J Int AIDS Soc. 2012 Oct 10;15(2):17426.

Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.

Petoumenos K, Worm SW, Fontas E, Weber R, De Wit S, Bruyand M, Reiss P, El-Sadr W, Monforte AD, Friis-Møller N, Lundgren JD, Law MG; D:A:D Study Group.
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Destroy user interface controlCollaborators (669)Collins S, Shortman N, Butcher D, Rode R, Powderly W, Worm SW, Sabin CA, Kamara D, Ellefson M, Smith C, Tverland J, Nielsen J, Mocroft A, Lundgren JD, Salbøl Brandt R, Rickenbach M, Fanti L, Krum E, Hillebregt M, Geffard S, Sundström A, Delforge M, Fontas E, Torres F, McManus H, Wright S, Kjær J, Sjøl A, de Wolf F, Zaheri S, Hillebregt M, Gras L, Prins JM, Kuijpers TW, Scherpbier HJ, Boer K, van der Meer JT, Wit FW, Godfried MH, Reiss P, van der Poll T, Nellen FJ, Lange JM, Geerlings SE, van Vugt M, Vrouenraets SM, Pajkrt D, van der Valk M, Schreij G, Lowe S, Oude Lashof A, Pronk MJ, Bravenboer B, van der Ende ME, de Vries-Sluijs TE, Schurink CA, van der Feltz M, Nouwen JL, Gelinck LB, Verbon A, Rijnders BJ, Slobbe L, Hartwig NG, Driessen GJ, Branger J, Kauffmann RH, Schippers EF, Groeneveld PH, Alleman MA, Bouwhuis JW, ten Kate RW, Soetekouw R, Kroon FP, van den Broek PJ, van Dissel JT, Arend SM, van Nieuwkoop C, de Boer MG, Jolink H, den Hollander JG, Pogany K, van Twillert G, Kortmann W, Vriesendorp R, Leyten EM, ten Napel CH, Kootstra GJ, Brinkman K, Blok WL, Frissen PH, Schouten WE, van den Berk GE, Juttmann JR, van Kasteren ME, Brouwer AE, Veenstra J, Lettinga KD, Mulder JW, van Gorp EC, Smit PM, Weijer S, van Eeden A, Verhagen DW, Sprenger HG, Doedens R, Scholvinck EH, van Assen S, Stek CJ, Koopmans PP, de Groot R, Keuter M, van der Ven AJ, ter Hofstede HJ, van der Flier M, Brouwer AM, Dofferhoff AS, Hoepelman AI, Mudrikova T, Schneider MM, Jaspers CA, Ellerbroek PM, Peters EJ, Maarschalk-Ellerbroek LJ, Oosterheert JJ, Arends JE, Wassenberg MW, van der Hilst JC, Danner SA, van Agtmael MA, de Vocht J, Perenboom RM, Claessen FA, Bierman WF, de Jong EV, bij de Vaate EA, Geelen SP, Wolfs TF, Richter C, van der Berg JP, Gisolf EH, van den Berge M, Stegeman A, van Houte DP, Polée MB, van Vonderen MG, Winkel C, Duits AJ, Salamon R, Beylot J, Dupon M, Le Bras M, Pellegrin JL, Ragnaud JM, Dabis F, Chêne G, Jacqmin-Gadda H, Thiébaut R, Lawson-Ayayi S, Lavignolle V, Balestre E, Blaizeau MJ, Decoin M, Formaggio AM, Delveaux S, Labarerre S, Uwamaliya B, Vimard E, Merchadou L, Palmer G, Touchard D, Dutoit D, Pereira F, Boulant B, Beylot J, Morlat P, Bernard N, Bonarek M, Bonnet F, Coadou B, Gelie P, Jaubert D, Nouts C, Lacoste D, Dupon M, Dutronc H, Cipriano G, Lafarie S, Chossat I, Lacut JY, Leng B, Pellegrin JL, Mercié P, Viallard JF, Faure I, Rispal P, Cipriano C, Tchamgoué S, Djossou F, Malvy D, Pivetaud JP, Ragnaud JM, Chambon D, De La Taille C, Galperine T, Lafarie S, Neau D, Ochoa A, Beylot C, Doutre MS, Bezian