Prediabetes defined by impaired glucose tolerance or impaired fasting glucose with low thresholds identified more individuals at increased risk for cardiovascular disease and all-cause mortality than other definitions of prediabetes, a meta-analysis showed.
Researchers noted an increased risk of composite cardiovascular disease and coronary heart disease at the lower cut points espoused by the American Diabetes Association of 100 mg/dL (kommentar 100/18 = 5.5 mmol/l) for impaired fasting glucose, and 5.7% DCCT for hemoglobin A1c (HbA1c) espoused by the American Diabetes Association.
The large meta-analysis of 53 prospective cohort studies involving over 1.6 million participants was reported by Yuli Huang, MD, of the affiliated Hospital at Shunde, Southern Medical University in China, and colleagues online in The BMJ.
Compared with individuals with normal glucose concentrations, those with prediabetes defined as impaired glucose tolerance (IGT), or impaired fasting glucose by ADA (IFG-ADA), or by World Health Organization (IFG-WHO) criteria had the following increased relative risks:
Composite CV disease: IFG-ADA 1.13; IFG-WHO 1.26; IGT 1.30
Coronary heart disease: IFG-ADA 1.10; IFG-WHO 1.18; IGT 1.20
Stroke: IFG-ADA 1.06; IFG-WHO 1.17; IGT 1.20
All cause mortality: IFG-ADA 1.13; IFG-WHO 1.13; IGT 1.32
Although the risk of composite cardiovascular events and coronary heart disease was higher in people with mild raised HbA1c (5.7%-6.4% or 6.0%-6.4%), the risk of stroke did not reach significance, likely due to the small number of studies analyzed, they said.
"These results support the lower cutoff point for impaired fasting glucose according to ADA criteria, as well as the incorporation of HbA1c in defining prediabetes," reported Huang and colleagues. "More prospective cohort studies that evaluate the level of HbA1c and health risks are needed," they wrote.
The lower cutoff points identified by the American Diabetes Association have been controversial because of the likelihood of increasing diagnoses on the basis of only conflicting, or at least inconsistent, data linking it with complications such as all cause mortality and cardiovascular events. As a result, it has yet to be adopted by other international guidelines for diabetes management, the researchers explained.
The increased risk of all cause mortality was significantly higher in the impaired glucose tolerance group than in groups according to other definitions of prediabetes (P<0.001). No significant differences were noted in risks of cardiovascular disease, coronary heart disease, and stroke with different definitions of prediabetes.
"These results suggest that impaired glucose tolerance is a stronger risk factor for all cause mortality, but not for cardiovascular disease, than other definitions of prediabetes, which might be caused by the significant association between impaired glucose tolerance and non-cardiovascular death, especially cancer mortality, they noted.
Researchers emphasized that "prediabetes is not a disease but rather a risk factor for future diabetes and cardiovascular disease, and the findings in our study do not mean that pharmacological treatment is warranted in everyone with prediabetes." Further studies are needed to determine which phenotype of prediabetes can benefit from pharmacological treatment, which in any case should be individualized on the basis of the known efficacy and safety of drugs and accompanied by lifestyle intervention programs, they noted.
Elizabeth Selvin, PhD, of John Hopkins Bloomberg School's Department of Epidemiology, who was not involved in the study, told MedPage Today that the research looks rigorous and makes an important contribution. "There is a fair amount of controversy regarding pharmacological treatment in the setting of prediabetes, although American guidelines suggest metformin might be appropriate in some patients," she added in an email.
Prediabetes Definitions
Fasting glucose concentration
ADA 100-125 mg/dLWHO 110-125 mg/dL
Impaired glucose tolerance (2 hour)
WHO 140-200 mg/dL
Hemoglobin A1c (HbA1c)
ADA DCCT 5.7%-6.4% NICE DCCT 6.0%-6.4%
Participants in the studies in the meta-analysis were derived from the general population, although nine of the studies did not include women. Follow-up ranged from 2 to 20 years, with a median duration of 9.5 years. All studies but one excluded people with fasting plasma glucose concentration ≥126 mg/dL.
A key limitation noted by researchers was the absence of adjustments for the future development of diabetes during the follow-up period in most studies, which leaves it unclear whether the long term health risk associated with prediabetes is because of a mild increase of blood glucose concentration, or because of future progression to diabetes.
This work was supported by the National Natural Science Foundation of China
The authors disclosed no potential conflicts of interest related to the research.
Primary Source
Source Reference: Huang Y, et al "Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis" BMJ 2016; DOI: 10.1136/bmj.i5953.
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