Type 2 diabetes mellitus (T2DM) is a significant global health concern, with its prevalence projected to increase substantially in the coming years. Genetic predisposition, lifestyle factors, and dietary patterns all contribute to T2DM development. Dietary fat, a crucial component of daily diets, has been linked to T2DM risk, although the specific roles of different fatty acid (FA) types remain a subject of debate. Some studies suggest that saturated FAs (SFAs) promote inflammation and insulin resistance, while omega-3 FAs exhibit anti-inflammatory properties and may improve insulin sensitivity. However, previous research has been limited by difficulties in accurately quantifying dietary FA subtypes. This study aimed to assess the association between dietary FAs and the risk of both impaired glucose tolerance (IGT) and T2DM using the comprehensive data available in the National Health and Nutrition Examination Survey (NHANES) database. The study focused on both the overall correlation between dietary FAs and the risk of IGT and T2DM, as well as any dose-dependent effects of different FA subtypes. By analyzing this large dataset, the researchers hoped to achieve a better understanding of the relationship between FAs and T2DM, informing future prospective studies and research into underlying biological mechanisms. The specific focus on subtypes and dose-response relationships is a key improvement over previous studies, which often lacked the detailed dietary data required for a precise analysis.

Existing literature presents conflicting views on the relationship between dietary fat and the risk of type 2 diabetes. While some studies link high-fat diets, particularly those rich in SFAs, to increased risk of T2DM and IGT, others highlight the potential benefits of unsaturated FAs. A recent study demonstrated that a high-fat diet can increase intestinal fructose metabolism, potentially leading to islet cell damage and glucose intolerance. The impact of various FAs is complex, with SFAs often considered pro-inflammatory and omega-3 FAs possessing anti-inflammatory effects. Long-chain SFAs, such as palmitic acid, have been shown to trigger insulin resistance in pancreatic beta-cells. In contrast, long-chain unsaturated FAs can promote glucagon-like peptide-1 secretion, thereby increasing insulin levels. Despite these insights, the precise associations between different dietary FA subtypes and T2DM risk have remained elusive due to the challenges in accurately measuring FA intake in past studies. Blood free FAs are not reliable indicators of dietary FA intake. The current study leverages the comprehensive dietary data available in the NHANES database to address these limitations.

This serial cross-sectional study utilized data from six cycles of the National Health and Nutrition Examination Survey (NHANES) 2005–2016, a nationally representative survey of the U.S. civilian non-institutionalized population. The study sample comprised 9082 participants after excluding individuals with incomplete data, those whose dietary intake was modified due to diagnosed diabetes (to mitigate Neyman bias), and those with missing key covariates. Dietary FA intake was assessed using two 24-hour dietary recalls, with the average used when both recalls were complete. The U.S. Department of Agriculture's Dietary Research Food and Nutrition Database for Dietary Studies was used to calculate daily FA intake. T2DM and IGT were diagnosed based on World Health Organization criteria using fasting plasma glucose and 2-hour oral glucose tolerance test results. Covariates, including age, sex, race, education level, poverty-to-income ratio, BMI, smoking status, hypertension, and physical activity, were collected through interviews and medical examinations. Statistical analyses incorporated sampling weights to account for the nationally representative nature of the data. Descriptive statistics were used to characterize the study population. Chi-square or ANOVA tests were used for comparing categorical and continuous variables, respectively, across the NGT, IGT, and T2DM groups. Dietary FA intakes were categorized into quartiles, with the first quartile serving as a reference. Factor analysis with varimax rotation was employed to identify uncorrelated FA factors. Multivariate logistic regression models were used to assess the association between FA intake and the risk of IGT and T2DM, adjusting for age, sex, race, BMI, education, poverty-to-income ratio, smoking status, hypertension, and physical activity in the fully adjusted model. The Benjamini-Hochberg approach was used to control for false discovery rate.

A total of 9082 participants were included in the final analysis, encompassing 6892 with normal glucose tolerance (NGT), 1434 with IGT, and 765 with T2DM. Individuals with IGT and T2DM were older, had higher BMIs, lower education levels, were less likely to smoke or exercise, and more likely to have hypertension compared to the NGT group. The intakes of total FA (TFA), monounsaturated FA (MUFA), and polyunsaturated FA (PUFA) were significantly lower in IGT and T2DM groups compared to the NGT group. Total saturated FA (TSFA) intake was also lower in the IGT group than in the NGT and T2DM groups. Multivariate logistic regression analysis revealed a negative association between TSFA and IGT risk (OR = 0.991, 95% CI: 0.985–0.998, P = 0.024) after adjusting for covariates. In the fully adjusted model, total FA at the fourth quintile was negatively correlated with T2DM risk (OR = 0.714, 95% CI: 0.532–0.959, P = 0.025) relative to the first quintile. Factor analysis identified four FA factors, with factor 4 (F4) showing a negative association with T2DM risk (OR = 0.824, 95% CI: 0.715–0.949, P = 0.029). F4 comprised four unsaturated FAs: octadecenoic acid (18:1), octadecadienoic acid (18:2), octadecatrienoic acid (18:3), and eicosenoic acid (20:1). Analysis of FA quartiles showed negative correlations between several FAs, particularly unsaturated ones, and the risk of IGT in various adjusted models. However, the associations between specific FAs and T2DM risk were less consistent across models.

The findings suggest a potential protective role of certain unsaturated FAs against T2DM. The negative correlation between total saturated FA and IGT risk is consistent with some existing literature. The identification of an unsaturated FA signature associated with reduced T2DM risk is a notable contribution. The study's focus on specific FA subtypes and dose-response relationships helps clarify the complex interplay between dietary FA composition and diabetes risk. The negative association observed between total FAs and T2DM risk may reflect the overall contribution of unsaturated FAs. However, the lack of significant associations between individual unsaturated FAs and T2DM risk highlights the complexity of the relationship. The unsaturated FA signature identified through factor analysis may be more meaningful than considering individual unsaturated FAs in isolation. These findings underscore the potential benefits of diets rich in unsaturated FAs, which are abundant in natural oils. This study provides valuable insights into the role of dietary FAs in diabetes risk, offering potential avenues for nutritional interventions.

This cross-sectional study suggests a negative association between dietary total FAs and the risk of T2DM in American adults. Unsaturated fatty acids, particularly the combination identified in factor 4, may play a protective role against T2DM. Future prospective studies are needed to confirm these findings and explore the underlying biological mechanisms. Further research should investigate the specific roles of the identified unsaturated FA signature in modulating glucose metabolism and insulin sensitivity.

The cross-sectional design limits the ability to establish causality. The 24-hour dietary recall method may introduce recall bias and might not accurately reflect long-term dietary habits. The relatively small sample sizes for IGT and T2DM groups may limit the statistical power to detect some associations. Residual confounding, despite the adjustment for multiple covariates, may also influence the results. Finally, the generalizability of the findings might be restricted to the American adult population.