Changes in circulating adiponectin, leptin, glucose and C-peptide in patients with ketosis-prone diabetes.

Abstract

To evaluate circulating adipokines in people with ketosis-prone diabetes, a heterogeneous disorder characterized by unprovoked ketoacidosis in people with previously unrecognized diabetes. Patients 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 β-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. At 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 HbA1c 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. In spite of the higher BMI in the ketosis-prone diabetes - insulin group, lower leptin and higher adiponectin levels may contribute to improved β-cell function and insulin sensitivity, as evidenced by lower glucose and higher C-peptide levels. This allows insulin therapy to be withdrawn.