A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. / Højlund, Kurt; Hansen, Torben; Lajer, Maria; Henriksen, Jan Erik; Levin, Klaus; Lindholm, Jörgen; Pedersen, Oluf; Beck-Nielsen, Henning.

In: Diabetes, Vol. 53, No. 6, 2004, p. 1592-8.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Højlund, K, Hansen, T, Lajer, M, Henriksen, JE, Levin, K, Lindholm, J, Pedersen, O & Beck-Nielsen, H 2004, 'A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene', Diabetes, vol. 53, no. 6, pp. 1592-8.

APA

Højlund, K., Hansen, T., Lajer, M., Henriksen, J. E., Levin, K., Lindholm, J., Pedersen, O., & Beck-Nielsen, H. (2004). A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. Diabetes, 53(6), 1592-8.

Vancouver

Højlund K, Hansen T, Lajer M, Henriksen JE, Levin K, Lindholm J et al. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. Diabetes. 2004;53(6):1592-8.

Author

Højlund, Kurt ; Hansen, Torben ; Lajer, Maria ; Henriksen, Jan Erik ; Levin, Klaus ; Lindholm, Jörgen ; Pedersen, Oluf ; Beck-Nielsen, Henning. / A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. In: Diabetes. 2004 ; Vol. 53, No. 6. pp. 1592-8.

Bibtex

@article{622f8840f70d466f970d4b010ca2d129,
title = "A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene",
abstract = "Recently, various subtypes of familial hyperinsulinemic hypoglycemia with an autosomal-dominant inheritance have been etiologically characterized. In the present study, we have delineated the genetics and metabolic phenotype of a novel form of hypoglycemia in a large pedigree with an apparent autosomal-dominant transmission. After initial investigations of the proband, her mother, and a sister, the study was extended to 19 family members in three generations. Glucose tolerance was assessed by a 5-h oral glucose tolerance test (OGTT) and insulin sensitivity by euglycemic-hyperinsulinemic clamp in six affected family members and six control subjects. To identify the genetic cause of hypoglycemia, linkage analysis and mutation analysis of genomic DNA from all family members were performed. All affected family members were characterized by postprandial hypoglycemia, fasting hyperinsulinemia, and an elevated serum insulin-to-C-peptide ratio. The 5-h OGTT demonstrated hyperinsulinemic hypoglycemia, and the clamp studies showed reduced insulin sensitivity and clearance of serum insulin in affected family members compared with control subjects. Linkage analysis and subsequent mutation screening revealed a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate the coexistence of severe postprandial hypoglycemia, insulin resistance, and impaired insulin clearance and suggest that hypoglycemia should be considered as a phenotype linked to heterozygote mutations in the insulin receptor gene.",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Child, Exercise, Genetic Linkage, Glucose Clamp Technique, Glucose Tolerance Test, Haplotypes, Heterozygote, Humans, Hyperinsulinism, Hypoglycemia, Lod Score, Middle Aged, Mutation, Pedigree, Phenotype, Point Mutation, Receptor, Insulin",
author = "Kurt H{\o}jlund and Torben Hansen and Maria Lajer and Henriksen, {Jan Erik} and Klaus Levin and J{\"o}rgen Lindholm and Oluf Pedersen and Henning Beck-Nielsen",
year = "2004",
language = "English",
volume = "53",
pages = "1592--8",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "6",

}

RIS

TY - JOUR

T1 - A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene

AU - Højlund, Kurt

AU - Hansen, Torben

AU - Lajer, Maria

AU - Henriksen, Jan Erik

AU - Levin, Klaus

AU - Lindholm, Jörgen

AU - Pedersen, Oluf

AU - Beck-Nielsen, Henning

PY - 2004

Y1 - 2004

N2 - Recently, various subtypes of familial hyperinsulinemic hypoglycemia with an autosomal-dominant inheritance have been etiologically characterized. In the present study, we have delineated the genetics and metabolic phenotype of a novel form of hypoglycemia in a large pedigree with an apparent autosomal-dominant transmission. After initial investigations of the proband, her mother, and a sister, the study was extended to 19 family members in three generations. Glucose tolerance was assessed by a 5-h oral glucose tolerance test (OGTT) and insulin sensitivity by euglycemic-hyperinsulinemic clamp in six affected family members and six control subjects. To identify the genetic cause of hypoglycemia, linkage analysis and mutation analysis of genomic DNA from all family members were performed. All affected family members were characterized by postprandial hypoglycemia, fasting hyperinsulinemia, and an elevated serum insulin-to-C-peptide ratio. The 5-h OGTT demonstrated hyperinsulinemic hypoglycemia, and the clamp studies showed reduced insulin sensitivity and clearance of serum insulin in affected family members compared with control subjects. Linkage analysis and subsequent mutation screening revealed a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate the coexistence of severe postprandial hypoglycemia, insulin resistance, and impaired insulin clearance and suggest that hypoglycemia should be considered as a phenotype linked to heterozygote mutations in the insulin receptor gene.

AB - Recently, various subtypes of familial hyperinsulinemic hypoglycemia with an autosomal-dominant inheritance have been etiologically characterized. In the present study, we have delineated the genetics and metabolic phenotype of a novel form of hypoglycemia in a large pedigree with an apparent autosomal-dominant transmission. After initial investigations of the proband, her mother, and a sister, the study was extended to 19 family members in three generations. Glucose tolerance was assessed by a 5-h oral glucose tolerance test (OGTT) and insulin sensitivity by euglycemic-hyperinsulinemic clamp in six affected family members and six control subjects. To identify the genetic cause of hypoglycemia, linkage analysis and mutation analysis of genomic DNA from all family members were performed. All affected family members were characterized by postprandial hypoglycemia, fasting hyperinsulinemia, and an elevated serum insulin-to-C-peptide ratio. The 5-h OGTT demonstrated hyperinsulinemic hypoglycemia, and the clamp studies showed reduced insulin sensitivity and clearance of serum insulin in affected family members compared with control subjects. Linkage analysis and subsequent mutation screening revealed a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate the coexistence of severe postprandial hypoglycemia, insulin resistance, and impaired insulin clearance and suggest that hypoglycemia should be considered as a phenotype linked to heterozygote mutations in the insulin receptor gene.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Child

KW - Exercise

KW - Genetic Linkage

KW - Glucose Clamp Technique

KW - Glucose Tolerance Test

KW - Haplotypes

KW - Heterozygote

KW - Humans

KW - Hyperinsulinism

KW - Hypoglycemia

KW - Lod Score

KW - Middle Aged

KW - Mutation

KW - Pedigree

KW - Phenotype

KW - Point Mutation

KW - Receptor, Insulin

M3 - Journal article

C2 - 15161766

VL - 53

SP - 1592

EP - 1598

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

ER -

ID: 38457364