Two young women, were reffered to our hospital on two different occasions with history of breathlessness and mental confusion, following consumption of two different bio-organic plant nutrient compounds with a suicidal intent. On examination, they had cyanotic mucous membranes, and their blood samples showed the classic ‘dark chocolate brown’ appearance. Work up revealed cyanosis unresponsive to oxygen supplementation and absence of cardiopulmonary abnormality. Pulse oximetry revealed saturation of 75% in case 1 and 80% in case 2, on 8 liters oxygen supplementation via face masks, although their arterial blood gas analysis was normal, suggestive of “saturation gap”. Methemoglobinemia was suspected based on these findings and was confirmed by Carbon monoxide-oximetry (CO-oximetry). Methylene blue was administered and the patients showed dramatic improvement. Both the patients developed evidence of hemolysis approximately 72 hours following admission which improved with blood transfusion and supportive treatment. The patients were eventually discharged without any neurological sequalae.

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BACKGROUND In addition to diet and nutrition, environmental changes may increase the incidence of diabetes mellitus and microvascular complication leading to ‘diabetic kidney disease (DKD)’. One such factor considered in this study is fluoride. Increased incidence of DKD lead to estimation of fluoride in fluoride endemic areas. Fluoride and advanced glycation end products lead to the development of microvascular complication in patients of diabetes leading to diabetic kidney disease or diabetic nephropathy which in turn leads to increase in expression of sirtuin 1; a regulatory protein mediating deacetylation of histone proteins which was analysed. METHODS Subjects recruited for this cross-sectional study were divided as - group 1 (healthy controls), group 2 (patients with type 2 diabetes) and group 3 (diabetic nephropathy patients) with 50 subjects in each group. Routine parameters were analysed in biochemistry section of central laboratory. RESULTS In patients with diabetic kidney disease, serum and urine fluoride levels were similar (0.2 and 0.28 ppm); whereas, in other two groups, urine fluoride values were more than the serum fluoride values indicating better renal function and fluoride clearance. Least sirtuin 1 median range was observed in group 1 [22.65 (11.78 - 91.10)] and 36.9 (27.38 - 56.23) in group 3 lesser than group 2 with a value of [42.7 (30.17 - 52.93)]. CONCLUSIONS Serum and urine fluoride estimation aids in assessing progression of disorder and hence helps in preventing complications. Fluoride may not be a cause of diabetes but may accelerate its microvascular complications as observed in this study. Sirtuin 1 levels in serum or plasma can be a marker for various damages caused by aging disorders. Sirtuin 1 correlation with diabetic parameters will help in health research to include it as a therapeutic target for various toxic conditions. KEY WORDS Advanced Glycation End product, Fluoride, Diabetic Kidney Disease, Sirtuin 1, Type 2 Diabetes Mellitus

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