Skip to main content
Erschienen in: Diabetologia 12/2006

01.12.2006 | Article

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

verfasst von: P. Achenbach, K. Warncke, J. Reiter, A. J. K. Williams, A. G. Ziegler, P. J. Bingley, E. Bonifacio

Erschienen in: Diabetologia | Ausgabe 12/2006

Einloggen, um Zugang zu erhalten

Abstract

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 < p < 0.03). Relatives whose autoantibody status changed from low- to high-risk categories had a higher risk of diabetes than relatives who remained in low-risk categories, and inclusion of autoantibody status during follow-up improved diabetes risk stratification in Cox proportional hazards models (p < 0.001).

Conclusions/interpretation

Changes in islet autoantibodies are relevant to pathogenesis, and are likely to signal alterations in the disease process. Detection of changes through follow-up measurement will improve diabetes risk stratification, particularly in young individuals.
Literatur
1.
Zurück zum Zitat Achenbach P, Bonifacio E, Ziegler AG (2005) Predicting type 1 diabetes. Curr Diab Rep 5:98–103PubMed Achenbach P, Bonifacio E, Ziegler AG (2005) Predicting type 1 diabetes. Curr Diab Rep 5:98–103PubMed
2.
Zurück zum Zitat Atkinson MA, Eisenbarth GS (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221–229PubMedCrossRef Atkinson MA, Eisenbarth GS (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221–229PubMedCrossRef
3.
Zurück zum Zitat Achenbach P, Bonifacio E, Koczwara K, Ziegler AG (2005) Natural history of type 1 diabetes. Diabetes 54:S25–S31PubMed Achenbach P, Bonifacio E, Koczwara K, Ziegler AG (2005) Natural history of type 1 diabetes. Diabetes 54:S25–S31PubMed
4.
Zurück zum Zitat Bonifacio E, Bingley PJ, Shattock M et al (1990) Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes. Lancet 335:147–149PubMedCrossRef Bonifacio E, Bingley PJ, Shattock M et al (1990) Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes. Lancet 335:147–149PubMedCrossRef
5.
Zurück zum Zitat Bingley PJ (1996) Interactions of age, islet cell antibodies, insulin autoantibodies, and first-phase insulin response in predicting risk of progression to IDDM in ICA+ relatives: the ICARUS data set. Islet cell antibody register users study. Diabetes 45:1720–1728PubMed Bingley PJ (1996) Interactions of age, islet cell antibodies, insulin autoantibodies, and first-phase insulin response in predicting risk of progression to IDDM in ICA+ relatives: the ICARUS data set. Islet cell antibody register users study. Diabetes 45:1720–1728PubMed
6.
Zurück zum Zitat Bingley PJ, Christie MR, Bonifacio E et al (1994) Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes 43:1304–1310PubMed Bingley PJ, Christie MR, Bonifacio E et al (1994) Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes 43:1304–1310PubMed
7.
Zurück zum Zitat Verge CF, Gianani R, Kawasaki E et al (1996) Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 45:926–933PubMed Verge CF, Gianani R, Kawasaki E et al (1996) Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 45:926–933PubMed
8.
Zurück zum Zitat Kulmala P, Savola K, Petersen JS et al (1998) Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. The Childhood Diabetes in Finland Study Group. J Clin Invest 101:327–336PubMedCrossRef Kulmala P, Savola K, Petersen JS et al (1998) Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. The Childhood Diabetes in Finland Study Group. J Clin Invest 101:327–336PubMedCrossRef
9.
Zurück zum Zitat Ziegler AG, Hummel M, Schenker M, Bonifacio E (1999) Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes 48:460–468PubMed Ziegler AG, Hummel M, Schenker M, Bonifacio E (1999) Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes 48:460–468PubMed
10.
Zurück zum Zitat Krischer JP, Cuthbertson DD, Yu L et al (2003) Screening strategies for the identification of multiple antibody-positive relatives of individuals with type 1 diabetes. J Clin Endocrinol Metab 88:103–108PubMedCrossRef Krischer JP, Cuthbertson DD, Yu L et al (2003) Screening strategies for the identification of multiple antibody-positive relatives of individuals with type 1 diabetes. J Clin Endocrinol Metab 88:103–108PubMedCrossRef
