A multidisciplinary team in Spain, working with biostatisticians at the University of Santiago de Compostela in Santiago de Compostela, Spain, and at Harvard in Massachusetts, analyzed real-world continuous glucose monitoring data of 514 adults without diabetes. Glycemic load emerged as a consistent predictor of postprandial glucose responses, with age, sex, BMI, and meal timing further shaping individual patterns.

Although the glycemic load of foods, which combines their glycemic index with their carbohydrate content, has long been considered an undervalued parameter, evidence now confirms its value as a predictor of the glycemic response to food intake.

This was demonstrated in a pioneering project by primary care researchers at the University Clinical Hospital of Santiago de Compostela, part of the Research Methodology Group at the Health Research Institute of Santiago de Compostela, in collaboration with biostatisticians from the universities of Santiago and Harvard.

Speaking with Medscape’s Spanish edition, Mar Calvo-Malvar, PhD, from the Department of Laboratory Medicine at the University Clinical Hospital of Santiago de Compostela and the first author of the study, said, “Until now, most research on this topic has been conducted in highly controlled environments, with a limited number of patients and standardized meals. We wanted to see what happens to people in their homes and daily lives, with the schedules, elements, and personal characteristics of each individual.”

The research, published in JAMA Network Open, analyzed the glycemic response of 514 adults in Spain who wore glucose sensors for 7 days. More than 1.3 million measurements were collected, which, according to Calvo-Malvar, “makes this work one of the largest projects carried out in a population without diabetes through continuous glucose monitoring.”

Real-World Data

Calvo-Malvar noted that participants followed their usual diet without any intervention or restriction; “that is, they ate what they wanted and when they wanted under completely free conditions (ad libitum). This was precisely one of the main strengths of the study since it allowed us to analyze the glycemic response in a real-life context, with the normal variability in times, types of food and consumption patterns.

“Furthermore, the participants came from a randomly selected cohort of the general population, with socioeconomic and educational levels representative of the average, which increases the validity and applicability of the results to other similar populations,” he added.

According to Calvo-Malvar, the findings provide new data on how the glycemic load, combined with individual characteristics, determines the glycemic response and helps update the traditional views of the glycemic index and glycemic load.

Methodological Innovation

Speaking with Medscape’s Spanish edition, Francisco Gude, MD, a family physician at the Concepción Arenal Primary Care Centre in Santiago de Compostela and a member of the methodology and platforms team at the Health Research Institute of Santiago de Compostela, said, “We used functional data analysis, an advanced statistical technique that allowed us to study the complete glucose curve during the 3 hours after each meal, considering individual factors such as age, sex, [BMI], and dietary composition. This differentiates us from other traditional studies, which focus on specific points, and shows more accurately how glucose varies between individuals and throughout the day.”

The analysis also showed that meal timing, especially midday and evening meals, strongly influenced responses to glycemic load.

According to Gude, the influence of circadian rhythms is clear. He said, “We have seen that midday and evening meals cause larger and more prolonged spikes in blood sugar, coinciding with the physiological decrease in insulin sensitivity. This demonstrates that it’s not just what we eat that matters, but also when we eat it.”

He added that these patterns help identify sustained glucose elevations linked to higher glycemic load, age, or BMI, even in people with normal A1c levels. This supports the use of continuous glucose monitoring as a tool for identifying metabolic risk profiles and guiding personalized preventive strategies.

Age Effects

Another finding of this study was the effect of age on responses to high glycemic loads. Specifically, this increase was more pronounced with age.

“Age showed a clear and progressive effect on the glycemic response: For each decade of life, we observed an increase of between 2 and 3.5 mg/dL in glucose levels after meals. This pattern reflects the physiological changes associated with aging, such as decreased insulin sensitivity and loss of muscle mass, and highlights the importance of adapting dietary recommendations and mealtimes according to age,” said Gude.

