nach oben

Erschienen in:

01.05.2007 | Article

The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes

verfasst von: M. K. Bulsara, C. D. J. Holman, F. M. van Bockxmeer, E. A. Davis, P. H. Gallego, J. P. Beilby, L. J. Palmer, C. Choong, T. W. Jones

Erschienen in: Diabetologia | Ausgabe 5/2007

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

Genetic factors may account for familial clustering related to diabetes complications. Studies have shown a significant relationship between the presence of the deletion (D) allele of the gene encoding ACE and risk of severe hypoglycaemia. This large prospective cohort study assesses this relationship in a large sample of children and adolescents with type 1 diabetes.

Subjects and methods

We studied 585 children and adolescents (mean age 11.9 ± 4 years, 48.4% males). The frequency of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was prospectively assessed over the 13-year period 1992–2004. Patients were seen with their parents every 3 months and data recorded at each visit. The ACE gene was detected using PCR.

Results

In our cohort of 585 children, 186 (31.8%) had at least one episode of severe hypoglycaemia, and of these 28.0% had the II genotype, 48.9% had the ID genotype and 23.1% had the DD genotype. This was in agreement with the Hardy–Weinberg proportion. A total of 477 severe hypoglycaemic episodes was recorded with a total of 3,404 person-years of follow-up, giving a total incidence of 14 per 100 patient-years. No significant increase in risk for DD genotype (incidence rate ratio = 0.97, 95% CI 0.61–1.55) relative to II genotype was observed.

Conclusions/interpretation

This large prospective study concludes that the presence of the D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia in type 1 diabetic children and adolescents.

Jones TW, Davis EA (2003) Hypoglycemia in children with type 1 diabetes: current issues and controversies. Pediatr Diabetes 4:143–150PubMedCrossRef

Bulsara MK, Holman CDAJ, Davis EA, Jones TW (2004) The Impact of a decade of changing treatment on rates of severe hypoglycemia in a population-based cohort of children with type 1 diabetes. Diabetes Care 27:2293–2298PubMedCrossRef

Cryer PE (2002) Hypoglycaemia: The limiting factor in the glycaemic management of Type I and Type II Diabetes. Diabetologia 45:937–948PubMedCrossRef

Sovik O, Thordarson H (1999) Dead-in-bed syndrome in young diabetic patients. Diabetes Care 22(Suppl 2):B40–B42PubMed

Cryer PE (2005) Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. Diabetes 54:3592–3601PubMedCrossRef

Bulsara MK, Holman CDJ, Davis EA, Jones TW (2004) Evaluating risk factors associated with severe hypoglycaemia in epidemiology studies—what method should we use? Diabetic Medicine 21:914–919PubMedCrossRef

The Diabetes Control and Complications Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group (1997) Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group. Diabetes 46:1829–1839CrossRef

Pedersen-Bjergaard U, Agerholm-Larsen B, Pramming S, Hougaard P, Thorsteinsson B (2003) Prediction of severe hypoglycaemia by angiotensin-converting enzyme activity and genotype in Type 1 Diabetes. Diabetologia 46:89–96PubMed

Herings RMC, de Boer A, Leufkens HGM, Porsius A, Stricker BHC (1995) Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme. Lancet 345:1195–1198PubMedCrossRef

10.

Morris A, Boyle D, McMahon A et al (1997) ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside, Scotland. Medicines Monitoring Unit. Diabetes Care 20:1363–1367PubMedCrossRef

11.

van Haeften TW, Kong N, Bates A et al (1995) ACE inhibitors and hypoglycaemia. Lancet 346:125–127PubMedCrossRef

12.

Petrie J, Morris A, Ueda S et al (1995) Do ACE inhibitors improve insulin sensitivity? Lancet 346:583–584PubMedCrossRef

13.

Strachan M, Frier B (1998) Risk of severe hypoglycemia in diabetes patients taking ACE inhibitors. Diabetes Care 21:470PubMedCrossRef

14.

Chaturvedi N, Fuller J (1998) ACE inhibitors and risk of hypoglycemia in people with diabetes. Diabetes Care 21:470–472PubMedCrossRef

15.

Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343–1346PubMed

16.

Morris BJ, Zee RYL, Schrader AP (1994) Different frequencies of angiotensin-converting enzyme genotypes in older hypertensive individuals. J Clin Invest 94:1085–1089PubMedCrossRef

17.

Gayagay G, Yu B, Hambly B et al (1998) Elite endurance athletes and the ACE I allele—the role of genes in athletic performance. Hum Genet 103:48–50PubMedCrossRef

18.

