Thiamin Status and Supplementation in the Management of Diabetes Mellitus and its Vascular Comorbidities

Abstract

The water soluble B vitamin, thiamin, in its coenzyme form as thiamin pyrophosphate (TPP), is necessary for key reactions in glucose metabolism. For this reason, associations between thiamin status or thiamin supplementation and diabetes have been the focus of recent research. Currently, it is not clear how occurrence of diabetes relates to parameters of thiamin status, such as plasma thiamin levels. However, there is strong evidence that the diabetic state increases urinary thiamin excretion and decreases the activity of transketolase (TK), a TPP-dependent enzyme of the hexose monophosphate (HMP) shunt in various body tissues. Impairment of TK activity and subsequent downregulation of the HMP shunt activates several pathways that contribute to vascular damage and development of diabetes-related comorbidities such as retinopathy, cardiomyopathy, and nephropathy. Thiamin supplementation has been shown to be effective in restoring TK activity in animal models of diabetes, and in type 1 and type 2 diabetic individuals. Thiamin supplementation has also been shown to be effective in preventing or reversing, either partially or completely, hyperglycemia-induced damage to vascular endothelial cells, and microalbuminuria associated with diabetic nephropathy. Here, we review from current literature examining the relationship between diabetes and thiamin status as well as intervention trials evaluating the effect of thiamin supplementation on glycemic control and prevention of vascular comorbidities of diabetes.

Benfotiamine and Type 2 Diabetes Mellitus

“…The TD in clinical DM may increase the fragility of vascular cells to the adverse effects of hyperglycemia and there by the increase of the risk of developing microvascular complications. A suppression of TKT activity, and subsequent down-regulation of the hexose monophosphate (HMP) shunt, resulting in accumulation of glyceraldehyde 3-phosphate (GA3P), fructose 6-phosphate (F6-P), and dihydroxyacetone phosphate may be at least one mechanism in the development of DM-induced vascular damage and other comorbidities [5,[8][9][10].…”

“…Restoring TKT activity via BFT or thiamin supplementation can increase the flux of glucose into HMP shunt, and also increase flux of GA3P and F6P into HMP shunt and away from hyperglycemiainduced pathways that lead to vascular damage [9].…”

“…Treatment with BFT has been shown to reduce activation of the polyol pathway of glucose metabolism and to increase TKT expression in the presence of hyperglycemia [5,15]. Activation of AGE receptors in DM, found on cardiomyocytes, pericytes, and podocytes, stimulates postreceptor signaling, intracellular reactive oxygen species formation, and altered gene expression, leading to vascular damage [9,17].…”

“…The results of our study revealed that the appointment of BFT to patients with T2DM and advances stage of CAN were accompanied by a decrease of the thromboxane B2 (TxB2) concentration and TxB2/6-keto-prostaglandin F1α ratio, which may contribute to the improvement of the functional state of the prostacyclin I2-TxA2 system [3]. Benfotiamine supplementation for 14 wks (100 mg/kg/d) to streptozotocin-induced diabetic mice completely corrected hyperglycemia-induced disruptions in Ca 2+ homeostasis and mechanical functioning of cardiomyocytes [9]. Cardiac OS is involved in heart failure that is induced by thiamine deprivation in rats.…”

Диабетическая Кардиальная Автономная Нейропатия: Каковы Перспективы В Лечении?

“…Применение комбинации тиамина и -ЛК имеет большое значение в лечении диабетиче-ской ангионейропатии. В частности, показано, что назначение бенфотиамина и -ЛК пациентам с СДТ1 сопровождалось нормализацией гипергликемии и при назначении в течение 4 недель способствовало норма-лизации активности простациклинсинтазы, подавлен-ной при сахарном диабете; увеличением активности ТК в моноцитах в 2-3 раза [76][77][78][79][80].…”