Predictive value of intravenous glucose tolerance test insulin secretion less than or greater than the first percentile in islet cell antibody positive relatives of Type 1 (insulin-dependent) diabetic patients

Abstract

We have followed-up 35 islet cell antibody-positive first degree relatives of patients with Type 1 (insulin-dependent) diabetes mellitus for an average of 1,300 days with sequential intravenous glucose tolerance tests. At the time of analysis and manuscript submission approximately half (18 of 35) had developed diabetes during follow-up. At initial intravenous glucose tolerance test, 11 had a 1 + 3 min insulin secretion below the first percentile of insulin secretion compared to 225 similarly studied normal control subjects. Six islet cell antibody positive relatives on follow-up developed an intravenous glucose tolerance test less than the first percentile. Fifteen out of 17 (88%) of these islet cell antibody positive relatives with secretion ever found to be below the first percentile are now overtly diabetic (positive predictive value = 88%) and insulin-treated, while only 3 of 18 (17%) without an intravenous glucose tolerance test demonstrating loss of first phase insulin secretion have progressed to diabetes (with approximately 1,300 days of follow-up for both groups relative risk or odds ratio with intravenous glucose tolerance test ever below vs never below the first percentile = 38, p less than 0.001). Intravenous glucose tolerance test response below the first percentile preceded diabetes by an average of 656 days. Even when first phase insulin secretion is below the first percentile, the absolute value of 1 + 3 min insulin above basal insulin correlates with the time to development of diabetes (r = 0.586, p less than 0.001). With our current duration of follow-up, the negative predictive value (intravenous glucose tolerance test never below the first percentile) is 83%, and overall accuracy 86%. Incidence rates of diabetes development amongst our islet cell antibody positive relatives with follow-up while intravenous glucose tolerance test is below the first percentile is 0.48 per year (15 conversions to diabetes amongst 17 relatives in 30.8 patient years of follow-up) vs 0.05 per year (three diabetic patients in 55.5 patient years) with intravenous glucose tolerance test greater than the first percentile.

Karlsburg Type I diabetes risk study of a general population: frequencies and interactions of the four major Type I diabetes-associated autoantibodies studied in 9419 schoolchildren

“…Intravenous glucose tolerance tests (IVGTTs) were done in schoolchildren at risk of developing diabetes expected from levels and co-occurrence of AAbs detected by primary screening and confirmed by the second AAb tests done with i. v. serum samples 8±12 weeks later. The firstphase insulin release (FPIR) was calculated as the sum of the 1 and 3 min insulin values after glucose injection according to the ICARUS protocol with 0.5 g glucose/kg of body weight as a 40 % solution injected over a 2-min period [22,23]. The first centile for FPIR is 215 pmol/l, and the 5th centile is 328 pmol/l determined in 120 healthy control subjects (mean age 12 3 years, ranging from 6 to 16; 64 girls, 56 boys).…”

Risk of Type 1 Diabetes Development in Children With Incidental Hyperglycemia

“…More importantly, these circulating autoantibodies may be present for months to years preceding the onset of clinical diabetes (2). The rate of ␤-cell destruction is quite variable, as it is rapid in some individuals and slow in others (3). Some patients, particularly children and adolescents, may present with ketoacidosis at the first manifestation of the disease (4).…”

Acetyl-L-Carnitine and Nicotinamide for Prevention of Type 1 Diabetes. I-Literature Review which Gave Support to the Treatment. II-Case Report, Evaluation of Five Years Treatment

“…The children were studied with IVGTT and by means of the same test the following data was measured: the first phase of insulin response (FPIR<48 µU insulin) [89,90], the integrated area of insulin secretion, the glucose disappearance rates (Kg), the equation and HOMA-IR [91].…”