Prediabetes Needs Proactive Management In India: Why?

Prediabetes, also termed intermediate hyperglycemia or non-diabetic hyperglycemia, a high-risk state for developing diabetes, is defined by glycaemic variables that are higher than normal but lower than the thresholds for diabetes. It includes impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (1). According to the American Diabetes Association (ADA), IFG 100-125 mg/dL (5.6 and 6.9 mmol/L) and HbA1c 5.7-6.4% (39 and 47 mmol/mol) are diagnostic of prediabetes. The World Health Organization (WHO) defines an IGT 140-199 mg/dL (7.8 and 11.0 mmol/L) and an IFG 110-125 mg/dL (6.1 and 6.9 mmol/L) as intermediate hyperglycemia (2).

Prediabetes Deserves More Attention: The prevalence of prediabetes is increasing worldwide (3). According to the ICMR-INDIAB-17 study, the prevalence of prediabetes in India is 15.3%, higher than the prevalence of diabetes (11.4%), which makes prediabetes a bigger problem than type 2 diabetes itself. The weighted prevalence of IFG (as per WHO cutoff) is much more than the IGT (10·1% vs 3·3%). IFG prevalence is significantly higher among females and IGT among males, but with similar trends in urban and rural areas (4).

Prediabetes Likely to Progress to Diabetes: The annual conversion rate of prediabetes to diabetes is 5%- 10% (3). About 19.4% of Indian normal glucose tolerance (NGT) patients developed diabetes, whereas 25.7% developed prediabetes, a total conversion rate to dysglycemia of 45.1%. Given these circumstances, a better awareness of prediabetes could benefit early identification and timely management, thereby lowering the development of diabetes and associated complications (2).

Indian Risk Factors for Prediabetes: Often, the risk of prediabetes increases with BMI. Obesity and hypertension increase the risk of prediabetes by 6.75% and 1.35%, respectively, in India (5). Other Indian risk factors for prediabetes include family history of diabetes and gestational diabetes mellitus, triglycerides (TG) level above 200 mg/dL, and high-density lipoprotein-cholesterol (HDL-C) level less than 35 mg/dL (2).

What Other Clinical Risks Ensue If Prediabetes is Not Treated?

Prediabetes increases the risk of all-cause mortality and the incidence of cardiovascular outcomes, coronary heart disease, stroke, chronic kidney disease, cancer, and dementia (6).

Prediabetes increases the risk of cardiovascular disease and all-cause mortality. A meta-analysis evaluating the association between prediabetes and the risk of all-cause mortality and incident cardiovascular disease indicated that in the general population, prediabetes was associated with an increased risk of all-cause mortality (relative risk/RR 1.13), composite cardiovascular disease (RR 1.15), coronary heart disease (RR 1.16), and stroke (RR 1.14) in a median follow-up time over 9.8 years. In patients with atherosclerotic cardiovascular disease, prediabetes increased the risk of all-cause mortality (RR 1.36), composite cardiovascular disease (RR 1.37), and coronary heart disease (RR 1.15) in a median follow-up time of 3.2 years. Therefore, timely screening and proper management of prediabetes might contribute to primary and secondary prevention of cardiovascular disease (1). Diabetic retinopathy is found to be present in about 6% of Asian Indians with prediabetes. It is further noted that higher HbA1c values among individuals with prediabetes doubled the risk for diabetic retinopathy (7).

Screening of Prediabetes:

American Diabetes Association Standard of Care-2024: The American Diabetes Association Standard of Care-2024 suggests that the testing for prediabetes should be done in adults with overweight or obese (BMI ≥25 kg/m2 or ≥23 kg/m2 in Asian American individuals) who have one or more risk factors, including first-degree relative with diabetes, history of cardiovascular disease, hypertension (≥130/80 mmHg or on therapy for hypertension), HDL cholesterol level <35 mg/dL (<0.9 mmol/L) and/or a triglyceride level >250 mg/dL (>2.8 mmol/L), individuals with polycystic ovary syndrome, physical inactivity, and other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) (8).

Indian Consensus on Prediabetes: The Indian Consensus Statement on Approach and Management of Prediabetes in India suggested using the Indian Diabetes Risk Score (IDRS) to screen prediabetes with clinical risk factors. The score predicts the probability of diabetes based on four simple parameters: age, abdominal obesity, family history of diabetes, and physical activity (2).

Latest International Diabetes Federation 2024 Position Statement: A new position statement from the International Diabetes Federation advises using 1-hour post-load plasma glucose (as defined by plasma glucose ≥ 155 mg/dL [8.6 mmol/L]) to improve the identification of people at risk for developing T2D, the risk for micro- and macrovascular complications and mortality, obstructive sleep apnoea, cystic fibrosis-related diabetes mellitus, metabolic dysfunction-associated steatotic liver disease and severity of hepatic fibrosis. The statement also noted that the 1-hour post-load plasma glucose also provides an opportunity for earlier detection and intervention in high-risk populations, benefits from lifestyle and pharmacologic interventions to reduce progression to T2D, and even reduces diagnostic complexity and confusion with current diagnostic criteria for intermedia hyperglycemia (9).

Pharmacotherapy as an Adjunct to Lifestyle Therapy: Lifestyle interventions can modify the progression of individuals towards overt diabetes, and it is known to reduce prediabetes by 58%. However, lifestyle interventions are centered around very intensive diet and adherence. Pharmacotherapy may be required and important in patients with severe hyperglycemia, individuals more susceptible to worsening dysglycemia, developing diabetes, developing CV complications, or having positive family history of diabetes (2).

Metformin in Prediabetes: Metformin is the pharmacological agent recommended for preventing or postponing T2D. The Indian Council of Medical Research (ICMR) and Research Society for the Study of Diabetes in India (RSSDI) recommend Metformin in prediabetes primarily for preventing T2D and delaying the onset of T2DM, secondary prevention of prediabetes, and primordial prevention of vascular ill health when metformin is given to prediabetes patients to prevent vascular complications (2).

The current ADA guidelines state that metformin should be considered in those with prediabetes, especially with BMI >35 kg/m2, age above 60 years, women with prior gestational diabetes mellitus, and individuals where lifestyle intervention is insufficiently effective in reducing body weight and improving glucose tolerance. The RSSDI guidelines recommend considering metformin at the dose of 500mg twice daily (2).

Metformin is Drug Controller General of India (DCGI) approved in the management of prediabetes for reducing the risk or delay of the onset of T2DM in adults, overweight patients with IGT, and/or IFG, and/or increased HbA1C who are at high risk for developing overt T2DM and still progressing towards T2DM despite implementing intensive lifestyle changes for 3 to 6 months (10).

Impact of Prediabetes Awareness Program: Prediabetes awareness and knowledge are significantly inadequate in India. A survey among Indian individuals with prediabetics showed that 90% had poor knowledge about prediabetes, which indicated that large-scale prediabetes screening and management programs are urgently needed. The survey also noted that implementing prediabetes education programs increased the self-management skills among people living with prediabetes. The study concluded that a prediabetes education program could significantly improve knowledge, attitude, and self-management practices among Indian people living with prediabetes and could be an effective strategy to prevent diabetes in this high-risk population (11).

ACT Against Prediabetes: Practice Pointers

• Prediabetes, a precursor for diabetes, has a higher prevalence than diabetes (15.3% vs 11.4%) in India (2).
• Obesity and hypertension are the two common risk factors for prediabetes (2).
• Prediabetes increases the risk of cardiovascular disease, all-cause mortality, and diabetic retinopathy.
• Early diagnosis and treatment of prediabetes aggressively with appropriate drugs, when indicated are the key for the management of prediabetes (2).
• Metformin is approved by DCGI India and is also approved in the United Kingdom and European Union for the management of prediabetes (10).
• Prediabetes education programs could significantly improve knowledge, attitude, and self-management practices among Indian people living with prediabetes (11).

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