First-phase insulin release during the intravenous glucose tolerance test as a risk factor for type 1 diabetes

Hp, Chase; Dd, Cuthbertson; Lm, Dolan; Kaufman, F.; Jp, Krischer; Da, Schatz; Nh, White; Dm, Wilson; Wolfsdorf, Joseph I.

doi:10.1067/mpd.2001.111274

Cited by 67 publications

(42 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…titre change did not cross the 75th percentile for titre of IAA or the 25th percentile for titre of IA-2A). A limitation of the study is the fact that we did not assess the metabolic makers that have been shown to provide added specificity for disease progression in autoantibody-positive relatives [18][19][20]. Similarly, we were unable to assess T cell reactivity, which might have provided further insights into the relevance of our findings to disease pathogenesis [21].…”

Section: Discussionmentioning

confidence: 94%

Type 1 diabetes risk assessment: improvement by follow-up measurements in young islet autoantibody-positive relatives

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis Combinations of autoantibody characteristics, including antibody number, titre, subclass and epitope have been shown to stratify type 1 diabetes risk in islet autoantibody-positive relatives. The aim of this study was to determine whether autoantibody characteristics change over time, the nature of such changes, and their implications for the development of diabetes. Methods Five-hundred and thirteen follow-up samples from 141 islet autoantibody-positive first-degree relatives were tested for islet autoantibody titre, IgG subclass, and GAD and IA-2 antibody epitope. All samples were categorised according to four risk stratification models. Relatives had a median follow-up of 6.8 years and 48 developed diabetes during follow-up. Survival analysis was used to determine the probability of change in risk category and of progression to diabetes. Results For each stratification model, the majority of relatives (71-81%) remained in the same risk category throughout follow-up. In the remainder, changes occurred both from lower to higher and from higher to lower risk categories. For all four models, relatives aged <15 years were more likely to change risk category than those aged >15 years (0.001

show abstract

Section: Discussionmentioning

confidence: 94%

Type 1 diabetes risk assessment: improvement by follow-up measurements in young islet autoantibody-positive relatives

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The metabolic abnormalities of the pre-diabetic period are less well understood. The intravenous glucose tolerance test (IVGTT) has been used as a measure of insulin secretion and abnormalities of the IVGTT such as a diminished first phase insulin response (FPIR) are known to be risk factors for T1D (10)(11)(12). Abnormalities of the oral glucose tolerance test (OGTT) have also been shown to precede the diagnosis of T1D (13,14).…”

mentioning

confidence: 99%

Pre-Type 1 Diabetes Dysmetabolism: Maximal Sensitivity Achieved with Both Oral and Intravenous Glucose Tolerance Testing

Barker

McFann

Harrison

et al. 2007

The Journal of Pediatrics

View full text Add to dashboard Cite

Objective-To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and identify an optimal testing strategy for detecting pre-clinical diabetes.Study design-Diabetes Prevention Trial Type 1 randomized subjects to oral (n=372) and parenteral (n=339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated.Results-Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of FPIR at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline BMI, FPIR and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal first phase insulin response (FPIR) and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs. 73%).Conclusions-Most (97%) subjects had abnormal IVGTTs and/or OGTTs prior to the development of diabetes. The highest sensitivity is achieved using both tests. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Keywords NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptA growing body of evidence supports the hypothesis that type 1 diabetes (T1D) is a chronic autoimmune disease. The autoimmune process is marked by the production of autoantibodies against the pancreatic islet (1-4). Prospective studies of individuals at risk for T1D have shown that subjects can express diabetes associated autoantibodies for years prior to the diagnosis of diabetes (5-9). The metabolic abnormalities of the pre-diabetic period are less well understood. The intravenous glucose tolerance test (IVGTT) has been used as a measure of insulin secretion and abnormalities of the IVGTT such as a diminished first phase insulin response (FPIR) are known to be risk factors for T1D (10-12). Abnormalities of the oral glucose tolerance test (OGTT) have also been shown to precede the diagnosis of T1D (13,14). Both OGTT and IVGTT may be affected by insulin resistance and by pancreatic insulin secretion (15).The Diabetes Prevention Trial-Type 1 (DPT-1) oral and parenteral insulin prevention trials (16) followed 258 subjects who developed diabetes and an additional 453 who were diabetesfree by the end of the study with serial IVGTTs and OGTTs. The prospective study des...

