. The combination of conventional treatment and constitution-improving treatment, which traditional Chinese medicine emphasizes, will prevent type 2 diabetes and improve treatment outcomes. I hope that this review of type 2 diabetes integrating Chinese medicine and Western medicine will serve as a guide and contribute to progress in medical research and the treatment of metabolic syndrome.

Finally, I gratefully acknowledge Toshiro Nagao for proofreading.

Wang Xianen