Exploratory Analysis of Type 2 Diabetes Mellitus Metabolic Phenotypes and Their Association With Vitamin D Status in Primary Care Patients

AIMS: This study aimed to perform an exploratory characterisation of metabolic phenotypes in primary care patients with type 2 diabetes mellitus (T2DM), using a predefined approach and examine their association with vitamin D status. MATERIALS AND METHODS: This cross-sectional study included 178 participants randomly selected in Sergipe, Brazil. Phenotypic clusters were derived using body mass index (BMI), glycated haemoglobin levels, age at diagnosis, insulin resistance (homeostatic model assessment (HOMA) for insulin resistance) and β-cell function (HOMA-B). To explore differences across phenotypes, we evaluated high-sensitivity C-reactive protein [hs-CRP] and serum ferritin levels, waist circumference and BMI, serum concentrations of 25-hydroxyvitamin D [25(OH)D] and therapeutic profile. Clustering was performed using the K-medoids algorithm. Group comparisons were performed using the Kruskal-Wallis and Fisher's exact tests and associations were assessed using multivariable logistic regression. A p-value of < 0.05 was considered significant. RESULTS: Four metabolic phenotypes were identified: two more severe clusters (severe insulin-deficient diabetes (SIDD)-like and severe insulin-resistant diabetes-like) and two milder clusters (mild obesity-related diabetes (MOD)-like and mild age-related diabetes (MARD)-like). Significant differences were observed in age, insulin use, waist circumference and fasting glucose, triglycerides and hs-CRP levels. Median 25(OH)D levels were lower in severe phenotypes compared with milder phenotypes. The SIDD-like group, characterised by marked insulin deficiency, showed 3.68-fold higher odds of vitamin D insufficiency (< 30 ng/mL) compared with the MARD-like phenotype (p = 0.013). CONCLUSIONS: The metabolic phenotypes were explored in a primary care T2DM cohort, supporting their reproducibility across clinical settings. Vitamin D status varied by phenotype severity, with more severe phenotypes more likely to exhibit insufficiency.