Diabetes and its complications

What is diabetes?

According to International Diabetes Federation, Diabetes is a chronic disease that occurs when the pancreas is no longer able to make insulin, or when the body cannot make good use of the insulin it produces.

Insulin is a hormone made by the pancreas, that acts like a key to let glucose from the food we eat pass from the blood stream into the cells in the body to produce energy. All carbohydrate foods are broken down into glucose in the blood. Insulin helps glucose get into the cells. 

Not being able to produce insulin or use it effectively leads to raised glucose levels in the blood (known as hyperglycemia). Over the long-term high glucose levels are associated with damage to the body and failure of various organs and tissues^[1].

Diabetes symptoms

According to American Diabetes Association, the following symptoms of diabetes are typical^[2].

● Urinating often

● Feeling very thirsty

● Feeling very hungry—even though you are eating

● Extreme fatigue

● Blurry vision

● Cuts/bruises that are slow to heal

● Weight loss—even though you are eating more (type 1)

However, some people with diabetes have symptoms so mild that they go unnoticed.

Diabetes and its complications^[3]

Reference：

[1] International Diabetes Federation. Available at: What is diabetes (idf.org)

[2] American Diabetes Association. Available at: Type 1 Diabetes - Symptoms | ADA

[3] International Diabetes Federation. Available at: Complications (idf.org)

Diabetes classification 

According to the guidelines released by the American Diabetes Association (ADA), there are basically four types of diabetes^[1]:

Among them, type 1 diabetes, type 2 diabetes and gestational diabetes are common clinical types.

Type 1 diabetes, also known as insulin-dependent diabetes, usually occurs in children and adolescents. Its etiology and pathogenesis are still unclear. Its significant pathophysiological and pathological features are the significant decrease and disappearance of the number of pancreatic β-cells resulting in a significant decrease in insulin secretion or missing, therefore, the body cannot produce the insulin that the body needs. Patients of this type will need to use insulin every day to control their blood sugar levels. If insulin is not injected in time, patients with type 1 diabetes will face life threats.

Type 2 diabetes, also known as insulin-independent diabetes, is the most common type of diabetes. It usually occurs in adults, but it is also uncommon in children and adolescents in recent years. Its etiology and pathogenesis are currently unclear. Its significant pathophysiology It is characterized by a decrease in insulin's ability to regulate glucose metabolism (insulin resistance) accompanied by a decrease (or a relative decrease) in insulin secretion caused by functional defects of pancreatic β-cells.

Gestational diabetes is diabetes or abnormal glucose regulation that is diagnosed during pregnancy, and does not include the high blood sugar state of pregnant diabetic patients who have been diagnosed. Gestational diabetes usually disappears after pregnancy, but untreated or poorly controlled gestational diabetes poses a serious health threat to pregnant women and fetuses.

Special type diabetes is a state of hyperglycemia with relatively clear etiology. For example, some well-defined monogenic diabetes, diabetes caused by some hormonal disorders related diseases, etc. With the in-depth research on the pathogenesis of diabetes, the types of special types of diabetes will gradually increase.

Type 1 diabetes

Type 1 Diabetes Mellitus (T1DM), also referred to as insulin-dependent diabetes mellitus (IDDM) or juvenile diabetes mellitus, typically develops before the age of 35 and accounts for less than 10% of diabetes. Type 1 diabetes is dependent on insulin therapy, which means that patients need to use insulin for treatment from the onset of onset and use it for life. The reason is that the insulin-producing cells of the pancreas in patients with type 1 diabetes have been completely damaged, thus completely losing the function of producing insulin. In the case of absolute lack of insulin in the body, blood sugar levels will continue to rise and diabetes will occur.

Etiology

Autoimmune system deficiency: because a variety of autoimmune antibodies can be detected in the blood of patients with type1diabetes, such as glutamate decarboxylase antibody (GAD antibody), islet cell antibody (ICA antibody), etc. These abnormal autoantibodies can damage the b cells that secrete insulin in the pancreatic islets of the human body, making them unable to secrete insulin normally.

Genetic factors: current research suggests that genetic defects are the basis of type 1 diabetes. This genetic defect is manifested in the abnormality of the HLA antigen of the sixth pair of chromosomes in humans. Scientists’ research suggests that type 1 diabetes has the characteristics of familial onset - if your parents have diabetes, you are more likely to develop this disease than people without this family history.

Virus infection: perhaps to your surprise, many scientists suspect that the virus can also cause type1diabetes. This is because patients with type 1 diabetes often have viral infections for a period of time before the onset of disease, and the "epidemic" of type 1 diabetes often occurs after the virus epidemic. Viruses, such as those that cause mumps and rubella, and the coxsackie family of viruses that can cause polio, can all play a role in type 1 diabetes.

