Skip to main content
Erschienen in: Diabetologia 3/2012

01.03.2012 | Article

Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds

verfasst von: S. Zoungas, J. Chalmers, T. Ninomiya, Q. Li, M. E. Cooper, S. Colagiuri, G. Fulcher, B. E. de Galan, S. Harrap, P. Hamet, S. Heller, S. MacMahon, M. Marre, N. Poulter, F. Travert, A. Patel, B. Neal, M. Woodward, for the ADVANCE Collaborative Group

Erschienen in: Diabetologia | Ausgabe 3/2012

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

There is conflicting evidence regarding appropriate glycaemic targets for patients with type 2 diabetes. Here, we investigate the relationship between HbA1c and the risks of vascular complications and death in such patients.

Methods

Eleven thousand one hundred and forty patients were randomised to intensive or standard glucose control in the Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Glycaemic exposure was assessed as the mean of HbA1c measurements during follow-up and prior to the first event. Adjusted risks for each HbA1c decile were estimated using Cox models. Possible differences in the association between HbA1c and risks at different levels of HbA1c were explored using linear spline models.

Results

There was a non-linear relationship between mean HbA1c during follow-up and the risks of macrovascular events, microvascular events and death. Within the range of HbA1c studied (5.5–10.5%), there was evidence of ‘thresholds’, such that below HbA1c levels of 7.0% for macrovascular events and death, and 6.5% for microvascular events, there was no significant change in risks (all p > 0.8). Above these thresholds, the risks increased significantly: every 1% higher HbA1c level was associated with a 38% higher risk of a macrovascular event, a 40% higher risk of a microvascular event and a 38% higher risk of death (all p < 0.0001).

Conclusions/interpretation

In patients with type 2 diabetes, HbA1c levels were associated with lower risks of macrovascular events and death down to a threshold of 7.0% and microvascular events down to a threshold of 6.5%. There was no evidence of lower risks below these levels but neither was there clear evidence of harm.

Trial Registration:

ClinicalTrial.gov NCT00145925

Funding:

Servier and the National Health and Medical Research Council of Australia (project grant ID 211086 and programme grant IDs 358395 and 571281)
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Coutinho M, Gerstein HC, Wang Y, Yusuf S (1999) The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 22:233–240PubMedCrossRef Coutinho M, Gerstein HC, Wang Y, Yusuf S (1999) The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 22:233–240PubMedCrossRef
2.
Zurück zum Zitat Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N (2004) Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med 141:413–420PubMed Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N (2004) Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med 141:413–420PubMed
3.
Zurück zum Zitat Selvin E, Marinopoulos S, Berkenblit G et al (2004) Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 141:421–431PubMed Selvin E, Marinopoulos S, Berkenblit G et al (2004) Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 141:421–431PubMed
4.
Zurück zum Zitat Stratton IM, Adler AI, Neil HA et al (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412PubMedCrossRef Stratton IM, Adler AI, Neil HA et al (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412PubMedCrossRef
5.
Zurück zum Zitat Gudbjörnsdottir S, Eliasson B, Eeg-Olofsson K, Zethelius B, Cederholm J, on behalf of the National Diabetes Register (NDR) (2011) Additive effects of glycaemia and dyslipidaemia on risk of cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register. Diabetologia 54(10):2544–2551PubMedCrossRef Gudbjörnsdottir S, Eliasson B, Eeg-Olofsson K, Zethelius B, Cederholm J, on behalf of the National Diabetes Register (NDR) (2011) Additive effects of glycaemia and dyslipidaemia on risk of cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register. Diabetologia 54(10):2544–2551PubMedCrossRef
6.
Zurück zum Zitat Emerging Risk Factors Collaboration (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375:2215–2222CrossRef Emerging Risk Factors Collaboration (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375:2215–2222CrossRef
7.
Zurück zum Zitat Currie CJ, Peters JR, Tynan A et al (2010) Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet 375:481–489PubMedCrossRef Currie CJ, Peters JR, Tynan A et al (2010) Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet 375:481–489PubMedCrossRef
8.
Zurück zum Zitat Selvin E, Steffes MW, Zhu H et al (2010) Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic patients. N Engl J Med 362:800–811PubMedCrossRef Selvin E, Steffes MW, Zhu H et al (2010) Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic patients. N Engl J Med 362:800–811PubMedCrossRef
9.
Zurück zum Zitat Duckworth W, Abraira C, Moritz T et al (2009) Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 360:129–139PubMedCrossRef Duckworth W, Abraira C, Moritz T et al (2009) Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 360:129–139PubMedCrossRef
10.
Zurück zum Zitat Gerstein HC, Miller ME, Byington RP et al (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559PubMedCrossRef Gerstein HC, Miller ME, Byington RP et al (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559PubMedCrossRef
11.
Zurück zum Zitat Patel A, MacMahon S, Chalmers J et al (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572PubMedCrossRef Patel A, MacMahon S, Chalmers J et al (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572PubMedCrossRef
12.
Zurück zum Zitat Turnbull FM, Abraira C, Anderson RJ et al (2009) Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 52:2288–2298, Erratum 52: 2470PubMedCrossRef Turnbull FM, Abraira C, Anderson RJ et al (2009) Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 52:2288–2298, Erratum 52: 2470PubMedCrossRef
13.
Zurück zum Zitat ADVANCE Management, Committee (2001) Study rationale and design of ADVANCE: action in diabetes and vascular disease-preterax and diamicron MR controlled evaluation. Diabetologia 44:1118–1120CrossRef ADVANCE Management, Committee (2001) Study rationale and design of ADVANCE: action in diabetes and vascular disease-preterax and diamicron MR controlled evaluation. Diabetologia 44:1118–1120CrossRef
15.
Zurück zum Zitat Easton DF, Peto J, Babiker AG (1991) Floating absolute risk: an alternative to relative risk in survival and case–control analysis avoiding an arbitrary reference group. Stat Med 10:1025–1035PubMedCrossRef Easton DF, Peto J, Babiker AG (1991) Floating absolute risk: an alternative to relative risk in survival and case–control analysis avoiding an arbitrary reference group. Stat Med 10:1025–1035PubMedCrossRef
16.
Zurück zum Zitat Cleveland WS (1979) Robust locally weighted regression and smoothing scatterplots. J Am Stat Assoc 74:829–836CrossRef Cleveland WS (1979) Robust locally weighted regression and smoothing scatterplots. J Am Stat Assoc 74:829–836CrossRef
17.
Zurück zum Zitat Molinari N, Daures JP, Durand JF (2001) Regression splines for threshold selection in survival data analysis. Stat Med 20:237–247PubMedCrossRef Molinari N, Daures JP, Durand JF (2001) Regression splines for threshold selection in survival data analysis. Stat Med 20:237–247PubMedCrossRef
18.
Zurück zum Zitat Dale AC, Midthjell K, Nilsen TI, Wiseth R, Vatten LJ (2009) Glycaemic control in newly diagnosed diabetes patients and mortality from ischaemic heart disease: 20-year follow-up of the HUNT Study in Norway. Eur Heart J 30:1372–1377PubMedCrossRef Dale AC, Midthjell K, Nilsen TI, Wiseth R, Vatten LJ (2009) Glycaemic control in newly diagnosed diabetes patients and mortality from ischaemic heart disease: 20-year follow-up of the HUNT Study in Norway. Eur Heart J 30:1372–1377PubMedCrossRef
19.
Zurück zum Zitat Kengne AP, Patel A, Colagiuri S et al (2010) The Framingham and UKPDS risk equations do not reliably estimate the probability of cardiovascular events in a large ethnically diverse sample of patients with diabetes: the ADVANCE Study. Diabetologia 53(5):821–831PubMedCrossRef Kengne AP, Patel A, Colagiuri S et al (2010) The Framingham and UKPDS risk equations do not reliably estimate the probability of cardiovascular events in a large ethnically diverse sample of patients with diabetes: the ADVANCE Study. Diabetologia 53(5):821–831PubMedCrossRef
Metadaten
Titel
Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds
verfasst von
S. Zoungas
J. Chalmers
T. Ninomiya
Q. Li
M. E. Cooper
S. Colagiuri
G. Fulcher
B. E. de Galan
S. Harrap
P. Hamet
S. Heller
S. MacMahon
M. Marre
N. Poulter
F. Travert
A. Patel
B. Neal
M. Woodward
for the ADVANCE Collaborative Group
Publikationsdatum
01.03.2012
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 3/2012
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2404-1

Weitere Artikel der Ausgabe 3/2012

Diabetologia 3/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.