11.
Zurück zum Zitat Achenbach P, Warncke K, Reiter J et al (2004) Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics. Diabetes 53:384–392PubMed Achenbach P, Warncke K, Reiter J et al (2004) Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics. Diabetes 53:384–392PubMed
12.
Zurück zum Zitat Gardner SG, Gale EA, Williams AJ et al (1999) Progression to diabetes in relatives with islet autoantibodies. Is it inevitable? Diabetes Care 22:2049–2054PubMed Gardner SG, Gale EA, Williams AJ et al (1999) Progression to diabetes in relatives with islet autoantibodies. Is it inevitable? Diabetes Care 22:2049–2054PubMed
13.
Zurück zum Zitat Dittler J, Seidel D, Schenker M, Ziegler AG (1998) GADIA2-combi determination as first-line screening for improved prediction of type 1 diabetes in relatives. Diabetes 47:592–597PubMed Dittler J, Seidel D, Schenker M, Ziegler AG (1998) GADIA2-combi determination as first-line screening for improved prediction of type 1 diabetes in relatives. Diabetes 47:592–597PubMed
14.
Zurück zum Zitat American Diabetes Association (1997) Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183–1197 American Diabetes Association (1997) Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183–1197
15.
Zurück zum Zitat Naserke HE, Bonifacio E, Ziegler AG (1999) Immunoglobulin G insulin autoantibodies in BABYDIAB offspring appear postnatally: sensitive early detection using a protein A/G-based radiobinding assay. J Clin Endocrinol Metab 84:1239–1243PubMedCrossRef Naserke HE, Bonifacio E, Ziegler AG (1999) Immunoglobulin G insulin autoantibodies in BABYDIAB offspring appear postnatally: sensitive early detection using a protein A/G-based radiobinding assay. J Clin Endocrinol Metab 84:1239–1243PubMedCrossRef
16.
Zurück zum Zitat Bonifacio E, Lampasona V, Bingley PJ (1998) IA-2 (islet cell antigen 512) is the primary target of humoral autoimmunity against type 1 diabetes-associated tyrosine phosphatase autoantigens. J Immunol 161:2648–2654PubMed Bonifacio E, Lampasona V, Bingley PJ (1998) IA-2 (islet cell antigen 512) is the primary target of humoral autoimmunity against type 1 diabetes-associated tyrosine phosphatase autoantigens. J Immunol 161:2648–2654PubMed
17.
Zurück zum Zitat Bonifacio E, Scirpoli M, Kredel K, Fuchtenbusch M, Ziegler AG (1999) Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation. J Immunol 163:525–532PubMed Bonifacio E, Scirpoli M, Kredel K, Fuchtenbusch M, Ziegler AG (1999) Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation. J Immunol 163:525–532PubMed
18.
Zurück zum Zitat Chase HP, Cuthbertson DD, Dolan LM et al (2001) First-phase insulin release during the intravenous glucose tolerance test as a risk factor for type 1 diabetes. J Pediatr 138:244–249PubMedCrossRef Chase HP, Cuthbertson DD, Dolan LM et al (2001) First-phase insulin release during the intravenous glucose tolerance test as a risk factor for type 1 diabetes. J Pediatr 138:244–249PubMedCrossRef
19.
Zurück zum Zitat Keskinen P, Korhonen S, Kupila A et al (2002) First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes. Diabetologia 45:1639–1648PubMedCrossRef Keskinen P, Korhonen S, Kupila A et al (2002) First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes. Diabetologia 45:1639–1648PubMedCrossRef
20.
Zurück zum Zitat Fourlanos S, Narendran P, Byrnes GB, Colman PG, Harrison LC (2004) Insulin resistance is a risk factor for progression to type 1 diabetes. Diabetologia 47:1661–1667PubMedCrossRef Fourlanos S, Narendran P, Byrnes GB, Colman PG, Harrison LC (2004) Insulin resistance is a risk factor for progression to type 1 diabetes. Diabetologia 47:1661–1667PubMedCrossRef
21.
Zurück zum Zitat Arif S, Tree TI, Astill TP et al (2004) Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J Clin Invest 113:451–463PubMedCrossRef Arif S, Tree TI, Astill TP et al (2004) Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J Clin Invest 113:451–463PubMedCrossRef
22.
Zurück zum Zitat Gale EA, Bingley PJ, Emmett CL, Collier T (2004) European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet 363:925–931PubMedCrossRef Gale EA, Bingley PJ, Emmett CL, Collier T (2004) European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet 363:925–931PubMedCrossRef
