Prediabetes, A 'Window of Opportunity' to Prevent Heart Disease?

Marlene Busko

July 21, 2020

People with prediabetes had a higher risk of cardiovascular disease (CVD) and dying from all causes during the next decade compared to people with normal glucose levels in a new large meta-analysis.

The increased risks remained even with different definitions of prediabetes in the subset of people with prediabetes and preexisting CVD.

These findings from a meta-analysis of 129 studies in more than 10 million people mainly from Europe, Asia, and North America were published online July 15 in BMJ by Xiaoyan Cai, MD, Southern Medical University, Foshan, China, and colleagues.

"Some argue that describing people as having prediabetes creates more problems than benefits in terms of prevention and treatment and would put an unsustainable burden on health care systems," senior author Yuli Huang, MD, PhD, The George Institute for Global Health, University of New South Wales, Sydney, Australia, said in a statement.

But this study suggests otherwise.

"Considering the high prevalence of prediabetes, and the robust and significant association between prediabetes and health risk shown in our study, successful intervention in this large population could have a major effect on public health," Cai and colleagues write.

"Screening and proper management of prediabetes might contribute to primary and secondary prevention of cardiovascular disease," they emphasize.

And prediabetes, which is commonly asymptomatic, "represents a window of opportunity to prevent progression to type 2 diabetes and its complications."

"What is especially concerning," said Huang, "is the many millions of people who are unaware they have either condition [prediabetes or diabetes] and don't act early enough."

"Early detection and proper treatment can have enormous benefits," he said, "but left unaddressed, the life-long complications and health impacts can be devastating."

The researchers hope the results of this study will turn prediabetes from a controversial term into a useful trigger for preventive care that will help address an escalating global health burden.

Is Prediabetes a 'Dubious Disease'? International Consensus Needed

Roughly 36% of people in the United States and China have prediabetes, the authors write, and the prevalence is increasing worldwide. 

By 2030 an estimated 470 million people will have prediabetes. And an expert panel of the American Diabetes Association (ADA) estimates up to 70% of people with prediabetes go on to develop type 2 diabetes.

Although many recent published studies have explored the links between prediabetes and CVD and mortality, the researchers write, "most of the studies had limited power to draw solid conclusions, however, and their results have been debated."

Notably, Cai and colleagues observe, "a recent contentious report in Science defined prediabetes as a 'dubious diagnosis' because of the inconsistent association of prediabetes with cardiovascular disease and mortality" (Science. 2019;363:1026-1031).

Given the controversy around the term prediabetes and the inconsistent findings, they write, "international consensus is urgently needed."

The group previously conducted a meta-analysis of 53 studies of more than 1.6 million people, which showed prediabetes increased the risk of CVD and all-cause mortality in the general population (BMJ. 2016;355:i5953).

The current meta-analysis included studies published up to April 25, 2020, and participants with and without CVD.

Prediabetes was defined as impaired fasting glucose (based on ADA or World Health Organization definitions) or impaired glucose tolerance (higher than normal blood glucose levels after eating) or elevated A1c (based on ADA or International Expert Committee criteria).

Outcomes were adjusted for at least five of six variables: sex, age, smoking, hypertension, body mass index, and serum cholesterol (or equivalent measures).

Prediabetes With/Without CVD Conferred Added Risk

The meta-analysis found that in the general population prediabetes was associated with a 13%, 15%, 16%, and 14% increased risk of all-cause mortality, CVD, coronary heart disease, and stroke, respectively, over a median follow-up of 9.8 years.  

Expressed differently, each year there were 7.4 more deaths, 8.8 more cases of CVD, 6.6 more cases of coronary heart disease, and 3.7 more strokes among 10,000 people with prediabetes than among the same number of people with normal blood glucose levels.

Among patients with preexisting atherosclerotic CVD, having prediabetes was associated with even higher risks: a 36%, 37%, and 15% increased risk of all-cause mortality, CVD, and coronary heart disease, respectively, over a median follow-up of 3.2 years. 

In this subset of patients with preexisting atherosclerotic CVD, there were 66 more deaths, 190 more cases of incident CVD, and 8.5 more strokes, all per 10,000 person-years, in patients with prediabetes as opposed to normal blood glucose levels.

"These results suggest that managing prediabetes in patients with established atherosclerotic [CVD] an important goal to lower their future risk of recurrent [CVD] and premature death," Cai and colleagues conclude.

The study was supported by the Guangdong Basic and Applied Basic Research Fund, Science and Technology Innovation Project from Foshan, Guangdong, and the Clinical Research Startup Program of Shunde Hospital, Southern Medical University, China. The authors have reported no relevant financial relationships.

BMJ. Published online July 15, 2020. Full text

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