Maintaining optimal glycemic control is crucial for reducing morbidity and mortality associated with diabetes. While HbA1c, fasting plasma glucose (FPG)/basal glucose (BG) are commonly used indicators, comprehensive control of HbA1c, BG, and postprandial glucose (PPG) is essential for preventing vascular complications. Studies have highlighted the importance of both FPG/BG and PPG in cardiovascular risk, with PPG showing a significant association with cardiovascular events and all-cause mortality. Previous research on the relative contributions of BG and PPG to HbA1c has yielded conflicting results due to variations in methodologies, study populations, and baseline criteria. Some studies used 5.5/5.6 mmol/L or 6.1 mmol/L as baseline values, while others incorporated the 24-hour glucose profile of the NGT group. This inconsistency necessitates the development of a more standardized and accurate method for evaluating these contributions, leveraging the capabilities of continuous glucose monitoring (CGM).

A review of 17 relevant studies published up to January 1, 2021, revealed inconsistent findings regarding the relative contributions of PPG to HbA1c. The studies varied significantly in patient populations, treatment regimens, and baseline criteria used for calculating PPG contribution. Eleven studies used 5.5/5.6 mmol/L as the baseline, aligning with the American Diabetes Association's recommendation for the upper limit of normal fasting glucose. Four studies employed 6.1 mmol/L, which is the World Health Organization's upper limit. One study utilized the 24-h glucose profile of the NGT group as a baseline, highlighting the potential for overestimation of PPG contribution when using fixed baseline values like 6.1 mmol/L. The conflicting findings may be attributed to differences in study design, glucose measurement methods (multipoint vs. CGM), and baseline selection. The emergence of new therapies targeting BG or PPG underscores the importance of clarifying the relationship between BG, PPG and HbA1c.

This prospective study enrolled 490 subjects categorized into NGT, IGT, NDDM, and T2DM groups. Participants aged 18–75 years met specific inclusion and exclusion criteria, excluding those with impaired liver or renal function, other comorbidities, or treatments like insulin, DPP-4 inhibitors, GLP-1 receptor agonists, and acarbose. Data collected included medical history, anthropometric measurements, OGTT results (plasma glucose measured by glucose oxidase method), HbA1c (measured by high-performance liquid chromatography), and biochemical parameters. Subjects followed individualized dietary plans formulated by a nutritionist and endocrinologist based on the China Medical Nutritional Therapy Guideline for Diabetes (2013). Three different methods were used to calculate the relative contribution of PPG to HbA1c, employing baseline values of 6.1 mmol/L, 5.6 mmol/L, and the 24-h glucose curve of the NGT group.

The study found that the relative contribution of PPG to HbA1c decreased progressively from the IGT group to the T2DM group, regardless of the baseline criterion used. Using the 24-h glucose curve of the NGT group as a baseline yielded the most accurate results. Compared to using the NGT curve, employing 6.1 mmol/L as the baseline overestimated the PPG contribution by approximately 13.16% in the IGT group and significantly in the NDDM and T2DM groups (p<0.01). In T2DM patients, using 6.1 mmol/L overestimated PPG contribution by 9.04%, and using 5.6 mmol/L overestimated it by 1.76% compared to the NGT curve baseline. The 24-h glucose curve of the NGT group reflected physiological fluctuations after meals, making it a superior baseline criterion for assessing BG and PPG contributions to HbA1c.

This study validates the authors’ previous findings, demonstrating the overestimation of PPG contribution when fixed glucose values (6.1 mmol/L or 5.6 mmol/L) are used as baselines compared to the 24-h NGT glucose profile. The use of a fixed value ignores the physiological fluctuations in glucose levels after meals observed in NGT individuals. Previous research has shown PPG to be crucial for achieving HbA1c targets, especially in patients with good glycemic control. However, BG contribution becomes more prominent as glucose homeostasis deteriorates. Discrepancies in prior studies are likely attributable to differences in glucose measurement methods (multipoint vs. CGM), baseline values, and the exclusion of glucose values below the baseline in some calculations. The study's findings suggest that a more dynamic, physiological baseline like the NGT curve is superior for evaluating the relative contributions of BG and PPG to HbA1c.

This study confirms a progressive shift in the relative contributions of BG and PPG to HbA1c with worsening glycemic control, with BG predominantly contributing at higher HbA1c levels. The 24-h NGT glucose curve serves as a more accurate baseline for assessing these contributions, considering physiological postprandial fluctuations. For practical applications, 5.6 mmol/L provides a suitable alternative when the NGT curve is unavailable. Future research should explore these relationships across broader populations, incorporating diverse treatment regimens and examining the impact of HbA1c levels on these contributions. This understanding will facilitate the development of more individualized diabetes management strategies.

The study's limitations include its single-center design, which may limit the generalizability of the findings to other populations in China. The exclusion of insulin-treated patients and those with diabetes-related complications also restricts the applicability of the results. Furthermore, the analysis focused on group differences rather than examining variations across different HbA1c levels within each group.