TYPE 2 DIABETES (T2D) subtypes show markedly different mortality risks, with new evidence indicating that insulin-deficient forms of T2D are linked to substantially higher all-cause mortality and greater years of life lost in South Asian populations.1
T2D is a metabolic disorder characterised by insulin resistance and progressive beta-cell dysfunction, where compensatory insulin secretion eventually fails, resulting in chronic hyperglycaemia.1
Rising Burden of Type 2 Diabetes and Metabolic Heterogeneity
T2D accounts for approximately 90% of all diabetes cases and is increasingly diagnosed in younger populations, alongside its more typical presentation in adults over 45 years.2 This shift is largely driven by rising obesity, physical inactivity and energy-dense diets. Central adiposity contributes to insulin resistance through inflammatory pathways, including dysregulated adipokine signalling and increased free fatty acid release, which further accelerates metabolic deterioration.2
Insulin-deficient Subtypes Show Highest Mortality Risk
In a large analysis of 14,036 South Asian participants, Jagannathan et al identified three type 2 diabetes subtypes using clustering of age, BMI, HbA1c, insulin resistance and beta-cell function: severe insulin-deficient diabetes (SIDD), mild insulin-deficient diabetes (MIDD) and severe insulin-resistant diabetes (SIRD).
Over a median 10.6-year follow-up, 1,076 deaths were recorded, including 405 cardiovascular deaths. Compared with normal glucose tolerance, SIDD showed the highest all-cause mortality risk (hazard ratio 3.34), followed by SIRD (1.67) and MIDD (1.39), with insulin-deficient phenotypes demonstrating the greatest excess years of life lost.¹
Among 4,992 individuals with prediabetes, two subtypes were identified: insulin-deficient prediabetes (IDPD) and insulin-resistant prediabetes (IRPD). IDPD was associated with higher all-cause mortality (hazard ratio 1.32) and cardiovascular mortality (1.53), while IRPD showed no significant increase in mortality risk. Insulin-deficient subtypes also accounted for a substantial proportion of adverse outcomes.¹
Implications for Stratified Diabetes Care
The findings align with established mechanisms in T2D, where insulin resistance initially triggers compensatory insulin secretion, but progressive beta-cell dysfunction leads to failure in maintaining glucose homeostasis. This transition is influenced by obesity-related inflammatory signalling and metabolic stress within adipose tissue, reinforcing the heterogeneity seen across patient populations.2
These findings suggest that metabolic subtyping may refine risk stratification in both T2D and prediabetes. However, as observational data, the results do not establish causality and require validation in broader populations. Future approaches may focus on identifying insulin-deficient phenotypes earlier to better target prevention and management strategies.
Reference
- Jagannathan R et al. Subtypes of type 2 diabetes and prediabetes: mortality and excess life lost in South Asians. Diabetes Care;DOI:10.2337/dc26-0043.
- Goyal R et al. Type 2 Diabetes (2023) Treasure Island: StatPearls. Available at: https://www.ncbi.nlm.nih.gov/books/NBK513253/. Last accessed: 18 May 2026.
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