The dual personality of hemoglobin A: precision medicine biomarker and population mortality predictor for both adult and geriatric patients
Editorial

The dual personality of hemoglobin A1c: precision medicine biomarker and population mortality predictor for both adult and geriatric patients

Andrew W. Lyon, Martha E. Lyon

Department of Pathology and Laboratory Medicine, Saskatoon Health Region, Saskatoon, SK, Canada

Correspondence to: Dr. Andrew W. Lyon. Department of Pathology and Laboratory Medicine, SHR, St. Paul’s Hospital, 1702 20th St. West, Saskatoon, SK S7M OZ9, Canada. Email: andrew.lyon@saskatoonhealthregion.ca.

Provenance: This is a Guest Editorial commissioned by Section Editor Xu-Hua Mao (Department of Clinical Laboratory, Yixing People’s Hospital, Wuxi, China).

Comment on: Palta P, Huang ES, Kalyani RR, et al. Hemoglobin A1c and Mortality in Older Adults With and Without Diabetes: Results From the National Health and Nutrition Examination Surveys (1988-2011). Diabetes Care 2017;40:453-60.


Received: 25 April 2017; Accepted: 26 April 2017; Published: 2 June 2017.

doi: 10.21037/jlpm.2017.05.06


The rapid rise in prevalence of diabetes and the upward shift of population age distributions are coincident demographic changes that explain why older adults have become the fastest growing diabetic population. In 2017 what do we know about diabetes in older adults? The initial clinical trials that elucidated the associations between glycemic control, hemoglobin A1c (HbA1c) as well as onset and development of diabetic complications focused on adults but often excluded ≥65 year olds (1,2). Subsequent trials found that geriatric patients had heterogeneous results (some benefit and some harm) from intensive glucose lower therapy (3-5). Compared to young adults, older adults have different onsets of symptoms, different outcomes as well as different co-morbidities and risks of hypoglycemia. The consensus panel recommendations from the American Diabetes Association (ADA), American Association of Clinical Endocrinologists, and European Association for the Study of Diabetes guidelines emphasized the importance of individualizing treatment recommendations of older adults, a call that is consistent with the aims of precision medicine (6-8). Precision medicine is an emerging approach for disease treatment and prevention that integrates individual variability in genes, environment, and lifestyle for each person. Given the clinical importance of managing diabetes in older adults and the ongoing emergence of new evidence, the April 2017 issue of Diabetes Care featured 11 articles to review the current state of knowledge. The 11 articles provide a comprehensive overview, expert perspectives on establishing the goals of care for individual geriatric patients in different settings as well as new insight into the association of diabetes and mortality among older adults.


Diabetes and mortality in older adults

Epidemiologic studies of observations can elucidate clinically and statistically important associations among variables that defy study by randomized control experiments. Epidemiologic studies of diabetes are often undermined by a large proportion of undiagnosed diabetes within the control group. To avoid that susceptibility, Palta et al. stratified patients into diabetic and non-diabetic groups and also created sub-categories by each patient’s initial HbA1c level (to enable the undiagnosed diabetics to be distinguished within the non-diabetic group by having HbA1c ≥6.5%). Palta et al. created the dataset of people ≥65 years at recruitment from linked NHANES datasets [1988–2011] to test the associations between risk of mortality among populations of diabetic and non-diabetic older adults with initial HbA1c level defined sub-groups (9). In this study design, only one HbA1c level (obtained at the beginning of the study) was used per patient to establish the HbA1c category for that patient. As a consequence, the HbA1c variable was fixed or was time-insensitive in the Cox proportional hazard multivariate model analysis and the association between initial HbA1c and mortality of older adults could be assessed.

The study was able to assess models for all cause mortality, cardiovascular disease mortality, cancer and non-cancer mortality and considered subgroups studies for age, sex, race/ethnicity, and treatments. There are several subtle findings, but overall Palta et al. demonstrated that among diabetic older adults as the HbA1c level for each strata increased, the hazard ratios (HR) for all-cause mortality increased from 1.0 (at HbA1c <6.5%) to 1.8 (at HbA1c ≥9.0%). Among the non-diabetic patients defined by questionnaire, an HbA1c ≥6.5% had a HR of 1.3 relative to the all-cause mortality compared to patients without diabetes with HbA1c 5.0–5.6%. These observations support the association of good glycemic control and lower HbA1c with lower risk of mortality for both diabetic and non-diabetics and this is the first study to use a nationally representative US population specifically that assesses older adults.

The ADA and American Geriatric Society (AGS) consensus statements of 2012 and 2014 that made recommendations of potentially less aggressive glycemic goals for older adults was largely based on expert opinion, a lower quality rank in evidence-based medicine scales (7,8,10). This epidemiologic study by Palta et al. shows that a general population of older US adults with diabetes, an HbA1c >8.0% is associated with increased risk of mortality and supports the ADA and AGS consensus statements used in current clinical practice, a higher quality rank in evidence-based medicine scales.

Regardless of diabetic status, older adults are heterogeneous group that will continue to require individual treatment goals and priorities associated with the principles of precision medicine. In current practice, HbA1c will be used as a biomarker to support diagnosis of diabetes and to assess treatment decisions and glycemic control in preceding weeks or months. This study by Palta et al. also revealed a seldom considered attribute that a single HbA1c measurement among older adults can predict mortality risk for both diabetic and non-diabetic patients.


Acknowledgements

None.


Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.


References

  1. 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 1998;352:854-65. [Crossref] [PubMed]
  2. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53. [Crossref] [PubMed]
  3. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59. [Crossref] [PubMed]
  4. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-39. [Crossref] [PubMed]
  5. Miller ME, Williamson JD, Gerstein HC, et al. Effects of randomization to intensive glucose control on adverse events, cardiovascular disease, and mortality in older versus younger adults in the ACCORD Trial. Diabetes Care 2014;37:634-43. [Crossref] [PubMed]
  6. American Geriatrics Society Expert Panel on Care of Older Adults with Diabetes Mellitus. Guidelines abstracted from the American Geriatrics Society Guidelines for Improving the Care of Older Adults with Diabetes Mellitus: 2013 update. J Am Geriatr Soc 2013;61:2020-6. [Crossref] [PubMed]
  7. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults. Diabetes Care 2012;35:2650-64. [Crossref] [PubMed]
  8. Cahn A, Raz I, Kleinman Y, et al. Clinical Assessment of Individualized Glycemic Goals in Patients With Type 2 Diabetes: Formulation of an Algorithm Based on a Survey Among Leading Worldwide Diabetologists. Diabetes Care 2015;38:2293-300. [Crossref] [PubMed]
  9. Palta P, Huang ES, Kalyani RR, et al. Hemoglobin A1c and Mortality in Older Adults With and Without Diabetes: Results From the National Health and Nutrition Examination Surveys (1988-2011). Diabetes Care 2017;40:453-60. [Crossref] [PubMed]
  10. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6. [Crossref] [PubMed]
doi: 10.21037/jlpm.2017.05.06
Cite this article as: Lyon AW, Lyon ME. The dual personality of hemoglobin A1c: precision medicine biomarker and population mortality predictor for both adult and geriatric patients. J Lab Precis Med 2017;2:21.

Refbacks

  • There are currently no refbacks.