From Detection to Prevention: Making Prediabetes Screening and Early Intervention Routine. - Dr Mahesh Chavan

Prediabetes - Higher Complications Risk than We Know

Prediabetes, conventionally understood as an intermediate stage between normoglycemia and T2DM, is now suggestive of a clinically significant condition associated with risk of early and progressive vascular damage (1). A 2020 meta-analysis of 129 studies, involving over 10 million individuals revealed that prediabetes was associated with a 13% increased risk in all-cause mortality, a 16% increased risk of coronary heart disease, and a 14% raised risk of stroke, compared to normoglycemic individuals (2). Early recognition, therefore, provides a critical window to prevent progression to diabetes and mitigate long-term cardiometabolic complications (1).

Deciphering the Natural History of Prediabetes in India: What is the Annual Transition Rate to T2D?

Studies indicate that almost 50% of Indian prediabetics progress to type 2 diabetes within five years, suggesting a compressed natural history (3). The CURES study from Chennai showed a 58.9% conversion rate from prediabetes to diabetes over 9.1 years. Supporting this observation, Narayan et al. reported annual transition rates of 8.6% from isolated impaired fasting glucose (iIFG) to diabetes and 13.9% from impaired glucose tolerance (IGT) to diabetes, highlighting the rapid progression of prediabetes in Indians (3).

Figure 1. Annual transition probabilities (%) between normoglycaemia, iIFG, IGT, and diabetes.

Who is at Higher Risk of Progression from Prediabetes to T2D and Why?

Key predictors of this progression included: advancing age, family history of diabetes, HbA1c, low HDL cholesterol, and physical inactivity (4). Accelerated progression in Indians is largely attributed to early β-cell dysfunction despite relatively mild insulin resistance, leading to inadequate insulin secretion and rapid β-cell exhaustion (3).

What is the First Step to Mitigate the Prediabetes Epidemic?

The simple answer is screen more. In India, 136 million adults are living with prediabetes, and nearly half remain unaware of their condition (5).

Early detection of prediabetes through screening is paramount for providing timely intervention and support, reducing the risk of type 2 diabetes and associated complications (6). The ADA 2026 Standards of Care recommend risk-based screening for prediabetes and diabetes in adults using HbA1c, fasting plasma glucose (FPG), or 2-hour plasma glucose (2-h PG) measured during a 75-g oral glucose tolerance test (OGTT) (7). The International Diabetes Federation (IDF) further recognizes a 1-hour plasma glucose value ≥155 mg/dL during a 75-g OGTT as a marker of intermediate hyperglycaemia, enabling identification of high-risk individuals who may be missed by conventional glycaemic tests (8). If results are normal, screening should be repeated at least every 3 years, with more frequent testing considered based on initial results and individual risk status (9).

Lifestyle Interventions are Foundational: But Are They Always Enough in the Real World?

While lifestyle modification remains the cornerstone of prediabetes management, 39.3% of individuals with impaired glucose tolerance developed diabetes over 3 years despite lifestyle intervention in the IDPP-1 study, highlighting the need for additional preventive strategies in selected high-risk individuals (4). Among available therapies, metformin has emerged as the most extensively studied and widely recommended option for prediabetes management, supported by robust clinical evidence across diverse populations (10).

Metformin for Prediabetes – Why it Seems a Simple, Cost-Effective Practical Intervention to Tackle Prediabetes?

• Metformin is currently the only antidiabetic medication recommended for consideration in prediabetes by ADA (2026 Standards of Care and has been approved for prediabetes in at least 66 countries (11).
• Supporting its role in early intervention, the UAE consensus 2026 states that metformin may be considered for the prevention of type 2 diabetes in selected individuals with prediabetes when lifestyle intervention alone is insufficient (12).
• In the CODYCE multicentre prospective study, patients with prediabetes, stable angina, and non-obstructive coronary stenosis who received metformin showed improved coronary endothelial function and a lower rate of major adverse cardiovascular events (MACE) at 24 months compared with untreated prediabetes, suggesting potential cardiovascular benefits beyond glycaemic control (13).

Metformin – Quick Take in Prediabetes

• Recommended by the ADA (2026) for selected adults with prediabetes who are at high risk of developing type 2 diabetes (10).
• May be considered alongside lifestyle intervention in selected high-risk individuals when lifestyle measures alone are insufficient (12).
• Provides cardiometabolic and vasculo-protective benefits beyond glycaemic control (13).
• Reduced relative risk of diabetes incidence by 31% in the Diabetes Prevention Program (DPP) study (15).

Expert Perspective

The key clinical challenge is to recognize prediabetes as a window of heightened metabolic and vascular risk, not merely a prelude to diabetes. Recognizing this will drive timely and opportunistic screening, thereby allowing for proactive intervention in prediabetes.

Practice Takeaways

• Prediabetes is more than a precursor to diabetes; it is a clinically actionable condition associated with increased cardiovascular risk and an opportunity for proactive early intervention.
• In Indians, where progression from prediabetes to T2D can be rapid, routine risk-based screening and timely risk stratification are critical to identifying those most likely to benefit from preventive strategies.
• The greatest opportunity to curb the diabetes epidemic may lie not in treating established disease, but in acting early; through timely intervention, sustained lifestyle modification, and appropriate use of metformin in high-risk individuals.

Abbreviations: ADA – American Diabetes Association, AACE – American Association of Clinical Endocrinology, ASCVD – Atherosclerotic Cardiovascular Disease, BMI – Body Mass Index, CI – Confidence Interval, CODYCE – Coronary Endothelial Dysfunction Study, CURES – Chennai Urban Rural Epidemiology Study, CVD – Cardiovascular Disease, DKA – Diabetic Ketoacidosis, DPP – Diabetes Prevention Program, FPG – Fasting Plasma Glucose, GDM – Gestational Diabetes Mellitus, GLP-1RA – Glucagon-Like Peptide-1 Receptor Agonist, GIP/GLP-1RA – Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide-1 Receptor Agonist, HbA1c – Glycated Hemoglobin A1c, HDL – High-Density Lipoprotein, HHS – Hyperglycemic Hyperosmolar State, IDF – International Diabetes Federation, IDPP-1 – Indian Diabetes Prevention Programme-1, IFG – Impaired Fasting Glucose, iIFG – Isolated Impaired Fasting Glucose, IGT – Impaired Glucose Tolerance, LSM – Lifestyle Modification, MACE – Major Adverse Cardiovascular Events, MET – Metformin, NOCS – Non-Obstructive Coronary Stenosis, OGTT – Oral Glucose Tolerance Test, PG – Plasma Glucose, SGLT2i – Sodium-Glucose Cotransporter-2 Inhibitor, SU – Sulfonylurea, T2D – Type 2 Diabetes, T2DM – Type 2 Diabetes Mellitus, TZD – Thiazolidinedione.