Prediabetes through the lens of current data and findings − and why hurry with intervention
Type 2 diabetes mellitus (DM2) is one of the most common causes of premature morbidity and mortality worldwide. The most serious impact on the health of the organism is mainly due to the macrovascular complications of this disease. However, their occurrence was often recorded before the diagnosis of DM2 was confirmed. Prediabetes itself thus represents a condition associated with the risk of developing cardiovascular (CV) complications with all their prognostic implications for patients.
Definition of prediabetes
Prediabetes is defined as the detection of impaired glucose tolerance (glucose level at 120 minutes of the oral glucose tolerance test [oGTT] 7.8−11.0 mmol/l) or elevated fasting glucose (value in venous plasma 5.6−6.9 mmol/l). Another possible criterion according to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) may be a glycated hemoglobin (HbA1c) value of 38 to < 48 mmol/mol. However, Czech laboratories have not yet achieved sufficient standardization, so this examination cannot be fully utilized, and the diagnosis must be confirmed by determining fasting glucose or oGTT when a higher HbA1c value is detected. Globally, more than 400 million people can be diagnosed with prediabetes, and by 2030, it is estimated that this number will increase to 470 million.
Pathophysiology of prediabetes and its complications
Pathophysiological processes typical for prediabetes and its progression to DM2 include insulin resistance and concurrently reduced insulin production by pancreatic beta cells. Gradually, metabolic dysregulation occurs. Lipolysis accelerates, levels of glucagon-like peptide-1 (GLP-1) decrease, and postprandial glucagon secretion is suppressed. Increased production of pro-inflammatory cytokines further accentuates the pathological state of the organism.
Macrovascular complications typical for type 2 diabetics (CV disease, stroke [CVA], lower limb ischemic disease [PAD]) have been recorded in patients even in the prediabetic stage. A recent meta-analysis of 35 studies confirmed a higher risk of both acute and chronic forms of coronary heart disease (CHD) and heart failure in these patients (the EPIC − Norfolk and Paris Prospective Study highlighted a twofold increase in CV mortality in patients with impaired glucose tolerance). The progression of prediabetes to DM2 and the occurrence of complications are also significantly influenced by the presence of typical components of the metabolic syndrome (primarily insulin resistance, abdominal obesity, hypertriglyceridemia, dyslipidemia, and hypertension). Patients with prediabetes have also been shown to have a higher risk of stroke, increased carotid artery atherosclerosis, and impaired functional cardiac parameters.
Microvascular complications associated with hyperglycemia can also be detected in the period before full development of DM2. According to study data, signs of retinopathy were found in nearly 8% of prediabetics, 16% showed peripheral neuropathy, and approximately 18% suffered from some degree of chronic renal insufficiency.
Intervention options
The universal way to prevent the development of DM2 is lifestyle changes, especially dietary adjustments and regular physical activity. The incidence of DM2 can be reduced by up to half with this intervention, and patients benefit from it for a relatively long time (up to 30 years). Lifestyle changes mainly influence the occurrence of macrovascular complications; the benefit in microvascular diseases has not been confirmed. Prevention of DM2 is associated with reduced cardiovascular and overall mortality.
From the possibilities of pharmacological intervention, the effects of metformin, thiazolidinediones, alpha-glucosidase inhibitors, and GLP-1 analogs were examined in clinical studies. All drugs except for metformin have shown effects on reducing the risk of disease progression; however, these drugs are not indicated or recommended for the treatment of prediabetes. The most significant effect in clinical study participants was brought about by lifestyle changes. Therefore, individuals with prediabetes should primarily be recommended to reduce body weight (by about 7%) and engage in regular physical activity (at least 150 minutes per week). It is necessary to carefully and regularly monitor the condition and progression of the disease.
In the case of prediabetes, metformin administration is additionally recommended if patients simultaneously have impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), type 2 diabetes in a direct relative, elevated triglycerides, reduced HDL cholesterol, and/or HbA1c > 45 mmol/mol. It is strongly recommended for patients under 60 years of age and for obese individuals (BMI ≥ 30 kg/m2).
Conclusion
The results of many studies have shown that prediabetes is significantly associated with increased CV morbidity and mortality. CV risk starts to rise long before DM2 is diagnosed, and clinical manifestations of microvascular and macrovascular complications associated with chronic hyperglycemia are already present. By early, consistent, and relatively simple lifestyle changes, possibly in combination with pharmacotherapy, it is possible to slow down or even reverse disease progression.
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Sources:
1. Brannick B., Dagogo-Jack S. Prediabetes and cardiovascular disease: pathophysiology and interventions for prevention and risk reduction. Endocrinol Metab Clin North Am 2018; 47 (1): 33−50, doi: 10.1016/j.ecl.2017.10.001.
2. Karen I., Svačina S. Prediabetes. Update 2022. Recommended diagnostic and therapeutic procedures for general practitioners. General Practice Society CLS JEP, Prague, 2022. Available at: www.svl.cz/files/files/Doporucene-postupy/2020/DP-PREDIABETES-2022.pdf
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