Type 2 diabetes

Type 2 diabetes accounts for more than 90% of diabetic patients and is also called adult-onset diabetes, as it occurs mostly in adults, especially middle-aged and elderly people. It usually develops after 35-40 years of age and the prevalence of diabetes has gradually increased from the age of 40, reaching a peak in the 60-year-old elderly. The ability to produce insulin in patients with type 2 diabetes is not completely lost. Some patients even produce too much insulin in their bodies, but the effect of insulin is greatly reduced. Therefore, the patients' insulin is relatively lacking. Certain oral drugs can be used to stimulate the secretion of insulin in the body. However, some patients still need insulin treatment like type 1 diabetes.

Some patients with type 2 diabetes mainly have insulin resistance and most of whom are overweight. Due to insulin resistance, insulin sensitivity decreases, and blood insulin increases to compensate for their insulin resistance. However, compared with patients with hyperglycemia, insulin secretion of diabetic patients is still relatively insufficient. The early symptoms of such patients are not obvious, and macrovascular and microvascular complications can often occur before they are diagnosed. Diet therapy and oral hypoglycemic drugs can be effective. Other patients mainly have insulin secretion defects and clinically need to supplement exogenous insulin.

Type 2 diabetes is generally mild and insidious with a longer course, and the typical symptoms of diabetes (three more and one less, etc.) rarely appear. Most patients with type 2 diabetes have family history and personal obesity history. Such patients often do not need to rely on the use of insulin to maintain their lives. However, if the blood sugar control with oral hypoglycemic drugs is not satisfactory, or because of acute or chronic complications, insulin is also required.

Differences between type 1 and type 2 Diabetes

According to data from the American Diabetes Association, type 1 diabetes patients account for only 5% of the total diabetes patients. The remaining 95% of diabetic patients have type 2 diabetes.

Age of onset

The age of onset of type 1 diabetes is generally under the age of 40. The vast majority of adolescents and children under the age of 20 have type 1 diabetes, with few exceptions; half of the age of onset of type 2 diabetes is over 40 years old, and there are very few patients with type 1 diabetes over 50 years old. In short, the younger the age, the more likely to be type 1 diabetes; the older the age, the more likely it is to be type 2 diabetes. Of course, it is becoming more and more common for young patients with type 2 diabetes, which may be closely related to daily life, physical fitness, and so on.

Clinical symptoms

Type 1 diabetes has obvious clinical symptoms, such as polydipsia, polyuria, polyphagia, etc., that is, "3P’s", while type 2 diabetes often does not have obvious "3P’s" symptoms, so many patients with type 2 diabetes may be in an undetected state for a long time after the onset. However, during this period, because blood sugar has not been well controlled, body damage has occurred unknowingly. Therefore, many patients are diagnosed with type 2 diabetes when serious complications occur. Type 1 diabetic patients are often able to pinpoint their onset time because of their prominent clinical symptoms.

Weight at onset

People who are overweight or obese when diabetes occurs are mostly type 2 diabetes. The more obese, the more likely it is to develop type 2 diabetes. Before the onset of type 1 diabetes, the weight is usually normal or low. It is worth mentioning that whether it is type 1 diabetes or type 2 diabetes, body weight can be reduced to varying degrees after the onset, and type 1 diabetes often has obvious symptoms of weight loss.

Prone to acute and chronic complications

Type 1 and type 2 diabetes cause various acute and chronic complications, but there are some differences in the types of complications. In terms of acute complications, type 1 diabetes is prone to ketoacidosis, and type 2 diabetes is less likely to occur ketoacidosis, but older patients are prone to nonketotic hyperosmolar coma. In terms of chronic complications, type 1 diabetes is prone to complication of fundus retinopathy, kidney disease and neuropathy, while arteriosclerotic lesions of the heart, brain, kidney or limbs are not very common; and type 2 diabetes is common in addition to type 1. In addition to the same retinopathy, nephropathy and neuropathy of the fundus in diabetes, the incidence of arteriosclerosis of the heart, brain, and kidney vessels is relatively high, and hypertension is often complicated. Therefore, the risk of coronary heart disease and cerebrovascular accidents in type 2 diabetic patients are much higher than that of type 1 sugar friends, which is a very obvious point of distinction.

Clinical treatment

At present, patients with type 1 diabetes can effectively control hyperglycemia and stabilize their condition only by injecting insulin and controlling their diet and exercise. Oral hypoglycemic drugs generally have no obvious effect.

Patients with type 2 diabetes can see obvious effects through reasonable diet control, appropriate exercise, and appropriate oral hypoglycemic drugs. When oral hypoglycemic drugs treatment fails, the function of pancreatic islet B cells tends to fail or appear severe emergency in the case of chronic complications, it is also an indication for insulin.

