Study Links Hemoglobin A1C Test to Increased Mortality in Non-diabetics

Author: Lorraine Savage

Article Date: 6/30/2008

"A New Zealand Linkage Study Examining the Association between A1C Concentration and Mortality," reported in the June 2008 issue of Diabetes Care, found a link between increasing hemoglobin A1C levels and subsequent mortality in people without a previous diagnosis of diabetes. The largest of its kind, this study confirmed previous smaller studies.

Methodology

The study gathered data between 1999 and 2001 from 47,904 people who volunteered to participate in a Hepatitis Foundation screening. Of the participants, 71% were Maori, only 408 had a previous diagnosis of diabetes, and mean age was 38.

A1C levels were measured in categories: less than 4.0%, 4.0% to less than 5.0% (this reference category consisted of 12,867 participants), 5.0% to less than 6.0% (the majority of patients: 30,222), 6.0% to less than 7.0%, and greater than 7.0%.

Data were analyzed using a Cox regression to create a hazard ratio adjusted for age, ethnicity, smoking, and gender. Study participants were linked to the national mortality database as of December 31, 2004. During the follow-up period, lasting an average of 4.4 years, 815 people died. Men and women presented with similar mortality rates.

Results

In previous studies, A1C levels were linked with increased mortality in patients diagnosed with Type 1 diabetes and nondiabetic chronic kidney disease and cardiovascular disease. In this study, as expected, the mortality rate was found to be higher for people with a prior diabetes diagnosis (an average A1C of 5.19). In people with diabetes, increased A1C levels could not fully explain the higher mortality rate.

In addition to diabetes, increased A1C levels were heavily linked to mortality from diseases of the circulatory system, as well as endocrine, nutritional, metabolic, and immunity disorders. Thirty-eight of 47 deaths attributed to the endocrine, nutritional, metabolic, or immunity disorders category were caused by diabetes.

In people without a diagnosis of diabetes at baseline, the hazard ratios for all-cause mortality progressively rose from the A1C reference category to the highest category - less than or equal to 7.0% had a hazard ratio of 2.36, with a 95% confidence interval of 1.72-3.25. In people without diabetes, an increased A1C level of only 1% lead to an increased mortality rate of 16%.

Study Limitations

This study was conducted with a majority Maori population and may not be indicative of a more diverse population of people with diabetes. Other limitations include follow-up time of only a few years, insufficient data on a variety of cardiovascular risk factors, misinterpretation of causes of death, and inability to determine current incident of diabetes at the time of the A1C test.

Recommendations

Physicians should not order the hemoglobin A1C test only for patients newly diagnosed with diabetes, but as a preliminary screening for patients in general, especially those with a tendency toward diabetes, cardiovascular, endocrine, metabolic, nutritional, and immunity disorders.