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Screen and Treat to Prevent Type 2

Object of meta-analysis to assess diagnostic accuracy of screening tests for prediabetes and efficacy of interventions (lifestyle or metformin) in preventing diabetes.

Trials and publications were identified from Medline, PreMedline, and Embase. Data extracted for screening tests included diagnostic accuracy and population prevalence. Two meta-analyses were performed, one summarizing accuracy of screening tests (with the oral glucose tolerance test as the standard) for identification of prediabetes, and the other assessing relative risk of progression to type 2 diabetes after either lifestyle intervention or treatment with metformin.

The prevalence of type 2 diabetes is rising globally; 422 million adults are living with diabetes, and the number expected to die from its complications is predicted to double between 2005 and 2030. There are two approaches to prevention: screen and treat, in which a subpopulation is identified as “high risk” and offered individual intervention, and a population-wide approach, in which everyone is targeted via public health policies on environmental moderators.

There is international inconsistency on how to identify individuals at high risk of diabetes.  In the US, the American Diabetes Association criteria recommend a diagnosis of prediabetes in people with a fasting plasma glucose concentration of 100-124mg/dL.  or HbA1c of 5.7-6.4%.

WHO (World Health Organization) and the International Expert Committee recommend a fasting plasma glucose cut off of 108-124mg/dL. and HbA1c of 6.0-6.4%. The term prediabetes is used to encapsulate these ranges and implies that if individuals do not take action they will develop diabetes (though in reality this is not always the case). Since the recognition of pre-disease states (impaired glucose tolerance, impaired fasting glucose, and raised HbA1c), trials of lifestyle interventions have been associated with reduced or delayed onset of type 2 diabetes. Studies of screening and intervention programs in real world settings, however, are sparse. Women with a history of gestational diabetes have a sevenfold risk of developing diabetes postpartum. These women might not be captured by the prediabetes umbrella term because many have normal glycemic markers at the six-week postpartum review and then fail to attend for annual review thereafter.  Gestational diabetes is common in certain minority ethnic groups, and in deprived multiethnic areas, a history of this condition could identify a considerable proportion of individuals who could benefit from preventive interventions.

Two questions were asked to inform national and local policy making on prevention of type 2 diabetes. Which (if any) screening test should be used to identify people at risk of developing type 2 diabetes? What is the efficacy of preventive interventions (lifestyle and/or metformin) in those identified as high risk by screening?

2,874 titles were scanned and 148 papers (covering 138 studies) reviewed in full. The final analysis included 49 studies of screening tests (five of which were prevalence studies) and 50 intervention trials. HbA1c had a mean sensitivity of 0.49 and specificity of 0.79, for identification of prediabetes, though different studies used different cut-off values. Fasting plasma glucose had a mean sensitivity of 0.25 (0.19 to 0.32) and specificity of 0.94 (0.92 to 0.96). Different measures of glycemic abnormality identified different subpopulations (for example, 47% of people with abnormal HbA1c had no other glycemic abnormality). Lifestyle interventions were associated with a 36% (28% to 43%) reduction in relative risk of type 2 diabetes over six months to six years, attenuating to 20% (8% to 31%) at follow-up in the period after the trails.

From the results, it was concluded that HbA1c is neither sensitive nor specific for detecting prediabetes; fasting glucose is specific but not sensitive. Interventions in people classified through screening as having prediabetes have some efficacy in preventing or delaying onset of type 2 diabetes in trial populations. As screening is inaccurate, many people will receive an incorrect diagnosis and be referred on for interventions while others will be falsely reassured and not offered the intervention. These findings suggest that “screen and treat” policies alone are unlikely to have substantial impact on the worsening epidemic of type 2 diabetes.

Practice Pearls:

  • HbA1c is neither sensitive nor specific for detecting prediabetes.
  • Fasting glucose is specific, but not sensitive.
  • Adherence to lifestyle changes across whole populations is the key to prevention,

BMJ 2017; 356 doi: http://dx.doi.org/10.1136/bmj.i6538 (Published 04 January 2017) Cite this as: BMJ 2017;356:i6538   View Abstract