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Prediabetes Increases Risk for All-Cause Mortality

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.

The question comes up after reviewing these studies as to whether we need to lower the cut-off point for defining prediabetes and that we might want to change the definition of prediabetes to a single number and not a range.

PrediabetesRisk864The health risks and mortality associated with prediabetes seem to increase at the lower cut-off point for blood sugar levels recommended by some guidelines, finds a large study published in The BMJ.

Prediabetes is a “pre-diagnosis” of diabetes — when a person’s blood glucose level is higher than normal, but not high enough to be considered diabetes. If left untreated, prediabetes can develop into type 2 diabetes. An estimated 79 million people in the U.S. are thought to be affected.

Doctors define prediabetes as impaired fasting glucose (higher than normal blood sugar levels after a period of fasting), impaired glucose tolerance (higher than normal blood sugar levels after eating), or raised hemoglobin levels.  But the cut-off points vary across different guidelines and remain controversial.

For example, the World Health Organization (WHO) defines prediabetes as fasting plasma glucose of 110-125 mg/dL.(6.1-6.9 mmol/L), while the American Diabetes Association (ADA) guideline recommends a cut-off point of 100-125 mg/dL.(5.6-6.9 mmol/L.)

Results of studies on the association between prediabetes and the risk of cardiovascular disease and all-cause mortality are also inconsistent. Furthermore, whether raised hemoglobin A1C  levels for defining prediabetes is useful for predicting future cardiovascular disease is unclear.

So a team of researchers from the affiliated Hospital at Shunde, Southern Medical University in China analyzed the results of 53 studies involving over 1.6 million individuals to shed more light on associations between different definitions of prediabetes and the risk of cardiovascular disease, coronary heart disease, stroke, and all-cause mortality.  They found that prediabetes, defined as impaired fasting glucose or impaired glucose tolerance, was associated with an increased risk of cardiovascular disease and all-cause mortality. The risk increased in people with a fasting glucose concentration as low as 100 mg/dL.(5.6 mmol/L) — the lower cut-off point according to ADA criteria.

Raised hemoglobin A1C levels were also associated with an increased risk of cardiovascular disease and coronary heart disease, but not with an increased risk of stroke and all-cause mortality.

The authors point to some study limitations that could have influenced their results, and say pulling observational evidence together in a systematic review and meta-analysis is a good way to consider all the evidence at once, “but we cannot make statements about cause and effect. We would need to look at experimental evidence for that.”  However, they say their findings “strongly support” the lower cut-off point for impaired fasting glucose and raised hemoglobin A1C levels proposed by the ADA guideline.

They conclude that lifestyle change — eating a healthy balanced diet, keeping weight under control, and doing regular physical activity — is the most effective treatment at this time.

In conclusion, researchers found that prediabetes defined as impaired fasting glucose or impaired glucose tolerance is associated with an increased risk of composite cardiovascular events, coronary heart disease, stroke, and all-cause mortality. There was an increased risk in people with fasting plasma glucose as low as 100 mg/dL (5.6 mmol/L). Additionally, the risk of composite cardiovascular events and coronary heart disease increased in people with raised A1c, over 5.6%. These results support the lower cut-off point for impaired fasting glucose according to ADA criteria as well as the incorporation A1C in defining prediabetes. At present, lifestyle modification is the mainstay management for people with prediabetes. High risk subpopulations with prediabetes, especially combined with other cardiovascular risk factors, should be selected for controlled trials of pharmacological treatment because at this time we have no FDA-approved medications for prediabetes.

Chief investigator Yunzhao Hu, MD, PhD, professor in the department of cardiology at First People’s Hospital of Shunde in Foshan, China, added that, “The risk increased in people with fasting glucose levels as low as 100 mg/dL and with HbA1c of 5.7%….So we believe people with prediabetes should be followed up clinically and keep a healthy lifestyle. Plus, we need to develop models for risk stratification in people with prediabetes, and we need to find a drug treatment that can prevent CVDs in them.”

Publisher’s Comment:  2 years ago I had the opportunity at AACE to interview a number of endocrinologists about what they were presenting at the AACE meeting.  My last question to many of those I interviewed was, “If you could have any A1C result for yourself, regardless of your current health, what would you like your A1C to be?  Every one of the endocrinologists answered with 5 or below 5%.

Practice Pearls:

  • Prediabetes defined as impaired glucose tolerance or impaired fasting glucose was associated with an increased risk of cardiovascular disease and all-cause mortality.
  • The risk increased in people with a fasting glucose concentration as low as 100 mg/dL (5.55 mmol/L).
  • A1C of 5.7%-6.5% (39-47 mmol/mol) or A1C of 6%-6.5% (42-47 mmol/mol) was associated with an increased risk of composite cardiovascular disease and coronary heart disease.
  • Lifestyle modification is now the main management for people with prediabetes.

Reference:

Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis, Yuli Huang, Xiaoyan Cai, Weiyi Mai, Meijun Li, Yunzhao Hu, The BMJ, doi: 10.1136/bmj.i5953, published 23 November 2016.