The extremely high relevance of the problem of prediabetes is explained by the significant prevalence of this condition, the significant risk of developing type 2 diabetes and the association with diabetic complications. Therefore, prediabetes should be recognized as a condition requiring active intervention. According to experts, the development of type 2 diabetes in people with prediabetes can be prevented through lifestyle modification, pharmacological interventions and bariatric surgery.
According to experts from the International Diabetes Federation (IDF), approximately 6.9% of adult patients currently have diabetes mellitus (DM) in the general population. By 2030, this figure may rise to 17%. In absolute terms, the prevalence of DM is striking: 382 million in 2013 and a projected increase to 0.5 billion in the next 10-15 years. More than 90% of cases of the disease occur in type 2 diabetes, so it is not surprising that its prevention is recognized as one of the most urgent tasks of modern health care. From the point of view of cost-effectiveness, the main efforts to prevent type 2 diabetes should be directed to risk groups and, first of all, to people with prediabetes. What is meant by this term and is there a need for treatment for this condition?
What is the danger of prediabetes?
Pre-diabetes is a pathological condition that predisposes to the development of type 2 diabetes and is characterized by intermediate levels of glycemia that exceed the norm, but not high enough to diagnose diabetes.
The term "prediabetes" combines two different from the point of view of pathophysiology, but similar in clinical significance, pathological conditions: an increase in fasting blood glucose (FG) and impaired glucose tolerance (IGT), characterized by an excessive increase in the level of glycemia after a carbohydrate load. Some individuals may have both disorders at the same time.
The relevance of the problem of prediabetes is due to several factors at once: the highest risk of developing type 2 diabetes, the relationship with other pathological conditions and a significant prevalence.
In parallel with the increase in the prevalence of obesity worldwide, the prevalence of not only type 2 diabetes, but also the pre-diabetes that preceded it, is increasing. According to the Centers for Disease Control and Prevention (CDC), in the United States in 2009-2012. Approximately 37% of patients over the age of 20 and more than 50% of those over the age of 65 had prediabetes (PHN and/or IGT). This means that there are more than 85 million people with prediabetes in the US alone. The prevalence of IGT in the world is approximately 350 million, and by 2035, according to IDF experts, it can reach 470 million.
Prediabetes is characterized by a very high annual conversion rate to DM (5-10%). The risk of developing type 2 diabetes in individuals with PHN increased by an average of 4.6 times compared to the general population; in patients with IGT – by 6.3 times, in the presence of PHN and NTG – 12.1 times.
Observational studies have found an association between prediabetes and complications such as nephropathy, neuropathy, retinopathy and cardiovascular disease. They can be detected already at the time of diagnosis of type 2 diabetes and even in individuals with PHN and/or IGT. It is assumed that these complications can be caused not only by hyperglycemia, but also by other factors associated with prediabetes and obesity (insulin resistance, dyslipidemia, etc.), which have a damaging effect on the vascular endothelium.
A clinically significant marker of microvascular damage is microalbuminuria, which occurs 2 times more often in patients with prediabetes than in patients with normal blood glucose levels.
According to the NHANES study, chronic kidney disease in patients with prediabetes occurs in 17.7% of cases compared with 10.6% of cases – in persons without disorders of carbohydrate metabolism. In the MONICA study, the prevalence of diabetic polyneuropathy was approximately 2-fold higher in individuals with PHN and IGT compared to those with normoglycemia. Similar data have been obtained for retinopathy.
Diagnosis of prediabetes
Because prediabetes is a largely asymptomatic condition, there is a need for screening to identify individuals with preclinical disorders of carbohydrate metabolism. What should be this screening – universal or targeted?
There is currently insufficient evidence to support universal screening for carbohydrate metabolism disorders (diabetes and pre-diabetes). There are grounds to assume insufficiently high economic efficiency of such measures. Therefore, most experts now support the so-called targeted screening, which is carried out in risk groups.
These groups are defined by the presence of one or more factors that increase the risk of developing prediabetes and its progression to type 2 diabetes, namely:
- old age;
- sedentary lifestyle;
- overweight or obese;
- family history of diabetes;
- cardiovascular disease;
- metabolic syndrome;
- arterial hypertension;
- dyslipidemia;
- history of gestational diabetes or having a baby weighing more than 4 kg;
- polycystic ovary syndrome;
- taking antipsychotic medications or antidepressants;
- ethnicity;
- intrauterine factors (nutrition deprivation with low birth weight, predisposing to a "thrifty" phenotype; intrauterine hyperglycemia), etc.
The optimal method for diagnosing prediabetes in individuals at risk can be considered OGTT, which allows you to simultaneously assess the level of fasting blood glucose and glucose tolerance. If there are organizational difficulties with OGTT, then it is better to determine HbA1c or just fasting glucose than not to determine anything.
Effectiveness of different methods of prevention of type 2 diabetes in people with prediabetes
A number of studies have shown the possibility of preventing type 2 diabetes in people with prediabetes through lifestyle modification (diet and/or exercise), pharmacotherapy and bariatric surgery.
Lifestyle modification in prediabetes
Lifestyle modification in the context of type 2 diabetes prevention refers to patient diet and increased physical activity. The main objective of these events – weight loss and, consequently, a decrease in the influence of risk factors associated with obesity. The beneficial effects of lifestyle modification on carbohydrate metabolism and a reduction in the risk of type 2 diabetes have been shown in several large studies.
Weight loss is the most significant contribution to the prevention of type 2 diabetes in individuals with prediabetes. However, it should be noted that the Da Qing study, which included participants with normal body weight, showed a positive effect of dieting and increased physical activity, even with a slight decrease in body weight. Therefore, lifestyle modification in the presence of dysglycemia is recommended not only in the presence of overweight or obesity.
