The effect of statin treatment on glucose metabolism and the risk of diabetes remains an issue of controversy. Since statins are drugs commonly prescribed for the prevention of cardiovascular disease ...even in patients with prediabetes or diabetes, it is of great importance to identify the role of statin treatment on glucose homeostasis. In this review, we have scrutinized available data with regard to the effect of every drug of the class on glycemic outcomes. Experimental data describing mechanisms through which these drugs potentially modify the metabolism of carbohydrates have been described. In order to identify statins which may be preferentially used to improve parameters of glycemic control, studies comparing different agents of this class as to their effect on glucose homeostasis have been discussed. According to experimental studies statin lipophilicity as well as the potential to inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase should be regarded as prognostic factors of an adverse impact of statin treatment on carbohydrate metabolism. On the other hand, the hypotriglyceridemic capacity, the endothelial-dependent increase in pancreatic islet blood flow, the anti-inflammatory properties along with the capacity of statins to alter circulating levels of several adipokines known to affect glucose homeostasis, including adiponectin, leptin, visfatin and resistin, may beneficially alter glycemic status. In clinical trials, a beneficial, neutral or adverse impact on glycemic control of different populations has been ascribed to various statins. From all drugs of the class pravastatin seems to beneficially affect glucose metabolism and decrease the risk of diabetes. Controversial findings have come to the fore with regard to other statins commonly prescribed in the clinical setting, including rosuvastatin, atorvastatin and simvastatin. More data are needed to clarify the exact role of lovastatin, fluvastatin and the newest statin pitavastatin on carbohydrate metabolism. Comparison trials suggest a potential preferable effect of the hydrophilic statins pravastatin, rosuvastatin and pitavastatin as compared to lipophilic components of the class, including atorvastatin and simvastatin.
Serum alkaline phosphatase (ALP) activity has been associated with atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with ...dyslipidemia.
We conducted a retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e., sex, age, hypertension, diabetes, smoking, and dyslipidemia), baseline ASCVD, and lipid-lowering treatment. ALP levels were stratified by tertiles as follows: low: <67 U/L, middle: 67-79 U/L, high: ≥79 U/L.
Overall, 1178 subjects were included; 44% were males, and their median age was 57 years (range: 49-65). During a 6-year median follow-up (interquartile range: IQR: 4-9), 78 new ASCVD events (6.6%) occurred. A statistically significant association between baseline ALP levels and incident ASCVD was demonstrated (Odds Ratio, OR: 6.99; 95% Confidence Interval, CI: 2.29-21.03,
= 0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24-4.41,
= 0.008).
The present study indicates an association between ALP and the development of ASCVD in patients with dyslipidemia, which underscores the potential of ALP as a predictive tool or a therapeutic target in the realm of ASCVD prevention within this population.
Statins are associated with new-onset type 2 diabetes (T2D), mainly in patients with metabolic syndrome (MetS). The fatty liver index (FLI) is used as a prognostic score for the diagnosis of ...non-alcoholic fatty liver disease (NAFLD), which is common in patients with MetS. We aimed to investigate the association of FLI with new-onset T2D in patients initiating statin therapy.
A retrospective observational study including 1241 individuals with dyslipidemia and followed up for ≥3 years. Patients with T2D and those receiving lipid-lowering treatment at the baseline visit were excluded. Models with clinical and laboratory parameters were used to assess the association of FLI with incident T2D.
Among the 882 eligible subjects, 11% developed T2D during the follow-up (6 years; IQR: 4-10 years). After adjusting for sex, age and MetS parameters, a multivariate analysis revealed that age (HR:1.05; 95%CI: 1.01-1.09,
< 0.05), fasting plasma glucose (HR: 1.09; 95%CI: 1.06-1.13,
< 0.001) and FLI (HR: 1.02; 95%CI: 1.01-1.04,
< 0.01) were independently associated with T2D risk. The subjects with probable NAFLD (FLI ≥ 60) had a three-fold increased T2D risk compared with the subjects with FLI < 60 (HR: 3.14; 95%CI: 1.50-6.59,
= 0.001). A ROC curve analysis showed that FLI had a significant, although poor, predictive value for assessing T2D risk (C-Statistic: 0.67; 95%CI: 0.58-0.77,
= 0.001). Higher FLI values were associated with reduced T2D-free survival (log-rank = 15.46,
< 0.001).
FLI is significantly and independently associated with new-onset T2D risk in patients initiating statin therapy.
Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic ...cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is estimated as being up to 1:300,000−400,000 for the homozygous and ~1:200−300 for the heterozygous form. Apart from its late diagnosis, FH is also undertreated, despite the available lipid-lowering therapies. In addition, elevated lipoprotein(a) (Lp(a)) (>50 mg/dL; 120 nmol/L), mostly genetically determined, has been identified as an important cardiovascular risk factor with prevalence rate of ~20% in the general population. Novel Lp(a)-lowering therapies have been recently developed and their cardiovascular efficacy is currently investigated. Although a considerable proportion of FH patients is also diagnosed with high Lp(a) levels, there is a debate whether these two entities are associated. Nevertheless, Lp(a), particularly among patients with FH, has been established as a significant cardiovascular risk factor. In this narrative review, we present up-to-date evidence on the pathophysiology, diagnosis, and treatment of both FH and elevated Lp(a) with a special focus on their association and joint effect on ASCVD risk.
