{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:31:14Z","timestamp":1788359474436,"version":"build-2803163510"},"reference-count":23,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":2755,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,3,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>To identify the clinical and genetic factors that explain why the rate of diabetes progression is highly variable between idividuals following diagnosis of type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>We studied 5,250 patients with type 2 diabetes using comprehensive electronic medical records in Tayside, Scotland, from 1992 onward. We investigated the association of clinical, biochemical, and genetic factors with the risk of progression of type 2 diabetes from diagnosis to the requirement of insulin treatment (defined as insulin treatment or HbA1c \u22658.5% [69 mmol\/mol] treated with two or more noninsulin therapies).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Risk of progression was associated with both low and high BMI. In an analysis stratified by BMI and HbA1c at diagnosis, faster progression was independently associated with younger age at diagnosis, higher log triacylglyceride (TG) concentrations (hazard ratio [HR] 1.28 per mmol\/L [95% CI 1.15\u20131.42]) and lower HDL concentrations (HR 0.70 per mmol\/L [95% CI 0.55\u20130.87]). A high Genetic Risk Score derived from 61 diabetes risk variants was associated with a younger age at diagnosis and a younger age when starting insulin but was not associated with the progression rate from diabetes to the requirement of insulin treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Increased TG and low HDL levels are independently associated with increased rate of progression of diabetes. The genetic factors that predispose to diabetes are different from those that cause rapid progression of diabetes, suggesting a difference in biological process that needs further investigation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc13-1995","type":"journal-article","created":{"date-parts":[[2013,11,2]],"date-time":"2013-11-02T02:17:21Z","timestamp":1383358641000},"page":"718-724","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":74,"title":["Clinical and Genetic Determinants of Progression of Type 2 Diabetes: A DIRECT Study"],"prefix":"10.2337","volume":"37","author":[{"given":"Kaixin","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A.","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Morris","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Franks","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Genetic & Molecular Epidemiology Unit, Lund University, Malm\u00f6, Sweden"},{"name":"Department of Nutrition, Harvard University, School of Public Health, Boston, MA"},{"name":"Department of Public Health & Clinical Medicine, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Jennison","sequence":"additional","affiliation":[{"name":"Department of Mathematical Sciences, University of Bath, Bath, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin N.A.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewan R.","family":"Pearson","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2014,2,11]]},"reference":[{"key":"2022031220303275100_B1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI7231","article-title":"The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus","volume":"104","author":"Weyer","year":"1999","journal-title":"J Clin Invest"},{"key":"2022031220303275100_B2","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.2337\/diab.44.11.1249","article-title":"U.K. prospective diabetes study 16. Overview of 6 years\u2019 therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group","volume":"44","year":"1995","journal-title":"Diabetes"},{"key":"2022031220303275100_B3","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/(SICI)1096-9136(199804)15:4<290::AID-DIA570>3.0.CO;2-M","article-title":"Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study","volume":"15","author":"Levy","year":"1998","journal-title":"Diabet Med"},{"key":"2022031220303275100_B4","doi-asserted-by":"crossref","first-page":"d7163","DOI":"10.1136\/bmj.d7163","article-title":"Risk models and scores for type 2 diabetes: systematic review","volume":"343","author":"Noble","year":"2011","journal-title":"BMJ"},{"key":"2022031220303275100_B5","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.2337\/diabetes.51.5.1596","article-title":"C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study","volume":"51","author":"Freeman","year":"2002","journal-title":"Diabetes"},{"key":"2022031220303275100_B6","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.2337\/diabetes.54.suppl_2.S11","article-title":"Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4)","volume":"54","author":"Herder","year":"2005","journal-title":"Diabetes"},{"key":"2022031220303275100_B7","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/ng.2383","article-title":"Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes","volume":"44","author":"Morris","year":"2012","journal-title":"Nat Genet"},{"key":"2022031220303275100_B8","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1056\/NEJMoa0804742","article-title":"Genotype score in addition to common risk factors for prediction of