1253-P: Markers of Beta-Cell Death and Insulin Secretion in Ketosis-Prone Diabetes (KPDM) Free

Approximately 50% of obese Black individuals present with diabetic ketoacidosis (DKA) at new-onset of diabetes undergo remission from insulin (fasting blood glucose [FBG <130 mg/dl, random BG < 180 mg/dl and HbA1c < 7% and off insulin therapy > 1 week) with intensive insulin treatment due to improved pancreatic beta(β)-cell secretion. Controversy exists whether KPDM is type 1 or type 2 diabetes and whether β-cell death contributes to DKA and β-cell secretion. Circulating unmethylated to methylated insulin DNA ratio (unMeth/MethINS) levels were found to correlate with β-cell death and β-cell secretion in patients at high risk for type 1 diabetes. In this exploratory study, we hypothesized that increased circulating unMeth/MethINS ratio at presentation of DKA correlates with decreased β-cell secretion in KPDM. Obese Black individuals presenting with DKA without GAD-65 antibodies were recruited 3-4 days after discharge from the hospital (Visit 1, n=22) and at insulin remission (Visit 2, n=19). Serum circulating unMeth/MethINS levels were measured at Visit 1. β-cell secretion was measured with glucagon stimulation tests (GST) performed at Visit 1 and Visit 2 and calculated as 6-min (maximum[Max]) and Delta (Max-baseline) C-peptide levels. At Visit 1, mean age was 38 ± 12 years and 7 (32%) were female. Mean BMI was 39.4 ± 10.6 kg/m2 with mean baseline HbA1c of 12.4 ± 1.8%. C-peptide levels increased significantly from Visit 1 to Visit 2 and expressed as median with minimum and maximum: Max (Visit 1: 2.94 [0.65, 12.07] vs. Visit 2: 5.87 [1.83, 12.11] ng/ml, p=0.011) and Delta (Visit 1: 1.57 (0.24, 6.88) vs. Visit 2: 2.80 [0.46, 9.01], p=0.047). UnMeth/MethINS ratio at Visit 1 was not significantly correlated (Spearman) with C-peptide levels at Visit 1 (Max: r=0.02, p=0.93, Delta: r=0.04, p=0.84) or at Visit 2 (Max: r=-0.07, p=0.79, Delta: r=0.03, p=0.89). Our data shows that in patients with KPDM, markers of β-cell death are not correlated with insulin secretion indicating that KPDM is consistent with type 2 diabetes.