© 2020 PFPC
"Diabetes has emerged as a major comorbidity in a large proportion of patients infected with COVID-19."
(Goyal et al., 2020)
Goyal A, Gupta S, Gupta Y, Tandon N - "Proposed guidelines for screening of hyperglycemia in patients hospitalized with COVID-19 in low resource settings" Diabetes Metab Syndr 14(5):753-756 (2020) doi: 10.1016/j.dsx.2020.05.039. Epub ahead of print. PMID: 32502958
Insulin resistance is the driving factor that leads to type 2 diabetes, gestational diabetes and prediabetes. Numerous studies in the last 10 years have documented an increase in insulin resistance, even at low fluoride intake (Lupo et a., 2011; Szczuko et al., 2019).
On the other hand, patients with diabetes are at higher risk of fluorosis (Wang et al., 2017; Seow & Thomsett, 1994; Klein, 1975; Greenberg et al., 1974).
"In the community-based analysis, there were significant associations found between higher concentrations of arsenic (β=0.268, P=0.013) and fluoride (β=0.202, P=0.005) in drinking water and higher incidence of type 1 diabetes."
(Chafe et al., 2018)
Chafe R, Aslanov R, Sarkar A, Gregory P, Comeau A, Newhook LA - "Association of type 1 diabetes and concentrations of drinking water components in Newfoundland and Labrador, Canada" BMJ Open Diabetes Res Care 6(1):e000466 (2018) doi: 10.1136/bmjdrc-2017-000466. PMID: 29527309; PMCID: PMC5841498.
Lupo M, Buzalaf MA, Rigalli A - "Effect of fluoridated water on plasma insulin levels and glucose homeostasis in rats with renal deficiency" Biol Trace Elem Res 140(2):198-207 (2011) doi: 10.1007/s12011-010-8690-5. Epub 2010 Apr 20. PMID: 20405337
Wang SC, Tao XB, Wang FF, Zhang N - "[Clinical observation of 5 cases of diabetes insipidus complicated with skeletal fluorosis]" Zhongguo Gu Shang 30(7):651-655 (2017) Chinese. doi: 10.3969/j.issn.1003-0034.2017.07.014. PMID: 29424157
"In this study of six affected members from two families with hereditary diabetes insipidus, it was found that two children who drank water fluoridated at optimum levels developed moderate to severe fluorosis."
Seow WK, Thomsett MJ - "Dental fluorosis as a complication of hereditary diabetes insipidus: studies of six affected patients" Pediatr Dent 16(2):128-32 (1994) PMID: 8015954
(Seow & Thomsett, 1994)
"Urinary fluoride excretion was decreased in diabetic mice exposed to fluoride. Subchronic fluoride exposure of mice with STZ-induced diabetes aggravated testicular damage and the spermatozoa function."
(Sánchez-Gutiérre et al., 2019)
Sánchez-Gutiérrez M, Martínez-Loredo E, Madrigal-Santillán EO, Betanzos-Cabrera G, Hernández-Zavala A, Mojica-Villegas MA, Izquierdo-Vega JA - "Exposure of Fluoride with Streptozotocin-Induced Diabetes Aggravates Testicular Damage and Spermatozoa Parameters in Mice" J Toxicol 2019:5269380 (2019) doi: 10.1155/2019/5269380. PMID: 31885555; PMCID: PMC6915027
"Drinking of large amounts of water, even with lower than accepted fluoride content, can produce fluorosis of the teeth. A mother and her four children affected by this disorder presented different degrees of fluorosis directly related to the stage at which hormonal therapy was introduced."
Klein H - "Dental fluorosis associated with hereditary diabetes insipidus" Oral Surg Oral Med Oral Pathol 40(6):736-41 (1975) doi: 10.1016/0030-4220(75)90441-7. PMID: 1060029
Greenberg LW, Nelsen CE, Kramer N - "Nephrogenic diabetes insipidus with fluorosis" Pediatrics 54(3):320-2 (1974) PMID: 4414789
https://pediatrics.aappublications.org/ ... -e-letters
M3 muscarinic receptors are essential for maintaining proper insulin secretion and glucose homeostasis (Gautam et al. 2007). M3 is coupled to Gq/11 (Budd et al., 2001).
Budd DC, Willars GB, McDonald JE, Tobin AB- "Phosphorylation of the Gq/11-coupled m3-muscarinic receptor is involved in receptor activation of the ERK-1/2 mitogen-activated protein kinase pathway" J Biol Chem 276(7):4581-7 (2001) doi: 10.1074/jbc.M008827200. Epub 2000 Nov 16. PMID: 11083874.
http://www.jbc.org/cgi/pmidlookup?view= ... d=11083874
Gautam D, Han SJ, Duttaroy A, Mears D, Hamdan FF, Li JH, Cui Y, Jeon J, Wess J - "Role of the M3 muscarinic acetylcholine receptor in beta-cell function and glucose homeostasis" Diabetes Obes Metab 9 Suppl 2:158-69 (2007) doi: 10.1111/j.1463-1326.2007.00781.x. PMID: 17919190
Harada T, Horinouchi T, Higa T, Hoshi A, Higashi T, Terada K, Mai Y, Nepal P, Horiguchi M, Hatate C, Miwa S - "Endothelin-1 activates extracellular signal-regulated kinases 1/2 via transactivation of platelet-derived growth factor receptor in rat L6 myoblasts" Life Sci 104(1-2):24-31 (2014). doi: 10.1016/j.lfs.2014.04.002. Epub 2014 Apr 13. PMID: 24735959
"Measurements of the levels of alpha-subunits of G proteins revealed that the expression of Gq/11 alpha, Gs alpha, and Gi-3 alpha was increased by 30 to 50%. These results indicate that during the course of experimental diabetes, peripheral nerves exhibit an abnormal production of inositol phosphates and cAMP, together with an abnormal expression and/or function of G proteins."
(Goraya et al., 1995)
Goraya TY, Wilkins P, Douglas JG, Zhou J, Berti-Mattera LN - "Signal transduction alterations in peripheral nerves from streptozotocin-induced diabetic rats" J Neurosci Res 41(4):518-25 (1995) doi: 10.1002/jnr.490410411. PMID: 7473883
(Souza et al., 2016)"Serum TSH was positively correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) index, triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)."
Souza LL, Guedes EP, Teixeira PF, Moreira RO, Godoy-Matos AF, Vaisman M -”Serum TSH levels are associated with cardiovascular risk factors in overweight and obese adolescents” J Pediatr (Rio J) 92(5):532-8 (2016)
"Gestational hypothyroidism induces long-term alterations in endocrine pancreas function, which may have implications for type 2 diabetes prevention in affected individuals."
(Kemkem et al., 2020)
Kemkem Y, Nasteska D, de Bray A, Bargi-Souza P, Peliciari-Garcia RA, Guillou A, Mollard P, Hodson DJ, Schaeffer M - "Maternal hypothyroidism in mice influences glucose metabolism in adult offspring" Diabetologia (2020) doi: 10.1007/s00125-020-05172-x. Epub ahead of print. PMID: 32472193
Fluoride, TSH and insulin esistance
Szczuko M, Splinter J, Zapałowska-Chwyć M, Ziętek M, Maciejewska D - "Fluorine may intensify the mechanisms of polycystic ovary syndrome (PCOS) development via increased insulin resistance and disturbed thyroid-stimulating hormone (TSH) synthesis even at reference levels" Med Hypotheses 128:58-63 (2019)