Progression rate from intermediate hyperglycemia to diabetes mellitus according to the different cut-off levels of fasting plasma glucose and HBA1C : a systematic review and meta-analysis

Abstract

Intermediate hyperglycemia (IH) or prediabetes is a high risk state of diabetes mellitus (DM) development where a glycaemic variance is higher than normal, but lower than that of diabetes thresholds. According to World Health Organization (WHO), prediabetes is defined as fasting plasma glucose (FPG) ranging from 110 to 125 mg/dl, and/or elevated HbA1c ranging from 6.0 to 6.49%, while American Diabetes Association (ADA) defined prediabetes as FPG ranging from 100 to 125 mg/dl and/or HbA1c ranges from 5.7 to 6.49%. The progression rate to type II diabetes (T2DM) may be varied according to the different definition of prediabetic state. Therefore, this systematic review and meta-analysis was conducted to estimate risk of T2DM progression and the regression to normoglycemia of different cut-off thresholds used to define prediabetic state. Studies were searched from MEDLINE and Embase databases from inception to 10th October 2019 and data extraction were independently performed by two reviewers. Frequency data on different cut-off levels from each study were extracted and risk of progression to T2DM according to different cut-off thresholds of FPG and HbA1c levels for each study were estimated by Poisson regression analysis. Then risk of progression to DM of each study according to different cut-off thresholds of FPG and HbA1c were pooled using mixed-effect Poisson regression model. A total 77 cohort studies were included. People with FPG 110 to 125 mg/dl and 100 to 125 mg/dl had significantly higher risk of T2DM progression than people with FPG < 100 mg/dl with RRs of 13.16 (95% CI: 12.75, 13.57) and 3.87 (95% CI: 3.74, 4.00), respectively. The pooled RR was 3.39 (95% CI: 3.30, 3.48) for people with FPG 110 to 125 mg/dl compared to FPG 100 to 109 mg/dl. People with HbA1c 6.0 to 6.49% and 5.7 to 5.99 % had significant higher risk of T2DM, when compared with HbA1c < 5.7%, with RR 8.36 (95% CI: 7.99, 8.75) and RR 2.86 (95% CI: 2.73. 3.00), respectively. The pooled RR was 2.92 (95% CI: 2.81, 3.03) for people with HbA1c 6.0 to 6.49% compared to HbA1c 5.7 to 5.99%. In addition, when FPG and HbA1c glycaemic measurement were combined, the pooled RRs for T2DM progression were 8.30 (95% CI: 7.15, 9.64), 8.35 (95% CI: 7.00, 9.96), 27.66 (95% CI: 24.06, 31.8) for people with combined FPG 100 to 125 mg/dl and HbA1c <5.7%, combined FPG <100 mg/dl and HbA1c 5.7 to 6.49%, combined FPG 100 to 125 mg/dl and HbA1c 5.7 to 6.49%, when compared with FPG < 100mg/dl and HbA1c < 5.7%, respectively. The pooled RRs were 1.00 (95%CI: 0.86, 1.16) and 3.32 (95% CI: 3.01, 3.67) for people with combined FPG <100 mg/dl and HbA1c 5.7 to 6.49% and combined FPG 100 to 125 mg/dl and HbA1c <5.7%, when compared with combined FPG 100 to 125 mg/dl and HbA1c <5.7%, respectively. The pooled RR was 3.31 (95% CI: 2.87, 3.80) for people with combined FPG 100 to 125 mg/dl and HbA1c 5.7 to 6.49%, when compared with combined FPG <100 mg/dl and HbA1c 5.7 to 6.49%. In conclusion, there is a significant increased risk of T2DM for all cut-off thresholds of FPG and HBA1c used to define prediabetic state, when compared with normoglycemia. Risk of progression to T2DM was increased when both FPG and HbA1c abnormalities are combined. These results might be useful for risk stratification in people with prediabetes and might be used as guidance for planning preventive strategies for a diabetes prevention program.