Montgomery HE, Marshall R, Hemingway H et al (1998) Human gene for physical performance. Nature 393:221–222PubMedCrossRef

19.

Taylor RR, Mamotte CDS, Fallon K, van Bockxmeer FM (1999) Elite athletes and the gene for angiotensin-converting enzyme. J Appl Physiol 87:1035–1037PubMed

20.

Nordfeldt S, Samuelsson U (2003) Serum ACE predicts severe hypoglycemia in children and adolescents with type 1 diabetes. Diabetes Care 26:274–278PubMedCrossRef

21.

Pedersen-Bjergaard U, Agerholm-Larsen B, Pramming S, Hougaard P, Thorsteinsson B (2001) Activity of angiotensin-converting enzyme and risk of severe hypoglycaemia in type 1 diabetes mellitus. Lancet 357:1248–1253PubMedCrossRef

22.

Davis EA, Keating B, Byrne GC, Russell M, Jones TW (1997) Hypoglycemia: incidence and clinical predictors in a large population-based sample of children and adolescents with IDDM. Diabetes Care 20:22–25PubMedCrossRef

23.

Haynes A, Bower C, Bulsara MK, Jones TW, Davis EA (2004) Continued increase in the incidence of childhood Type 1 diabetes in a population-based Australian sample (1985–2002). Diabetologia 47:866–870PubMedCrossRef

24.

Haynes A, Bulsara MK, Bower C, Codde JP, Jones TW, Davis EA (2006) Independent effects of socioeconomic status and place of residence on the incidence of childhood type 1 diabetes in Western Australia. Pediatr Diabetes 7:94–100PubMedCrossRef

25.

Miller SA, Dykes DD, Polesky HF (1998) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215CrossRef

26.

Rigat B, Hubert C, Corvol P, Soubrier R (1992) PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 20:1433PubMedCrossRef

27.

Shanmugam V, Sell KW, Saha BK (1993) Mistyping ACE heterozygotes. PCR Methods Appl 3:120–121PubMed

28.

Alcolado J (1998) Genetics of diabetic complications. Lancet 351:230–231PubMedCrossRef

29.

Craig ME, Handelsman P, Donaghue KC et al (2002) Predictors of glycaemic control and hypoglycaemia in children and adolescents with type 1 diabetes from NSW and the ACT. Med J Aust 177:235–238PubMed

30.

Rewers A, Chase HP, Mackenzie T et al (2002) Predictors of acute complications in children with type 1 diabetes. JAMA 287:2511–2518PubMedCrossRef

31.

Tiret L, Rigat B, Visvikis S et al (1992) Evidence, from combined segregation and linkage analysis, that a variant of the Angiotensin I-converting Enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 51:197–205PubMed

32.

van Bockxmeer FM, Mamotte CDS, Burke V (2000) Angiotensin-converting enzyme gene polymorphism and premature coronary heart disease. Clin Sci 99:247–251PubMedCrossRef

33.

Bloem LJ, Manatunga AK, Pratt JH (1996) Racial difference in the relationship of Angiotensin I-coverting enzyme gene polymorphism to serum Angiotensin I-converting enzyme activity. Hypertension 27:62–66PubMed

34.

Crisan D, Carr J (2000) Angiotensin I-converting enzyme: genotype and disease associations. J Mol Diagn 2:105–115PubMed

35.

Morris BJ (1996) Hypothesis: An Angiotensin converting enzyme gentotype, present in one in three Caucasians, is associated with an increased mortality rate. Clin Exp Pharmacol Physiol 23:1–10PubMed

36.

Geddes J, Zammitt NN, Warren RE, Ashby PJ, Deary IJ, Frier BM (2006) Does serum angiotensin converting enzyme (ACE) concentration predict risk of severe hypoglycemia in type 1 diabetes? American Diabetes Association Scientific Conference, Washington DC, USA

37.

Holstein A, Plaschke A, Böttcher Y, Stumvoll M, Kovacs P (2006) The insertion/deletion polymorphism in the angiotensin-converting enzyme gene and hypoglycemia awareness in patients with type 1 Diabetes. Horm Metab Res 38:603–606PubMedCrossRef

Titel: The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes
verfasst von: M. K. Bulsara
C. D. J. Holman
F. M. van Bockxmeer
E. A. Davis
P. H. Gallego
J. P. Beilby
L. J. Palmer
C. Choong
T. W. Jones
Publikationsdatum: 01.05.2007
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 5/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-007-0613-4

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

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

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes