Clinical Phenotyping of Newly Diagnosed Type 2 Diabetes in Yemen

Objective: To identify clinical phenotypes of type 2 diabetes (T2D) among adults presenting with a first diagnosis of diabetes.

Research Design And Methods: A total of 500 consecutive patients were subject to clinical assessment and laboratory investigations. We used data-driven cluster analysis to identify phenotypes of T2D based on clinical variables and Homeostasis Model Assessment (HOMA2) of insulin sensitivity and beta-cell function estimated from paired fasting blood glucose and specific insulin levels.

Results: The cluster analysis identified three statistically different clusters: cluster 1 (high insulin resistance and high beta-cell function group), which included patients with low insulin sensitivity and high beta-cell function; cluster 2 (low insulin resistance and low beta-cell function group), which included patients with high insulin sensitivity but very low beta-cell function; and cluster 3 (high insulin resistance and low beta-cell function group), which included patients with low insulin sensitivity and low beta-cell function. Insulin sensitivity, defined as median HOMA2-S, was progressively increasing from cluster 1 (35.4) to cluster 3 (40.9), to cluster 2 (76) (p<0.001). On the contrary, beta-cell function, defined as median HOMA2-β, was progressively declining from cluster 1 (78.3) to cluster 3 (30), to cluster 2 (22.3) (p<0.001). Clinical and biomarker variables associated with insulin resistance like obesity, abdominal adiposity, fatty liver, and high serum triglycerides were mainly seen in clusters 1 and 3. The highest median hemoglobin A1c value was noted in cluster 2 (88 mmol/mol) and the lowest in cluster 1.

Conclusion: Cluster analysis of newly diagnosed T2D in adults has identified three phenotypes based on clinical variables central to the development of diabetes and on specific clinical variables of each phenotype.