Reference：

[1] American Diabetes Association; 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care 1 January 2021; 44 (Supplement_1): S15–S33. https://doi.org/10.2337/dc21-S002

Diabetes diagnosis

Blood glucose value: diagnosis and efficacy evaluation index

⦁ Blood Glucose (BG): it reflects instantaneous blood glucose state

⦁ Fasting blood glucose (FPG/FBG): it reflects the basal blood glucose level throughout the day, without energy intake for at least 8  hours, normal people <6.1 mmol/L

⦁ Postprandial blood glucose (PPG/PBG): it reflects the blood glucose level after a meal, 2 hours after the first bite, normal people <7.8 mmol/L

Oral glucose tolerance test (OGTT): if fasting blood glucose ≥6.1 mmol/L or random blood glucose ≥7.8 mmol/L, OGTT is recommended

⦁ Subjects took 75 g of anhydrous glucose powder dissolved in 300 ml of water orally after fasting (8-10 h), and took it within 5 min;

⦁ Start timing from the first mouthful of sugar, and collect blood from the forearm before and 2 hours after taking sugar;

⦁ During the test, the subjects do not drink tea and coffee, do not smoke, do not do strenuous exercise, but they do not need to stay in bed absolutely;

⦁ Within 3 days before the test, the daily carbohydrate intake should not be less than 150 g;

⦁ Drugs that may affect OGTT, such as contraceptives, diuretics, or phenytoin, should be stopped for 3 to 7 days before the test.

*Eating is prohibited before blood draws, except for water.

Generally speaking, the diagnostic criteria for judging diabetes are: OGTT 2 h blood glucose value ≥ 11.1 mmol/L^b

*Blood sugar unit conversion: mg/dl=mmol/L×18

1. If 1 molecule of water glucose is used, it is 82.5 g, for children, it is 1.75 g/kg body weight, and the total amount does not exceed 75 g

2. Diabetes is diagnosed when three points on the OGTT curve exceed the diagnostic criteria: 125 mg/dl for 0 min, 190 mg/dl for 30 min, 180 mg/dl for 60 min, 140 mg/dl for 120 min, and 125 mg for 180 min/dl

Glucose metabolism status classification^[1]

Glucose metabolism status distribution diagram

Diabetes diagnosis criteria

2020 guidelines: in laboratories with strict quality control, glycosylated hemoglobin (HbA1c) measured by standardized testing methods can be used as a supplementary diagnosis standard for diabetes^[2]

References:

[1] World Health Organization. (‎1999)‎. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation. Part 1, Diagnosis and classification of diabetes mellitus. World Health Organization. https://apps.who.int/iris/handle/10665/66040

[2] Chinese Medical Association Diabetes Branch. Guidelines for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition) [J] . Chinese Journal of Diabetes, 2021, 13(4) : 315-409. DOI: 10.3760/cma.j.cn115791-20210221-00095. https://rs.yiigle.com/CN115791202104/1315489.htm 

Diabetes treatment

Figure 1 Simple pathway for the treatment of hyperglycemia in patients with type 2 diabetes

Image source: Introduction: Standards of Medical Care in Diabetes—2021

Diet therapy and exercise therapy are essential measures to control hyperglycemia in type 2 diabetes. When diet and exercise do not meet the standard of blood glucose control, medication should be used in a timely manner. Type 2 diabetes is a progressive disease in which the function of islet β cells gradually declines with the prolongation of the course of the disease, and the degree of insulin resistance does not change much. Therefore, as the course of the disease progresses, the dependence on exogenous glycemic control methods gradually increases. Oral hypoglycemic agents and a combination of oral and injectable hypoglycemic agents are often clinically required^[1].

Oral anti-diabetic drugs

Drug therapy for diabetes is generally based on correcting the two main pathophysiological changes that lead to an increase in blood glucose, namely insulin resistance and impaired insulin secretion. According to the different effects of action, oral hypoglycemic drugs can be divided into drugs that promote insulin secretion as the main role and drugs that lower blood glucose through other mechanisms, the former mainly including sulfonylureas, glinides, dipeptyl peptidase IV inhibitors (DPP-4), and drugs that reduce blood glucose through other mechanisms mainly include biguanides, thiazolidinediones (TZDs), α-glycosidase inhibitors and sodium-glucose cotransporter 2 inhibitors (SGLT-2)^[1].

