Fasting plasma glucose variability levels and risk of adverse outcomes among patients with type 2 diabetes: a systematic review and meta-analysis

Authors: Zhao Q, Zhou F, Zhang Y, Zhou X, Ying C.O.

Geographical coverage: Not reported

Sector: Biomedical

Sub-sector: Diagnosis, biomarker

Equity focus: Not reported

Study population: Patients with type 2 diabetes mellitus

Review type: Other review

Quantitative synthesis method: Not applicable

Qualitative synthesis method: Narrative synthesis

Background: Intermittent elevation of blood sugar levels has been linked to a decline in endothelial function, and increased risk of vascular complications and all-cause mortality in patients with type 2 diabetes mellitus (T2DM). Glycaemic variability (GV) is an independent risk factor for long term complications of diabetes. In addition, it is a sensitive indicator for assessing low and high blood glucose levels.

Objectives: To assess the association between fasting plasma glucose (FPG) variability levels and the risk of retinopathy and all-cause mortality in patients with T2DM.

Main findings: The search identified 99 articles, of which only eight were included in this meta-analysis, which involved 100,616 patients with T2DM. All studies were of high quality. Of the eight included studies, five assessed the impact of FPG variability on overall mortality and revealed that high FPG variability was associated with the risk of overall mortality (HR 1.28, 95% CI 1.12-1.46, p = 0.000; three studies). For median or mean FPG variability ranges from 10-20%, the relationship between all-cause mortality and FPG variability was not significant (HR 1.01, 95% CI 0.86-1.18; p = 0.929; three studies). Three studies assessed the association of FPG variability and the risk of diabetic retinopathy and showed that high FPG fluctuations were strongly associated with the risk of diabetic retinopathy (odds ratio (OR) = 3.68; 95% CI 1.01-13.4, p = 0.04). The publication bias was not assessed, as the number of the included studies was less than 10.

Methodology: Searches were conducted (through 14 June 2018) on PubMed and EMBASE to identify studies assessing the association between FPG variability and the risk of retinopathy or all-cause mortality in patients with T2DM. The authors also searched the grey literature sources. The screening was conducted by two reviewers independently. The studies were included if they reported relevant data and provided standard deviation (SD) or the coefficient of variation (CV) for FPG variability.

The data was extracted by two reviewers independently. A fixed-effects model was used for the pooled analyses, however, a random-effects model was applied when heterogeneity was found. The review authors calculated the pooled hazard ratio (HR) for CV of FPG. However, the authors performed narrative synthesis due to a lack of adequate studies. Heterogeneity was assessed using the Cochran Q test and I² statistic. The publication bias was assessed using funnel plots.

Applicability/external validity: The authors did not discuss the applicability or external validity of the results.

Geographic focus:

The geographic region of included studies was not reported in the review.

Summary of quality assessment:

The authors employed suitable techniques for analysing the review findings and for the screening and data extraction of the included studies. However, the comprehensiveness of the literature searches was insufficient to completely avoid publication bias. Consequently, the conclusions about the effects of this review are regarded with a medium level of confidence.