Growing prevalence of diabetes (type 2 as well as type 1) and its related morbidity due to vascular complications creates a large burden on medical care worldwide. Understanding the molecular pathogenesis of chronic micro-, macro-and avascular complications mediated by hyperglycemia is of crucial importance since novel therapeutic targets can be identified and tested. Thiamine (vitamin B1) is an essential cofactor of several enzymes involved in carbohydrate metabolism and published data suggest that thiamine metabolism in diabetes is deficient. This review aims to point out the physiological role of thiamine in metabolism of glucose and amino acids, to present overview of thiamine metabolism and to describe the consequences of thiamine deficiency (either clinically manifest or latent). Furthermore, we want to explain why thiamine demands are increased in diabetes and to summarise data indicating thiamine mishandling in diabetics (by review of the studies mapping the prevalence and the degree of thiamine deficiency in diabetics). Finally, we would like to summarise the evidence for the beneficial effect of thiamine supplementation in progression of hyperglycemia-related pathology and, therefore, to justify its importance in determining the harmful impact of hyperglycemia in diabetes. Based on the data presented it could be concluded that although experimental studies mostly resulted in beneficial effects, clinical studies of appropriate size and duration focusing on the effect of thiamine supplementation/therapy on hard endpoints are missing at present. Moreover, it is not currently clear which mechanisms contribute to the deficient action of thiamine in diabetes most. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given. Key words: Diabetes; Thiamine; Vitamin B1; Transketolase; Benfotiamine; Hyperglycemia; Nephropathy; Metabolic syndrome; Cardiovascular disease; Chronic kidney disease Core tip: Published data suggest deficient action of thiamine in diabetes, however, it is not currently clear by which mechanisms. Plasma levels might be decreased in diabetics (although renal function has a prevailing effect), nevertheless, intracellular concentration of thiamine diphosphate is the crucial parameter and there is not a direct relationship with the plasma thiamine since the rate of transmembrane transport (via thiamine transporters) and intracellular activation by thiamine pyrophosphokinase might affected by hyperglycemia at first place. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given.
Of many vitamin D extraskeletal functions, its modulatory role in insulin secretion and action is especially relevant for gestational diabetes mellitus (GDM). The aims of the present study were to determine midgestational and early postpartum vitamin D status in pregnant women with and without GDM and to describe the relationship between midgestational and postpartum vitamin D status and parallel changes of glucose tolerance. A total of 76 pregnant women (47 GDM and 29 healthy controls) were included in the study. Plasma levels of 25(OH)D were measured using an enzyme immunoassay. Vitamin D was not significantly decreased in GDM compared to controls during pregnancy; however, both groups of pregnant women exhibited high prevalence of vitamin D deficiency. Prevalence of postpartum 25(OH)D deficiency in post-GDM women remained significantly higher and their postpartum 25(OH)D levels were significantly lower compared to non-GDM counterparts. Finally, based on the oGTT repeated early postpartum persistent glucose abnormality was ascertained in 15% of post-GDM women; however, neither midgestational nor postpartum 25(OH)D levels significantly differed between subjects with GDM history and persistent postpartum glucose intolerance and those with normal glucose tolerance after delivery.
The results support the role of 'functional' thiamine deficiency in the development of hyperglycaemia-related pathology. Limited intracellular availability of active TKT co-factor seems to be a dominant abnormality.
Aims/hypothesis In the present study we investigated potential associations of a set of 45 single nucleotide polymorphisms (SNP) in 20 candidate genes on eight chromosomes with diabetic nephropathy (DN) in type 2 diabetes mellitus. We aimed to compare two methodological approaches suitable for analysing susceptibility to complex traits: single-and multi-locus analyses. Materials and methods The study comprised a total of 647 subjects in one of three groups: diabetes with or without DN, or no diabetes. Genotypes were detected by PCRbased methodology (PCR only, PCR plus RFLP, or allelespecific PCR). Haplotypes were inferred in silico. Set association (tested using SUMSTAT software) was used for multilocus analysis.
Genetic variability in rate-limiting enzymes of pathways proposed to confer hypothetical protection against hyperglycemia might act as an important determinant of hyperglycemia toxicity in long-standing diabetes.
<b><i>Background:</i></b> Vitamin D is a hormone regulating not only calcium and phosphate homeostasis but also, at the same time, exerting many other extraskeletal functions via genomic effects (gene transcription) and probably by non-genomic effects as well. Availability is ensured by dietary intake of its precursors and by de novo production via sunlight. Yet, vitamin D deficiency and insufficiency are very common across the globe and are connected to many pathophysiological states, for example, diabetes mellitus, allergies, autoimmune diseases, pregnancy complications, and recently have also been associated with worse COVID-19 clinical outcomes. <b><i>Summary:</i></b> In this review, we summarize current knowledge about vitamin D metabolism in general, its role in diabetes mellitus (mainly type 2) and diabetic complications (mainly diabetic kidney disease), and potential therapeutic perspectives including vitamin D signalling as a druggable target. <b><i>Key Messages:</i></b> Vitamin D is not only a vitamin but also a hormone involved in many physiological processes. Its insufficiency or deficiency can lead to many pathological states.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.