JH, Moreau JF, Taupin JL, Conri C, Constans J, Couzigou P, Castera L, Fleury H, Lafon ME, Masquelier B, Pellegrin I, Trimoulet P, Moreau F, Mestre C, Series C, Taytard A, Law M, Petoumenos K, McManus H, Wright S, Bendall C, Moore R, Edwards S, Hoy J, Watson K, Roth N, Nicholson J, Bloch M, Franic T, Baker D, Vale R, Carr A, Cooper D, Chuah J, Ngieng M, Nolan D, Skett J, Calvo G, Torres F, Mateu S, Domingo P, Sambeat MA, Gatell J, Del Cacho E, Cadafalch J, Fuster M, Codina C, Sirera G, Vaqué A, Clumeck N, De Wit S, Gerard M, Kabeya K, Konopnicki D, Libois A, Payen MC, Van Laethem Y, Neaton J, Bartsch G, El-Sadr WM, Krum E, Thompson G, Wentworth D, Luskin-Hawk R, Telzak E, Abrams DI, Cohn D, Markowitz N, Arduino R, Mushatt D, Friedland G, Perez G, Tedaldi E, Fisher E, Gordin F, Crane LR, Sampson J, Baxter J, Kirk O, Mocroft A, Ellefson M, Phillips AN, Lundgren JD, Losso M, Elias C, Vetter N, Zangerle R, Karpov I, Vassilenko A, Mitsura VM, Suetnov O, Clumeck N, De Wit S, Poll B, Colebunders R, Vandekerckhove L, Hadziosmanovic V, Kostov K, Begovac J, Machala L, Rozsypal H, Sedlacek D, Nielsen J, Kronborg G, Benfield T, Larsen M, Gerstoft J, Katzenstein T, Hansen AB, Skinhøj P, Pedersen C, Oestergaard L, Zilmer K, Smidt J, Ristola M, Katlama C, Viard JP, Girard PM, Livrozet JM, Vanhems P, Pradier C, Dabis F, Neau D, Rockstroh J, Schmidt R, van Lunzen J, Degen O, Stellbrink HJ, Staszewski S, Bogner J, Fätkenheuer G, Kosmidis J, Gargalianos P, Xylomenos G, Perdios J, Panos G, Filandras A, Karabatsaki E, Sambatakou H, Banhegyi D, Mulcahy F, Yust I, Turner D, Burke M, Pollack S, Hassoun G, Maayan S, Chiesi A, Esposito R, Mazeu I, Mussini C, Arici C, Pristera R, Mazzotta F, Gabbuti A, Vullo V, Lichtner M, Chirianni A, Montesarchio E, Gargiulo M, Antonucci G, Testa A, Narciso P, Vlassi C, Zaccarelli M, Lazzarin A, Finazzi R, Galli M, Ridolfo A, d'Arminio Monforte A, Rozentale B, Aldins P, Chaplinskas S, Hemmer R, Staub T, Reiss P, Bruun J, Maeland A, Ormaasen V, Knysz B, Gasiorowski J, Horban A, Bakowska E, Prokopowicz D, Flisiak R, Boron-Kaczmarska A, Pynka M, Beniowski M, Mularska E, Trocha H, Jablonowska E, Malolepsza E, Wojcik K, Antunes F, Valadas E, Mansinho K, Maltez F, Duiculescu D, Rakhmanova A, Vinogradova E, Buzunova S, Jevtovic D, Mokráš M, Staneková D, Tomazic J, González-Lahoz J, Soriano V, Martin-Carbonero L, Labarga P, Moreno S, Clotet B, Jou A, Paredes R, Tural C, Puig J, Bravo I, Gatell JM, Miró JM, Domingo P, Gutierrez M, Mateo G, Sambeat MA, Karlsson A, Persson PO, Flamholc L, Ledergerber B, Weber R, Francioli P, Cavassini M, Hirschel B, Boffi E, Furrer H, Battegay M, Elzi L, Kravchenko E, Chentsova N, Kutsyna G, Servitskiy S, Antoniak S, Krasnov M, Barton S, Johnson AM, Mercey D, Phillips A, Johnson MA, Mocroft A, Murphy M, Weber J, Scullard G, Fisher M, Leen C, Morfeldt L, Thulin G, Sundström A, Åkerlund B, Koppel K, Karlsson A, Flamholc L, Håkangård