Analysis of metabolic progression to type I diabetes in ICA⁺ relatives of patients with type I diabetes

We intensively studied 5 islet cell-antibody-positive (ICA⁺) first-degree relatives of type I (insulin-dependent) diabetic patients before overt diabetes. In total, 55 intravenous glucose tolerance tests (IVGTTs) and 83 fasting plasma glucose determinations were made over a maximum 4-yr period before diabetes. The 5 prediabetic relatives (not diabetic when initially studied but subsequently progressed to overt diabetes) as a group showed a progressive rise in fasting glucose (r = 0.58, P < 0.001, slope = 23.1 mg · dl^-1 · yr^-1) and glucose at 60 min in IVGTT (r = 0.46, P = 0.01, slope = 47.5 mg · dl^-1 · yr^-1) beginning 1.5 yr before diabetes. During the 4.0- to 1.5-yr period before overt diabetes, no change was observed in fasting glucose or glucose at 60 min on IVGTT (fasting glucose: r = 0.21, P = 0.18, slope = 2.1 mg · dl^-1 · yr^-1; 60-min glucose: r = 0.08, P = 0.72, slope = 2.9 mg · dl^-1 · yr^-1). The positive predictive value for a fasting glucose >108 mg/dl to be within 1.5 yr of diabetes was 100% (11 of 11 values). The negative predictive value of a stimulated insulin (1-min + 3-min insulin - 2 × basal insulin) level >24 μU/ml to be >1.5 yr from diabetes was 90% (9 of 10 values) and 100% (10 of 10 values) at >1 yr from overt diabetes. We tested these predictive values by applying fasting glucose >108 mg/dl and stimulated insulin >24 μU/ml to another prediabetic group (n = 14) not included in the original analysis because each individual had fewer measurements. Once again, the positive predictive value that diabetes would develop within 1.5 yr from the time of fasting glucose >108 mg/dl was 100% (5 of 5 values), and the negative predictive value of stimulated insulin >24 μU/ml was 63% (5 of 8 values) for 1.5 yr and 89% (6 of 7 values) for 1 yr. Finally, 16 ICA⁺ relatives who had not yet become diabetic lacked raised fasting glucose levels (14 of 16 patients) and had stimulated insulin levels >24 μU/ml.