Stimulating insulin secretion

Sulfonylureas: Sulfonylureas are classified as insulin secretagogues and their primary mechanism of action is to stimulate pancreatic β cells to secrete insulin, effectively lowering blood glucose levels. However, caution is needed when using sulfonylureas, as improper use can lead to hypoglycemia, especially in elderly patients and those with liver or kidney failure. In addition, weight gain is a potential side effect of these drugs. For patients with mild renal insufficiency, gliquidone is the preferred choice of sulfonylurea. Despite their potential drawbacks, sulfonylureas remain an important first-line option for oral hypoglycaemic treatment in many countries and regions. The third-generation sulfonylurea, glimepiride, is characterized by its dual action of stimulating insulin secretion and increasing insulin sensitivity. Its long-acting nature reduces the risk of hypoglycemia, which has led to its gradual replacement by second-generation products such as glipizide and gliquidone.

Glinides: Glinides are the new short-acting non-sulfonylurea insulin secretagogues. They work by stimulating pancreatic βcells to secrete insulin more rapidly and effectively after meals, thereby controlling postprandial hyperglycemia. The main glinides are repaglinide, mitiglinide and nateglinide. Glinides have several advantages over sulphonylureas, including rapid onset of action, short duration of action, and a lower risk of hypoglycemia. These drugs are mainly metabolized in the body by the liver and gallbladder, making them suitable for use in elderly patients with diabetes and those with mild to moderate hepatic and renal insufficiency.

DPP-4 inhibitors: DPP-4 inhibitors work by inhibiting the activity of dipeptidase-4 (DPP-4), which reduces the breakdown and inactivation of the incretin GLP-1 (glucagon-like peptide-1), leading to increased endogenous levels of GLP-1. GLP-1 plays a critical role in promoting insulin release from pancreatic β cells in response to glucose levels while suppressing glucagon secretion from pancreatic α cells. This unique mechanism of action allows DPP-4 inhibitors to increase insulin levels and lower blood glucose while reducing the risk of hypoglycemia and weight gain. The most important DPP-4 inhibitors include sitagliptin, saxagliptin and linagliptin.

Other mechanisms

Biguanides: Biguanides, of which metformin is the most widely used representative drug in patients with type 2 diabetes, exert their hypoglycaemic effects by various mechanisms. Metformin inhibits gluconeogenesis, reducing hepatic glucose output and increasing glucose uptake and utilization in peripheral tissues. This results in improved insulin sensitivity and a significant reduction in blood glucose levels. In addition to its glucose-lowering effects, metformin has been shown to reduce body weight and reduce the risk of cardiovascular events. Because of its proven efficacy and compatibility with most other oral hypoglycaemic agents, metformin is considered a first-line treatment for diabetes in current national and international guidelines. It serves as a foundation drug in combination therapy, making it a fundamental component of many diabetes treatment regimens.

α-glucosidase inhibitors: α-glucosidase inhibitors, including acarbose and voglibose, act in the gut to control blood glucose levels. Although their sites of action are similar, their mechanisms of action are slightly different. Acarbose competitively inhibits α-glucosidase in the cells of the small intestinal wall, preventing the breakdown of starch into disaccharides and further conversion into monosaccharides. Voglibose, on the other hand, inhibits intestinal α-glucosidase, interrupting the process of breaking down disaccharides into monosaccharides. Both acarbose and voglibose are effective in controlling postprandial blood glucose levels, with no significant difference in control. However, voglibose, such as bloating, causes fewer gastrointestinal side effects than acarbose.

Thiazolidinediones(TZDs): TZDs are classified as insulin sensitizers because they effectively reduce insulin resistance and increase insulin action by selectively activating peroxisome proliferator-activated receptors (PPARγ). This mechanism leads to a significant reduction in blood glucose levels. The main TZDs available are rosiglitazone and pioglitazone. When used alone, TZDs do not usually cause hypoglycemia. However, combining them with insulin or insulin secretagogues can increase the risk of hypoglycemia and side effects such as weight gain and edema.

SGLT-2 inhibitors: SGLT-2 inhibitors act independently of insulin secretion and primarily target the kidneys. By inhibiting sodium-glucose cotransporter-2 (SGLT-2), they inhibit glucose reabsorption in the kidneys, leading to increased urinary glucose excretion. This mechanism effectively lowers blood glucose levels. Commonly prescribed SGLT-2 inhibitors include dapagliflozin, empagliflozin, and canagliflozin. SGLT-2 inhibitors have many benefits, such as improving glycated hemoglobin levels, promoting weight loss, lowering blood pressure, and protecting kidney function. However, they can also cause certain adverse effects, particularly urinary and reproductive tract infections and side effects associated with hypovolemia. Diabetic ketoacidosis (DKA) is a rare but potentially serious side effect.

Injectable anti-diabetic drugs

Insulin

Insulin therapy plays a crucial role in managing hyperglycemia. For patients with type 1 diabetes, insulin is essential for their survival, and it is also necessary to control high blood sugar levels and mitigate the risk of diabetic complications. In type 2 diabetes, while insulin may not be required to sustain life, it becomes necessary when oral hypoglycemic drugs prove ineffective or are contraindicated. Insulin therapy is then employed to effectively control hyperglycemia and reduce the risk of diabetic complications. As the disease progresses, especially with a long-standing course, insulin therapy can become the most important or even indispensable approach for patients to regulate blood sugar levels.

