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Dietary dicarbonyls may improve insulin sensitivity and reduce type 2 diabetes risk

Dicarbonyls are heterogenous reactive compounds that are formed endogenously as a by-product of lipid oxidation and glycolysis. These compounds are also formed during food processing, particularly during the heat treatment linked to caramelization or Maillard reaction.

Some common dicarbonyls include glyoxal (GO), methylglyoxal (MGO), and 3-deoxyglucosone (3-DG), some of which are major precursors of advanced glycation end products (AGEs).  

A recent American Journal of Clinical Nutrition study investigates how dietary intake of dicarbonyls impacts insulin sensitivity and β-cell function and, as a result, the incidence of type 2 diabetes.


Higher habitual consumption of dicarbonyls like MGO and GO leads to its higher prevalence in plasma. In fact, previous research has revealed that higher intake of MGO causes elevated skin autofluorescence, which can be measured based on AGE accumulation in tissues. This finding indicates the absorption of dicarbonyls from the diet and its contribution to AGEs in the body.

Higher levels of dicarbonyls and AGEs are associated with the development of diabetes and cardiovascular disease. Experimental models have revealed that the increased concentration of dicarbonyls leads to impaired insulin sensitivity and affects β-cell function, thus contributing to the development of type 2 diabetes. Similarly, a high level of the MGO metabolite D-lactate in humans has been associated with insulin resistance.

Animal models have shown that a high amount of MGO decreases insulin secretion by the pancreatic β-cells, thereby inducing insulin resistance and impaired glucose tolerance. Similarly, one previous human study revealed that higher dicarbonyls consumption is associated with less low-grade inflammation, which is a common occurrence in type 2 diabetes. These findings emphasize the importance of determining the level of dietary dicarbonyls that would affect the progression of type 2 diabetes in humans.

About the study

The current observational population-based study included individuals with type 2 diabetes to investigate the relationship between dietary dicarbonyls with β-cell function, insulin sensitivity, and glucose metabolism status. For this study, data were obtained from the Maastricht Study, which is a prospective population-based cohort study.

The study cohort included all individuals between 40 and 75 years of age who were diagnosed with type 2 diabetes and lived in the southern part of the Netherlands. A total of 6,282 participants were recruited in this study, which comprised an almost equal number of men and women.

The habitual intake of MGO, GO, and 3-DG was estimated using Food Frequency Questionnaires (FFQ). Moreover, β-cell function, insulin sensitivity, and glucose metabolism status were evaluated by a seven-point oral glucose tolerance test.

Insulin sensitivity was determined using the Matsuda index and was measured as HOMA2-IR. The c-peptidogenic index was used to assess β-cell function.

Linear and logistic regressions were used to study the association between dietary dicarbonyls and the studied health outcomes.

Study findings

Higher habitual consumption of MGO and 3-DG were linked to greater insulin sensitivity and a lower incidence of type 2 diabetes. Thus, there appears to be a potential protective role of these dietary dicarbonyls against the development of type 2 diabetes.

Although higher GO consumption was correlated with greater insulin sensitivity and lower occurrence of type 2 diabetes, this finding was not robust in the sensitivity analyses. An inconsistent association between dicarbonyls intake and indices of β-cell function was observed. Higher consumption of GO and 3-DG was linked to glucose fasting and HbA1c, which supports an association with type 2 diabetes.

Consistent with previous studies, the current study revealed that individuals with a higher intake of MGO exhibit less low-grade inflammation. This finding similarly suggests the beneficial effects of dietary MGO intake. 

Hormesis is an adaptive response in which an organism experiences beneficial effects following low-dose exposures to stressors. To this end, the current study revealed that small increases in MGO have a positive role in modulating physiology. The protective effect of dietary MGO against insulin sensitivity and glucose metabolism could be due to the upregulation of Nrf2, which is a regulator of oxidative stress that increases the production of glyoxalase-1.

Nevertheless, the researchers failed to confirm the relationship between dicarbonyl intake and β-cell function, as GO and 3-DG consumption rates were individually linked with one β-cell function measurement. The explorative evaluations with sequential adjustment for dicarbonyls consumption from major food groups revealed that the observed outcome was not influenced by a particular food group.


The current study has several limitations, including the analysis of self-reported data from a questionnaire, which could have been underreported and consist of biased data. Another limitation of this study is its cross-sectional design which did not allow for causality assessment. In addition, there is a possibility of the presence of residual confounding factors.

Despite these limitations, the study findings highlight the association between habitual intakes of GO, MGO, and 3-DG and lower incidence of type 2 diabetes. In addition, a higher intake of MGO and 3-DG was linked to improved insulin sensitivity, thus indicating the protective role of food-derived dicarbonyls against type 2 diabetes.

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