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Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests.

ABSTRACT: OBJECTIVE:Determine if autoantibody titer magnitude and variability predict glucose abnormalities in subjects at risk for type 1 diabetes. RESEARCH DESIGNS AND METHODS:Demographic information, longitudinal autoantibody titers, and oral glucose tolerance test (OGTT) data were obtained from the TrialNet Pathway to Prevention study. Subjects (first and second degree relatives of individuals with type 1 diabetes) with at least 2 diabetes autoantibodies were selected for analysis. Autoantibody titer means were calculated for each subject for the duration of study participation and the relationship between titer tertiles and glucose value tertiles from OGTTs (normal, impaired, and diabetes) was assessed with a proportional odds ordinal regression model. A matched pairs analysis was used to examine the relationship between changes in individual autoantibody titers and 120-minute glucose values. Titer variability was quantified using cumulative titer standard deviations. RESULTS:We studied 778 subjects recruited in the TrialNet Pathway to Prevention study between 2006 and 2014. Increased cumulative mean titer values for both ICA512 and GAD65 (estimated increase in proportional odds = 1.61, 95% CI = 1.39, 1.87, P < 1 × 10-9 and 1.17, 95% CI = 1.03, 1.32, P = .016, respectively) were associated with peak 120-minute glucose values. While fluctuating titer levels were observed in some subjects, no significant relationship between titer standard deviation and glucose values was observed. CONCLUSION:ICA512 autoantibody titers associate with progressive abnormalities in glucose metabolism in subjects at risk for type 1 diabetes. Fluctuations in autoantibody titers do not correlate with lower rates of progression to clinical disease.

SUBMITTER: Sanda S

PROVIDER: S-EPMC5849060 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests.

Sanda Srinath S

Pediatric diabetes 20170714 2

<h4>Objective</h4>Determine if autoantibody titer magnitude and variability predict glucose abnormalities in subjects at risk for type 1 diabetes.<h4>Research designs and methods</h4>Demographic information, longitudinal autoantibody titers, and oral glucose tolerance test (OGTT) data were obtained from the TrialNet Pathway to Prevention study. Subjects (first and second degree relatives of individuals with type 1 diabetes) with at least 2 diabetes autoantibodies were selected for analysis. Auto ...[more]

PMID: 28707353

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Project description:Background/objectiveThere is no international consensus about the optimal approach to screening and diagnosis of gestational diabetes mellitus (GDM). Fasting plasma glucose (FPG) has been proposed as an alternative universal screening test to simplify the diagnosis of GDM. We investigate the ability of the FPG to predict a 2-hour glucose value below the cut-off for GDM, thereby "ruling out" the necessity of a full OGTT and assess the proportion of GDM-related complications associated with the identified FPG level.Materials and methodsThis study included secondary data from four Norwegian pregnancy cohorts (2002-2013), encompassing 2960 women universally screened with late mid-pregnancy 75g OGTT measuring FPG and 2-hour glucose. For a range of FPG thresholds, we calculated sensitivity to predict elevated 2-hour glucose, number of OGTTs needed and percentage of GDM cases missed, applying modified World Health Organization (WHO) 2013 criteria (2013WHO) and 2017 Norwegian criteria (2017Norwegian). We analyzed pregnancy outcomes for women above and below our selected threshold.ResultsThe prevalence of GDM was 16.6% (2013WHO) and 10.1% (2017Norwegian). A FPG threshold of 4.7 mmol/L had a sensitivity of 76% (2013WHO) and 80% (2017Norwegian) for detecting elevated 2-hour glucose, with few missed GDM cases (2.0% of those ruled out and 7.5% of all GDM cases for 2013WHO, and 1.1% of those ruled out and 7% of all GDM cases for 2017Norwegian). When excluding women with FPG <4.7mmol/l and those with GDM based on FPG, only 24% (2013WHO) and 29% (2017Norwegian) would require OGTT. Women with FPG <4.7mmol/l, including missed GDM cases, had low risk of large-for-gestational-age newborns, cesarean section and operative vaginal delivery.ConclusionA FPG threshold of 4.7mmol/l as a first step when screening for GDM could potentially eliminate the need for OGTT in 70-77% of pregnancies. Women with FPG below this threshold appear to carry low risk of GDM-associated adverse pregnancy outcomes.

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Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests.

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Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests.

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