Background/Objectives: Seasonal variation in hemoglobin A1c (HbA1c) values has been previously documented, with physical activity (PA) and macronutrient intake (MNI) suggested as potential drivers. This study combines seasonal mean HbA1c values from the Dutch (pre)diabetes population with national survey data on PA and MNI from 2018 to 2021 to identify key associations. Methods: HbA1c data were collected from 24 laboratory organizations in the Netherlands and Dutch Caribbean. MNI and total energy intake data were extracted from the Dutch National Food Consumption Survey, while PA data came from the Dutch National Sports Participation Index Survey. Weighting factors were applied to align PA and MNI data with HbA1c data. Seasonal averages were analyzed for significant differences, and a prediction model compared PA and MNI with actual HbA1c values. Results: Among 5,635,920 HbA1c results, the average HbA1c increased by 0.71 mmol/mol (NGSP 0.06%) over four years, with an overall mean of 52.4 mmol/mol (NGSP 7.0%). Seasonal HbA1c variation showed a dip in summer–autumn and a peak in winter–spring (1.2 mmol/mol; NGSP 0.11%; p < 0.0001). MNI, except for total energy intake (which peaked in summer; p < 0.001), showed no significant trends or association with HbA1c (p = 0.157). PA decreased by 7.2% over the study period, with seasonal peaks in summer–autumn, showing an inverse relationship with HbA1c (p < 0.0001). During the COVID-19 lockdowns, PA significantly decreased, and mean HbA1c values increased more markedly than in previous years. The prediction model confirmed PA as a significant driver of seasonal HbA1c variation (p = 0.004). Conclusions: These findings suggest that PA is the strongest driver of seasonal variation in HbA1c. Public health initiatives and support programs promoting physical activity are essential for improving HbA1c regulation.
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