AimsTo evaluate circulating adipokines in people with ketosis-prone diabetes, a heterogeneous disorder characterized by unprovoked ketoacidosis in people with previously unrecognized diabetes. MethodsPatients presenting with ketoacidosis with no previous diabetes diagnosis were compared with patients with previously established Type 1 diabetes. Baseline assessments of autoimmune status (A+/A-), and -cell function (B+/B-), as well as leptin and adiponectin levels during a standardized mixed-meal tolerance test of 120min, were performed. In all, 20 patients with heterogeneous ketosis-prone diabetes and 12 patients with Type 1 diabetes were evaluated at baseline, 12 and 24months. ResultsAt baseline, during a mixed-meal tolerance test, glucose and adiponectin concentrations were lower in patients with ketosis-prone diabetes than in those with Type 1 diabetes (P=0.0023 and P<0.0001, respectively), whereas C-peptide concentrations were higher, with no significant difference in leptin concentrations. Within 12months, 11 patients with ketosis-prone diabetes (all A-/B+) were discontinued from insulin treatment (ketosis-prone diabetes - insulin group), while nine patients (four A-B-, four A+B- and one A-B+) were maintained on insulin (ketosis-prone diabetes + insulin group). Fasting C-peptide levels increased significantly over 24months in the ketosis-prone diabetes - insulin group (P=0.01), while HbA(1c) levels decreased (P<0.0001). Overall, the ketosis-prone diabetes - insulin group had a higher BMI (P=0.018), yet a lower fasting glucose concentration (P=0.003) compared with the ketosis-prone diabetes + insulin group. Over 24months, the mixed-meal tolerance test area-under-the-curve of C-peptide increased in the ketosis-prone diabetes - insulin group, with no change in ketosis-prone diabetes + insulin (P<0.0001). At 24months, in spite of the higher BMI in the ketosis-prone diabetes - insulin group, mixed-meal tolerance test glucose and leptin concentrations were significantly lower (P<0.0001 and P=0.017, respectively), while adiponectin levels were higher (P=0.023) compared with the ketosis-prone diabetes + insulin group. ConclusionsIn spite of the higher BMI in the ketosis-prone diabetes - insulin group, lower leptin and higher adiponectin levels may contribute to improved -cell function and insulin sensitivity, as evidenced by lower glucose and higher C-peptide levels. This allows insulin therapy to be withdrawn. What's new? Ketosis-prone diabetes is a heterogeneous disorder. At the time of presentation, patients with this disorder have unprovoked ketoacidosis and have not been previously identified as having diabetes (either Type 1 or Type 2). People with ketosis-prone diabetes do not necessarily have the typical phenotype of autoimmune Type 1 diabetes but can be classified based on the presence/absence of autoantibodies (A+/A-) and maintenance of a minimal -cell function (B+/B-). People with A-B+ ketosis-prone diabetes comprise the largest subgroup of those with this disorder (50%), the majority of whom (50-80%) are able to maintain long-term -cell functional reserve and successfully withdraw from insulin therapy after resolution of ketoacidosis. In the present study evaluating adipokines, patients who could be withdrawn from insulin (all patients with A-B+ disease) had lower leptin and higher adiponectin levels, suggesting that, despite the patients having a higher BMI, these adipokines may contribute to their improved insulin sensitivity.