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

Anumesh K Pathak; Vandana Tiwari; Manish Raj Kulshrestha; Shivani Singh; Shefali Singh; Vikram Singh

doi:10.1007/s40200-023-01193-6

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

J Diabetes Metab Disord. 2023 Feb 8;22(1):703-712. doi: 10.1007/s40200-023-01193-6. eCollection 2023 Jun.

Authors

Anumesh K Pathak¹, Vandana Tiwari¹, Manish Raj Kulshrestha¹, Shivani Singh¹, Shefali Singh¹, Vikram Singh²

Affiliations

¹ Department of Biochemistry, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, 226010 India.
² Department of General Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India.

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.

Keywords: Fetuin-A; Insulin resistance; Non-obese diabetes; Obesity; Obesity-related type 2 diabetes mellitus.

© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.