Inflammation, Oxidative Stress, and Antioxidant Micronutrients as Mediators of the Relationship Between Sleep, Insulin Sensitivity, and Glycosylated Hemoglobin

In the scientific paper titled Inflammation, Oxidative Stress, and Antioxidant Micronutrients as Mediators of the Relationship Between Sleep, Insulin Sensitivity, and Glycosylated Hemoglobin, authored by Thirumagal Kanagasabai, Michael C. Riddell, and Chris I. Ardern, the researchers explore how poor sleep affects the body’s ability to manage blood sugar, potentially raising the risk of diabetes. The authors focus on how biological factors like inflammation and oxidative stress, as well as antioxidant micronutrients (such as vitamins C and D), may mediate the relationship between sleep patterns — including both sleep quality and duration — and two key markers of metabolic health: fasting insulin concentration and glycosylated hemoglobin (HbA1c). By analyzing data from a large-scale U.S. health survey, the study aims to shed light on the pathways through which sleep influences diabetes risk and offers insights into potential strategies for prevention.

Getting enough good-quality sleep is essential for maintaining overall health, but many people don't sleep well or long enough. Most adults need about 7–9 hours of sleep each night, but poor sleep quality and short sleep duration are common problems. These sleep problems can have a significant impact on our health. They are linked to a number of diseases, like heart problems, nerve disorders, and diabetes . Specifically, poor sleep can cause an increase in inflammation and oxidative stress. In this state, the body has too many harmful molecules (free radicals) and not enough antioxidants to neutralize them. This state can damage cells and lead to insulin resistance, where the body does not respond well to insulin. Insulin is a hormone that helps regulate blood sugar; resistance to it can increase blood sugar levels, increasing the risk of diabetes.

The researchers in this study wanted to understand more about how certain substances in the body might mediate or act as middlemen in the connection between sleep and diabetes risk. They focused on C-reactive protein (CRP), which is a marker of inflammation, gamma-glutamyl transferase (GGT), a marker of oxidative stress, and several antioxidant micronutrients like bilirubin, carotenoids, uric acid, and vitamins A, C, D, and E. The goal was to see how these substances affect the relationship between sleep patterns — duration and quality — and two crucial health measures: fasting insulin concentration and glycosylated hemoglobin (HbA1c). HbA1c is a measure of how well blood sugar has been controlled over the past few months.

The study analyzed data from the 2005-2006 U.S. National Health and Nutrition Examination Survey (NHANES), which collected information from a nationally representative group of 1,946 adults aged 20 and older. Participants completed the Sleep Disorders Questionnaire, which asked them to report their usual sleep habits over the past month.

The researchers used a statistical technique called "mediation analysis" to determine how much these markers might explain the link between sleep patterns and health outcomes like insulin levels and HbA1c. This technique helps understand if a third factor (like CRP or vitamin C) plays a significant role in the relationship between two other factors (like sleep and insulin sensitivity).

The study revealed some key points about how sleep patterns affect insulin sensitivity and blood sugar control:

The researchers found that several substances in the blood, like GGT, carotenoids, uric acid, and vitamins C and D, were influential in explaining how sleep duration affects fasting insulin levels. The study notes, "GGT, carotenoids, uric acid, and vitamins C and D provided large and statistically significant contributions to the sleep duration–fasting insulin concentration relationship." This means that people who got different amounts of sleep had various levels of these substances, which could help explain why their insulin levels varied.

For sleep quality, CRP, bilirubin, and vitamin C were found to be significant mediators in the relationship with fasting insulin levels. These substances help explain how poor sleep quality can lead to changes in insulin levels. However, other markers like GGT, carotenoids, uric acid, and vitamin D had less impact. The study states, "CRP, bilirubin, and vitamin C made large and statistically significant contributions to the sleep quality–fasting insulin concentration relationship."

The study found weaker connections between sleep patterns and HbA1c, which measures long-term blood sugar control. Only vitamins C and D showed modest contributions. As the researchers explain, "The mediating effect of these micronutrients was only weak-to-modest when the outcome was HbA1c."

Overall, the study found that the effects of sleep on insulin levels were more significant than on HbA1c levels. This suggests that poor sleep may have a more immediate impact on how the body handles insulin and blood sugar rather than long-term blood sugar control.

The findings suggest that factors like inflammation, oxidative stress, and antioxidant levels are essential in how sleep affects insulin resistance and blood sugar control. In simple terms, not getting enough sleep or having poor-quality sleep can cause changes in the body that make it harder to manage blood sugar levels, which could raise the risk of diabetes.

Improving sleep hygiene, or good sleep habits, could be a helpful strategy for managing diabetes risk. This could involve going to bed at the same time every night, creating a comfortable sleep environment, and avoiding caffeine or screens before bedtime. Additionally, reducing inflammation and oxidative stress by eating a healthy diet rich in antioxidants, such as fruits and vegetables, could also help. As the study suggests, "Interventions that collectively target modifiable lifestyle behaviors, including sleep hygiene, reduce systemic inflammation/oxidative stress, and optimize antioxidant intake, remain mutually beneficial targets for diabetes risk."

This study shows that sleep duration and quality are closely linked to how the body manages insulin and blood sugar levels, with several key substances — like GGT, CRP, and antioxidant micronutrients — acting as important mediators in these relationships. It highlights that poor sleep can contribute to increased inflammation and oxidative stress, which may lead to insulin resistance and a higher risk of diabetes. The findings suggest that improving sleep habits, reducing inflammation and oxidative stress, and ensuring adequate intake of antioxidants could be effective strategies for reducing diabetes risk.

By focusing on these modifiable factors, such as promoting better sleep hygiene and a diet rich in antioxidants, healthcare providers and individuals may better manage or even prevent conditions like diabetes. As the study emphasizes, targeting these areas offers a promising approach to improving overall metabolic health and reducing the burden of diabetes in the community.