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      Thiamine deficiency in diabetes, obesity and bariatric surgery: Recipes for diabetic ketoacidosis

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          A BSTRACT

          Diabetic ketoacidosis (DKA) is a life-threatening condition affecting individuals with diabetes characterised by hyperglycaemia, metabolic acidosis and ketonemia. The incidence and financial burden of DKA is still high. Thiamine deficiency is well documented in patients with DKA and could be associated with cardiac dysfunction in those patients. Thiamine deficiency leads to cardiac dysfunction, neuronal death and worsens the prognosis of DKA. There is an existing metabolic relationship between thiamine deficiency in diabetes, obesity and bariatric surgery. Careful monitoring of thiamine, along with other vitamins, is essential for diabetic patients, obese individuals and postbariatric surgery. Further research and clinical studies are urgently needed to assess the following: (1) Whether diabetes, obesity and bariatric surgery make individuals more prone to have DKA related to thiamine deficiency and (2) Whether supplementation of thiamine can protect diabetic patients, obese subjects and individuals undergoing bariatric surgery from DKA. This review summarises the biochemistry of thiamine and the existing metabolic relationships between thiamine deficiency in DKA, diabetes, obesity and bariatric surgery. Primary and family physicians have an important role in ensuring adequate replacement of thiamine in individuals with diabetes, obesity and bariatric surgery.

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          The return of metabolism: biochemistry and physiology of the pentose phosphate pathway

          The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares reactions with the Entner–Doudoroff pathway and Calvin cycle and divides into an oxidative and non-oxidative branch. The oxidative branch is highly active in most eukaryotes and converts glucose 6-phosphate into carbon dioxide, ribulose 5-phosphate and NADPH. The latter function is critical to maintain redox balance under stress situations, when cells proliferate rapidly, in ageing, and for the ‘Warburg effect’ of cancer cells. The non-oxidative branch instead is virtually ubiquitous, and metabolizes the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate as well as sedoheptulose sugars, yielding ribose 5-phosphate for the synthesis of nucleic acids and sugar phosphate precursors for the synthesis of amino acids. Whereas the oxidative PPP is considered unidirectional, the non-oxidative branch can supply glycolysis with intermediates derived from ribose 5-phosphate and vice versa, depending on the biochemical demand. These functions require dynamic regulation of the PPP pathway that is achieved through hierarchical interactions between transcriptome, proteome and metabolome. Consequently, the biochemistry and regulation of this pathway, while still unresolved in many cases, are archetypal for the dynamics of the metabolic network of the cell. In this comprehensive article we review seminal work that led to the discovery and description of the pathway that date back now for 80 years, and address recent results about genetic and metabolic mechanisms that regulate its activity. These biochemical principles are discussed in the context of PPP deficiencies causing metabolic disease and the role of this pathway in biotechnology, bacterial and parasite infections, neurons, stem cell potency and cancer metabolism.
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            Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy.

            Three of the major biochemical pathways implicated in the pathogenesis of hyperglycemia induced vascular damage (the hexosamine pathway, the advanced glycation end product (AGE) formation pathway and the diacylglycerol (DAG)-protein kinase C (PKC) pathway) are activated by increased availability of the glycolytic metabolites glyceraldehyde-3-phosphate and fructose-6-phosphate. We have discovered that the lipid-soluble thiamine derivative benfotiamine can inhibit these three pathways, as well as hyperglycemia-associated NF-kappaB activation, by activating the pentose phosphate pathway enzyme transketolase, which converts glyceraldehyde-3-phosphate and fructose-6-phosphate into pentose-5-phosphates and other sugars. In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy. The ability of benfotiamine to inhibit three major pathways simultaneously might be clinically useful in preventing the development and progression of diabetic complications.
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              Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association.

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                Author and article information

                Journal
                J Family Med Prim Care
                J Family Med Prim Care
                JFMPC
                J Family Med Prim Care
                Journal of Family Medicine and Primary Care
                Wolters Kluwer - Medknow (India )
                2249-4863
                2278-7135
                May 2024
                24 May 2024
                : 13
                : 5
                : 1620-1627
                Affiliations
                [1 ] Department of Medicine, Mater Hospital, Brisbane, Australia
                [2 ] The Medical School, University of Buckingham, Buckingham, Buckinghamshire, UK
                [3 ] College of Medicine, Ajman University, Ajman, United Arab Emirates
                [4 ] Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
                [5 ] Faculty of Medicine, Alexandria University, Alexandria, Egypt
                [6 ] Department of Medicine and HIV Metabolic Clinic, Milton Keynes University Hospital NHS Foundation Trust, Eaglestone, Milton Keynes, Buckinghamshire, UK
                [7 ] Department of Geriatric Medicine, Milton Keynes University Hospital NHS Foundation Trust, Eaglestone, Milton Keynes, Buckinghamshire, UK
                [8 ] Honorary Senior Lecturer of the Faculty of Medicine and Health Sciences, University of Buckingham, UK
                Author notes
                Address for correspondence: Dr. Mohamed H Ahmed, Department of Medicine and HIV Metabolic Clinic, Milton Keynes University Hospital NHS Foundation Trust, Eaglestone, Milton Keynes, Buckinghamshire, UK. E-mail: Mohamed.Hassan-Ahmed@ 123456mkuh.nhs.uk
                Article
                JFMPC-13-1620
                10.4103/jfmpc.jfmpc_1413_23
                11213416
                49301fc8-7b79-4456-b51a-21307c430bca
                Copyright: © 2024 Journal of Family Medicine and Primary Care

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 26 August 2023
                : 23 September 2023
                : 10 November 2023
                Categories
                Review Article

                bariatric surgery,diabetes,diabetic ketoacidosis,obesity,thiamine deficiency

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