Diabetes prevention

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Primary prevention: preventing the development of type 2 diabetets 

The goal of primary prevention is to control the risk factors of type 2 diabetes mellitus (T2DM) and prevent the development of T2DM.

Primary prevention of T2DM is to educate the general population about the importance of adopting a healthy lifestyle. This includes promoting awareness and encouraging participation in diabetes prevention and treatment, maintaining a balanced diet, managing weight, engaging in moderate exercise, limiting salt intake, quitting smoking, restricting alcohol consumption, and maintaining psychological well-being. By implementing these measures, overall awareness of diabetes prevention and treatment can be increased within the community.

Lifestyle interventions

Studies have shown that appropriate lifestyle interventions can delay or even prevent the onset of T2DM. These interventions include increasing vegetable intake, reducing alcohol and simple sugar intake, encouraging overweight or obese patients to lose weight, and increasing daily physical activity by performing at least 20 minutes per day or at least 150 minutes per week of moderate-intensity activity.

For prediabetic patients, it is recommended to consume a low-fat diet with less than 25% or 30% of total calories from fat to achieve weight loss or to restrict calorie intake if weight loss goals are not met. These lifestyle interventions have been shown to be effective in reducing the risk of T2DM, and their benefits in preventing T2DM can last for many years.

Medication prevention

The results of clinical trials of medication interventions in the prediabetic population have shown that the hypoglycemic drugs like metformin, α-glucosidase inhibitors, thiazolidinediones (TZDs), glucagon-like peptide-1 (GLP-1) receptor agonists, and the weight-loss drug like orlistat can reduce the risk of diabetes in the prediabetic population. Among them, metformin and acarbose have been shown to be safe for long-term use in the prediabetic population, while the long-term use of other drugs requires comprehensive consideration of cost, adverse effects and tolerability. 

It is recommended that patients with prediabetes should reduce the risk of diabetes through proper diet and exercise. Regular follow-up and psychosocial support should also be given to ensure that the patient's lifestyle changes can be adhered to in the long term; check blood sugar regularly; pay close attention to other cardiovascular risk factors such as smoking, hypertension, dyslipidemia, etc., and give appropriate interventions. The specific goals are:

⦁ To make the body mass index of overweight or obese individuals reach or approach 24 kg/m², or to reduce body weight by at least 7%.

⦁ Reduce total daily dietary calories by at least 400~500 kcal (1 kcal=4.184 kJ), and overweight or obese individuals should reduce 500~750 kcal.

⦁ Saturated fatty acid intake should account for less than 30% of total fatty acid intake

⦁ The total amount of salt consumed per person per day should not exceed 5 g.

⦁ Moderate intensity physical activity should be maintained at least 150 min/week.

⦁ After 6 months of intensive lifestyle intervention with poor results, medication intervention may be considered.

Secondary prevention: preventing diabetes complications in patients diagnosed with type 2 diabetes

The goal of secondary prevention is to early detect, diagnose, and treat patients with T2DM and to prevent diabetes complications among diagnosed patients.

Secondary prevention among prevention and treatment of T2DM refers to diabetes screening, timely detection of diabetes, and timely health interventions for those at risk. Patients with T2DM often have one or more components of the metabolic syndrome, such as hypertension, dyslipidemia, and obesity, which significantly increase the risk, rate of progression, and harm of T2DM complications. Therefore, for diagnosed patients, it is important to prevent the occurrence of diabetic complications. A scientific and rational treatment strategy for T2DM should be comprehensive, including glycemic, blood pressure, lipid, and weight control.

Diabetes screening

The detection of high-risk groups can be done through channels such as resident health records, basic public health services, and opportunistic screening (e.g., during health checkups or at the time of consultations for other diseases). Diabetes screening can help detect diabetes early and improve the prevention and treatment of diabetes and its complications. Therefore, diabetes screening should be targeted at high-risk groups. For people at high risk for diabetes, it is advisable to start screening for diabetes early; for those with normal first screening results, it is advisable to repeat screening at least once every 3 years.

For those at risk with at least one risk factor, further fasting glucose or point-of-care glucose screening should be performed, of which fasting glucose screening is a simple and easy method and should be used as a routine screening method, but there is a possibility of underdiagnosis. If fasting glucose is ≥6.1 mmol/L or random glucose is ≥7.8 mmol/L, an oral glucose tolerance test (OGTT) is recommended, and both fasting glucose and 2-h post-glucose load glucose should be measured.

