Victor Mondal1, Zubaer Hosen2, Faruk Hossen1, Abu Eabrahim Siddique1, Selim Reza Tony1, Zohurul Islam1, Md Shofikul Islam2, Shakhawoat Hossain1, Khairul Islam3, Md Khalequzzaman Sarker4, M M Hasibuzzaman5, Ling-Zhi Liu6, Bing-Hua Jiang6, Md Mominul Hoque1, Zahangir Alam Saud1, Lian Xin7, Seiichiro Himeno8, Khaled Hossain9. 1. Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi 6205, Bangladesh. 2. Department of Applied Nutrition and Food Technology, Islamic University, Kushtia 7003, Bangladesh. 3. Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science & Technology University, Tangail 1902, Bangladesh. 4. Department of Gastroenterology, Rajshahi Medical College, Rajshahi 6000, Bangladesh. 5. Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, United States. 6. Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States. 7. Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan. 8. Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan; Division of Health Chemistry, School of Pharmacy, Showa University, Tokyo 142- 8555, Japan. 9. Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi 6205, Bangladesh. Electronic address: khossain@ru.ac.bd.
Abstract
BACKGROUND: Alargebodyof evidence has shown a link between arsenic exposure and diabetes, but the underlying mechanisms have not yet been clarified. OBJECTIVE: We explored the association between arsenic exposure and the reduction of skeletal muscle mass as a potential mechanism of insulin resistance for developing arsenic-related hyperglycemia. METHODS: A total of 581 subjects were recruited from arsenic-endemic and non-endemic areas in Bangladesh and their fasting blood glucose (FBG), serum insulin, and serum creatinine levels were determined. Subjects' arsenic exposure levels were assessed by arsenic concentrations in water, hair, and nails. HOMA-IR and HOMA-β were used to calculate insulin resistance and β-cell dysfunction, respectively. Serum creatinine levels and lean body mass (LBM) were used as muscle mass indicators. RESULTS: Water, hair and nail arsenic concentrations showed significant positive associations with FBG, serum insulin and HOMA-IR and inverse associations with serum creatinine and LBM in a dose-dependent manner both in males and females. Water, hair and nail arsenic showed significant inverse associations with HOMA-β in females but not in males. FBG and HOMA-IR were increased with the decreasing levels of serum creatinine and LBM. Odds ratios (ORs)of hyperglycemia were significantly increased with the increasing concentrations of arsenic in water, hair and nails and with the decreasing levels of serum creatinine and LBM. Females' HOMA-IR showed greater susceptibility to the reduction of serum creatinine and LBM, possibly causing the greater risk of hyperglycemia in females than males. Path analysis revealed the mediating effect of serum creatinine level on the relationship of arsenic exposure with HOMA-IR and hyperglycemia. CONCLUSION: Arsenic exposure elevates FBG levels and the risk of hyperglycemia through increasing insulin resistance with greater susceptibility in females than males. Additionally, arsenic exposure-related reduction of skeletal muscle mass may be a mechanism underlying the development of insulin resistance and hyperglycemia.
BACKGROUND: Alargebodyof evidence has shown a link between arsenic exposure and diabetes, but the underlying mechanisms have not yet been clarified. OBJECTIVE: We explored the association between arsenic exposure and the reduction of skeletal muscle mass as a potential mechanism of insulin resistance for developing arsenic-related hyperglycemia. METHODS: A total of 581 subjects were recruited from arsenic-endemic and non-endemic areas in Bangladesh and their fasting blood glucose (FBG), serum insulin, and serum creatinine levels were determined. Subjects' arsenic exposure levels were assessed by arsenic concentrations in water, hair, and nails. HOMA-IR and HOMA-β were used to calculate insulin resistance and β-cell dysfunction, respectively. Serum creatinine levels and lean body mass (LBM) were used as muscle mass indicators. RESULTS:Water, hair and nail arsenic concentrations showed significant positive associations with FBG, serum insulin and HOMA-IR and inverse associations with serum creatinine and LBM in a dose-dependent manner both in males and females. Water, hair and nail arsenic showed significant inverse associations with HOMA-β in females but not in males. FBG and HOMA-IR were increased with the decreasing levels of serum creatinine and LBM. Odds ratios (ORs)of hyperglycemia were significantly increased with the increasing concentrations of arsenic in water, hair and nails and with the decreasing levels of serum creatinine and LBM. Females' HOMA-IR showed greater susceptibility to the reduction of serum creatinine and LBM, possibly causing the greater risk of hyperglycemia in females than males. Path analysis revealed the mediating effect of serum creatinine level on the relationship of arsenic exposure with HOMA-IR and hyperglycemia. CONCLUSION:Arsenic exposure elevates FBG levels and the risk of hyperglycemia through increasing insulin resistance with greater susceptibility in females than males. Additionally, arsenic exposure-related reduction of skeletal muscle mass may be a mechanism underlying the development of insulin resistance and hyperglycemia.
Authors: Abby F Fleisch; Sudipta Kumer Mukherjee; Subrata K Biswas; John F Obrycki; Sheikh Muhammad Ekramullah; D M Arman; Joynul Islam; David C Christiani; Maitreyi Mazumdar Journal: Environ Health Date: 2022-01-14 Impact factor: 5.984