{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:22:12Z","timestamp":1791332532256,"version":"4.3.1"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,5,8]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014The common insulin resistance syndrome, with obesity, dyslipidemia, hyperglycemia, and hypertension, is associated with increased risk of atherosclerosis. Early atherosclerosis in rare monogenic forms of insulin resistance, however, has not been extensively documented. Cardiovascular end points were thus evaluated in subjects with Dunnigan-type familial partial lipodystrophy (FPLD) due to mutations at\n            <jats:italic>LMNA<\/jats:italic>\n            codon 482.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014FPLD subjects \u226535 years old were stratified by genotype for either the\n            <jats:italic>LMNA<\/jats:italic>\n            R482Q or R482W mutation. Twenty-three subjects were heterozygous mutation carriers, and 17 were R482\/R482 homozygous family control subjects. All\n            <jats:italic>LMNA<\/jats:italic>\n            mutation carriers had FPLD with insulin resistance. In addition,\n            <jats:italic>LMNA<\/jats:italic>\n            mutation carriers had significantly more type 2 diabetes, hypertension, and dyslipidemia than normal family control subjects. Eight\n            <jats:italic>LMNA<\/jats:italic>\n            mutation carriers had coronary heart disease (CHD), compared with 1 normal control subject (OR 5.9, 95% CI 1.2 to 30.2). Six\n            <jats:italic>LMNA<\/jats:italic>\n            mutation carriers had CHD end points before age 55 years, and 4 of these, all women, had been hospitalized for CABG surgery between the ages of 35 and 54 years.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Rare\n            <jats:italic>LMNA<\/jats:italic>\n            mutations that underlie FPLD with insulin resistance and hyperinsulinemia are also associated with early CHD, notably in women. This suggests that abnormalities of the nuclear envelope can result in a phenotype that recapitulates most of the important attributes of the common insulin resistance syndrome, including accelerated cardiovascular disease. FPLD thus appears to be an appropriate human monogenic model for the common insulin resistance syndrome.\n          <\/jats:p>","DOI":"10.1161\/01.cir.103.18.2225","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:09:32Z","timestamp":1339459772000},"page":"2225-2229","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":126,"title":["Premature Atherosclerosis Associated With Monogenic Insulin Resistance"],"prefix":"10.1161","volume":"103","author":[{"given":"Robert A.","family":"Hegele","sequence":"first","affiliation":[{"name":"From the John P. Robarts Research Institute, London, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1995.75.3.473"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"e_1_3_2_3_2","first-page":"1383","volume":"334","year":"1994","unstructured":"4S Investigators. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;334:1383\u20131389.","journal-title":"Lancet"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.2.120"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.2.128"},{"key":"e_1_3_2_6_2","first-page":"170","volume":"84","year":"1999","unstructured":"Garg A, Peshock RM, Fleckenstein JL. Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety). J Clin Endocrinol Metab. 1999;84:170\u2013174.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_7_2","first-page":"1776","volume":"85","year":"2000","unstructured":"Garg A. Gender differences in the prevalence of metabolic complications in familial partial lipodystrophy (Dunnigan variety). J Clin Endocrinol Metab. 2000;85:1776\u20131782.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.1.109"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.23.2.258"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.10.5.652"},{"key":"e_1_3_2_11_2","first-page":"3431","volume":"85","year":"2000","unstructured":"Hegele RA, Cao H, Anderson CM, et al. Heterogeneity of nuclear lamin A mutations in Dunnigan-type familial partial lipodystrophy. J Clin Endocrinol Metab. 2000;85:3431\u20133435.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199604113341504"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.303.6807.893"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200006153422406"},{"key":"e_1_3_2_15_2","first-page":"39","volume":"413","year":"1996","unstructured":"Bjornstad PG, Foerster A, Ihlen H. Cardiac findings in generalized lipodystrophy. Acta Paediatr Suppl. 1996;413:39\u201343.","journal-title":"Acta Paediatr Suppl"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199109263251307"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.19.12.2975"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)32011-3"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7901"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/43448"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/72807"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/302836"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/6799"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199912023412302"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.2000.3.1.39"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199908053410604"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.15.4308"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.103.18.2225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T13:00:36Z","timestamp":1715518836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.103.18.2225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5,8]]},"references-count":27,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2001,5,8]]}},"alternative-id":["10.1161\/01.CIR.103.18.2225"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.103.18.2225","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5,8]]},"assertion":[{"value":"2000-12-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-02-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-05-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}