Blood glucose control

Maintaining strict control over blood sugar levels in patients with early-stage diabetes is a crucial factor in reducing the risk of developing diabetic microangiopathy. Research indicates that early implementation of tight glycemic control can lower the risk of diabetic microangiopathy, as well as myocardial infarction and mortality during long-term follow-up.

To ensure the most effective management of diabetes, glycemic control objectives should be tailored to each individual's needs. For young individuals newly diagnosed with T2DM and without significant complications or concurrent conditions, it is advisable to initiate and maintain strict glycemic control at an early stage.

Blood pressure control

Maintaining strict control over blood pressure in individuals newly diagnosed with T2DM can significantly decrease the risk of both diabetic macroangiopathy and microangiopathy. Analysis of the Hypertension Optimal Treatment Trial (HOT), as well as other diabetes subgroups of anti-hypertensive treatment clinical trials, also showed that tight blood pressure control significantly reduced the risk of cardiovascular events in diabetic patients without significant vascular complications.

Lipid control:

Several large clinical studies have shown that lowering low-density lipoprotein cholesterol (LDL-C) with statins can significantly reduce the risk of cardiovascular events in diabetic patients without significant vascular complications.

It is recommended that patients with T2DM without significant vascular complications but at high or very high risk of cardiovascular risk should be treated with glucose-lowering, blood pressure lowering, lipid regulation (mainly LDL-C lowering), and rational aspirin application to prevent cardiovascular events and diabetic microangiopathy.

Near-term goal of diabetes treatment: to eliminate diabetic symptoms and prevent acute metabolic complications by controlling hyperglycemia and related metabolic disorders

Long-term goal of diabetes treatment: to prevent chronic complications, improve quality of life and extend life expectancy through good metabolic control

The primary principle in setting comprehensive management goals for patients with T2DM is individualization, which should be considered based on the patient's age, disease duration, life expectancy, and severity of complications or comorbidities.

Tertiary prevention: delaying the progression of complications, reducing disability and mortality, and improving quality of life for patients with existing diabetes complications

The goal of tertiary prevention is to delay the progression of existing diabetes complications, reduce disability and mortality, and improve the quality of life for patients.

Continued glycemic control

Maintaining tight control over blood sugar levels can reduce the likelihood of further progressions of early diabetic microangiopathy, such as non-proliferative retinopathy and microalbuminuria. However, the benefits of tight glycemic control in reducing the risk of cardiovascular events and death are less pronounced in individuals who have had diabetes for a longer duration, are older, or have multiple cardiovascular risk factors or preexisting cardiovascular disease. The ACCORD study found that in these populations, tight glycemic control may actually increase the risk of all-cause mortality.

Continued blood pressure and lipid control

There is ample clinical research evidence that in patients with T2DM with cardiovascular disease, a combination of antihypertensive, lipid-regulating, and antiplatelet therapy should be used to reduce the patient's risk of cardiovascular events and death.

For people with T2DM who have been living with the condition for an extended period, are advanced in age, or have already been diagnosed with cardiovascular disease, it is imperative to implement a comprehensive management plan. Such a plan should include measures to regulate glucose levels, lower blood pressure, regulate lipid levels (with emphasis on lowering LDL-C), and antiplatelet therapy, all aimed at reducing the risk of cardiovascular events, as well as slowing the progression of microvascular complications and mortality. If a patient has developed severe, chronic complications of diabetes, it is highly recommended that they receive treatment from the appropriate medical specialty.

Early diabetes screening

More than half of the patients with T2DM have no obvious clinical manifestations in the early stages of the disease. Screening for diabetes allows for early detection and treatment of these patients and helps to improve the efficiency of the prevention and treatment of diabetes and its complications.

The target population for screening is people at high risk of diabetes. Adults at high risk include:

⦁ A history of prediabetes

⦁ Age ≥ 40 years

⦁ Body mass index (BMI) ≥ 24 kg/m2 and/or central obesity (waist circumference ≥ 90 cm for men and 85 cm for women)

⦁ History of diabetes mellitus in first-degree relatives

⦁ Lack of physical activity

⦁ Women with a history of delivery of a large child or a history of gestational diabetes

⦁ Women with a history of polycystic ovary syndrome

⦁ Women with acanthosis nigricans

⦁ Women with a history of hypertension or who are receiving antihypertensive treatment

⦁ HDL cholesterol <0.90 mmol/L and/or triacylglycerol >2.22 mmol/L, or on lipid-modifying therapy

⦁ History of atherosclerotic cardiovascular disease (ASCVD)

⦁ History of steroid use

⦁ Long-term treatment with antipsychotics or antidepressants

⦁ Total diabetes risk score in China ≥25

Children and adolescents at high risk include those whose BMI falls at or above the 85th percentile for their age and sex, and who exhibit at least one of the following three risk factors: maternal diabetes during pregnancy (including gestational diabetes), a history of diabetes in a first- or second-degree relative, or the presence of clinical conditions that are commonly associated with insulin resistance, such as acanthosis nigricans, polycystic ovary syndrome, hypertension, and dyslipidemia.

