Phenotypic clusters of type 2 diabetes mellitus among North Indians reveal higher levels of insulin deficiency along with insulin resistance.

BACKGROUND: Type 2 diabetes is now considered a heterogenous disease. Distinct clusters have been identified with patterns varying between Europeans and South Asians as well as between South Indians who have described a novel cluster; Combined Insulin-Resistant and Deficient Diabetes, and individuals from West and East India who have reported that insulin deficiency is the primary driver of heterogeneity. Therefore, North Indian patients may also have a distinct, novel clustering pattern due to unique genetic, epigenetic, and environmental factors. We aim to identify clusters of type 2 diabetes in North Indians and to describe the different characteristics of these clusters. METHODS: The K value for the optimal number of clusters was obtained from two-step clustering. K means clustering was done with this K value using SPSS 29.0 software. Variables used for clustering were age, BMI, HbA1c, HOMA-beta, HOMA-IR, and waist circumference. RESULTS: Four phenotypically different clusters were identified in 469 individuals with type 2 diabetes. Cluster 1 was severe insulin deficient diabetes (15%), Cluster 2 was severe insulin resistant diabetes (22%), Cluster 3 was moderate obesity-related diabetes (35%), and Cluster 4 was moderate age-related diabetes (27%). Clusters 1 and 2 were similar to earlier studies but in different proportions. Clusters 3 and 4 characteristics were different from earlier studies, with greater impairment in beta cell function and higher HbA1c levels. Significant insulin resistance was noted in all clusters. CONCLUSION: The phenotypic clusters of type 2 diabetes identified in the present study were characterized by high levels of insulin deficiency along with important contributions from insulin resistance.

Postprandial triglyceride responses and endothelial function in prediabetic first-degree relatives of patients with diabetes.

BACKGROUND: Only a few studies have reported on postprandial lipid responses and endothelial function in prediabetic subjects. None of the study has compared role of familial predisposition in determining postprandial endothelial dysfunction and postprandial hypertriglyceridemia in subjects with prediabetes. OBJECTIVE: The objective was to study the postprandial triglyceride (PPTG) responses and endothelial function in prediabetic first-degree relatives of patients with diabetes. METHODS: Thirty-nine subjects were recruited on the basis of oral glucose tolerance test into 3 groups: group 1, prediabetic subjects who had a first-degree relative with diabetes; group 2, prediabetic subjects without family history of diabetes; and group 3, normal glucose tolerance subjects without family history of diabetes. Oral fat challenge test was performed in all study subjects and PPTG responses were measured up to 8 hours. Postprandial endothelial function after 4 hours of fat challenge was estimated by flow-mediated dilation. RESULTS: Postprandial endothelial dysfunction was greatest in group 1 and significantly higher in group 1 compared with group 2 (P < .001) and group 2 compared with group 3 (P < .001). PPTG responses (TG-AUC, TG-peak, TG-6 hour, and TG-8 hour) were significantly higher in group 1 compared with groups 2 and 3. However, they were similar between groups 2 and 3. Endothelial function showed significant negative correlation with TG-6 hour and TG-8 hour. CONCLUSION: Prediabetic subjects respond to fat challenge with a greater degree of TG response and endothelial dysfunction compared with normal glucose tolerance subjects especially if they have a first-degree relative with diabetes. This may contribute to enhanced cardiovascular risk reported in prediabetic individuals.