show abstract

“…Controversial results have been reported on the association of IAA and FPIR in relatives of patients with Type I diabetes. In a sub-study of DPT-1, low FPIRs were observed in subjects with high titres of IAA [14], whereas in a Finnish study such an association was not observed [13]. In this study, the first FPIR values were lower in children with a higher number of detectable autoantibodies, a phenomenon possibly reflecting rapid epitope spreading from one to multiple beta-cell antigens in these children.…”

Section: Discussionmentioning

confidence: 54%

“…The association between low FPIRs and high ICA titres, reported earlier in close relatives of patients with Type I diabetes [13,14], suggests that conspicuous amounts of antigens are most likely released during beta-cell destruction, resulting in a strong humoral immune response. Despite the fact that the mechanisms of decline in the functional secretory capacity of the beta cells remain speculative, ICA titres could to some extent be used as indicators of the stage of impairment of insulin-secretory capacity of the beta cells [13].…”

Section: Discussionmentioning

confidence: 97%

“…However, interpretation of the FPIR data obtained previously during the course of prediabetes is difficult because of the wide age range of the subjects studied and the heterogeneity of the stage of their prediabetes, due to the unknown duration of the period when the subjects had had circulating diabetes-associated autoantibodies. Consequently, the sensitivity, specificity and predictive value of FPIR in diabetes prediction and the time scale of the FPIR loss before the onset of clinical Type I diabetes have remained poorly defined [5,6,7,11,12,13,14].…”

mentioning

confidence: 99%

See 1 more Smart Citation

First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes

Keskinen¹,

Korhonen²,

Kupila³

et al. 2002

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis. A reduced first-phase insulin response to intravenous glucose is perceived as a sign of far-advanced deterioration of beta-cell function during the development of Type I (insulin-dependent) diabetes mellitus, but data on insulin responses at the onset of diabetes-related autoimmunity are lacking. We studied the first-phase insulin responses of small children soon after observed seroconversion to autoantibody positivity. Methods. In the Type I Diabetes Prediction and Prevention Study newborn infants are screened for HLA-DQB1-associated genetic risk for Type I diabetes and those with increased risk are followed-up for the emergence of islet-cell antibodies. If antibodies are detected, autoantibodies to three other antigens (insulin, GAD65 and IA-2) are also measured. To measure first-phase insulin responses, intravenous glucose tolerance tests were carried out in 52 (1 to 5-year-old) children who had recently seroconverted to islet-cell antibody positivity.Results. The first-phase insulin response was subnormal (<38 mU/l, the 5 th percentile of insulin responses of 20 islet-cell antibody negative healthy children at this age) in 22 of the 52 children (42%). Stepwise multiregression analysis showed that islet-cell antibody greater than 20 JDFU (p=0.0005), insulin autoantibodies (p=0.0009) and an increasing number of positive autoantibodies (p=0.0011) were independent predictors of low first-phase insulin response. Conclusion/interpretation. A decreased first-phase insulin response could be an early phenomenon in the course of prediabetes in young children, implying a rapid autoimmune destruction or loss of function of beta cells as well as possible metabolic compensation mechanisms, since 11 out of the 22 high risk children remain nondiabetic for a considerable period of time despite low insulin responses. [Diabetologia (2002[Diabetologia ( ) 45:1639[Diabetologia ( -1648 Keywords Autoantibodies, HLA risk markers, insulin secretion, prediabetic state, Type I diabetes. Corresponding author: Dr. P. Keskinen, The JDRF Center for Prevention of Type I Diabetes in Finland. E-mail: paivi.keskinen@uta.fi Abbreviations: DIPP, Type I Diabetes Prediction and Prevention project; FPIR, first-phase insulin response; GAD65, 65 kilodalton isoform of glutamic acid decarboxylase; GADA, antibodies to GAD65; IAA, insulin autoantibodies; IA-2A, antibodies to the protein tyrosine phosphatase related IA-2

show abstract

First-phase insulin release during the intravenous glucose tolerance test as a risk factor for type 1 diabetes

Cited by 67 publications

References 22 publications

Type 1 diabetes risk assessment: improvement by follow-up measurements in young islet autoantibody-positive relatives

Type 1 diabetes risk assessment: improvement by follow-up measurements in young islet autoantibody-positive relatives

Pre-Type 1 Diabetes Dysmetabolism: Maximal Sensitivity Achieved with Both Oral and Intravenous Glucose Tolerance Testing

First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes

Contact Info

Product

Resources

About