The screening procedure used a two-step method that involved measuring fasting glucose levels and conducting a 75 g oral glucose tolerance test (OGTT) to measure 2-hour blood glucose levels. Individuals with normal screening results are advised to undergo screening every three years, while those with pre-diabetes should undergo annual screening.

Reference：

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

Diabetes remission

There is a continuous rise in blood glucose levels and an associated increase in the risk of developing diabetes complications as an individual progresses from normoglycemia to prediabetes and ultimately to diabetes. The diagnosis criteria for diabetes are based on the blood glucose or glycated hemoglobin (HbA1c) levels that are associated with an increased risk of retinopathy, rather than representing a point of inflection in blood glucose levels. Theoretically, any intervention that addresses the underlying pathophysiological changes that cause elevated blood glucose levels - such as impaired insulin secretion, insulin resistance, and obesity - can slow the rate of increase in blood glucose levels or even bring them down from high levels to lower levels. Clinical studies have confirmed this theoretical speculation.

Research studies have demonstrated that lifestyle modifications, medication therapies and metabolic surgery interventions can all help to slow down the progression of pre-diabetes to diabetes (i.e., diabetes prevention) or bring down elevated blood glucose levels to a lower level (i.e., diabetes remission). The persistence of interventions is necessary to maintain the inverse resolution state because there is no way to effectively stop T2DM's natural progression through staged therapies. Remission of T2DM can lead to a longer period without the need for hypoglycemic drugs, lower psychological burden, improve quality of life, increase confidence to adopt a healthy lifestyle, and reduce the risk of lifelong complications. The overall risk of lifelong complications associated with diabetes is also reduced.

Definition of T2DM remission

As per the American Diabetes Association (ADA)'s Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes released in 2021, T2DM remission is defined as the state where blood glucose levels are normal without the use of glucose-lowering medication. However, there are still ongoing research and debate regarding the specific criteria, duration, and definition of T2DM remission. It is crucial to note that T2DM is not considered cured, and even after achieving remission, some patients may experience a rise in blood glucose levels that require glucose-lowering medication.

Basic conditions for T2DM remission

Remission of T2DM is often linked to the correction of obesity, improvement of body mass, reduction in fatty liver and fatty pancreas, improvement of insulin resistance and hyperinsulinemia, and correction of hyperglycemic toxicity, as well as islet β-cell dedifferentiation and transdifferentiation. However, the remission of T2DM requires certain basic conditions to be met. Clinically, the "ABCD" assessment method is usually used to determine the basic conditions for T2DM remission.

There is no clinical evidence of diabetes remission in the following special populations:

⦁ Specific types of diabetes, including cortisol hyperplasia, growth hormone tumors, glucagonomas, and some genetic causes of diabetes, require treatment for correctable causes in order to achieve remission.

 ⦁ Autoimmune diabetes is a group of patients with progressive decline in islet beta cells due to ongoing autoimmune attacks, and it is a relatively low percentage of overweight and obese patients. There is no clinical evidence of diabetes remission in this population.

 ⦁ Patients with longer duration of disease, more severe complications, and poorer islet function (fasting C-peptide <1.0 μg/L at glycemic compliance) in T2DM. There is no clinical evidence of diabetes remission in this population.

Four dimensions for assessing the chances of remission in patients with T2DM (ABCD assessment method)

Note: BMI= body mass index, GADA= glutamic acid decarboxylase antibody

Approaches to T2DM remission

T2DM has a low rate of spontaneous remission without significant intervention, so it requires a robust regimen for remission.

Intensive lifestyle interventions

Intensive lifestyle interventions are recommended by The Consensus of Experts as the cornerstone of such a program for the remission of T2DM. Maintaining a healthy lifestyle is not only the most effective way to prevent diabetes, but it is also a highly effective treatment for achieving remission of T2DM which is associated with poor lifestyle habits and excess weight.

