Higher Antioxidant Intake Associated with Lower Risk of Latent Autoimmune Diabetes in Adult Subjects

by | Oct 5, 2023 | 2023, Antioxidants, Autoimmune Disease, Diabetes, Vitamin C, Vitamin E

Written by Taylor Woosley, Staff Writer. Results of the retrospective study using data from ESTRID shows that high vitamin C and vitamin E intake was inversely associated with LADAhigh. 

antioxidantsLatent autoimmune diabetes in adults (LADA), a disease with a phenotype like type 2 diabetes (T2D), has been recognized by the American Diabetes Association as a form of type 1 diabetes1. Autoimmune diabetes is characterized by the presence of specific autoantibodies directed against pancreatic β-cells islet and initial requirement of insulin therapy2. People identifying as having LADA account for 2-12% of all patients with diabetes3.

Diabetes mellitus (DM) is associated with oxidative stress, leading to an increased production of ROS or reduction of the antioxidant defense system4. Research has shown that an antioxidant-rich diet can aid in decreasing oxidative markers accompanied with improved insulin sensitivity5. Furthermore, compounds with antioxidant activity can down-regulate the expression of cyclooxygenase-2 (COX2) related genes to release pro-inflammatory mediators, increase glucose tolerance, reduce inflammatory cells, and reduce cytokine levels6.

Lampousi et al. conducted a study using data from the Swedish population-based case-control Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes (ESTRID) to analyze whether the intake of antioxidants reduces the risk of LADA with subjects experiencing autoimmunity or type 2 diabetes. Additionally, researchers used a two-sample Mendelian randomization design to investigate whether circulating beta-carotene, vitamin C, and vitamin E are causally linked to LADA, type 1, or type 2 diabetes. Subject inclusion consisted of participants with LADA and type 2 diabetes who were cases and controls between 2010 and 2019 who had reported plausible energy intakes. 584 subjects with LADA, 1989 participants with type 2 diabetes, and 2276 controls were included in the final analysis.

Subjects’ diabetes diagnosis was confirmed through blood samples and analysis of antibodies against glutamic acid decarboxylase (GADA) using the enzyme-linked immunosorbent assay. Serum C-peptide was assessed using the IMMULITE 2000 immunoassay system or the Cobas e601 analyzer. LADA classification among participants included being age ≥35 years, GADA positivity (≥10 U/mL), and C-peptide ≥ 0.2nmol/L (IMMULITE) or ≥ 0.3 nmol/L (Cobas) to distinguish from type 1 diabetes. LADA cases were further subclassified based on median GADA levels as LADAlow (<250 U/mL) and LADAhigh (≥250 U/mL). Type 2 diabetes classification amongst subjects included being age ≥35 years, GADA negativity (<10 U/mL), and C-peptide >0.6 nmol/L (IMMULITE) or >0.72 nmol/L (Cobas). iPlex was utilized to analyze blood samples for genotyping.

Dietary intake was analyzed using a 132-item semi-quantitative food frequency questionnaire (FFQ). Furthermore, a comprehensive questionnaire was completed to provide information on lifestyle, demographic, and clinical characteristics such as physical activity levels, smoking status, education level, weight, height, and family history of cardiovascular disease and diabetes. Two-sample Mendelian randomization (MR) analyses were performed using available statistics from a European genome-wide association study (GWAS) of LADA (2634 cases and 5947 controls) and GWAS meta-analyses of type 1 diabetes (9266 cases and 15574 controls) and of type 2 diabetes (80,154 cases and 853,816 controls).

Mean age of inclusion was 59.1 (SD 12.4) years in LADA, 63.3 (SD 10.4) years in type 2 diabetes subjects, and 59.0 (SD 13.8) years in controls. Those with LADA had lower HOMA-IR and HOMA-B and were more likely to be treated with insulin compared to type 2 diabetes subjects. Significant findings of the study are as follows:

  • A reduced risk of LADA was observed in relation to vitamin C (OR for high vs. low intake: 0.66, 95% CI 0.49, 0.88).
  • Inverse associations between vitamin C and E were noted with LADAhigh ORs for LADAhigh were estimated at 0.51 (95% CI 0.35, 0.76) for high vs. low intake and at 0.84 (95% CI 0.73, 0.98) per 1 SD increase in vitamin C. Estimates for vitamin E were 0.66 (95% CI 0.45, 0.97) and 0.80 (95% CI 0.69, 0.94), respectively.
  • A positive association was noted between the intake of vitamin E and HOMA-B in LADA (β100, 95% CI 0.021, 0.179) and type 2 diabetes (β 0.027, 95% CI 0.000, 0.054), corresponding to a 10% increase in HOMA-B in LADA and 3% in type 2 diabetes per 1 SD higher vitamin E intake.
  • MR analyses show that genetically predicted circulating beta-carotene, vitamin C, and vitamin E were not significantly associated with the risk of LADA, type 1, or type 2 diabetes.

Results of the study show that subjects with higher intake of vitamin C and vitamin E were associated with a reduced risk of LADAhigh. Further research should continue to explore the effects of high antioxidant intake on LADA. Study limitations include the self-reported dietary intake and the retrospective study design.

Source: Lampousi, Anna-Maria, Josefin E. Löfvenborg, Emma Ahlqvist, Tiinamaija Tuomi, Alicja Wolk, and Sofia Carlsson. “Antioxidant Nutrients and Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes: A Swedish Case-Control Study and Mendelian Randomization Analysis.” Nutrients 15, no. 11 (2023): 2546.

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Posted October 5, 2023.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

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