A simple glucose test is no longer the definitive tool for diagnosing diabetes. As the understanding of the disease expands beyond types 1 and 2, with researchers identifying newer phenotypes and their unique challenges, diabetologists argue that a glucose-centric approach fails to capture the full spectrum of this chronic condition, often detecting it too late. The future of early diabetes diagnosis lies in a comprehensive metabolic health assessment rather than isolated glucose values, according to Dr. Rajiv Kovil, head of diabetology at Zandra Healthcare in Mumbai.
Limitations of Glucose-Centric Diagnosis
Relying solely on fasting glucose, postprandial sugars, or the glycated haemoglobin (HbA1c) test trivializes diabetes, detecting it only after significant metabolic damage has already occurred, Dr. Kovil explains. Fatty liver disease often precedes diabetes and is now recognized as a hepatic manifestation of insulin resistance. Imaging of fatty liver, along with blood-based tests such as validated fibrosis scores (to detect liver scarring) and steatosis scores (that quantify liver fat), can serve as important markers of diabetes risk.
Dr. Kovil adds that body fat percentage and measurements of visceral and ectopic fat provide far better insight into metabolic risk than body mass index (BMI). The triglyceride-to-HDL ratio, triglyceride-glucose (TyG) index, and postprandial lipid tests are also strong predictors of future diabetes and cardiovascular disease.
New Diabetes Phenotypes
India, known as the diabetes capital of the world, is witnessing a paradigm shift in understanding diabetes with the recognition of phenotypes such as Type 3 (linking diabetes with Alzheimer's disease), Type 4 (occurring in lean, elderly individuals), and Type 5 (resulting from childhood malnutrition). These types have atypical metabolic profiles that require tailored diagnostic approaches.
A recent study by doctors at Pune's BJ Govt Medical College reported the case of a male infant born at 27 weeks weighing 720 grams, who exhibited frequent urination and no weight gain despite regular breastfeeding. Initially presumed to have Type 1 diabetes, genetic testing revealed a different cause. Dr. Pragathi Kamath, the study author, explains that during the early neonatal period, the baby developed persistent hyperglycaemia due to insulin deficiency, an extremely rare condition called Neonatal Diabetes Mellitus (NDM). Although the baby initially required insulin therapy, the diabetes resolved spontaneously, confirming the diagnosis.
Genetic testing uncovered a homozygous mutation in the MS4A6A gene, which had never been associated with NDM before. This case highlights that a newborn's genetic profile is crucial for determining the true cause of diabetes and preventing lifelong insulin therapy. The study was published in the journal Cureus.
Advanced Diagnostic Tools
Other diagnostic tools include dual-energy X-ray absorptiometry (DEXA), an imaging technique being repurposed to quantify visceral fat, a significant risk factor for metabolic syndrome and Type 2 diabetes. Visceral fat is also associated with increased secretion of pro-inflammatory cytokines and adipokines, leading to insulin resistance and beta-cell dysfunction.
Dr. Kovil notes that continuous glucose monitoring (CGM) offers a powerful early detection tool, revealing post-meal excursions, glycemic variability, and time-above-range long before conventional criteria are met. While fasting insulin levels are a hallmark of Type 2 diabetes and provide insight into the degree of insulin resistance, the Hyperinsulinemic-Euglycemic Clamp Technique remains the gold standard for assessing whole-body insulin sensitivity.
Conclusion
Although glucose-based criteria remain necessary for diagnosis, experts insist that to differentiate between diabetes types, clinicians must consider context, history, phenotype, and autoantibodies or C-peptide tests when needed. This comprehensive approach promises earlier detection and more personalized treatment for the growing diabetes epidemic.
