Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes

An analysis of the ACCORD randomised trial

Faramarz Ismail-Beigi, Timothy Craven, Mary Ann Banerji, Jan Basile, Jorge Calles, Robert M. Cohen, Robert Cuddihy, William Cushman, Saul Genuth, Richard H. Grimm, Bruce P. Hamilton, Byron Hoogwerf, Diane Karl, Lois Katz, Armand Krikorian, Patrick O'Connor, Rodica Pop-Busui, Ulrich Schubart, Debra Simmons, Harris Taylor & 3 others Abraham Thomas, Daniel Weiss, Irene Hramiak

Research output: Contribution to journalArticle

697 Citations (Scopus)

Abstract

Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes. ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA 1c concentrations (>7·5), and cardiovascular disease (or ≥2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A 1c [HbA 1c ] of <6·0) or standard (7·0-7·9) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291·7 μmol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620. 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1·00, 95 CI 0·88-1·14; p=1·00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0·96, 0·89-1·02; p=0·19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0·95, 95 CI 0·85-1·07, p=0·42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0·95, 0·89-1·01, p=0·12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0·05). Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia. US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.

Original languageEnglish (US)
Pages (from-to)419-430
Number of pages12
JournalThe Lancet
Volume376
Issue number9739
DOIs
StatePublished - Aug 1 2010

Fingerprint

Hyperglycemia
Type 2 Diabetes Mellitus
Therapeutics
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)
National Institute on Aging (U.S.)
Cardiovascular Diseases
National Eye Institute (U.S.)
National Heart, Lung, and Blood Institute (U.S.)
Hemoglobin A
Albuminuria
Mortality
Light Coagulation
Vitrectomy
National Institutes of Health (U.S.)
Peripheral Nervous System Diseases
Centers for Disease Control and Prevention (U.S.)
Random Allocation
North America
Peripheral Nerves
Hypoglycemia

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Ismail-Beigi, F., Craven, T., Banerji, M. A., Basile, J., Calles, J., Cohen, R. M., ... Hramiak, I. (2010). Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: An analysis of the ACCORD randomised trial. The Lancet, 376(9739), 419-430. https://doi.org/10.1016/S0140-6736(10)60576-4

Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes : An analysis of the ACCORD randomised trial. / Ismail-Beigi, Faramarz; Craven, Timothy; Banerji, Mary Ann; Basile, Jan; Calles, Jorge; Cohen, Robert M.; Cuddihy, Robert; Cushman, William; Genuth, Saul; Grimm, Richard H.; Hamilton, Bruce P.; Hoogwerf, Byron; Karl, Diane; Katz, Lois; Krikorian, Armand; O'Connor, Patrick; Pop-Busui, Rodica; Schubart, Ulrich; Simmons, Debra; Taylor, Harris; Thomas, Abraham; Weiss, Daniel; Hramiak, Irene.

In: The Lancet, Vol. 376, No. 9739, 01.08.2010, p. 419-430.