Drugs for prediabetes
Dieting and increased physical activity are effective in preventing type 2 diabetes, but they are associated with poor compliance in most patients, especially in the long term. Therefore, the search for effective drugs for the prevention of type 2 diabetes remains relevant. To date, several classes of hypoglycemic drugs and weight loss drugs have demonstrated this ability.
Metformin. When used as a hypoglycemic agent in type 2 diabetes, metformin has been shown to have additional beneficial effects such as weight loss and improved blood lipid profile. These effects may be helpful in pre-diabetes.
According to the results of a meta-analysis of the three largest intervention studies, the use of metformin in patients with IGT resulted in a 45% reduction in the risk of type 2 diabetes in people with prediabetes.
Glitazones. Like metformin, these drugs increase glucose uptake and utilization in peripheral organs and reduce hepatic gluconeogenesis, thereby reducing insulin resistance. However, at present, glitazones, despite their significant prophylactic effect, cannot be recommended for use in patients with prediabetes due to safety concerns, since these drugs promote weight gain, have hepatotoxicity, increase the incidence of cardiovascular complications and, possibly, bladder cancer. .
α-glucosidase inhibitors. Antidiabetic drugs in this group, such as acarbose and voglibose, reduce the absorption of glucose in the intestine and, accordingly, blood glucose levels. Unfortunately,
Orlistat. This gastrointestinal lipase inhibitor is used to treat obesity by inhibiting the absorption of dietary fat (by about 30%), thereby significantly reducing the overall energy content of the diet.
Insulin. Good glycemic control achieved with insulin glargine prevents patients from progressing to pre-diabetes and type 2 diabetes for 5 years, maintaining a mean HbA1c of approximately 6.5%. However, this observation can be considered more curative than preventive.
Glucagon-like peptide-1 (aGLP-1) agonists. These hypoglycemic drugs increase insulin secretion, glucagon and suppress glucose production in the liver, slow gastric emptying, reduce appetite and thus contribute to weight loss in individuals with obesity. Exenatide and liraglutide have demonstrated long-term efficacy for sustained weight loss in obese patients and have also been shown in experimental studies to reduce the incidence of prediabetes and diabetes. However, this effect still needs to be confirmed in controlled randomized clinical trials.
The most common side effects of this class of drugs are nausea and vomiting, which can significantly reduce adherence to therapy. Also, the limitation of their wide clinical use is associated with the rather high cost of these drugs and the parenteral route of administration.
Dipeptidyl peptidase-4 (iDPP-4) inhibitors. The main mechanism of action of this class of drugs is to increase the activity of endogenous GLP-1 by preventing its destruction by the DPP-4 enzyme, which improves glycemic control in patients with diabetes 2 types. However, their protective effect on the risk of developing type 2 diabetes still needs to be studied.
Bile acid sequestrants. Colesevelam has been shown to increase insulin sensitivity and improve β-cell function in individuals with prediabetes and type 2 diabetes. Further research should explore the possibility of preventing type 2 diabetes in prediabetic individuals with this drug.
New drugs. Some new drugs may be useful in the future for prediabetes. In particular, certain hopes are associated with new drugs for the treatment of obesity – phentermine, topiramate, lorcaserin. Bromocriptine mesylate also has a certain potential for the treatment of prediabetes, which, by regulating the activity of neurotransmitters, can improve the control of carbohydrate and lipid metabolism.
Bariatric Surgery
Bariatric surgery refers to the surgical treatment of obesity, aimed at reducing the intake of nutrients (due to malabsorption and/or reduced food intake) followed by the normalization of body weight. Since morbid obesity is a significant risk factor for prediabetes and type 2 diabetes, bariatric interventions are considered to be an effective method of their prevention.Practical recommendations for patients with prediabetes
Currently, there are no unified clinical guidelines for the management of patients with prediabetes. The choice of necessary interventions should be individual – taking into account gender, age, ethnicity, cultural characteristics, socioeconomic status, patient motivation and other factors.
The main and most successful strategy for the prevention of type 2 diabetes currently is lifestyle modification, including diet (rational nutrition) and increased physical activity.
Dietary recommendations for patients with prediabetes include the following: reducing the total energy content of the diet; limiting light carbohydrates and saturated fats; reducing the consumption of highly refined foods; increased consumption of fruits, vegetables, unrefined cereals with a high fiber content; Eating adequate amounts of vegetable oil low in saturated fat (such as olive oil), nuts, legumes, dairy products, and fish (as a source of protein).
Increased physical activity means at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes of vigorous-intensity exercise (eg, 30 minutes 5 times a week or 50 minutes 3 times a week). You should start with shorter and easier classes, gradually bringing them to the required time and intensity. It is also desirable to perform anaerobic power loads involving all muscle groups 2 or more times a week.
Maintaining long-term adherence of patients to lifestyle interventions is a major challenge.
Special educational and social programs with the participation of doctors and psychologists can improve compliance. Participation in support groups can be helpful.
Medicated prevention of type 2 diabetes is still a subject of study. To date, metformin has demonstrated the best ratio of efficacy and safety as a pharmacological method for the prevention of type 2 diabetes in people with prediabetes. However, it should be remembered that in our country the officially registered indication for the use of this drug is only type 2 diabetes. Other hypoglycemic drugs do not have an optimal ratio of efficacy and safety and / or sufficient evidence base, therefore, they cannot currently be recommended for widespread clinical use as a means of preventing type 2 diabetes. In overweight/obese patients with prediabetes, orlistat may be considered, and in the case of morbid obesity –
Finally, public support for healthy lifestyles and personal awareness of the risks associated with prediabetes are urgently needed. The most important role in solving these problems is given to practicing doctors.
According to http://health-ua.com/
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