Insulin can be categorized based on its source and chemical structure into three main types: animal insulin, human insulin, and insulin analogues. Furthermore, insulin can be classified into various subtypes based on its duration and action profile, ultra-short-acting insulin analogues, regular (short-acting) insulins, intermediate-acting insulins, long-acting insulins, long-acting insulin analogues, premixed insulins, premixed insulin analogues, and dual insulin analogues.

Timing of Initiating Insulin Therapy

(1) Patients with type 1 diabetes require insulin therapy at the onset of the disease and require life-long insulin replacement therapy.

(2) In cases of newly diagnosed type 2 diabetes with evident symptoms of hyperglycemia, ketosis, or diabetic ketoacidosis (DKA), insulin therapy is the most recommended treatment option. Once blood sugar is effectively managed, and symptoms show significant improvement, the subsequent treatment plan will be determined based on the patient's individual condition. 

(3) For patients with newly diagnosed diabetes, especially when it's hard to distinguish between type 1 and type 2 diabetes, insulin therapy may be considered as the most recommended treatment option. Once blood sugar is well controlled, and symptoms show significant improvement, further evaluation and classification of the diabetes type will be performed. Based on the determined classification and the patient's specific condition, a tailored follow-up treatment plan will be formulated.

(4) For type 2 diabetic patients, if blood sugar levels fail to reach the target despite lifestyle modifications and oral hypoglycemic drug treatment, a combination of oral hypoglycemic drugs and insulin therapy may be initiated. When HbA1c levels remain at or above 7.0% even after three months of adequate oral hypoglycemic drug treatment, it may be appropriate to consider starting insulin therapy. 

(5) In the course of diabetes (including newly diagnosed type 2 diabetes), insulin therapy should be used as soon as possible when there is a significant weight loss without obvious incentives.

Options for Initiating Insulin Therapy

According to the specific situation of the patient, basal insulin, premixed insulin or dual insulin analogues can be used as the starting insulin for treatment. 

(1) Basal insulin: Basal insulin includes both intermediate-acting insulin and long-acting insulin analogues. When using only basal insulin for treatment, the existing various oral hypoglycemic drugs can be continued, and there is no need to discontinue insulin secretagogues.

(2) Premixed insulin: Premixed insulin includes both premixed human insulin and premixed insulin analogs. Depending on the patient's blood sugar levels, a 1-2 times daily injection regimen can be chosen. In cases of elevated HbA1c, a twice-daily injection schedule may be employed. During the honeymoon stage of type 1 diabetes (T1DM), short-term injections of premixed insulin, 2 to 3 times a day, can be considered. 

(3) Dual insulin analogues: Currently, the only available dual insulin analogs in the market are insulin degludec aspart (IDegAsp). Patients using this medication should adjust their dosage based on their fasting blood glucose levels until they achieve the target range. For patients with obesity or HbA1c levels above 8.0%, starting with a higher dose may be a suitable option. Insulin degludec aspart is typically administered once a day. If postprandial (after-meal) blood sugar levels remain poorly controlled even after reaching the target dose, or if the patient consumes two main meals a day, consideration may be given to switching to a twice-daily injection regimen instead.

Multiple Subcutaneous Injections of Insulin

After initial insulin treatment and appropriate dose adjustments, if the patient's blood sugar levels still do not reach the target or if repeated hypoglycemic episodes occur, it becomes necessary to further optimize the treatment plan. Intensive insulin therapy can be considered, involving the use of mealtime insulin in combination with basal insulin, administered 2-4 times a day. Alternatively, patients may opt for premixed insulin analogues, injected 2-3 times a day.

Figure 2 Pathway for insulin therapy in patients with type 2 diabetes

Image reference: Guidelines for Prevention and Treatment of Type 2 Diabetes in China (2020 Edition)

(1) Mealtime + basal insulin: insulin dosage is adjusted based on blood sugar levels before each major meal (breakfast, lunch, and dinner) and at bedtime. The basal insulin dosage is also adjusted before going to bed, guided by the fasting blood sugar level. These insulin adjustments are typically made every 3-5 days. The dose adjustments are typically done in increments of 1-4 units per change in blood sugar levels until the desired target is reached. 

(2) Premixed insulin 2-3 times a day (premixed human insulin 2 times a day, premixed insulin analogues 2-3 times a day): adjust the insulin dose according to the blood sugar levels at bedtime and before three meals, Adjust once every 3-5 days until the blood sugar reaches the target.

