Published online Aug 15, 2026. doi: 10.4239/wjd.122101
Revised: May 13, 2026
Accepted: July 3, 2026
Published online: August 15, 2026
Processing time: 117 Days and 20.6 Hours
Adults presenting with ketosis or diabetic ketoacidosis at diabetes onset pose a diagnostic challenge because ketosis-prone (KP) type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADAs) share overlapping clinical features but require fundamentally different long-term management strategies. In many clinical settings, limited access to islet autoantibody testing further com
To characterize the clinical, metabolic, and endocrine features of ketosis-onset diabetes in adults and to identify potential non-antibody biomarkers to differentiate LADA from KP-T2DM and distinguish ketosis-onset from nonketotic diabetes.
A total of 294 newly diagnosed adult patients were classified into LADA, KP-T2DM, and nonketotic T2DM groups. Clinical and metabolic characteristics were compared. Multivariable logistic regression was performed to identify factors associated with ketosis onset and LADA classification, and receiver operating characteristic analysis was used to evaluate the discriminatory per
LADA accounted for 27.3% of ketosis-onset cases. Compared with patients with KP-T2DM, those with LADA exhibited significantly impaired β-cell function and lower insulin resistance. Multivariable analysis identified postprandial C-peptide as the strongest independent discriminator between LADA and KP-T2DM. Receiver operating characteristic analysis demonstrated that 2-hour C-peptide showed good discriminatory performance for differentiating LADA from KP-T2DM (area under the curve = 0.852). Other metabolic parameters, including high-density lipoprotein cholesterol, gamma-glutamyl transferase, alkaline phosphatase, free triiodothyronine, fasting plasma glucose, and homeostasis model assessment of insulin resistance, showed additional but more limited discriminatory value.
Among adults presenting with ketosis at diabetes onset, LADA represents a substantial proportion of cases and should be considered in the differential diagnosis. Readily available non-antibody biomarkers, particularly 2-hour postprandial C-peptide, demonstrated promising discriminatory performance for differentiating LADA from KP-T2DM, whereas other metabolic markers provided supplementary information. These findings may support the clinical evaluation of atypical diabetes in settings where autoantibody testing is unavailable; however, independent validation is required before routine clinical application.
Core Tip: More than one-quarter of adults presenting with ketosis at diabetes onset in our cohort were diagnosed with latent autoimmune diabetes in adults, highlighting the importance of considering autoimmune diabetes in this clinical setting. We identified a panel of readily available non-antibody biomarkers, including 2-hour C-peptide, high-density lipoprotein cholesterol, gamma-glutamyl transferase, homeostasis model assessment of insulin resistance, alkaline phosphatase, free triiodothyronine, and fasting plasma glucose, that demonstrated discriminatory value for differentiating latent autoimmune diabetes in adults from ketosis-prone type 2 diabetes mellitus and for distinguishing ketosis-onset from nonketotic diabetes within the study cohort. These findings may provide supportive information for the clinical evaluation of atypical diabetes when islet autoantibody testing is unavailable; however, independent validation is required before routine clinical application.