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dc.contributor.authorHulman, Aen
dc.contributor.authorSimmons, Rebeccaen
dc.contributor.authorBrunner, EJen
dc.contributor.authorWitte, DRen
dc.contributor.authorFærch, Ken
dc.contributor.authorVistisen, Den
dc.contributor.authorIkehara, Sen
dc.contributor.authorKivimaki, Men
dc.contributor.authorTabák, AGen
dc.date.accessioned2017-06-06T08:44:34Z
dc.date.available2017-06-06T08:44:34Z
dc.date.issued2017-06-01en
dc.identifier.issn0012-186X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/264649
dc.description.abstract$\textbf{AIMS/HYPOTHESIS}$: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. $\textbf{METHODS}$: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI$_{0,120}$) among 120 South Asian and 867 white participants who developed diabetes during follow-up (1991-2013). We fitted cubic mixed-effects models to longitudinal data with adjustment for a wide range of covariates. $\textbf{RESULTS}$: Compared with white individuals, South Asians had a faster increase in FPG before diagnosis (slope difference 0.22 mmol/l per decade; 95% CI 0.02, 0.42; p = 0.03) and a higher FPG level at diagnosis (0.27 mmol/l; 95% CI 0.06, 0.48; p = 0.01). They also had higher FSI and 2hSI levels before and at diabetes diagnosis. South Asians had a faster decline and lower HOMA2-S (log e -transformed) at diagnosis compared with white individuals (0.33; 95% CI 0.21, 0.46; p < 0.001). HOMA2-B increased in both ethnic groups until 7 years before diagnosis and then declined; the initial increase was faster in white individuals. ISI$_{0,120}$ declined steeply in both groups before diagnosis; levels were lower among South Asians before and at diagnosis. There were no ethnic differences in 2hPG trajectories. $\textbf{CONCLUSIONS/INTERPRETATION}$: We observed different trajectories of plasma glucose, insulin sensitivity and secretion prior to diabetes diagnosis in South Asian and white individuals. This might be due to ethnic differences in the natural history of diabetes. South Asian individuals experienced a more rapid decrease in insulin sensitivity and faster increases in FPG compared with white individuals. These findings suggest more marked disturbance in beta cell compensation prior to diabetes diagnosis in South Asian individuals.
dc.description.sponsorshipAH, RKS and DRW are supported by the Danish Diabetes Academy. The Danish Diabetes Academy is funded by the Novo Nordisk Foundation. RKS is further supported by the Aarhus Institute of Advanced Studies. KF is supported by the Novo Nordisk Foundation. EJB is supported by the British Heart Foundation (RG/13/2/30098). The UK Medical Research Council (MR/K013351/1; G0902037), the British Heart Foundation (RG/13/2/30098) and the US National Institutes of Health (R01HL36310, R01AG013196) have supported collection of data in the Whitehall II study.
dc.languageengen
dc.language.isoenen
dc.publisherSpringer
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectcohort studyen
dc.subjectethnicityen
dc.subjectglucoseen
dc.subjectglycaemic trajectoryen
dc.subjectinsulinen
dc.subjectSouth Asiaen
dc.titleTrajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort studyen
dc.typeArticle
prism.endingPage1260
prism.issueIdentifier7en
prism.publicationDate2017en
prism.publicationNameDiabetologiaen
prism.startingPage1252
prism.volume60en
dc.identifier.doi10.17863/CAM.10247
dcterms.dateAccepted2017-03-15en
rioxxterms.versionofrecord10.1007/s00125-017-4275-6en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-06-01en
dc.contributor.orcidSimmons, Rebecca [0000-0002-7726-8529]
dc.identifier.eissn1432-0428
rioxxterms.typeJournal Article/Reviewen
cam.issuedOnline2017-04-13en
cam.orpheus.successThu Jan 30 12:53:47 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
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