Impact of fluorosis on molecular predictors in pathogenesis of type 2 diabetes associated microvascular complications.

Diabetes is a non-communicable chronic metabolic disorder developed when the body either cannot utilize insulin efficiently or the pancreas does not produce enough of it [1]. It is characterized by the disruption of vital metabolic processes that are involved in the regulation of glucose metabolism and the storage of carbohydrates and lipids [2]. Diabetes prevalence has been progressively rising over the last few decades. According to the International Diabetes Federation (IDF), over 500 million people are affected by diabetes globally, and this figure is expected to rise by 30% by 2045 [3]. In India, the prevalence of diabetes and pre-diabetes has also seen a significant increase. As per the IDF, 77 million Indians were anticipated to have diabetes in 2019, with an approximate incidence of 8.9% among adolescents [4]. Approximately 1.3 billion people worldwide suffer from diabetes, leading to detrimental effects on health outcomes such as health-related quality of life and medication adherence, etc [5], [6], [7]. According to the literature review, neuropathy (3–65%), nephropathy (1–63%), and retinopathy (2–33%) were reported among the diabetic population [8]. Several factors contribute to diabetes, including environmental influences, sedentary lifestyles, and hereditary factors. One often overlooked environmental toxin implicated in diabetes and its complications is fluoride.

Fluoride, an often overlooked environmental toxin, has been implicated in the occurrence of diabetes and related complications [9]. It forms when water is more exposed to minerals and salts from underlying rocks due to a lack of rainfall [10]. It forms when water is exposed to minerals and salts from underlying rocks, particularly in areas with low rainfall. Around 180 million people are potentially impacted worldwide, with most residing in Asia (51–59%) and Africa (37–46%) [11]. Studies have shown that persistent exposure to excessive fluoride, more than 0.07–0.4 mg/kg/day, impairs glucose tolerance and acts as a precursor to type 2 diabetes (T2D) [12].

Fluoride exposure has been shown to disrupt glucose metabolism and insulin signalling pathways, thereby exacerbating insulin resistance, a hallmark feature of type 2 diabetes. This disruption contributes to the dysregulation of key molecular players involved in microvascular complications, such as advanced glycation end products (AGEs), oxidative stress pathways, and inflammatory mediators [13]. It has a severe effect on glomerular filtration, involves mitochondrial dysfunction, and exacerbates oxidative stress. All of these alterations play a crucial role in making the complications severe among the population suffering from the condition.

This article aims to elucidate the mechanistic pathways connecting diabetes, fluoride exposure, and related complications, as well as to identify new and sensitive biomarkers for early diagnosis. Biomarkers are invaluable for indicating the course of the disease, forecasting treatment outcomes, and assisting in precise diagnosis. Integrating multiple biomarkers may enhance the sensitivity and specificity of prediabetes detection, enabling more accurate risk assessments, personalized treatment plans, and improved outcomes for individuals with or at risk of developing diabetes.