Research questions:

This systematic review evaluated the evidence to address the following research questions:

What is the test reproducibility of the diagnosis of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)?

What is the relationship between IFG and IGT? For those individuals identified with IFG or IGT, what are the short- and long-term risks for developing negative health outcomes? Does this risk vary by subpopulation, such as sex, race, obesity, age, or other such risk factors as blood pressure or elevated lipid levels?

What is the effectiveness of pharmaceutical and behavioral interventions for reducing the risks associated with IFG/IGT? Are some treatments more effective than others, and does the effectiveness of interventions vary by subpopulation (e.g., age, sex, and obesity)?

What is known about the development of IFG/IGT in the pediatric population?

Data sources:

Studies were identified by searching the following databases: MEDLINE, Cochrane Central Register of Controlled Trials, HealthSTAR, CINAHL, AMED (alternative medicines), PsycINFO, and EMBASE as well as the personal files of the advisory team and the reference lists of included articles.

Eligibility criteria:

Primary studies were eligible for further evaluation if they assessed subjects with IFG or IGT, were published after 1978, and were written in English. Study design eligibility varied with the research question. For the diagnosis of IFG or IGT research questions (with a maximum of eight-week re-test for reproducibility), all study designs were eligible. Similarly, for the children's (age 0 to 18 years) research questions, all designs were considered. For prognosis, prospective cohort studies, randomized controlled trials (RCTs) or controlled clinical trial (CCTs) with a minimum of one-year follow-up were eligible. Any RCT that analyzed the effects of lifestyle or behavioral or pharmaceutical treatment (with a minimum of six months' follow-up) was evaluated for the research question on treatment.

Data collection and analysis:

Data were extracted for all studies and included the sample size, age of subjects, population characteristics, criteria used for diagnosis, and the study duration. For the prognosis questions, proportions were extracted to estimate risk for disease progression (annualized risk, unadjusted relative risk, and attributable risk). Adjusted estimates of risk reported in studies were also extracted. Similarly, estimates of risk were extracted for studies related to the treatment of IFG or IGT. The methodological quality of studies was assessed.

Main results:

Diagnosis: Although, the number of evaluated studies was small, the reproducibility for both IFG and IGT categorization was shown to be poor. Comparison of IFG and IGT categories shows a wide degree of variation among populations. The prevalence of IGT is greater than IFG in almost all studies. High-risk populations have an equal or greater proportion of IFG compared to IGT diagnoses. The kappa coefficients varied from 0.04 to 0.56 for IGT and from 0.22 to 0.44 for IFG.

Statistically, the proportion of study participants classified as IGT by the 2-hour plasma glucose (2-hr PG) alone, is greater than the proportion classified by the diagnostic criteria, combined 2-hr PG/fasting plasma glucose (FPG). This will affect the conclusions of prognosis and possibly treatment data in population studies using only 2-hr PG criteria.

Prognosis: There is consistent evidence that IFG and IGT are both risk factors for the development of diabetes mellitus (DM). The pooled relative risk for new DM is 6.02 (95% CI 4.66 to 7.38) in people with IGT, 4.70 (95% CI 2.71 to 6.70) in people with IFG, and 12.21 (95% CI 4.32 to 20.10) in people with both disorders. They are also both risk factors for fatal and nonfatal cardiovascular outcomes; however, the evidence is less consistent for these outcomes. The pooled relative risk ranged from 1.48 to 1.66 for cardiovascular disease (CVD) mortality and all-cause mortality in people with IGT, and from 1.19 to 1.28 for nonfatal myocardial infarction (MI), nonfatal CVD, CVD mortality, and all-cause mortality in people with IFG.

Treatment: Fourteen RCTs evaluated the effect of lifestyle or pharmacotherapeutic interventions on individuals with IFG or IGT. Trials that evaluated the effect of a combined diet and exercise program on the risk for developing DM found a significant risk reduction (46%). Dietary advice alone significantly reduced the risk for progressing to DM in one of two trials. Exercise alone significantly reduced progression to DM in one trial. Two of four studies that evaluated the effect of pharmacotherapeutic interventions (acarbose, metformin) on the risk for progressing to DM in IGT subjects showed evidence of reduced risk (25%). Two retrospective subgroup analyses evaluating the effect of statin therapy (pravastatin) on individuals with IFG with a previous MI found CVD benefits.

Pediatric populations: Only 2 out of 36 articles provided data specific to the pediatric population. However, neither of these studies provided substantive information. A gap in the literature has been identified.

Conclusions:

Diagnosis: The reproducibility for both IGT and IFG categorization is poor. Therefore, an absolute FPG and 2-hr PG measurement may be more informative than categorization into IFG and IGT, respectively. The distribution of study participants in the IGT category varies significantly with the diagnostic criteria used. This will affect findings in epidemiological studies evaluating prognosis and treatment.

Prognosis: Many studies consistently show that both IFG and IGT are strong risk factors for the development of DM. Fewer studies show that they are also risk factors for future CVD, all-cause mortality, and lipid disturbances.

Treatment: There is evidence that combined diet and exercise, and drug therapy (metformin, acarbose), are effective at preventing progression to DM in IGT subjects.

Pediatric populations: The literature on pediatric subjects with IFG or IGT is limited and future research is warranted.