OBJECTIVE: To assess the adequacy of the first-phase insulin response for predicting development of insulin-dependent diabetes. RESEARCH DESIGN AND METHODS: Determinations were made of 1- and 3-min insulin responses to glucose (0.5 g/kg i.v.), islet cell antibodies (ICAs), insulin autoantibodies (IAAs), and HLA. We studied 220 first-degree relatives (aged 3-29 yr) of diabetic patients; 75 underwent two or more tests. RESULTS: At the first test, insulin responses correlated with age in ICA- children less than or equal to 11 yr old (r = 0.46, p less than 0.001). Individual responses varied widely in all ages, and low values were common (5th percentile: 108 pM in children less than 5 yr old, 180 pM thereafter). No correlation was found between insulin responses and IAAs or HLA. The responses of 15 ICA+ subjects were not significantly different from those of ICA- subjects after excluding the influence of age. At subsequent tests, ICA+ and ICA- subjects displayed distinct changes; the mean +/- SE insulin response increased in ICA- subjects from 619.2 +/- 40.8 to 716.4 +/- 50.4 pM (P less than 0.001) but declined in ICA+ subjects from 403.2 +/- 91.8 to 313.8 +/- 67.2 pM (P less than 0.02). During follow-up, 5 of 9 (56%) consistently ICA+ siblings developed diabetes or impaired glucose tolerance compared with 1 of 54 (2%) consistently ICA- subjects. The sensitivity and specificity of two or more low insulin responses (300 pM) for predicting progression to diabetes were 60 and 96%, respectively; the predictive value was 43%. The highest predictive value (75%) was achieved by the combination consistently ICA+, consistently low insulin response, and HLA-DR3/4. However, in no subject could the time of onset of diabetes be deduced from the decline of the insulin response. CONCLUSIONS: Consecutive intravenous glucose tolerance tests are a useful complement for predicting progression to diabetes but not its onset.
OBJECTIVE: To assess the adequacy of the first-phase insulin response for predicting development of insulin-dependent diabetes. RESEARCH DESIGN AND METHODS: Determinations were made of 1- and 3-min insulin responses to glucose (0.5 g/kg i.v.), islet cell antibodies (ICAs), insulin autoantibodies (IAAs), and HLA. We studied 220 first-degree relatives (aged 3-29 yr) of diabeticpatients; 75 underwent two or more tests. RESULTS: At the first test, insulin responses correlated with age in ICA- children less than or equal to 11 yr old (r = 0.46, p less than 0.001). Individual responses varied widely in all ages, and low values were common (5th percentile: 108 pM in children less than 5 yr old, 180 pM thereafter). No correlation was found between insulin responses and IAAs or HLA. The responses of 15 ICA+ subjects were not significantly different from those of ICA- subjects after excluding the influence of age. At subsequent tests, ICA+ and ICA- subjects displayed distinct changes; the mean +/- SE insulin response increased in ICA- subjects from 619.2 +/- 40.8 to 716.4 +/- 50.4 pM (P less than 0.001) but declined in ICA+ subjects from 403.2 +/- 91.8 to 313.8 +/- 67.2 pM (P less than 0.02). During follow-up, 5 of 9 (56%) consistently ICA+ siblings developed diabetes or impaired glucose tolerance compared with 1 of 54 (2%) consistently ICA- subjects. The sensitivity and specificity of two or more low insulin responses (300 pM) for predicting progression to diabetes were 60 and 96%, respectively; the predictive value was 43%. The highest predictive value (75%) was achieved by the combination consistently ICA+, consistently low insulin response, and HLA-DR3/4. However, in no subject could the time of onset of diabetes be deduced from the decline of the insulin response. CONCLUSIONS: Consecutive intravenous glucose tolerance tests are a useful complement for predicting progression to diabetes but not its onset.
Authors: I Truyen; P De Pauw; P N Jørgensen; C Van Schravendijk; O Ubani; K Decochez; E Vandemeulebroucke; I Weets; R Mao; D G Pipeleers; F K Gorus Journal: Diabetologia Date: 2005-10-07 Impact factor: 10.122
Authors: W A Hagopian; C B Sanjeevi; I Kockum; M Landin-Olsson; A E Karlsen; G Sundkvist; G Dahlquist; J Palmer; A Lernmark Journal: J Clin Invest Date: 1995-04 Impact factor: 14.808
Authors: F Sun; B Knebelmann; M E Pueyo; H Zouali; S Lesage; M Vaxillaire; P Passa; D Cohen; G Velho; C Antignac Journal: J Clin Invest Date: 1993-09 Impact factor: 14.808
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Authors: T Simell; J Mäenpää; E A Kaprio; A Hakulinen; J Hakalax; I Sipilä; H K Akerblom; O Simell Journal: Diabetologia Date: 1995-01 Impact factor: 10.122
Authors: Maarit K Koskinen; Johanna Lempainen; Eliisa Löyttyniemi; Olli Helminen; Anne Hekkala; Taina Härkönen; Minna Kiviniemi; Olli Simell; Mikael Knip; Jorma Ilonen; Jorma Toppari; Riitta Veijola Journal: J Clin Endocrinol Metab Date: 2018-08-01 Impact factor: 5.958