1. Dietary nutrition therapy

For T2DM patients comorbid with obesity, it is suggested that calorie-restricted diet (CRD) and calorie-restricted Mediterranean diet with exercise are recommended as the basic regimens for T2DM remission. There are currently 3 main types of CRD:

(1) Reduce energy intake by a certain percentage (30% to 50%) from the target energy intake; 

(2) Reduce energy intake by about 500 kcal per day from the target intake;

(3) Daily intake of 1,000 ~ 1,500 kcal. In addition, short-term dietary patterns, such as high protein diets, low carbohydrate diets (LCDs), very low energy diets (VLCDs), intermittent fasting, and ketogenic diets, can aid in weight loss and managing T2DM. However, it is important to note that these dietary patterns should be customized by a nutritionist based on the patient's habits and physical condition, and the results should be regularly monitored and adjusted accordingly.

At the same time, during the weight loss process, you can use evaluated supplementary glycemic foods or functional foods to enhance satiety, slow down the absorption of carbohydrates, supplement nutrients, and assist in glycemic control, thus facilitating weight loss and alleviating T2DM. It is important to thoroughly assess the rationality and safety of the formula when utilizing meal replacement products, and ensure that they are appropriately integrated with the individual's general diet. The ideal meal replacement should contain sufficient protein, fiber, and micronutrients to meet basic nutritional requirements while managing caloric intake. There are three primary categories of meal replacements: 

(1) powders designed to replace staple foods, such as buns, bread, and noodles, with 80% of their starch content removed; 

(2) cookies intended to serve as meal replacements; 

(3) soups that can be utilized as a substitute for a full meal.

In addition, it is important to consider appetite management, for example:

(1) slow down the speed of meals: increase the number of chewing, chewing 20-40 times for each bite of food; pause between each bite, reduce the volume of each bite of food, use non-dominant hand-held chopsticks, or use a fork.

(2) Drink water before meals and consume a little number of nuts, such as 10 almonds or 20 peanuts. Nuts contain unsaturated fatty acids, which increase the release of the appetite suppressant cholecystokinin after consumption through the vagus nerve and non-vagus nerve pathway.

(3) Reasonable arrangement of meal order: 1. Drink soup before meals, easy to produce a sense of satiety. 2. Vegetables and low-sugar fruits, which are bulky and low in energy, slow down absorption and induce a feeling of satiety. 3. To enhance the feeling of fullness, serve meat (high energy) as the third course of a meal. 4. Eat small amounts of staple foods and carbohydrates at the end of the meal for slow absorption to reduce post-meal blood sugar fluctuations.

(4) Increase dietary fiber-rich foods: Dietary fiber empties slowly the stomach and makes it easy to feel full. You can increase the intake of foods such as oats, whole wheat bread made from meal replacement powder with 80% of starch removed, green leafy vegetables, and low-sugar fruits.

2. Exercise interventions

Exercise is one of the most effective ways to manage body weight. Exercise is the basis of T2DM treatment, and diabetic patients can achieve blood glucose control by directly consuming part of their energy through exercise. Consistent exercise can also increase muscle mass and lead to sustained improvements in insulin sensitivity. Additionally, exercise improves patients' blood lipids, blood pressure, and cardiovascular health and enhances their sense of pleasure.

The Consensus of Experts states that aerobic exercise is the optimal strategy for reducing overall body fat. The recommended duration is at least 150 minutes of moderate-intensity aerobic exercise per week. Resistance training should also be incorporated into the routine at least twice a week. To ensure safe and effective exercise interventions, it is crucial to follow a structured process that includes a health assessment, goal setting, program selection, intensity setting, exercise training, evaluation of outcomes, and adjustment when necessary.

(1) Health assessment: It includes taking a medical history, recording hyperglycemia, hypertension, hyperlipidemia, degree of obesity and cardiovascular disease conditions and other diseases affecting exercise; assessing exercise capacity, including endurance, upper body strength, lower body strength, balance, flexibility; assessing exercise safety and cardiorespiratory endurance, for example, calculating the appropriate heart rate range corresponding to aerobic exercise intensity.

(2) Goal setting: Create an exercise plan for Monday to Friday and weekends, including the frequency of exercise and the type of exercise you like.

(3) program selection: It is best for you to choose your favorite and appropriate program. You can consider walking, jogging, swimming, gardening, ball games, dancing, fitness, dumbbells, etc.

