Associations between Type 2 diabetes subtypes and complications

Abstract

Background: The aim of the study was to investigate type 2 diabetes (DM2) subtypes and associations with complications in a multiethnic Asian population.

Methods: Analytical cohort (n = 60,946), extracted from 2019 Malaysia National Diabetes Registry, included 63.8% Malay, 16.7% Chinese, 11.3% Indian, and 11.3% other. A K-means cluster analysis was performed with complete data on six variables: age, DM2 duration, body mass index, metabolic syndrome severity, triglyceride-glucose index, and glycated hemoglobin­. Separate Cox regression models and time-to-event analysis (from DM2 diagnosis) assessed the hazard ratio (HR) and time-to-complications, adjusting for sex, age, and ethnicity.

Results: Four clusters emerged: mild age-related diabetes (MARD) in 21,059 (35.6%), severe insulin-deficient diabetes (SIDD) in 11,751 (19.3%), mild obesity-related diabetes (MOD) in 14,700 (24.1%), and severe insulin-resistant diabetes (SIRD) in 13,436 (22.0%). Each cluster was compared to MARD. SIDD had later-onset and lowest HR for chronic kidney disease (CKD) (HR 0.25 (0.24 - 0.26)), retinopathy (HR 0.28 (0.27 - 0.30)), cerebrovascular disease (HR 0.57 (0.47 - 0.69)), and ischemic heart disease (HR 0.83 (0.76 - 0.91)). MOD had lowest HR (0.53 (0.34 - 0.84)) for limb amputations, and low HR for CKD, retinopathy, and cerebrovascular disease. SIRD had highest HR (1.43 (1.13 - 1.81)) for foot ulcers, and low HR (0.59 (0.56 - 0.63)) for retinopathy and CKD (HR 0.77 (0.74 - 0.80)). Known severe CKD cases were excluded from National Diabetes Registry.

Conclusions: DM2 subtypes associate differently with complications in Malaysia, similar to patterns found in European cohorts. DM2 subtypes complications, particularly for advanced CKD, are affected by registry-related selection bias and deserve further longitudinal investigation.