Short-term Intensive Insulin Therapy

Glucagon-like peptide-1 receptor agonist (GLP-1RA)

Glucagon-like peptide-1 (GLP-1) is a polypeptide hormone produced by specialized cells in the intestines known as L cells. Its primary role involves promoting the release of insulin from pancreatic β cells in response to blood sugar levels, thereby aiding in the regulation of glucose in the body. However, GLP-1 is susceptible to degradation by an enzyme called dipeptidyl peptidase when present in the body, leading to a loss of its functional activity. These compounds can replicate the effects of natural GLP-1 by enhancing insulin secretion from the pancreas and reducing the secretion of glucagon. Beyond glucose control, GLP-1 receptor agonists offer additional benefits like weight reduction, blood pressure moderation, and safeguarding cardiovascular and kidney health. Notable examples of these agonists include liraglutide, dulaglutide, and semaglutide, which can be administered through injections or oral formulations.

Diabetes diet

A diabetes diet aims to create a healthy eating plan that helps people with diabetes manage their blood sugar levels. This plan prioritizes nutrient-rich, lower-calorie foods with a higher healthy fat content. It emphasizes the inclusion of fruits, vegetables, and whole grains. In fact, the diabetes diet is suitable for not only diabetic patients but a wider range of people.

The "Guidelines for Diet and Nutrition for Adults with Diabetes (2023 Edition)" published on the official website of National Health Commission of the People's Republic of China, presents a set of eight fundamental principles and recommendations regarding dietary and nutritional practices for people with diabetes (Figure 3)^[2].

Figure 3 Principles and recommendations of diet and nutrition for adult diabetics

Image reference: Guidelines for Diet and Nutrition for Adults with Diabetes (2023 Edition)

Among people with diabetes, making appropriate dietary adjustments has great significance in managing the condition and averting potential complications, thereby potentially delaying their onset. It's worth noting that some people with diabetes misconstrue "diet adjustment" as "going on a diet". However, this is not right. By adhering to the principles of a well-balanced diet and making suitable modifications, people with diabetes can continue to enjoy a diverse selection of foods.

The American Diabetes Association (ADA) provides us with important healthy eating plans, including the following:

⦁ Fruits and vegetables

⦁ Lean meats and plant-based source of protein

⦁ Less added sugar

⦁ Less processed foods^[3]

The quantity of carbohydrates present in your food has an impact on your blood sugar levels. The rate at which carbohydrates elevate your blood sugar varies based on the type of food and the manner in which you consume it. For instance, consuming fruit in juice form will lead to a quicker increase in blood sugar compared to consuming the whole fruit. Combining carbohydrates with foods high in protein, fat, or dietary fiber can decelerate the rate at which blood sugar levels rise.

In this regard, people with diabetes need to set up a regular and balanced meal plan to avoid high or low blood sugar levels. In diabetes diet, Counting Carbs and The Plate Method are two common methods that can make meal planning easier and easier to stick to.

Counting Carbs

Counting carbs effectively maintains blood glucose levels within the desired range by monitoring daily carbohydrate consumption and moderating intake during each meal. Typically, people require guidance from a physician or a registered dietitian to determine their daily and per-meal carbohydrate limits. They can refer to a provided list of typical carbohydrate-containing foods to strategically allocate carbohydrates across their three daily meals.

The Counting Carbs method calculates the amount of carbohydrate intake from each meal and helps determine the matching dosage of insulin. This method works best for diabetics using mealtime insulin^[4].

The Plate Method

The Plate Method is one of the easiest methods in healthy diet to control blood sugar. With this method, patients can create a healthy meal with a perfect ratio of vegetables, proteins, and carbohydrates, and there is no need to do any calculations or weighing.

1. Fill half with non-starchy vegetables, such as salad, green beans, broccoli, cabbage and carrots.

2. Fill a quarter with lean proteins, such as chicken, pork tenderloin, beans, tofu and eggs.

3. Fill a quarter with carbohydrate foods. Foods high in carbohydrates include grains, starchy vegetables (such as potatoes, peas, sweet potatoes, and squash), rice, pasta, fruit and yogurt.

*Note: Milk and soy milk count as carbonhydrate foods.

4. Choose water or low-calorie beverages such as unsweetened coffee and tea.

People with diabetes can develop a personal nutritional eating plan under the guidance of a healthcare professional. Below is a list of nutritious foods for your reference.

