Looking in the mirror: Situs inversus totalis

No Abstract

Synopsis and meta-analysis of genetic association studies in osteoporosis for the focal adhesion family genes: the CUMAGAS-OSTEOporosis information system

<p>Abstract</p> <p>Background</p> <p>Focal adhesion (FA) family genes have been studied as candidate genes for osteoporosis, but the results of genetic association studies (GASs) are controversial. To clarify these data, a systematic assessment of GASs for FA genes in osteoporosis was conducted.</p> <p>Methods</p> <p>We developed Cumulative Meta-Analysis of GAS-OSTEOporosis (CUMAGAS-OSTEOporosis), a web-based information system that allows the retrieval, analysis and meta-analysis (for allele contrast, recessive, dominant, additive and codominant models) of data from GASs on osteoporosis with the capability of update. GASs were identified by searching the PubMed and HuGE PubLit databases.</p> <p>Results</p> <p>Data from 72 studies involving 13 variants of 6 genes were analyzed and catalogued in CUMAGAS-OSTEOporosis. Twenty-two studies produced significant associations with osteoporosis risk under any genetic model. All studies were underpowered (<50%). In four studies, the controls deviated from the Hardy-Weinberg equilibrium. Eight variants were chosen for meta-analysis, and significance was shown for the variants collagen, type I, α₁(<it>COL1A1</it>) G2046T (all genetic models), <it>COL1A1 </it>G-1997T (allele contrast and dominant model) and integrin β-chain β₃(<it>ITGB3</it>) T176C (recessive and additive models). In <it>COL1A1 </it>G2046T, subgroup analysis has shown significant associations for Caucasians, adults, females, males and postmenopausal women. A differential magnitude of effect in large versus small studies (that is, indication of publication bias) was detected for the variant <it>COL1A1 </it>G2046T.</p> <p>Conclusion</p> <p>There is evidence of an implication of FA family genes in osteoporosis. CUMAGAS-OSTEOporosis could be a useful tool for current genomic epidemiology research in the field of osteoporosis.</p

A Horse, a Jockey, and a Therapeutic Dilemma: Choosing the Best Option for a Patient with Diabetes and Coronary Artery Disease

Current guidelines for the management of hyperglycemia recommend the use of agents with proven cardiovascular (CV) benefit in patients with type 2 diabetes (T2D) and established CV disease. Although both glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of major adverse CV events (MACE) in high-risk populations with T2D, the ideal choice between the two classes for people with coronary artery disease remains controversial. SGLT2i reduce CV risk primarily through hemodynamic effects and changes in energy metabolism, making them the first choice in cases where heart failure or chronic kidney disease predominates. On the other hand, GLP-1 RA exert powerful anti-atherogenic properties that are the main drivers of their cardioprotection, and seem to have a consistent benefit in the atherosclerotic components of MACE. However, most people with diabetes and CV disease could take advantage of the complementary effects of the two drug categories on glycemic control, body weight, and diabetic complications. Future mechanistic studies and clinical head-to-head trials are expected to shed more light on this intriguing clinical dilemma and provide clear guidance for daily practice. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG

Non-insulin agents for the management of gestational diabetes: lack of evidence versus lack of action

[No abstract available

Sodium-Glucose Co-transporter 2 Inhibitors Versus Metformin as the First-Line Treatment for Type 2 Diabetes: Is It Time for a Revolution?

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a promising therapeutic option for hyperglycemia and its complications. However, metformin remains the first-line pharmacological treatment in most algorithms for type 2 diabetes (T2D). Although metformin is generally believed to exert positive effects on cardiovascular (CV) outcomes, relevant data are mainly observational and potentially overinterpreted. Yet, it exerts numerous pleiotropic actions that favorably affect metabolism and diabetes comorbidities. CV outcome trials have demonstrated cardiorenal protection with SGLT2i among people at high CV risk and mostly on concomitant metformin therapy. However, post hoc analyses of these trials suggest that the cardiorenal effects of gliflozins are independent of background treatment and consistent across the full spectrum of CV risk. Considering the importance of addressing hyperglycemia as a means of preventing diabetic complications and significant knowledge gaps, particularly regarding the cost-effectiveness of SGLT2i in drug-naïve populations with T2D, the position of metformin in the management of people with diabetes at low CV risk remains solid for the moment. On the other hand, available evidence—despite its limitations—suggests that specific groups of people with T2D, particularly those with heart failure and kidney disease, could probably benefit more from treatment with SGLT2i. This narrative mini-review aims to discuss whether current evidence justifies the use of SGLT2i as the first-line treatment for T2D. © 2021, Springer Science+Business Media, LLC, part of Springer Nature