{"doi":"10.2337/diabetes.48.4.924","title":"Altered beta-cell characteristics in impaired glucose tolerant carriers of a GAA trinucleotide repeat polymorphism in the frataxin gene.","abstract":"<jats:p>Friedreich's ataxia is associated with GAA trinucleotide repeat expansions in the frataxin gene. In the general population, these trinucleotide expansions are variable in length, and three types of expansions are seen: short, intermediate, and long repeats. Friedreich's ataxia patients are generally homozygous for the long repeats and exhibit diabetes as pronounced comorbidity. Ristow et al. recently reported an association between the intermediate-length normal allele in the frataxin gene and type 2 diabetes. We have investigated in 94 subjects with impaired glucose tolerance (IGT) as to whether the length of the GAA trinucleotide repeat polymorphism in the frataxin gene associates with parameters reflecting beta-cell function. A hyperglycemic clamp at 10 mmol/l glucose for 3 h was used to quantitate beta-cell characteristics. Carriers of one or two intermediate repeat alleles (n = 32) had a 50% higher median first- phase insulin response to glucose than the noncarriers. Furthermore, they needed less time to reach peak insulin. An analysis of the distribution of the various repeat lengths in elderly type 2 diabetic (n = 179) and control subjects (n = 183), with the same age and ethnic background, did not provide evidence for an association of the intermediate-length repeat allele with type 2 diabetes in Dutch Caucasians.</jats:p>","journal":"Diabetes","year":1999,"id":616065,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1588165,"name":"J B Ruige","orcid":null,"position":1,"is_corresponding":false},{"id":1588166,"name":"J M Dekker","orcid":null,"position":2,"is_corresponding":false},{"id":1588167,"name":"C D Stehouwer","orcid":null,"position":3,"is_corresponding":false},{"id":1588169,"name":"J A Maassen","orcid":null,"position":4,"is_corresponding":false},{"id":1588171,"name":"R J Heine","orcid":null,"position":5,"is_corresponding":false},{"id":1588164,"name":"L M t Hart","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Altered beta-cell characteristics in impaired glucose tolerant carriers of a GAA trinucleotide repeat polymorphism in the frataxin gene.","abstract":"<jats:p>Friedreich's ataxia is associated with GAA trinucleotide repeat expansions in the frataxin gene. In the general population, these trinucleotide expansions are variable in length, and three types of expansions are seen: short, intermediate, and long repeats. Friedreich's ataxia patients are generally homozygous for the long repeats and exhibit diabetes as pronounced comorbidity. Ristow et al. recently reported an association between the intermediate-length normal allele in the frataxin gene and type 2 diabetes. We have investigated in 94 subjects with impaired glucose tolerance (IGT) as to whether the length of the GAA trinucleotide repeat polymorphism in the frataxin gene associates with parameters reflecting beta-cell function. A hyperglycemic clamp at 10 mmol/l glucose for 3 h was used to quantitate beta-cell characteristics. Carriers of one or two intermediate repeat alleles (n = 32) had a 50% higher median first- phase insulin response to glucose than the noncarriers. Furthermore, they needed less time to reach peak insulin. An analysis of the distribution of the various repeat lengths in elderly type 2 diabetic (n = 179) and control subjects (n = 183), with the same age and ethnic background, did not provide evidence for an association of the intermediate-length repeat allele with type 2 diabetes in Dutch Caucasians.</jats:p>","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10102715","pmcid":null,"openalex_id":"https://openalex.org/W2074544916","authors":[],"funders":[],"total_grants":0,"fwci":0.3266,"citation_percentile":0.46569129,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2019,"count":1},{"year":2021,"count":1},{"year":2025,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://journals.org/diabetes/diabetes/article-pdf/48/4/924/364696/10102715.pdf","host_type":"publisher"},{"url":"https://diabetesjournals.org/diabetes/article-pdf/48/4/924/364696/10102715.pdf","host_type":"publisher"},{"url":"https://doi.org/10.2337/diabetes.48.4.924","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10102715","host_type":"repository"},{"url":"https://research.vu.nl/en/publications/d69d34a7-033f-4510-8f8b-ef87cd600f3a","host_type":"repository"}],"fields_of_study":["Genetic Neurodegenerative Diseases","Mitochondrial Function and Pathology"],"mesh_terms":["Insulin Secretion","Frataxin","Aged","Alleles","Female","Humans","Insulin","Islets of Langerhans","Male","Middle Aged","Phosphotransferases (Alcohol Group Acceptor)","Glucose Intolerance","Trinucleotide Repeat Expansion","Iron-Binding Proteins"],"keywords":["Frataxin","Trinucleotide repeat expansion","Biology","Allele","Ataxia","Diabetes mellitus","Type 2 diabetes","Genetics","Population","Endocrinology","Internal medicine","Impaired glucose tolerance","Gene","Medicine","Iron-binding proteins"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T21:51:57.934664Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}