Leafy Green Vegetables

Abundant in vital vitamins, minerals, and nutrients, leafy green vegetables exert minimal impact on blood sugar levels. Moreover, their notable antioxidant content proves beneficial for individuals with diabetes. It is advisable for diabetics to incorporate a substantial portion of leafy green vegetables around 200 g or more into their daily diet, which can delay the rise of blood sugar after meals. Leafy green vegetables include:

⦁Spinach ⦁ Rape ⦁ Kale ⦁ Capers ⦁ Oleander ⦁ Broccoli ⦁ Cabbage

Whole Grain

In contrast to refined grains, whole grains offer reduced energy content while preserving higher levels of protein, fat, vitamins, and minerals. Additionally, they contain an enhanced presence of biologically active components like beta-glucan, flavonoids, and polyphenols. These constituents contribute not only to elevated nutrient density but also support functions such as intestinal peristalsis, blood glucose moderation, blood lipid regulation, and bolstered antioxidant capacity. Whole wheat and other whole grains possess a lower glycemic index (GI) compared to refined grains like rice, noodles, and steamed buns. Consequently, their impact on post-meal blood sugar levels is milder, rendering them a favorable choice for individuals with diabetes. Whole grains include:

⦁ Brown rice ⦁ Whole wheat bread ⦁ Buckwheat ⦁ Quinoa ⦁ Wheat ⦁ Rye ⦁ Oats ⦁ Barley

Fish

For people with diabetes, an essential component for augmenting nutrient intake is protein. Research indicates that fish is particularly noteworthy due to its abundance of unsaturated fatty acids. These compounds contribute to the regulation of blood lipids, diminishing the likelihood of cardiovascular and cerebrovascular ailments, while also exhibiting cholesterol-lowering properties. Moreover, the nutrient profile of fish is beneficial for both brain and retinal nerve health. Additionally, its easy digestibility renders it highly suitable for the diabetic demographic. Fishes include:

⦁ Carp ⦁ Grass carp ⦁ Silver carp ⦁ Yellow croaker ⦁ Striped bass ⦁ Sea bass

Legumes

Incorporating legumes into the diet is recommended for people with diabetes. Legumes offer not only substantial nutritional value but also a high fiber content. This fiber content contributes to a greater sense of fullness post-consumption, stabilizes blood sugar levels, and effectively reduces blood pressure and cholesterol. Additionally, legumes provide essential minerals and top-quality protein, while being low in saturated fat, aligning well with the dietary needs of people with diabetes. Legumes include:

⦁ Soy bean ⦁ Kidney bean ⦁ Pinto bean ⦁ Black bean ⦁ Red bean ⦁ Adzuki bean

Fruit

People with diabetes often show lower levels of vitamin C. While vitamin C supplements are an option for supplementation, opting for natural sources such as citrus fruits proves advantageous. Citrus fruits not only boast high vitamin C content but also offer a wealth of minerals and dietary fiber, rendering them a superior selection. Fruits include:

⦁ Oranges ⦁ Grapefruits  ⦁ Lemons

Berries stand out for their elevated levels of vitamins, minerals, fiber, and antioxidants. Notably, they are abundant in anthocyanins, compounds that hold significance for people with diabetes. Anthocyanins aid diabetic patients by impeding specific digestive enzymes, thereby retarding the digestion process and mitigating blood glucose surges following the consumption of starchy foods^[5]. Berries include:

⦁ Grapes ⦁ Blueberries ⦁Blackberries ⦁ Strawberries ⦁ Raspberries ⦁ Mulberries

Beyond adopting a diet rich in healthy and nourishing options, people with diabetes should also be mindful of dietary restrictions. The following foods are high in calories and high in sugar, which can easily cause blood sugar to rise after eating. It is advisable to either minimize their intake or entirely avoid them.

• Foods high in oil, saturated fats, and even trans fats, such as fried dishes, pastries, popcorn, and animal organ meats, ect.

• Foods high in salt, such as ham, bacon and pickles, ect.

• Foods high in sugar, such as baked desserts, candies, preserved fruit, honey and ice cream, ect.

• Sugar-sweetened beverages such as fruit juices, sodas, etc.

In daily life, it is recommended that diabetics drink more water, drink less sugar-sweetened drinks, and consider adding a small amount of sugar substitutes to coffee or tea. In addition, drinking alcohol should be moderate, especially while using insulin or other hypoglycemic drugs, drinking alcohol will cause a sudden drop in blood sugar, induce hypoglycemia, and endanger life and health.

Diabetes and exercise

Exercise is essential for people with diabetes. Sensible, effective and safe exercise not only improves glucose metabolism and lowers blood sugar, but also increases muscle strength and flexibility and reduces body fat. In addition, exercise has positive effects on weight, sleep, memory and mental performance.