Research output: Contribution to journalArticle

Ismail-Beigi, F, Craven, T, Banerji, MA, Basile, J, Calles, J, Cohen, RM, Cuddihy, R, Cushman, W, Genuth, S, Grimm, RH, Hamilton, BP, Hoogwerf, B, Karl, D, Katz, L, Krikorian, A, O'Connor, P, Pop-Busui, R, Schubart, U, Simmons, D, Taylor, H, Thomas, A, Weiss, D & Hramiak, I 2010, 'Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: An analysis of the ACCORD randomised trial', The Lancet, vol. 376, no. 9739, pp. 419-430. https://doi.org/10.1016/S0140-6736(10)60576-4
Ismail-Beigi, Faramarz ; Craven, Timothy ; Banerji, Mary Ann ; Basile, Jan ; Calles, Jorge ; Cohen, Robert M. ; Cuddihy, Robert ; Cushman, William ; Genuth, Saul ; Grimm, Richard H. ; Hamilton, Bruce P. ; Hoogwerf, Byron ; Karl, Diane ; Katz, Lois ; Krikorian, Armand ; O'Connor, Patrick ; Pop-Busui, Rodica ; Schubart, Ulrich ; Simmons, Debra ; Taylor, Harris ; Thomas, Abraham ; Weiss, Daniel ; Hramiak, Irene. / Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes : An analysis of the ACCORD randomised trial. In: The Lancet. 2010 ; Vol. 376, No. 9739. pp. 419-430.
@article{7c9c11efdd62421abbae1374673ad2c5,
title = "Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: An analysis of the ACCORD randomised trial",
abstract = "Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes. ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA 1c concentrations (>7·5), and cardiovascular disease (or ≥2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A 1c [HbA 1c ] of <6·0) or standard (7·0-7·9) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291·7 μmol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620. 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1·00, 95 CI 0·88-1·14; p=1·00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0·96, 0·89-1·02; p=0·19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0·95, 95 CI 0·85-1·07, p=0·42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0·95, 0·89-1·01, p=0·12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0·05). Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia. US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.",
author = "Faramarz Ismail-Beigi and Timothy Craven and Banerji, {Mary Ann} and Jan Basile and Jorge Calles and Cohen, {Robert M.} and Robert Cuddihy and William Cushman and Saul Genuth and Grimm, {Richard H.} and Hamilton, {Bruce P.} and Byron Hoogwerf and Diane Karl and Lois Katz and Armand Krikorian and Patrick O'Connor and Rodica Pop-Busui and Ulrich Schubart and Debra Simmons and Harris Taylor and Abraham Thomas and Daniel Weiss and Irene Hramiak",
year = "2010",
month = "8",
day = "1",
doi = "10.1016/S0140-6736(10)60576-4",
language = "English (US)",
volume = "376",
pages = "419--430",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9739",

}

TY - JOUR

T1 - Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes

T2 - An analysis of the ACCORD randomised trial

AU - Ismail-Beigi, Faramarz

AU - Craven, Timothy

AU - Banerji, Mary Ann

AU - Basile, Jan

AU - Calles, Jorge

AU - Cohen, Robert M.

AU - Cuddihy, Robert

AU - Cushman, William

AU - Genuth, Saul

AU - Grimm, Richard H.

AU - Hamilton, Bruce P.

AU - Hoogwerf, Byron

AU - Karl, Diane

AU - Katz, Lois

AU - Krikorian, Armand

AU - O'Connor, Patrick

AU - Pop-Busui, Rodica

AU - Schubart, Ulrich

AU - Simmons, Debra

AU - Taylor, Harris

AU - Thomas, Abraham

AU - Weiss, Daniel

AU - Hramiak, Irene

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes. ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA 1c concentrations (>7·5), and cardiovascular disease (or ≥2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A 1c [HbA 1c ] of <6·0) or standard (7·0-7·9) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291·7 μmol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620. 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1·00, 95 CI 0·88-1·14; p=1·00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0·96, 0·89-1·02; p=0·19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0·95, 95 CI 0·85-1·07, p=0·42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0·95, 0·89-1·01, p=0·12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0·05). Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia. US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.

AB - Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes. ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA 1c concentrations (>7·5), and cardiovascular disease (or ≥2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A 1c [HbA 1c ] of <6·0) or standard (7·0-7·9) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291·7 μmol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620. 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1·00, 95 CI 0·88-1·14; p=1·00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0·96, 0·89-1·02; p=0·19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0·95, 95 CI 0·85-1·07, p=0·42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0·95, 0·89-1·01, p=0·12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0·05). Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia. US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.

UR - http://www.scopus.com/inward/record.url?scp=77955585592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955585592&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(10)60576-4

DO - 10.1016/S0140-6736(10)60576-4

M3 - Article

VL - 376

SP - 419

EP - 430

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9739

ER -