Sex Differences

Data showed different responses between sexes, with men exhibiting lower glucose levels than women after main meals. When asked about the causes of these differences, Calvo-Malvar said, “Indeed, in our middle-aged cohort, men showed lower glucose levels than women during the late postprandial period after lunch and dinner, with differences of up to 4.6 mg/dL (95% CI, 1.6-7.6). One possible explanation is the effect of menopause and hormonal variations on insulin sensitivity, where the decrease in estrogen associated with menopause may increase insulin resistance and, therefore, glycemic responses in middle aged women.”

BMI Influence

BMI also contributed to the glycemic response, although less strongly than age or sex. When asked whether this finding was surprising, Gude noted that the effect was modestly unexpected.

“[BMI] is a known risk factor for diabetes, and aging is associated with beta-cell dysfunction and an increased risk of diabetes. However, few studies using continuous glucose monitoring have analyzed its impact on people without diabetes. In this sense, understanding how [BMI], age, and the metabolic changes of menopause influence it may be key to detecting early signs of glycemic deterioration.”

Global Context

Calvo-Malvar noted that although glycemic load has been a reliable predictor in controlled settings, its performance in real life had been uncertain, which helps explain its inconsistent inclusion in dietary guidelines across countries: “Thus, while some countries require the inclusion of the glycemic index on food labels, others do not.”

Gude added, “It could be said that the glycemic index has been undervalued, especially after the latest recommendations from the World Health Organization, which prioritize fiber and whole grains as indicators of carbohydrate quality, demonstrating that the effect of the glycemic index on diabetes risk was limited. These recommendations opened the debate about whether the glycemic index and glycemic load should really be included in food nutrition information, and recent studies, including meta-analyses and international cohorts, have shown that diets with a low glycemic index or glycemic load are associated with better long term glycemic control and a lower risk of diabetes.

“Our study,” he continued, “provides direct evidence in people without diabetes, under real-life conditions, that the glycemic load of meals is a reliable predictor of the glycemic response, further modulated by age, sex, [BMI], and meal timing. This reinforces the importance of considering the glycemic index and load within personalized and preventive nutrition strategies.”

Calvo-Malvar emphasized the value of incorporating glycemic load in major international dietary recommendations and said, “Since it is a parameter that provides information on the real effect of a portion of food on blood glucose, something that calories or total carbohydrate content do not provide. Having these values would help consumers understand better how foods affect their blood glucose and would help them make healthier choices, especially if presented in the context of portion sizes and mealtimes.

“Furthermore, with advances in precision nutrition and the availability of continuous glucose monitoring devices, this information would facilitate the development of personalized digital tools to plan diets tailored to each person’s metabolic profile,” Calvo-Malvar said.

Clinical Guidance

Regarding practical implications, Calvo-Malvar said that “glucose spikes after meals are associated with a higher risk of cardiovascular disease, inflammation, and metabolic impairment, even when they fall within ranges considered normal. We are accustomed to managing blood glucose cutoff points at specific times, but the information provided by continuous glucose monitoring devices opens the door to expanding the traditional management of blood glucose.

“On the other hand, our study shows that meals with a higher glycemic load cause more intense and prolonged spikes in blood sugar, especially at midday and in the evening, whereas breakfast is managed better. In practice, this suggests prioritizing foods with a higher glycemic load in the morning and opting for higher protein or lower glycemic load meals in the afternoon and evening.”

Future Research

Gude confirmed that several research lines are underway in Spain involving metabolism; prediction of the risk for diabetes and other chronic diseases; and advanced statistical approaches to analyze the glycemic response, define its determinants, and assess its relevance for health.

“These perspectives will allow us to delve deeper into how individual factors and daily habits influence blood glucose levels, their relationship with chronic diseases, and their usefulness in designing personalized prevention strategies,” he concluded.

Calvo-Malvar and Gude reported having no relevant conflicts of interest.

This story was translated from Medscape’s Spanish edition.