N Engl J Med. 2011 Mar 3;364(9):829-841. doi: 10.1056/NEJMoa1008862.
Diabetes mellitus, fasting glucose, and risk of cause-specific death.
Rao Kondapally Seshasai S1,
Kaptoge S1,
Thompson A#1,
Di Angelantonio E#1,
Gao P#1,
Sarwar N#1,
Whincup PH2,
Mukamal KJ3,
Gillum RF4,
Holme I5,
Njølstad I6,
Fletcher A7,
Nilsson P8,
Lewington S9,
Collins R9,
Gudnason V10,
Thompson SG11,
Sattar N12,
Selvin E13,
Hu FB3,
Danesh J1;
Emerging Risk Factors Collaboration.
Tipping RW, Ford CE, Simpson LM, Folsom AR, Chambless LE, Selvin E, Wagenknecht LE, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C, Knuiman M, Goldbourt U, Benderly M, Tanne D, Whincup PH, Wannamethee SG, Morris RW, Kiechl S, Willeit J, Oberhollenzer F, Mayr A, Wald N, Ebrahim S, Lawlor DA, Yarnell JW, Gallacher J, Casiglia E, Tikhonoff V, Nietert PJ, Sutherland SE, Bachman DL, de Boer IH, Kizer JR, Mukamal KJ, Tybjærg-Hansen A, Nordestgaard BG, Benn M, Frikke-Schmidt R, Giampaoli S, Palmieri L, Panico S, Vanuzzo D, Pilotto L, Gómez de la Cámara A, Rubio MA, Simons L, McCallum J, Friedlander Y, Fowkes FG, Lee AJ, Taylor J, Guralnik JM, Phillips CL, Wallace R, Guralnik JM, Phillips CL, Blazer DG, Guralnik JM, Phillips CL, Phillips CL, Guralnik JM, Khaw KT, Brenner H, Raum E, Müller H, Rothenbacher D, Jansson JH, Wennberg P, Nissinen A, Donfrancesco C, Giampaoli S, Salomaa V, Harald K, Jousilahti P, Vartiainen E, Woodward M, D'Agostino RB Sr, Vasan RS, Fox CS, Pencina MJ, Bladbjerg E, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, Wilhelmsen L, Eriksson H, Svärdsudd K, Welin L, Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Björkelund C, Lissner L, Bengtsson C, Cremer P, Nagel D, Strandberg TE, Salomaa V, Tilvis RS, Miettinen TA, Tilvis RS, Strandberg TE, Kiyohara Y, Arima H, Doi Y, Ninomiya T, Rodriguez B, Dekker JM, Nijpels G, Stehouwer CD, Hu FB, Sun Q, Rimm EB, Willett WC, Iso H, Kitamura A, Yamagishi K, Noda H, Goldbourt U, Nyyssönen K, Tuomainen TP, Salonen JT, Deeg D, Poppelaars JL, Meade TW, Cooper JA, Hedblad B, Nilsson P, Engström G, Verschuren WM, Blokstra A, Cushman M, Folsom AR, Psaty BM, Shea S, Döring A, Koenig W, Meisinger C, Verschuren WM, Blokstra A, Bueno-de-Mesquita HB, Wilhelmsen L, Rosengren A, Lappas G, Fletcher A, Hewitt J, Nitsch D, Kuller LH, Grandits G, Selmer R, Tverdal A, Nystad W, Gillum RF, Mussolino M, Hu FB, Sun Q, Manson JE, Hankinson SE, Salomaa V, Harald K, Jousilahti P, Vartiainen E, Cooper JA, Bauer KA, Davidson KW, Kirkland S, Shaffer JA, Korin MR, Kitamura A, Iso H, Sato S, Holme I, Selmer R, Tverdal A, Nystad W, Ducimetiere P, Jouven X, Bakker SJ, Gansevoort RT, Hillege HL, Crespo CJ, Garcia-Palmieri M, Amouyel P, Arveiler D, Evans A, Ferrières J, Schulte H, Assmann G, Westendorp RG, Buckley BM, Packard CJ, Sattar N, Cantin B, Lamarche B, Després JP, Dagenais GR, Barrett-Connor E, Wingard DL, Bettencourt R, Gudnason V, Aspelund T, Sigurdsson G, Thorsson B, Trevisan M, Witteman J, Kardys I, Tiemeier H, Hofman A, Tunstall-Pedoe H, Tavendale R, Lowe GD, Woodward M, Howard BV, Zhang Y, Best L, Umans J, Ben-Shlomo Y, Davey-Smith G, Onat A, Hergenç G, Can G, Njølstad I, Mathiesen EB, Løchen ML, Wilsgaard T, Zethelius B, Risérus U, Berne C, Ingelsson E, Gaziano JM, Stampfer M, Ridker P, Gaziano JM, Ridker P, Ulmer H, Diem G, Concin H, Tosetto A, Rodeghiero F, Manson JE, Tinker L, Liu S, Howard BV, Marmot M, Clarke R, Collins R, Fletcher A, Brunner E, Shipley M, Ridker P, Buring J, Shepherd J, Cobbe SM, Ford I, Robertson M, Marín Ibañez A, Feskens EJ, Kromhout D, Walker M, Watson S, Alexander M, Di Angelantonio E, Collins R, Gao P, Gobin R, Haycock P, Kaptoge S, Seshasai SR, Lewington S, Pennells L, Sarwar N, Thompson A, Thompson SG, Walker M, Watson S, White IR, Wood AM, Wormser D, Danesh J.
