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MetS is important because it is rapidly growing in prevalence and is strongly related to the development of cardiovascular disease. To define etiology, pathogenesis and expression of MetS, we have studied patients, specifically Canadian families and communities. One example is familial partial lipodystrophy (FPLD), a rare monogenic form of insulin resistance caused by mutations in either LMNA, encoding nuclear lamin A\/C (subtype FPLD2), or in PPARG, encoding peroxisomal proliferator-activated receptor-\u03b3 (subtype FPLD3). Because it evolves slowly and recapitulates key clinical and biochemical attributes, FPLD seems to be a useful monogenic model of MetS. A second example is the disparate MetS prevalence between two Canadian aboriginal groups that is mirrored by disparate prevalence of diabetes and cardiovascular disease. Careful phenotypic evaluation of such special cases of human MetS by using a wide range of diagnostic methods, an approach called \u201cphenomics,\u201d may help uncover early presymptomatic disease biomarkers, which in turn might reveal new pathways and targets for interventions for MetS, diabetes, and atherosclerosis. <\/jats:p>","DOI":"10.1152\/ajpregu.00275.2005","type":"journal-article","created":{"date-parts":[[2005,5,13]],"date-time":"2005-05-13T00:25:59Z","timestamp":1115943959000},"page":"R663-R669","source":"Crossref","is-referenced-by-count":39,"title":["Genetic and physiological insights into the metabolic syndrome"],"prefix":"10.1152","volume":"289","author":[{"given":"Robert A.","family":"Hegele","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Pollex","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Agarwal AK and Garg A. 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