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Impact of essential metals on insulin sensitivity and fetuin in obesity-related type 2 diabetes pathogenesis

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Abstract

Purpose

Essential metals may be crucial in obesity and type 2 diabetes (T2DM); diabesity pathogenesis and consequences. This study aimed to determine the metal levels in obese and non-obese patients with and without T2DM and their relationships with fetuin-A(Fet-A) levels, insulin sensitivity, and insulin resistance.

Methods

A total of 314 participants were enrolled, with 160 newly diagnosed T2DM patients and 154 non-T2DM subjects categorized into diabetic obese (n = 57), diabetic non-obese (n = 103), non-diabetic obese (n = 48), and non-diabetic non-obese (n = 106) subgroups. Fet-A, insulin sensitivity (QUCKI)/resistance (HOMA-IR), fasting glucose, and body mass index (BMI) were assessed. The essential metals were measured using inductively coupled plasma mass spectroscopy (ICP-MS).

Results

Fet-A levels were 3-fold higher (1391.4 ± 839.8 ng/ml) in T2DM patients than in non-T2DM (2165.6 ± 651.9 vs. 424.3 ± 219.1 ng/ml, p < 0.0001). Fet-A levels were 2.3-fold higher in the diabetic obese group than in the diabetic non-obese group (p < 0.0001). Fet-A levels were 2.0-fold higher in the diabetic non-obese group than in the non-diabetic obese group (p < 0.0001). Fet-A levels were positively correlated with insulin resistance (HOMA-IR) (r = 0.34, p < 0.0001) and negatively correlated with insulin sensitivity (QUIKI) (r = −0.41, p < 0.0001).

Cu, Se, Zn, and Fe levels were significantly lower in diabetic patients than in non-diabetic patients (p < 0.05). Se and Zn were significantly correlated with Fet-A (r = −0.41, p = 0.049 and r = −0.42, p = 0.001, respectively). Se and Zn were also correlated with insulin resistance (HOMA-IR) (r = −0.45, p = 0.049 and r = −0.36, p = 0.012, respectively) and insulin sensitivity (QUIKI) (r = 0.49, p = 0.042 and r = 0.30, p = 0.003, respectively). Similarly, Fe was negatively correlated with insulin levels (r = −0.33, p = 0.04) and insulin sensitivity (r = −0.34, p = 0.30). However, Mn was significantly correlated with Fet-A (r = 0.37, p = 0.001) and insulin resistance/sensitivity (r = 0.24, p = 0.026 and r = −0.24, p = 0.041) respectively in the diabetic obese group. Mg was an independent predictor of diabesity.

Conclusions

Mg play a significant role in obesity-related T2DM pathogenesis and complications via Fet-A, insulin sensitivity, and resistance modifications.

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Funding

The authors acknowledge an Intramural Research Grant (IEC-24/18) to Dr. Vandana Tiwari from Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, for their financial support.

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Authors and Affiliations

  1. Department of Biochemistry, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, 226010, India

    Anumesh K. Pathak, Vandana Tiwari, Manish Raj Kulshrestha, Shivani Singh & Shefali Singh

  2. Department of General Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India

    Vikram Singh

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Contributions

Anumesh Pathak- Manuscript drafting and writing, data analysis, tables and graphs preparation.

Vandana Tiwari: conceptualization, funding acquisition, execution of the experiment, validation of data, and draft editing.

Manish Raj Kulshrestha- Manuscript preparation and editing.

Shivani Singh- Sample collection & data collection, help in tables preparation.

Shefali Singh- Sample collection & enrolled patients.

Vikram Singh- Clinical history & patient details.

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Correspondence to Vandana Tiwari.

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Pathak, A.K., Tiwari, V., Kulshrestha, M.R. et al. Impact of essential metals on insulin sensitivity and fetuin in obesity-related type 2 diabetes pathogenesis. J Diabetes Metab Disord 22, 703–712 (2023). https://doi.org/10.1007/s40200-023-01193-6

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