Exercise is different from person to person. Adherence should be gradual and cyclic, placing emphasis on persistence while prioritizing safety. According to the "China Diabetes Exercise Guidelines," a preference is given to exercises of moderate intensity and lower levels. This approach steers clear of the drawbacks associated with high-intensity workouts. High-intensity exercise can provoke the release of insulin antagonist hormones, leading to an elevation in blood glucose levels. Simultaneously, it encourages the upsurge of oxidized lipids in the bloodstream, contributing to a state of oxidative stress that can exacerbate pre-existing organ function impairments. Moderate-intensity exercise, on the other hand, confers multiple benefits. It allows diabetic patients to gradually adapt to the exercise routine's rhythm, while also facilitating effective utilization of glucose and free fatty acids by the muscles, thereby promoting the burning of body fat^[6].

Hence, it is advisable for people with diabetes to engage in physical activities of moderate intensity (40% - 70% of their maximum heart rate) for a minimum of 150 minutes each week, with no more than three-day intervals between sessions. The emphasis should be on aerobic exercise, with the inclusion of some resistance training that targets major muscle groups such as the legs, hips, back, abdomen, chest, shoulders, and arms, as deemed appropriate. For patients with type 2 diabetes and no contraindications, it is recommended to perform resistance training three times a week.

Moderate-intensity aerobic exercises include:

• Brisk walking • Doing housework • Jogging • Dancing • Swimming • Bicycling • Kicking shuttlecock

Here are some tips for diabetic patients on how to start exercising:

• Choose an exercise that you find enjoyable. This is crucial since if you don't enjoy the activity, it's unlikely that you will continue doing it regularly.

• Begin with small, manageable goals. Prior to embarking on any exercise regimen, start with simple exercises and gradually work your way up to the recommended amount of physical activity. For instance, you could begin with gentle activities such as walking and climbing stairs, then gradually increase the duration and intensity of exercise each week.

• Look for an exercise partner. Consider finding an exercise partner to help increase accountability and motivation.

• Set specific and achievable exercise goals, such as walking 1 km per day for a month or exercising for 30 minutes every weekday.

• Establish a regular exercise schedule that works well with your daily routine, such as walking with a friend after dinner.

It's worth noting that exercise is one of the treatment methods for diabetic patients, and it is important to be aware of the indications and contraindications to prevent any adverse effects, such as cardiovascular events (angina attack, sudden death, etc.), metabolic disorders, or joint ligament injuries due to improper exercise patterns or intensities. Therefore, it is recommended to consult with a medical professional for an exercise prescription before starting any exercise program.

Precautions:

•  Avoid exercising on an empty stomach or 60 to 90 minutes after using glucose-lowering medication. Please measure the blood sugar level 30 to 60 minutes before starting exercise. If blood sugar < 5.6 mmol/L, you should intake some food with an appropriate sugar supplement, such as 30 g of raisins, half glass of fruit juice, or sugary drinks to avoid severe hypoglycemia during exercise.

• When fasting blood glucose is too high (>16.7 mmol/L), it needs to be brought down to normal values before starting exercise to avoid the risk of ketoacidosis - a serious diabetic complication that requires immediate treatment.

• Blood glucose levels should be monitored before, during, and after exercise when starting an exercise regimen.

• When exercising, make sure to wear appropriate sports shoes that fit your feet comfortably and allow for proper ventilation. After sweating excessively, drink water in small amounts several times to replenish your body's water needs and prevent dehydration.

• After exercise, please check your feet for sores, blisters, cuts, or other injuries. If there is no sign of relief after 2 days of injury, contact a healthcare provider.

• Avoid injecting insulin into the skeletal muscle area involved in the exercise.

• Avoid doing exercise at night to lower risk of nocturnal hypoglycemia, or make appropriate dietary and medication adjustmen.

There are numerous ways to do exercise, and the most suitable exercise for your body is the best one. It is crucial for diabetic patients to follow a regular exercise routine and monitor their blood sugar levels in real-time to maximize the benefits of exercise.

Reference:

[1] Chinese Medical Association Diabetes Branch. Guidelines for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition) [J] . Chinese Journal of Diabetes, 2021, 13(4): 315-409. DOI: 10.3760/cma.j.cn115791-20210221-00095.

[2] General Office of the National Health and Wellness Commission. Diabetes Dietary Guidelines for Adults (2023 Edition) [EB/OL], 2023-01-18.

[3] American Diabetes Association. Available at: Eating Well | ADA (diabetes.org)

[4] Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association[J]. Diabetes Care, 2008, 31(Suppl1): S61～78

[5] Oliveira H, Fernandes A, F Brás N, Mateus N, de Freitas V, Fernandes I. Anthocyanins as Antidiabetic Agents-In Vitro and In Silico Approaches of Preventive and Therapeutic Effects. Molecules. 2020; 25(17): 3813. Published 2020 Aug 21. doi:10.3390/molecules25173813

[6] Chinese Medical Association Diabetes Branch. Guidelines for diabetes mellitus exercise therapy in China [M]. Beijing: China Medical Electronic Audio and Video Publishing House, 2017