Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 9/2012

01-09-2012 | Commentary

Low HbA1c and mortality: causation and confounding

Author: M. K. Rutter

Published in: Diabetologia | Issue 9/2012

Login to get access

Abstract

This commentary provides an overview of the clinically important data linking low or lowered HbA1c to increased total and CVD mortality in the general population, and in patients with diabetes. This sets the scene for a contribution in this issue of Diabetologia by Andersson et al (DOI: 10.​1007/​s00125-012-2584-3) that suggests that BMI might modify the relationship between HbA1c and mortality in patients with type 2 diabetes. The commentary provides a framework for the interpretation of epidemiological data from observational studies and clinical trials, and it addresses the clinical implications of this work. Finally, it highlights new research that is likely to advance this field.
Literature
1.
Andersson C, van Gaal L, Caterson ID, et al (2012) Relationship between HbA1c levels and risk of cardiovascular adverse outcomes and all-cause mortality in overweight and obese cardiovascular high-risk women and men with type 2 diabetes. Diabetologia. doi:10.​1007/​s00125-012-2584-3
2.
Sarwar N, Gao P, Seshasai SR et al (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375:2215–2222PubMedCrossRef
3.
de Vegt F, Dekker JM, Ruhe HG et al (1999) Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia 42:926–931PubMedCrossRef
4.
Khaw KT, Wareham N, Luben R et al (2001) Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk). BMJ 322:15–18PubMedCrossRef
5.
Selvin E, Coresh J, Golden SH, Brancati FL, Folsom AR, Steffes MW (2005) Glycemic control and coronary heart disease risk in persons with and without diabetes: the atherosclerosis risk in communities study. Arch Intern Med 165:1910–1916PubMedCrossRef
6.
Levitan EB, Liu S, Stampfer MJ et al (2008) HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women. Diabetologia 51:267–275PubMedCrossRef
7.
Gerstein HC, Swedberg K, Carlsson J et al (2008) The hemoglobin A1c level as a progressive risk factor for cardiovascular death, hospitalization for heart failure, or death in patients with chronic heart failure: an analysis of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program. Arch Intern Med 168:1699–1704PubMedCrossRef
8.
Selvin E, Steffes MW, Zhu H et al (2010) Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med 362:800–811PubMedCrossRef
9.
Currie CJ, Peters JR, Tynan A et al (2010) Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. Lancet 375:481–489PubMedCrossRef
10.
Carson AP, Fox CS, McGuire DK et al (2010) Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes. Circ Cardiovasc Qual Outcomes 3:661–667PubMedCrossRef
11.
Eeg-Olofsson K, Cederholm J, Nilsson PM et al (2010) New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR). J Intern Med 268:471–482PubMedCrossRef
12.
Colayco DC, Niu F, McCombs JS, Cheetham TC (2011) A1C and cardiovascular outcomes in type 2 diabetes: a nested case–control study. Diabetes Care 34:77–83PubMedCrossRef
13.
Huang ES, Liu JY, Moffet HH, John PM, Karter AJ (2011) Glycemic control, complications, and death in older diabetic patients: the diabetes and aging study. Diabetes Care 34:1329–1336PubMedCrossRef
14.
Kerr D, Partridge H, Knott J, Thomas PW (2011) HbA1c 3 months after diagnosis predicts premature mortality in patients with new onset type 2 diabetes. Diabet Med 28:1520–1524PubMedCrossRef
15.
Pfister R, Sharp SJ, Luben R, Khaw KT, Wareham NJ (2011) No evidence of an increased mortality risk associated with low levels of glycated haemoglobin in a non-diabetic UK population. Diabetologia 54:2025–2032PubMedCrossRef
16.
Aguilar D, Bozkurt B, Ramasubbu K, Deswal A (2009) Relationship of hemoglobin A1C and mortality in heart failure patients with diabetes. J Am Coll Cardiol 54:422–428PubMedCrossRef
17.
Greenfield S, Billimek J, Pellegrini F et al (2009) Comorbidity affects the relationship between glycemic control and cardiovascular outcomes in diabetes: a cohort study. Ann Intern Med 151:854–860PubMed
18.
Frier BM, Schernthaner G, Heller SR (2011) Hypoglycemia and cardiovascular risks. Diabetes Care 34(Suppl 2):S132–S137PubMedCrossRef
19.
Miller ME, Bonds DE, Gerstein HC et al (2010) The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study. BMJ 340:b5444PubMedCrossRef
20.
United Kingdom Prospective Diabetes Study Group (1998) Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352:854–865
21.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA (2008) 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359:1577–1589PubMedCrossRef
22.
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
23.
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
24.
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
25.
Turnbull FM, Abraira C, Anderson RJ et al (2009) Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 52:2288–2298PubMedCrossRef
26.
Bonds DE, Miller ME, Bergenstal RM et al (2010) The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 340:b4909PubMedCrossRef
27.
Riddle MC, Ambrosius WT, Brillon DJ et al (2010) Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care 33:983–990PubMedCrossRef
28.
Zoungas S, Patel A, Chalmers J et al (2010) Severe hypoglycemia and risks of vascular events and death. N Engl J Med 363:1410–1418PubMedCrossRef
29.
Zoungas S, Chalmers J, Ninomiya T et al (2012) Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds. Diabetologia 55:636–643PubMedCrossRef
30.
Rutter MK, Nesto RW (2011) Blood pressure, lipids and glucose in type 2 diabetes: how low should we go? Re-discovering personalized care. Eur Heart J 32:2247–2255PubMedCrossRef
31.
Inzucchi SE, Bergenstal RM, Buse JB et al (2012) Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 55:1577–1596PubMedCrossRef
Metadata
Title
Low HbA1c and mortality: causation and confounding
Author
M. K. Rutter
Publication date
01-09-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 9/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2620-3

Other articles of this Issue 9/2012

Diabetologia 9/2012 Go to the issue

Letter

Diabetes and amputation: don’t forget outcomes

Article

Trends in maternal BMI, glycaemic control and perinatal outcome among type 1 diabetic pregnant women in 1989–2008

Short Communication

Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers

Article

KCNQ1 SNPS and susceptibility to diabetic nephropathy in East Asians with type 2 diabetes

Then and Now

Diabetic nephropathy in type 1 diabetes: has the outlook improved since the 1980s?

Article

Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits