Many recent studies have acknowledged postprandial hypetriglyceridemia as a distinct risk factor for cardiovascular disease. This dysmetabolic state is the result of the hepatic overproduction of ...very low-density lipoproteins (VLDLs) and intestinal secretion of chylomicrons (CMs), which leads to highly atherogenic particles and endothelial inflammation. Postprandial lipid metabolism does not only depend on consumed fat but also on the other classes of nutrients that a meal contains. Various mechanisms through which carbohydrates exacerbate lipidemia have been identified, especially for fructose, which stimulates de novo lipogenesis. Glycemic index and glycemic load, despite their intrinsic limitations, have been used as markers of the postprandial glucose and insulin response, and their association with metabolic health and cardiovascular events has been extensively studied with contradictory results. This review aims to discuss the importance and pathogenesis of postprandial hypertriglyceridemia and its association with cardiovascular disease. Then, we describe the mechanisms through which carbohydrates influence lipidemia and, through a brief presentation of the available clinical studies on glycemic index/glycemic load, we discuss the association of these indices with atherogenic dyslipidemia and address possible concerns and implications for everyday practice.
Patients with diabetes usually exhibit diabetic dyslipidaemia.
The aim of the review is to present the quantitative and qualitative alterations of lipids and lipoproteins and the associated ...mechanisms in patients with diabetic dyslipidaemia.
The main quantitative changes observed in patients with diabetic dyslipidaemia are increased triglycerides and decreased high-density lipoprotein (HDL) cholesterol levels. Qualitative abnormalities mainly include increased small dense low-density lipoprotein (LDL) particles (despite similar serum LDL cholesterol levels as non-diabetic subjects) and alterations in the apolipoprotein content of HDL particles. Alterations in the activities of enzymes involved in lipoprotein metabolism, such as cholesteryl ester transfer protein, and the lipoprotein content of lipid particles, along with their glycation and oxidation, play a role in the pathogenesis of diabetic dyslipidaemia.
Diabetic dyslipidaemia is associated with quantitative and qualitative alterations of lipids and lipoproteins, which are associated with increased cardiovascular risk.
Abstract The focus of this review is on the role of apolipoprotein C-II (apoC-II) in lipoprotein metabolism and the potential effects on the risk of cardiovascular disease (CVD). We searched ...PubMed/Scopus for articles regarding apoC-II and its role in lipoprotein metabolism and the risk of CVD. Apolipoprotein C-II is a constituent of chylomicrons, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein (HDL). Apolipoprotein C-II contains 3 amphipathic α -helices. The lipid-binding domain of apoC-II is located in the N-terminal, whereas the C-terminal helix of apoC-II is responsible for the interaction with lipoprotein lipase (LPL). At intermediate concentrations (approximately 4 mg/dL) and in normolipidemic subjects, apoC-II activates LPL. In contrast, both an excess and a deficiency of apoC-II are associated with reduced LPL activity and hypertriglyceridemia. Furthermore, excess apoC-II has been associated with increased triglyceride-rich particles and alterations in HDL particle distribution, factors that may increase the risk of CVD. However, there is not enough current evidence to clarify whether increased apoC-II causes hypertriglyceridemia or is an epiphenomenon reflecting hypertriglyceridemia. A number of pharmaceutical interventions, including statins, fibrates, ezetimibe, nicotinic acid, and orlistat, have been shown to reduce the increased apoC-II concentrations. An excess of apoC-II is associated with increased triglyceride-rich particles and alterations in HDL particle distribution. However, prospective trials are needed to assess if apoC-II is a CVD marker or a risk factor in high-risk patients.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. These drugs also affect many anthropometric and metabolic parameters with various ...mechanisms of action. Areas covered: We present the available evidence regarding these effects. SGLT2 inhibitors can decrease body weight mainly due to a reduction of total fat mass. SGLT2 inhibitors can decrease blood pressure levels and serum uric acid levels and may also reduce the degree of diabetes-related albuminuria. These effects may have contributed in the beneficial cardiovascular effects seen in the EMPA-REG OUTCOME trial. On the other hand, the SGLT2 inhibition-induced natriuresis and osmotic diuresis could lead to a decrease of extracellular volume. A small increase in serum low-density lipoprotein cholesterol has been observed with SGLT2 inhibitors. A small increase in serum phosphate concentration has been reported with these drugs due to increased phosphate reabsorption, which combined with an increase in serum parathormone may adversely affect bone homeostasis. In rare cases, SGLT2 inhibitors administration may be followed by euglycemic diabetic ketoacidosis. Expert opinion: SGLT2 inhibitors improve many aspects of human metabolism and may be beneficial in diabetic patients if certain precautions are followed by clinicians during the administration of these drugs.