23.
Zurück zum Zitat Diabetes Prevention Trial—Type 1 Diabetes Study Group (2002) Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685–1691CrossRef Diabetes Prevention Trial—Type 1 Diabetes Study Group (2002) Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685–1691CrossRef
24.
Zurück zum Zitat Skyler JS, Krischer JP, Wolfsdorf J et al (2005) Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial — Type 1. Diabetes Care 28:1068–1076PubMed Skyler JS, Krischer JP, Wolfsdorf J et al (2005) Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial — Type 1. Diabetes Care 28:1068–1076PubMed
25.
Zurück zum Zitat Vardi P, Ziegler AG, Mathews JH et al (1988) Concentration of insulin autoantibodies at onset of type I diabetes. Inverse log–linear correlation with age. Diabetes Care 11:736–739PubMed Vardi P, Ziegler AG, Mathews JH et al (1988) Concentration of insulin autoantibodies at onset of type I diabetes. Inverse log–linear correlation with age. Diabetes Care 11:736–739PubMed
26.
Zurück zum Zitat Achenbach P, Ziegler AG (2005) Diabetes-related antibodies in euglycemic subjects. Best Pract Res Clin Endocrinol Metab 19:101–117PubMedCrossRef Achenbach P, Ziegler AG (2005) Diabetes-related antibodies in euglycemic subjects. Best Pract Res Clin Endocrinol Metab 19:101–117PubMedCrossRef
27.
Zurück zum Zitat Bingley PJ, Williams AJ, Gale EA (1999) Optimized autoantibody-based risk assessment in family members. Implications for future intervention trials. Diabetes Care 22:1796–1801PubMed Bingley PJ, Williams AJ, Gale EA (1999) Optimized autoantibody-based risk assessment in family members. Implications for future intervention trials. Diabetes Care 22:1796–1801PubMed
28.
Zurück zum Zitat Hummel M, Bonifacio E, Schmid S, Walter M, Knopff A, Ziegler AG (2004) Brief communication: early appearance of islet autoantibodies predicts childhood type 1 diabetes in offspring of diabetic parents. Ann Intern Med 140:882–886PubMed Hummel M, Bonifacio E, Schmid S, Walter M, Knopff A, Ziegler AG (2004) Brief communication: early appearance of islet autoantibodies predicts childhood type 1 diabetes in offspring of diabetic parents. Ann Intern Med 140:882–886PubMed
29.
Zurück zum Zitat Bingley PJ, Gale EA; The European Nicotinamide Diabetes Intervention Trial (ENDIT) Group (2006) Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial: the role of additional immune, genetic and metabolic markers of risk. Diabetologia 49:881–890PubMedCrossRef Bingley PJ, Gale EA; The European Nicotinamide Diabetes Intervention Trial (ENDIT) Group (2006) Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial: the role of additional immune, genetic and metabolic markers of risk. Diabetologia 49:881–890PubMedCrossRef
30.
Zurück zum Zitat Achenbach P, Koczwara K, Knopff A, Naserke H, Ziegler AG, Bonifacio E (2004) Mature high-affinity immune responses to (pro)insulin anticipate the autoimmune cascade that leads to type 1 diabetes. J Clin Invest 114:589–597PubMedCrossRef Achenbach P, Koczwara K, Knopff A, Naserke H, Ziegler AG, Bonifacio E (2004) Mature high-affinity immune responses to (pro)insulin anticipate the autoimmune cascade that leads to type 1 diabetes. J Clin Invest 114:589–597PubMedCrossRef
31.
Zurück zum Zitat Mrena S, Virtanen SM, Laippala P et al (2006) Models for predicting type 1 diabetes in siblings of affected children. Diabetes Care 29:662–667PubMedCrossRef Mrena S, Virtanen SM, Laippala P et al (2006) Models for predicting type 1 diabetes in siblings of affected children. Diabetes Care 29:662–667PubMedCrossRef
Metadaten
Titel
Type 1 diabetes risk assessment: improvement by follow-up measurements in young islet autoantibody-positive relatives
verfasst von
P. Achenbach
K. Warncke
J. Reiter
A. J. K. Williams
A. G. Ziegler
P. J. Bingley
E. Bonifacio
Publikationsdatum
01.12.2006
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 12/2006
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0451-9

Weitere Artikel der Ausgabe 12/2006

Diabetologia 12/2006 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.