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Why Prediabetes?

Jan 14, 2017

Can we answer the question of how you can have a pre-disease that increases your risk of death? You either have it or you don’t!

The ADA, ESAD, and AACE say that if you have an A1c of 5.7% to 6.4% you are prediabetic or have prediabetes.  ADA says if you have an A1c of 7% or higher you have diabetes and the AACE says that if you have an A1c of 6.5% or higher you have diabetes.  So the question is, who is correct?  How can you have two major medical organizations saying two different things? Who should we believe? What do we tell our patients?


On the other hand, what difference does it make?  Both numbers mean that the amount of sugar in your blood is causing damage to every organ in your body.  If you lose your eyesight or lose a leg or a kidney or even die from a heart attack, what difference does it make for your patients?

Study data show fasting glucose concentrations of at least 100 mg/dL (5.6 mmol/L) or an HbA1c of at least 5.7% (39 mmol/mol) were determining factors.1  

New research has shown that if you have prediabetes your risk for heart attacks and strokes goes up.  So why do we wait for an A1c of 6.5 or 7% before we start to treat our patients?

I guess we need to look to the FDA, ADA and other diabetes organizations to ask the question, “Why don’t we have any approved medications to treat prediabetes?”  We have drugs like metformin that could make a major difference in preventing elevated blood sugars. We now have drugs like the SGLT-2 inhibitors that have been shown to reduce the risk of cardiovascular disease and even death by up to 38%. And if that is not a reason to treat patients earlier, than what about a drug like cycloset that has been shown to reduce heart attacks and strokes (MACE) by 58%?

Do you remember when the definition of diabetes was a fasting blood sugar of 180 mg/dl, then it went to 140mg/dl, and then it went to 126mg/dL. and now we are defining prediabetes to a fasting blood sugar over 100mg/dL. So if you have a fasting blood sugar of 99 mg/dl, you are normal or an A1c of 5.6% you are normal and there is no reason to treat with pharmaceuticals.  But we know that as we get older, are not as careful with our diet and don’t have time to exercise, our numbers will always go up.  So why not treat much earlier?

The current information is telling us that defining prediabetes based on hemoglobin (Hb)A1c, an indicator of average long-term blood glucose levels, predicts long-term diabetes complications more accurately than other definitions of prediabetes, according to a study now online in Lancet Diabetes Endocrinology.

Elizabeth Selvin, PhD, Co-Director of the Cardiovascular Disease Epidemiology Training Program at Johns Hopkins Bloomberg School of Public Health, and colleagues wrote, that after demographic adjustment, compared with fasting glucose-based definitions, HbA1c-based definitions of prediabetes had higher hazard ratios and better risk discrimination for several common diabetes complications.

The results of this current study showed C (concordance)-statistics of 0.640 for chronic kidney disease, 0.672 for cardiovascular disease, 0.722 for peripheral arterial disease, and 0.688 for death from any cause.

Participants identified as having prediabetes according to an A1C test-based definition had a 50% greater risk of developing kidney disease, twice the odds of developing cardiovascular disease, and a 60% increased risk of overall mortality compared with those with normal A1C, the researchers reported.

In the absence of a national or international consensus on an optimal definition, a clear definition of prediabetes is needed so we can know who to target for lifestyle modifications and other types of interventions, such as possibly glucose-lowering drugs.

A clear definition of prediabetes, treatment recommendations, and reimbursement for interventions such as weight loss and nutritional counseling can be a problem. To that end, researchers compared five different definitions of prediabetes, including two fasting glucose-based, two HbA1c-based, and one 2-hour glucose-based definition accepted by the American Diabetes Association (ADA), the World Health Organization (WHO), or the International Expert Committee (IEC).

The prospective cohort study analyzed fasting glucose and hemoglobin A1C levels of a large, community-based population (n=10,884) from the Atherosclerosis Risk in Communities Study (ARIC). None of the participants had been diagnosed with diabetes. They were between 47 and 70 years of age when the study began in the early 1990s, and were followed for about 20 years. Detailed methods of the ARIC study have been previously published.

Specifically, A1c-based definitions were found to have higher relative-risk associations and showed small, but statistically significant, improvements in risk discrimination for a broad range of clinical complications.

Practice Pearls:

  • Note that this large, observational cohort study evaluating different diagnostic criteria for prediabetes found that a hemoglobin A1C-based definition better predicted relevant outcomes compared with fasting glucose definitions.
  • Researchers additionally found evidence of under diagnosis in minority communities.
  • It is critically important to identify individuals at high risk of diabetes in order to allow early interventions.
  • The difference between the effects of fasting glucose and 2-hour glucose based definitions of prediabetes was negligible.


1 – Prediabetes Increases Risk for All-Cause Mortality. Diabetes in Control. http://www.diabetesincontrol.com/prediabetes-increases-risk-for-all-cause-mortality/

2 – Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study. The Lancet: Diabetes & Endocrinolgy. http://www.thelancet.com/journals/landia/article/PIIS2213-8587(16)30321-7/abstract

3 – Defining pre-diabetes based on hemoglobin (Hb)A1c, an indicator of average long-term blood glucose levels, predicted long-term diabetes complications more accurately than other definitions of pre-diabetes, according to a study now online in Lancet Diabetes Endocrinology.

4 – The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. PunMed. https://www.ncbi.nlm.nih.gov/pubmed/2646917