type 2 diabetes","volume":"359","author":"Meigs","year":"2008","journal-title":"N Engl J Med"},{"key":"2022031220303275100_B9","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1056\/NEJMoa0801869","article-title":"Clinical risk factors, DNA variants, and the development of type 2 diabetes","volume":"359","author":"Lyssenko","year":"2008","journal-title":"N Engl J Med"},{"key":"2022031220303275100_B10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/qjmed\/hcg040","article-title":"Deteriorating beta-cell function in type 2 diabetes: a long-term model","volume":"96","author":"Bagust","year":"2003","journal-title":"QJM"},{"key":"2022031220303275100_B11","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/S0140-6736(97)03062-6","article-title":"UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes","volume":"350","author":"Turner","year":"1997","journal-title":"Lancet"},{"key":"2022031220303275100_B12","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/(SICI)1096-9136(199804)15:4<297::AID-DIA572>3.0.CO;2-W","article-title":"UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years","volume":"15","author":"Matthews","year":"1998","journal-title":"Diabet Med"},{"key":"2022031220303275100_B13","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1046\/j.1464-5491.2002.00689.x","article-title":"Adherence to prescribed oral hypoglycaemic medication in a population of patients with Type 2 diabetes: a retrospective cohort study","volume":"19","author":"Donnan","year":"2002","journal-title":"Diabet Med"},{"key":"2022031220303275100_B14","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.diabet.2009.11.006","article-title":"Time to insulin treatment and factors associated with insulin prescription in Swedish patients with type 2 diabetes","volume":"36","author":"Ringborg","year":"2010","journal-title":"Diabetes Metab"},{"key":"2022031220303275100_B15","doi-asserted-by":"crossref","first-page":"995","DOI":"10.2337\/diacare.28.5.995","article-title":"Glycemic control continues to deteriorate after sulfonylureas are added to metformin among patients with type 2 diabetes","volume":"28","author":"Cook","year":"2005","journal-title":"Diabetes Care"},{"key":"2022031220303275100_B16","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1161\/CIRCULATIONAHA.104.509224","article-title":"Increased cardiovascular morbidity and mortality in type 2 diabetes is associated with the glutathione S transferase theta-null genotype: a Go-DARTS study","volume":"111","author":"Doney","year":"2005","journal-title":"Circulation"},{"key":"2022031220303275100_B17","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1161\/01.ATV.0000147897.57527.e4","article-title":"Cardiovascular risk in type 2 diabetes is associated with variation at the PPARG locus: a Go-DARTS study","volume":"24","author":"Doney","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2022031220303275100_B18","first-page":"213","article-title":"Slow response to loss of glycemic control in type 2 diabetes mellitus","volume":"9","author":"Brown","year":"2003","journal-title":"Am J Manag Care"},{"key":"2022031220303275100_B19","doi-asserted-by":"crossref","first-page":"541","DOI":"10.7326\/0003-4819-150-8-200904210-00008","article-title":"Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry","volume":"150","author":"Cornelis","year":"2009","journal-title":"Ann Intern Med"},{"key":"2022031220303275100_B20","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/ng.2385","article-title":"Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways","volume":"44","author":"Scott","year":"2012","journal-title":"Nat Genet"},{"key":"2022031220303275100_B21","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.tem.2009.05.004","article-title":"Beta-cell deterioration during diabetes: what\u2019s in the gun?","volume":"20","author":"Robertson","year":"2009","journal-title":"Trends Endocrinol Metab"},{"key":"2022031220303275100_B22","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.2337\/dc11-2006","article-title":"Genetic risk score constructed using 14 susceptibility alleles for type 2 diabetes is associated with the early onset of diabetes and may predict the future requirement of insulin injections among Japanese individuals","volume":"35","author":"Iwata","year":"2012","journal-title":"Diabetes Care"},{"key":"2022031220303275100_B23","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1007\/s00125-007-0661-9","article-title":"TCF7L2 in the Go-DARTS study: evidence for a gene dose effect on both diabetes susceptibility and control of glucose levels","volume":"50","author":"Kimber","year":"2007","journal-title":"Diabetologia"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/37\/3\/718\/621679\/718.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/37\/3\/718\/621679\/718.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T22:31:19Z","timestamp":1647124279000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/37\/3\/718\/29167\/Clinical-and-Genetic-Determinants-of-Progression"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,11]]},"references-count":23,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,2,11]]},"published-print":{"date-parts":[[2014,3,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc13-1995","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,11]]}}}