Hypertriglyceridemia has been identified as a risk factor for cardiovascular disease and acute pancreatitis. To date, there are only few drug classes targeting triglyceride levels such as fibrates ...and ω-3 fatty acids. These agents are at times insufficient to address very high triglycerides and the residual cardiovascular risk in patients with mixed dyslipidemia. To address this unmet clinical need, novel triglyceride-lowering agents have been in different phases of early clinical development. In this review, the latest and experimental therapies for the management of hypertriglyceridemia are presented. Specifically, ongoing trials evaluating novel apolipoprotein C-III inhibitors, ω-3 fatty acids, as well as fibroblast growth 21 analogues are discussed.
Familial hypercholesterolemia (FH) and type 2 diabetes mellitus (T2DM) are both associated with a high risk of atherosclerotic cardiovascular disease (ASCVD). Little is known about the prevalence of ...T2DM and its association with ASCVD risk in FH patients. This was a cross-sectional analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH) including adults with FH (n = 1719, mean age 51.3 ± 14.6 years). Of FH patients, 7.2% had a diagnosis of T2DM. The prevalence of ASCVD, coronary artery disease (CAD), and stroke was higher among subjects with T2DM compared with those without (55.3% vs. 23.3%, 48.8% vs. 20.7%, 8.3% vs. 2.7%, respectively, p < 0.001). When adjusted for age, systolic blood pressure, smoking, body mass index, hypertension, waist circumference, triglyceride levels, high-density lipoprotein cholesterol levels, and gender, T2DM was significantly associated with prevalent ASCVD OR 2.0 (95% CI 1.2−3.3), p = 0.004. FH patients with T2DM were more likely to have undergone coronary revascularization than those without (14.2% vs. 4.5% for coronary artery bypass graft, and 23.9% vs. 11.5% for percutaneous coronary intervention, p < 0.001). T2DM is associated with an increased risk for prevalent ASCVD in subjects with FH. This may have implications for risk stratification and treatment intensity in these patients.
Hyperemesis gravidarum (HG) is a complication mainly of the first trimester of pregnancy, which sometimes leads to metabolic disorders such as hypovolemia and acute kidney injury (AKI). Herein, we ...present the case of a 25-year-old woman at week 10 of gestation who exhibited a constellation ofsevere abnormalities, namely AKI (serum creatinine 6.15 mg/dl), transaminasemia (serum aminotransferases >1,000 IU/l), alkalemia (arterial pH7.667), hyponatremia (serum sodium 117 mEq/l), hypochloremia (serum chloride 54 mEq/l), hypokalemia (serum potassium 2.2 mEq/l) and hyperuricemia (serum uric acid 20 mg/dl). Despite a thorough work-up, no other disorder was found apart from HG. All symptoms and metabolic abnormalities resolved with targeted administration of intravenous fluids. The differential diagnosis of these disorders and therapeutic challenges are discussed.
Hyperemesis gravidarum is a severe form of vomiting during pregnancy that typically occurs in the first trimester.It may lead to severe metabolic abnormalities including acute kidney injury (AKI), and electrolyte and acid-base disturbances.Early detection, thorough diagnostic evaluation and prompt management with fluid resuscitation are essential for the well-being of both the mother and the fetus.
Objective To assess the risk of progression from normoglycemia or prediabetes to overt diabetes among individuals treated with statins alone or in combination with ezetimibe. Methods This was a ...retrospective study conducted in Greece including 877 subjects treated for dyslipidemia. We included individuals without overt diabetes at baseline and divided them in 2 subgroups according to their baseline fasting glucose: <100 (normal glucose) and 100 to 125 mg/dL (prediabetes). High and moderate-intensity statin therapy was defined according to the expected low-density lipoprotein cholesterol reduction (≥50% and 30 to <50%, respectively). We identified the predictors of incident diabetes and assessed the risk of new-onset diabetes among subgroups on various intensity statin or no statin treatment at all. Similar analyses were performed across different potency of statin monotherapy or combination of statin plus ezetimibe treatment. Results A total of 877 subjects were eligible and followed-up for a median of 7 years. There were no differences between statins regarding diabetes development. However, a higher risk of incident diabetes was observed in prediabetic individuals receiving high-intensity statin therapy compared with those on moderate intensity (adjusted odds ratio OR = 2.12, 95% confidence interval CI = 1.06–4.24, P < .05) and those not taking a statin (adjusted OR = 4.90; 95% CI = 1.16–20.66, P < .05). The addition of ezetimibe to statin treatment did not increase the risk of incident diabetes in prediabetic individuals (adjusted OR = 0.89; 95% CI = 0.36–2.22, P > .05). Baseline fasting glucose, presence of metabolic syndrome, family history of diabetes, and follow-up duration were independent predictors of new-onset diabetes. Conclusion High-intensity statin treatment is associated with a higher risk of incident diabetes in prediabetic individuals, whereas the addition of ezetimibe to statin therapy has a neutral effect on glucose metabolism.
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