(4) Intensity setting: It is recommended to aim for at least 30 minutes of moderate-intensity aerobic exercise daily. If it's challenging to allocate a continuous 30-minute slot, breaking it down into three 10-minute sessions throughout the day is a viable alternative. Strength training should be performed for 30 minutes, at least two times per week. It is crucial to prioritize safety during exercise by selecting suitable exercises, intensity, and equipment, and adjusting accordingly to avoid injuries. Regular monitoring of body mass changes is essential to adjust the exercise load appropriately. Additionally, keeping track of the exercise effects can help to determine the efficacy of the exercise program.

Weight-loss drugs

According to The Consensus of Experts, Orlistat should be used as a supplementary treatment for type 2 diabetes remission in patients with a BMI of 27 kg/m² or higher and combined type 2 diabetes, for a brief period of 12-24 weeks. Orlistat is a lipase inhibitor that prevents the breakdown of dietary fat in the gastrointestinal tract, leading to its elimination from the body. It is the only weight loss medication approved for managing body weight in China and was authorized by the State Drug Administration in 2007 as an over-the-counter weight loss drug recommended for type 2 diabetes patients with a BMI of 27 kg/m² or higher. Orlistat is effective in reducing body weight, maintaining it, and preventing weight regain.

Non-insulin hypoglycemic drugs

The Consensus of Experts states that in patients with T2DM who do not meet the HbA1c standard and in whom intensive lifestyle interventions are not effectively implemented, short-term (8-12 weeks) adjuvant non-insulin drug combinations that can significantly improve body mass, such as glucagon-like peptide-1 (GLP-1) receptor agonists and their combination regimens, can help alleviate T2DM.

Insulin

The Consensus of Experts states that for HbA1c ≥10% and FPG ≥11.1 mmol/L, adjunctive application of short-term (2 weeks) early insulin-intensive therapy can help to alleviate T2DM. Intensive insulin therapy improves islet β-cell function and insulin resistance in patients with newly diagnosed T2DM but does not alter the natural course of progressive decline in islet β-cell function.

Metabolic surgery

According to The Consensus of Experts, metabolic surgery can be considered for managing T2DM in the Asian people with a body mass index (BMI) of 32.5 kg/m2 or greater if non-surgical interventions fail to effectively improve metabolic disturbances and body weight. Metabolic surgery for T2DM requires the patient to have sufficient islet functional reserve as a prerequisite. In addition, the selection of a suitable surgical procedure, adequate preoperative evaluation, and preparation, enhanced postoperative follow-up, and nutritional and exercise guidance are also key to improving the effectiveness and safety of the procedure.

Evaluation of T2DM remission

One way to diagnose remission of T2DM is by achieving an HbA1c level of <6.5% after discontinuing glucose-lowering drugs or implementing lifestyle interventions for at least 3 months. However, in certain cases where HbA1c does not accurately reflect blood glucose levels, such as in the presence of hemoglobin variants or irregularities in the HbA1c assay, an alternative diagnostic criterion can be used. This may involve measuring fasting blood glucose (FPG) levels of <7.0 mmol/L or estimating glycated hemoglobin (eA1c) levels of <6.5% through ambulatory glucose monitoring. It is important to continue monitoring HbA1c, FPG, or eA1c every 3 to 6 months after achieving remission from diabetes.

Improved prognosis of T2DM remission

The Consensus of Experts states that maintaining early remission of diabetes for a longer duration can considerably decrease the incidence of diabetes complications and all-cause mortality. The root cause of diabetes is often linked to unhealthy lifestyle choices, and interventions that focus on lifestyle improvements can effectively lower the risk of diabetes and its associated complications. Lifestyle interventions in people at high risk for diabetes can significantly reduce the risk of death and macrovascular and microvascular events in this population in all directions. This has important social and economic benefits for reducing mortality and disability rates, improving patients' quality of life, and reducing health care costs.

Diabetes is a complex disease, and the recommended remission regimen may not stop the drug treatment in every patient with early T2DM, but the implementation of the remission regimen can allow more T2DM patients to regain a healthy life and improve their quality of life. Helping patients relieve T2DM is not only to reduce drugs, stop drugs, and control blood sugar steadily, but also to teach patients a scientific lifestyle of healthy and long life, and benefit life, as well as benefit the patient's family and the country.

Reference:

Committee of Consensus of Chinese Experts on the Remission of Type 2 Diabetes Mellitus. Consensus of Chinese Experts on the Remission of Type 2 Diabetes Mellitus　[J]. Chinese General Practice, 2021, 24(32): 4037-4048. DOI: 10.12114/j.issn.1007-9572.2021.01.105.