Understand diabetes, conquer diabetes

Diabetes is an ancient disease, with records of "xiao ke" (thirst and hunger) in the Huangdi Neijing dating back over two thousand years, which resembles modern medical definitions of diabetes. Subsequently, renowned ancient Chinese medical scholars renamed "xiao ke" to "xiao ke syndrome." In the Tang Dynasty, medical experts licked the urine of patients with xiao ke syndrome and found it sweet, likely marking the first recorded evidence of excessive sugar excretion through urine in diabetic individuals.

Diabetes Mellitus is the internationally recognized term for diabetes. "Diabetes": derived from the Greek word meaning "to pass through," referring to the polyuria symptom caused by high blood sugar. In the 2nd century AD, Aretaeus was the first to accurately describe diabetes and name it. "Mellitus": from the Latin word meaning "sweet." In the 17th century, Thomas Willis added "mellitus" to "diabetes," emphasizing the sweet taste of urine and describing the presence of sugar in it. The translation "Diabetes Mellitus" as diabetes is entirely appropria

The prevalence of diabetes is rapidly increasing, primarily due to changes in lifestyle and habits: in the early 1980s, the prevalence rate was 0.69%, and 30 years later, it soared to 12%, a 17-fold increase. Genetic factors play a decisive role in certain types of diabetes. Diabetes is classified into four categories: type 1 diabetes, type 2 diabetes, gestational diabetes mellitus (GDM), and specific types; specific types further include monogenic diabetes (MODY, also known as young-onset adult diabetes and mitochondrial diabetes MDM) and secondary diabetes (pancreatic diabetes, endocrine disorders, drug-induced diabetes, and infection-related diabetes). Therefore, MODY and MDM are caused by gene mutations, accounting for approximately 1%. Over 90% of diabetes cases are type 2 diabetes, where patients lack genetic mutations, but epigenetic changes and single nucleotide polymorphisms also contribute to the pathophysiology of diabetes. Consequently, researchers believe that the primary risk factor for type 2 diabetes is environmental factors, with genetic factors accounting for about 30%.

Type 2 diabetes can be prevented: both the Daqing study in China and lifestyle intervention studies in Europe and America have demonstrated that lifestyle interventions not only reduce or delay the onset of diabetes by 50% but also prevent the occurrence of complications.

Type 2 diabetes can be reversed (mitigated): The author proposed in the 14th edition of Principles of Internal Medicine(2013) that some patients may achieve reversal. Numerous successful cases of Type 2 diabetes reversal have been reported both domestically and internationally, with evidence indicating that shorter disease duration, milder symptoms, and higher body weight are associated with easier reversal.

Criteria for reversal:

- Short-term reversal: Maintaining blood glucose within the normal range (fasting blood glucose ≤ 7 mmol/L, HbA1c ≤ 7%) for 3 months after discontinuing medication.

- Long-term reversal: Maintaining blood glucose within the normal range for >1 year after discontinuing medication.

- Cure: Defined as maintaining blood glucose within the normal range for >5 years after discontinuing medication.

Some patients with type 2 diabetes can be cured: 60% of bariatric surgery patients achieve normal blood sugar levels without medication after 5 years, and nearly 40% remain medication-free after 10 years, indicating potential cure. Intensive lifestyle interventions can reverse the condition in some patients, with remission lasting over 5 years, but few reach a state of cure. The author believes that type 2 diabetes is fundamentally curable, though only a small number of highly motivated patients achieve this in practice.

From merely controlling blood glucose to treating all four diseases together: researchers have found that 80% of type 2 diabetes patients suffer from atherosclerosis (AS), with over 50% also developing fatty liver (metabolism-related fatty liver disease, MAFLD) and obesity. AST, T2DM, MAFLD, and obesity are considered four interconnected conditions. The common pathophysiological mechanism of these four diseases is inflammation, which primarily manifests in three forms: infectious, traumatic, and metabolic. Metabolic inflammation occurs when metabolic byproducts (such as endotoxin LPS and free fatty acids FFA) excessively polarize macrophages. LPS mainly originates from gut microbiota dysbiosis (e.g., excessive gram-negative bacilli and reduced gram-positive bacilli). Polarized macrophages enter the arterial bloodstream, engulf cholesterol to form foam-like cells, which deposit in the vascular intima, leading to AS development. When polarized macrophages enter the liver, MAFLD occurs; or when they enter adipose tissue, obesity results. These polarized macrophages produce large amounts of inflammatory factors, which interfere with insulin receptor substrates, causing insulin resistance. Inflammatory factors also disrupt the differentiation of pancreatic islet cells, leading to dedifferentiation—reduced production of islet cells. Insulin resistance and islet cell dedifferentiation are the primary causes of T2DM. The first disease classified as a metabolic inflammatory disorder is AS, followed by type 2 diabetes (T2DM) being termed a metabolic inflammatory disease. Inflammation is an essential response in human pathophysiological processes. Chinese researchers have proposed a new concept: the Metabolic Inflammatory Syndrome (MIS). If a patient exhibits two or more of the aforementioned four conditions, MIS can be diagnosed. The introduction of MIS serves as a reminder to both patients and medical professionals to screen for the remaining three metabolic diseases when one is diagnosed, enabling early detection and treatment. This advances a new strategy of treating and preventing all four diseases simultaneously.

Diseases come from the mouth. In the past ten years, research authors have paid close attention to the close relationship between gastrointestinal dysfunction and diabetes and MIS. The total weight of intestinal bacteria can reach 1kg, the number of bacteria can reach one million billion, 10 times the number of human cells, and the total number of bacterial genes (specific) is more than 100 times the number of human genes. The coordination of gut microbiota is crucial for maintaining energy and electrolyte balance in the human body, but the imbalance of gut microbiota is also a major cause of metabolic diseases. Balancing the imbalance of gut microbiota has become an effective measure for preventing and treating metabolic diseases. Research has shown that crude fiber foods not only lower blood sugar levels, but also prevent the occurrence of T2DM.

To defeat diabetes, we must vigorously carry out prevention work and control the prevalence of diabetes at zero or negative growth; Raise the reversal rate of T2DM to over 50% and continuously improve the cure rate. Although the prevention and treatment of diabetes is an arduous systematic project, it is believed that with the support and leadership of the government and the participation of the whole people, the desire to defeat diabetes will be realized.

Hu Renming, MD.PHD

President of Asia Pacific Alliance for Integrated diabetes Prevention and Control (Macao)

Zhu Dalong, MD

former President  of diabetes Branch of Chinese Medical Association