C, Moroni M, Antinori A, Carosi G, Cauda R, Chiodo F, Di Perri G, Galli M, Ghinelli F, Iardino R, Ippolito G, Lazzarin A, Mazzotta F, Panebianco R, Pastore G, Perno CF, Ammassari A, Antinori A, Balotta C, Bonfanti P, Capobianchi MR, Castagna A, Ceccherini-Silberstein F, Cozzi-Lepri A, De Luca A, Gervasoni C, Girardi E, Lo Caputo S, Maggiolo F, Murri R, Mussini C, Puoti M, Torti C, Cozzi-Lepri A, Fanti I, Formenti T, Montroni M, Giacometti A, Costantini A, Riva A, Tirelli U, Martellotta F, Pastore G, Ladisa N, Suter F, Maggiolo F, Chiodo F, Verucchi G, Fiorini C, Carosi G, Cristini G, Torti C, Minardi C, Bertelli D, Quirino T, Abeli C, Manconi PE, Piano P, Vecchiet J, Farenga M, Carnevale G, Lorenzotti S, Ghinelli F, Sighinolfi L, Leoncini F, Mazzotta F, Pozzi M, Pagano G, Cassola G, Viscoli G, Alessandrini A, Piscopo R, Mazzarello G, Soscia F, Tacconi L, Orani A, Rossotto R, Tommasi D, Congedo P, Chiodera A, Castelli P, Galli M, Lazzarin A, Rizzardini G, Schlacht I, Ridolfo AL, Foschi A, Castagna A, Salpietro S, Merli S, Melzi S, Moioli MC, Cicconi P, Formenti T, Esposito R, Mussini C, Gori A, Abrescia N, Chirianni A, Izzo CM, De Marco M, Viglietti R, Manzillo E, Ferrari C, Pizzaferri P, Baldelli F, Camanni G, Magnani G, Ursitti MA, Arlotti M, Ortolani P, Cauda R, Andreoni M, Antinori A, Antonucci G, Narciso P, Tozzi V, Vullo V, Zaccarelli M, Acinapura R, De Longis P, Trotta MP, Lichtner M, Carletti F, Mura MS, Madeddu G, Caramello P, Di Perri G, Orofino GC, Raise E, Ebo F, Pellizzer G, Buonfrate D, Pradier C, Fontas E, Caissotti C, Dellamonica P, Bentz L, Bernard E, Cua E, De Salvador-Guillouet F, Durant J, Farhad R, Ferrando S, Mondain-Miton V, Perbost I, Prouvost-Keller B, Pugliese P, Rahelinirina V, Roger PM, Vassallo M, Dollet K, Barth J, Bernasconi E, Böni J, Bucher HC, Burton-Jeangros C, Calmy A, Cavassini M, Cellerai C, Dubs R, Egger M, Elzi L, Fehr J, Flepp M, Francioli P, Furrer H, Fux CA, Gorgievski M, Günthard H, Hasse B, Hirsch HH, Hirschel B, Hösli I, Kahlert C, Kaiser L, Keiser O, Kind C, Klimkait T, Kovari H, Ledergerber B, Martinetti G, Martinez de Tejada B, Müller N, Nadal D, Pantaleo G, Rauch A, Regenass S, Rickenbach M, Rudin C, Schmid P, Schultze D, Schöni-Affolter F, Schüpbach J, Speck R, Taffé P, Telenti A, Trkola A, Vernazza P, von Wyl V, Weber R, Yerly S.

SourceAHOD, The Kirby Institute, University of New South Wales, Sydney, Australia. kpetoumenos@kirby.unsw.edu.au

Abstract
INTRODUCTION: HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population.

METHODS: All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined.

RESULTS: Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of <200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m(2).

CONCLUSIONS: The D:A:D equation performed well in predicting the short-term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham.


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