Type 2 diabetes mellitus (T2DM) is a serious health problem with epidemic proportions and associated with high cardiovascular morbidity and mortality. Thus, the prevention or at least delaying the ...onset of T2DM is imperative. Subjects with impaired glucose metabolism (prediabetes) are highly likely to develop overt T2DM. Treatment of accompanied cardiovascular risk factors, such as hypertension and dyslipidemia, in these patients is frequently complicated as it can impair the already altered glucose homeostasis. This review discusses the pathophysiology of lipid disorders and hypertension in prediabetes along with the effects of lipid modifying and antihypertensive drugs in glucose/insulin metabolism. A critical overview and suggestions of different treatment options for prediabetic patients with dyslipidemia and/or hypertension are also presented.
Proprotein convertase subtilisin/kexin type 9(PCSK9) plays a paramount role in the degradation of lowdensity lipoprotein(LDL) receptors(LDLR) on the hepatic cells surface and subsequently affects LDL ...particles catabolism and LDL cholesterol(LDL-c) levels. The anti-PCSK9 monoclonal antibodies lead to substantial decrease of LDL-c concentration. PCSK9(which is also expressed in pancreatic delta-cells) can decrease LDLR and subsequently decrease cholesterol accumulation in pancreatic beta-cells, which impairs glucose metabolism and reduces insulin secretion. Thus, a possible adverse effect of PCSK9 inhibitors on carbohydrate metabolism may be expected by this mechanism, which has been supported by the mendelian studies results. On the other hand, clinical data have suggested a detrimental association of PCSK9 with glucose metabolism. So, the inhibition of PCSK9 may be seen as a double-edged sword regarding carbohydrate metabolism. Completed clinical trials have not shown a detrimental effect of PCSK9 inhibitors on diabetes risk, but their short-term duration does not allow definite conclusions.
Object Electrolyte abnormalities are frequently observed in patients with hyponatremia. The aim of this study was to determine the incidence of various electrolyte abnormalities encountered in ...hyponatremic patients admitted to an internal medicine clinic, as well as to investigate the possible pathogenetic mechanisms responsible for these abnormalities. Patients and Methods We prospectively studied 204 adult patients who either on admission to our clinic or during their hospitalization were found to have hyponatremia. Results Ninety-two patients (45.5%) had at least one additional electrolyte abnormality. Hypophosphatemia was the most frequent electrolyte disorder observed (35 patients, 17%). Hypokalemia was seen in 32 patients (15.8%), hypomagnesemia in 31 patients (15.2%) and hyperkalemia in 12 patients (5.9%). Moreover, 5 patients (2.5%) had hyperphosphatemia, 4 patients (1.9%) exhibited hypermagnesemia, 3 patients (1.4%) had hypercalcemia, and 6 patients (2.9%) had true hypocalcemia. There were no statistically significant differences regarding the incidence of these electrolyte abnormalities (as a whole) between the main subgroups of hyponatremic patients (diuretic-induced, syndrome of inappropriate antidiuretic hormone, hypovolemia-induced and edematous state-related). However, hypokalemia and hypomagnesemia were more frequently observed in patients with diuretic-induced hyponatremia, while hyperkalemia was more frequently seen in edematous state-related hyponatremia. Conclusions Additional electrolyte abnormalities are frequently encountered in patients with hyponatremia of any origin admitted to an internal medicine clinic.
Apolipoprotein CIII and diabetes. Is there a link? Christopoulou, Eliza; Tsimihodimos, Vasilios; Filippatos, Theodosios ...