- 1
- University of Cambridge, Cambridge, United Kingdom.
- 2
- St. George's University of London, London.
- 3
- Harvard University, Boston.
- 4
- Centers for Disease Control and Prevention, Atlanta.
- 5
- Ullevål University Hospital, Oslo.
- 6
- University of Tromsø, Tromsø, Norway.
- 7
- London School of Hygiene and Tropical Medicine, London.
- 8
- Lund University, Lund, Sweden.
- 9
- University of Oxford, Oxford, United Kingdom.
- 10
- Icelandic Heart Association and the University of Iceland, Reykjavik.
- 11
- Medical Research Council Biostatistics Unit, Cambridge, United Kingdom.
- 12
- University of Glasgow, Glasgow, United Kingdom.
- 13
- Johns Hopkins University, Baltimore.
- #
- Contributed equally
Abstract
BACKGROUND:
The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain.
METHODS:
We calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97 prospective studies.
RESULTS:
After adjustment for age, sex, smoking status, and body-mass index, hazard ratios among persons with diabetes as compared with persons without diabetes were as follows: 1.80 (95% confidence interval [CI], 1.71 to 1.90) for death from any cause, 1.25 (95% CI, 1.19 to 1.31) for death from cancer, 2.32 (95% CI, 2.11 to 2.56) for death from vascular causes, and 1.73 (95% CI, 1.62 to 1.85) for death from other causes. Diabetes (vs. no diabetes) was moderately associated with death from cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast. Aside from cancer and vascular disease, diabetes (vs. no diabetes) was also associated with death from renal disease, liver disease, pneumonia and other infectious diseases, mental disorders, nonhepatic digestive diseases, external causes, intentional self-harm, nervous-system disorders, and chronic obstructive pulmonary disease. Hazard ratios were appreciably reduced after further adjustment for glycemia measures, but not after adjustment for systolic blood pressure, lipid levels, inflammation or renal markers. Fasting glucose levels exceeding 100 mg per deciliter (5.6 mmol per liter), but not levels of 70 to 100 mg per deciliter (3.9 to 5.6 mmol per liter), were associated with death. A 50-year-old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths.
CONCLUSIONS:
In addition to vascular disease, diabetes is associated with substantial premature death from several cancers, infectious diseases, external causes, intentional self-harm, and degenerative disorders, independent of several major risk factors. (Funded by the British Heart Foundation and others.).
Figure 1Hazard Ratios for Death from Cancer and from Noncancer, Nonvascular Causes among Participants with Diabetes as Compared with Those without Diabetes at Baseline
Panel A shows hazard ratios for deaths from cancer, and Panel B shows hazard ratios for deaths from noncancer, nonvascular causes. With the exception of the classifications “site unspecified or other” in Panel A and “other noncancer, nonvascular deaths” in Panel B, causes of death are presented in descending order according to their estimated hazard ratios. All analyses were stratified on the basis of study, sex, and trial group (where applicable) and adjusted for baseline age, smoking status (current smoker vs. any other status), and body-mass index. There was evidence of heterogeneity in hazard ratios among cancer sites and among the noncancer, nonvascular causes of death (P<0.001 for both comparisons). Participants with known preexisting cardiovascular disease at baseline were excluded from all analy ses. The sizes of the data markers are proportional to the inverse of the variance of the loge hazard ratios. In Panel A, risk estimates for cancer of the colorectum were broadly similar to those for cancer at subsites (i.e., colon cancer vs. cancer of the rectosigmoid and anus). In Panel B, death from endocrine disorders does not include death coded as being due to diabetes. Other noncancer, nonvascular deaths are those that could not be attributed to a major organ or system. COPD denotes chronic obstructive pulmonary disease.
N Engl J Med. 2011 Mar 3;364(9):829-841.
Figure 2Hazard Ratios for Major Causes of Death, According to Baseline Levels of Fasting Glucose
History of diabetes at baseline was defined according to a self-reported history of diabetes or treatment for diabetes. Glucose levels for participants without a known history of diabetes at baseline were classified as less than 4.0, 4.0 to less than 4.5, 4.5 to less than 5.0, 5.0 to less than 5.5, 5.5 to less than 6.0, 6.0 to less than 6.5, 6.5 to less than 7.0, 7.0 to less than 7.5, and 7.5 mmol per liter or higher. Hazard ratios were plotted against the mean fasting glucose level in each group (reference category, 5.0 to <5.5 mmol per liter). The sizes of the data markers are proportional to the inverse of the variance of the loge hazard ratios. All analyses were stratified or adjusted for sex and adjusted for baseline age, smoking status (current smoker vs. any other status), and body-mass index. Participants with known preexisting cardiovascular disease at baseline were excluded from all analyses. To convert values for fasting glucose to milligrams per deciliter, divide by 0.05551.
N Engl J Med. 2011 Mar 3;364(9):829-841.
Figure 3Diabetes and Survival, According to Sex and Diabetes Status
Panel A shows estimated survival curves that were plotted by applying hazard ratios for death from any cause (specific for sex and age at risk) from the present analyses to mortality data for the European Union in 2000. Panel B shows the estimated numbers of years of life lost owing to diabetes. Participants with known preexisting cardiovascular disease at baseline were excluded from both analyses.
N Engl J Med. 2011 Mar 3;364(9):829-841.
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