Prediabetes is an intermediate state of high blood sugar where the glucose levels are higher than normal but still below the levels described for the diabetes threshold.
Diabetes is a metabolic disorder where either the cells of the pancreas fail to produce insulin (type 1) or the cells of the body fail to respond to the insulin produced by the pancreas (type 2). While type 1 diabetes has autoimmune origins, type 2 has a more complicated etiology that is multifactorial in nature. Type 2 diabetes leads to severe complications such as kidney disease (nephropathy), issues with eyesight (retinopathy) and in extreme cases, nerve damage (neuropathy). Type 2 diabetes is also associated with increased risks of cardiovascular disease, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis.
Many studies suggest an association between prediabetes and complications of diabetes such as early nephropathy, and early retinopathy. According to a study published in the Indian Journal of Medical Research in 2018, the estimated prevalence of prediabetes in India is 14%.
Various organizations have defined prediabetes that are not uniform across the world. The World Health Organization (WHO) has defined prediabetes as a state of intermediate hyperglycemia using two specific parameters, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Impaired Fasting Glucose is defined when the fasting plasma glucose level is between 110 to 125 mg/dL. Impaired Glucose Tolerance is when plasma glucose level is between 140-200 mg/dL present after 2 hours of 75 g of oral glucose ingestion.
The efficiency of IFG and IGT as diabetes and prediabetes parameters have been questioned as they fail to capture the exact pathology related to diabetes and probability of developing diabetes in future. Hemoglobin A1c (HbA1c) measures the average blood glucose over the 3 months and is believed to pinpoint hyperglycemia more accurately. However, HbA1c is substantially determined by genetic factors independent of blood glucose levels and may be an imprecise tool to measure average blood sugar.
Many scientists state that prediabetes defined by various alternative criterions consists of individuals who have other metabolic or underlying issues that impairs their glucose metabolism. These underlying issues include stress, thyroid malfunction, impaired sleeping patterns, ovarian or uterine disorders etc. The presence of both IFG and IGT in individuals with a history or susceptibility for these disorders tend to have advanced impairment in overall glucose homeostasis.
Apart from progressing to diabetes if not screened early on, several studies have shown that prediabetes can lead to other complications such as.
- chronic kidney disease and early nephropathy
- reduced heart rate variability and decreased parasympathetic modulation of the heart
- painful sensory neuropathy
- increased prevalence of male erectile dysfunction
- diabetic retinopathy
- increased prevalence of coronary heart disease
One of the most effective treatments include lifestyle interventions that can effectively reduce the risk of progressing to diabetes by 40%-70% in adults with prediabetes. Lifestyle intervention programs aim to change the modifiable risk factors of prediabetes and diabetes by targeting obesity through physical activity and dietary changes.
Several groups of antidiabetic drugs such as Thiazolidinediones, GLP-1 analogies and non-antidiabetic drugs and therapies such as anti-obesity drugs, and bariatric surgery have been studied as possible pharmacotherapies for prediabetes. Metformin, a drug popularly used to control diabetes also has additional favorable outcomes such as body mass index (BMI) reduction and improved cholesterol profile. A 2009 study showed that metformin was able to reduce the risk of development to diabetes by 45% in individuals with IGT.
Drugs such as glitazones and α-glucosidase inhibitors which increase glucose uptake and prolong overall carbohydrate digestion time have been used in various trials to help treat prediabetes. However, these drugs are associated with severe adverse effects when taken long term. Secondary intervention with pharmacotherapy with metformin is advocated for high-risk individuals but criteria for such consideration benefit of early intervention, long term cost effectiveness of such interventions and the end point of therapy remain unclear.
Despite being an asymptomatic disease, prediabetes is considered to be an at risk state, with high chances of developing diabetes. Screening asymptomatic adults for prediabetes and type 2 diabetes may allow earlier detection, diagnosis, and treatment, with the ultimate goal of improving health outcomes.