Prediabetes: From diagnosis to prognosis

Abstract

Pre-diabetes is a condition of intermittent hyperglycemia, insufficient to define diabetes, which is characterized by combination of insulin resistance, alpha and beta cell dysfunction. It carries a risk for type 2 diabetes, often with pre-existing vascular complications, atherosclerotic cardiovascular disease, fatty liver and kidney disease. A reliable diagnosis is made on the basis of the oral glucose tolerance test (oGTT) and the levels of glycosylated hemoglobin, HbA1c. Based on that, the presence of 3 basic disorders within pre-diabetes is determined: elevated fasting glycemia, glucose intolerance or both. However, this is not enough to predict the outcome. Extensive epidemiological studies have defined the minimum tests that should be performed in people with pre-diabetes. These are: calculation of body mass index (BMI), analysis of body composition, oGTT with analysis of glycemia, insulin and c-peptide in 0, 60 and 120 min, or just analysis of insulin and c-peptide with calculation of HOMA IR and HOMA B index, triglycerides, HDL cholesterol, transaminases, gamma GT, albuminuria and glomerular filtration according to CKD-EPI creatinine formula. Based on these parameters, 6 subtypes of pre-diabetes have been proposed that can predict outcomes: 1. Moderately obese with initial disturbance in insulin sensitivity, but normal insulin secretion; 2. Normal body weight with normal insulin sensitivity of tissues, but somewhat reduced insulin secretion; 3. Moderate obesity or grade I obesity with moderately reduced insulin sensitivity and insulin secretion; 4. Grade I obesity, more subcutaneous than visceral fat, with preserved insulin sensitivity and secretion; 5. Grade I, II degree or morbidly obese with fatty liver and low insulin sensitivity and secretion and 6. Obesity I, II degree or morbidly obese with increased visceral adipose tissue and risk of kidney disease. Monitoring of outcomes found that the metabolically healthier subtypes of pre-diabetes are 1, 2 and 4. Type 2 diabetes is most common in subtypes 3 and 5. Phenotype 5 has the highest cardiovascular risk and phenotype 6 has the highest mortality. Chronic kidney disease is most common in subtype 6. The presence of fatty liver increases mortality. Identification of pre-diabetes has preventive therapeutic potential. It is important to make a diagnosis, clarify the prognosis and prevent comorbidity by proper diet and physical activity and drugs to treat type 2 diabetes and obesity.