Diabetes/metabolism research and reviews,
March 2019, Letnik:
35, Številka:
3
Journal Article
Recenzirano
Summary
Apolipoprotein CIII (ApoCIII), a small protein that resides on the surface of lipoprotein particles, is a key regulator of triglyceride metabolism. The inhibition of lipoprotein lipase (LPL), ...the increased assembly and secretion of very low‐density lipoproteins (VLDL) and the decreased reuptake of triglyceride‐rich lipoproteins (TRLs) by the liver are mechanisms associating elevated serum ApoCIII levels and hypertriglyceridemia. ApoCIII concentration is high in individuals with diabetes mellitus, indicating a possible positive correlation with impairment of glucose metabolism. The aim of this review (based on a Pubmed search until August 2018) is to present the possible mechanisms linking ApoCIII and deterioration of carbohydrate homeostasis. ApoCIII enhances pancreatic β‐cells apoptosis via an increase of the cytoplasmic Ca2+ levels in the insulin‐producing cells. In addition, overexpression of ApoCIII enhances non‐alcoholic fatty liver disease and exacerbates inflammatory pathways in skeletal muscles, affecting insulin signalling and thereby inducing insulin resistance. Moreover, recent studies reveal a possible mechanism of body weight increase and glucose production through a potential ApoCIII‐induced LPL inhibition in the hypothalamus. Also, the presence of ApoCIII on the surface of high‐density lipoprotein particles is associated with impairment of their antiglycemic and atheroprotective properties. Modulating ApoCIII may be a potent therapeutic approach to manage hypertriglyceridemia and improve carbohydrate metabolism.
Sotagliflozin is a dual sodium-glucose co-transporter (SGLT) 2 inhibitor, manifesting a 20-fold higher inhibitory activity for SGLT2 than for SGLT1. Differences in SGLT2 over SGLT1 selectivity of the ...available agents have been proposed to relate to variability in efficacy and safety characteristics. In contrast to other SGLT2 inhibitors, the cardiorenal effects of sotagliflozin in type 2 diabetes had not been explored until recently, when the results of SOLOIST-WHF (focusing on heart failure HF outcomes) and SCORED (focusing on renal outcomes) were published. In SOLOIST-WHF, sotagliflozin reduced the risk of the primary composite outcome of cardiovascular (CV) death and hospitalizations and urgent visits for HF. The findings showed that the risk reduction was consistent in people with reduced but also in those with preserved ejection fraction (EF). In SCORED, sotagliflozin significantly reduced the primary end point of CV deaths, hospitalizations for HF, and urgent visits for HF. A reduction in glycated hemoglobin was evident even in participants with estimated glomerular filtration rate values below 30 mL/min/1.73 m
. SCORED is also the first trial to illustrate the benefits of the class across the full range of albuminuria. Moreover, the endpoint of stroke was significantly reduced by 34% in the sotagliflozin compared with the placebo group. The findings of the two studies provide novel insights into the clinical utility of SGLT2 inhibitors, particularly with respect to the early initiation in stable HF, the benefits in HF with preserved EF, the glucose-lowering efficacy in people with severe renal impairment and their potential to improve atherosclerotic vascular disease, including stroke, outcomes.
Type 2 diabetes mellitus is characterized by increased cardiovascular morbidity and mortality. Atherogenic dyslipidemia is common in this population, consisting of the triad of increased ...triglycerides, increased small dense low-density lipoprotein (LDL) particles and decreased high-density lipoprotein cholesterol (HDL-C) levels, leading to increased cardiovascular risk. Areas covered: Aim of the review is the presentation of pharmacokinetic characteristics of the currently available sodium-glucose cotransporters 2 (SGLT-2) inhibitors and the effects of these drugs on lipid metabolism. SGLT-2 inhibitors share a common favorable pharmacokinetic profile, are orally administered with long half-lives (allowing for a once daily dosing) and have been proven to be effective in reducing blood glucose levels. However, the SGLT-1 inhibitory capacity differs between these drugs, an effect that may affect their antidiabetic and cardiovascular effects. SGLT-2 inhibitors alter serum lipids modestly in a similar manner. Specifically, an increase of total cholesterol, LDL cholesterol, and HDL-C levels as well as a decrease of triglycerides concentration is observed. Additionally, the administration of these agents may reduce the atherogenic small dense LDL particle levels, an effect that could provide additional cardiovascular protection in the long term. Expert opinion: The effect of SGLT-2 inhibitors on diabetic dyslipidemia may be one of their cardioprotective mechanisms.
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