SGLT1 inhibition boon or bane for diabetes‐associated cardiomyopathy

Abstract

Chronic hyperglycaemia is a peculiar feature of diabetes mellitus (DM). Sequential metabolic abnormalities accompanying glucotoxicity are some of its implications. Glucotoxicity most likely corresponds to the vascular intricacy and metabolic alterations, such as increased oxidation of free fatty acids and reduced glucose oxidation. More than half of those with diabetes also develop cardiac abnormalities due to unknown causes, posing a major threat to the currently available marketed preparations which are being used for treating these cardiac complications. Even though impairment in cardiac functioning is the principal cause of death in individuals with type 2 diabetes (T2D), reducing plasma glucose levels has little effect on cardiovascular disease (CVD) risk. In vitro and in vivo studies have demonstrated that inhibitors of sodium glucose transporter (SGLT) represent a putative therapeutic intervention for these pathological conditions. Several clinical trials have reported the efficacy of SGLT inhibitors as a novel and potent antidiabetic agent which along with its antihyperglycaemic activity possesses the potential of effectively treating its associated cardiac abnormalities. Thus, hereby, the present review highlights the role of SGLT inhibitors as a successful drug candidate for correcting the shifts in deregulation of cardiac energy substrate metabolism together with its role in treating diabetes‐related cardiac perturbations.

Plasma gonadotropin levels in metformin‐treated men with prediabetes: a non‐randomized, uncontrolled pilot study

“…Prediabetes is an intermediate state of hyperglycemia with glycemic parameters above normal but below the diabetes threshold, reflecting the presence of either, or both, impaired fasting glucose and impaired glucose tolerance [23,24]. Prediabetes, the prevalence of which is increasing rapidly throughout the world, is the major risk factor for the future development of type 2 diabetes and is associated with increased risk for adverse cardiovascular outcomes and death [23–25]. Therefore, the aim of the present study was to compare plasma levels of FSH and LH and other hormones in metformin‐treated prediabetic men with elevated gonadotropin levels and gonadotropin levels within the reference range.…”

Germinated and non-germinated cooked whole millet (Pennisetum glaucum (L.) R. Br.) flours show a promising effect on protein quality, biochemical profile and intestinal health in vivo

“…Although millet consumption was not able to increase the expression of this transporter in our study, recent research indicates that SGLT1 inhibition could be a therapeutic strategy for the management of diabetes, which can be associated with cardiomyopathy. In animal models with type 2 diabetes mellitus 29,[70][71][72] and clinical studies, 73,74 increased SGLT1 intestinal expression is observed in the small intestinal epithelium, which enhances the postprandial hyperglycaemia and its cardiovascular complications. Other studies with caco-2 cells indicate that the phytochemicals, such as polyphenols and tannins, have the capacity to suppress glucose uptake in intestinal cells, by the inhibition of SGLT1.…”

Sodium‐glucose cotransporter 2 inhibitors: A comprehensive review from cells to bedside

“…53 Contrary to the SGLT1 gene, the SGLT2 gene is not expressed in human myocardial tissue in either normal or pathological conditions, and its expression is mainly restricted to the renal tissues. 54,55 Some of these mechanisms are through alteration in glucose and insulin metabolism. It has been hypothesized that SGLT2is may increase ketone body production by the liver.…”

“…Different underlying mechanisms for this cardioprotective effect have been suggested 53 . Contrary to the SGLT1 gene, the SGLT2 gene is not expressed in human myocardial tissue in either normal or pathological conditions, and its expression is mainly restricted to the renal tissues 54,55 . Some of these mechanisms are through alteration in glucose and insulin metabolism.…”