Gestational Diabetes Mellitus Subtypes Derived by Clustering Analysis Show Heterogeneity in Glucometabolic Parameters Already at Early Pregnancy

<b>Background/Objectives:</b> The classification of patients with diabetes into phenotypes with distinct risks and therapeutic needs is crucial for individualized care. We recently introduced a clustering model for gestational diabetes mellitus (GDM). This study aims to further characterize the proposed clusters and to identify cluster-specific differences in glucometabolic parameters during early pregnancy in an independent cohort. The metabolic profiles and dietary habits of GDM clusters will be compared with those of a normal glucose-tolerant (NGT) control group. <b>Methods:</b> 1088 women (195 who developed GDM and 893 who remained NGT) underwent a broad risk evaluation at early pregnancy. GDM patients were further categorized into the three proposed GDM subtypes (CL1 to CL3). <b>Results:</b> Among GDM patients, 7.7% were classified as CL1, 35.9% as CL2, and 56.4% as CL3. CL1 showed higher age, pregestational BMI, and increased glucose concentrations both at fasting and during the diagnostic oral glucose tolerance test. CL2 was characterized by elevated BMI and fasting glucose, while CL3 showed higher glucose concentrations after the oral glucose load, with BMI levels comparable to NGT mothers. Women in the CL1 group exhibited impaired insulin sensitivity and β-cell function at early pregnancy and showed elevated lipid levels. Compared to NGT women, a positive family history of diabetes was more prevalent in CL1 and CL3, but not in CL2. Dietary patterns were similar across all groups. <b>Conclusions</b>: Our study showed distinct alterations in glucometabolic parameters already at early pregnancy among GDM subtypes. Patients in CL1 exhibited the most unfavorable risk constellation and could benefit from lifestyle changes and nutrition therapy in early pregnancy, despite showing similar dietary patterns as the NGT group.