The latest medical research on Metabolic Syndrome
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about metabolic syndrome gathered by our medical AI research bot.
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The causal effect of systolic blood pressure lowering on vascular outcomes in diabetes: a Mendelian randomization study.Clinical Endocrinology
The effect of lowering systolic blood pressure (SBP) on clinical outcomes in diabetic patients is controversial.
We used Two-sample Mendelian randomization (MR) to study the causal effect of decreasing SBP on the risk of macro- and micro-vascular outcomes in diabetic patients.
We used 362 SBP-related genetic variants from a large genome-wide association study (n=299,024) and UK Biobank (n=375,256) as exposure. We evaluated five macro- and micro-vascular complications up to 60,742 cases as outcomes in diabetes, including coronary artery disease (CAD); peripheral artery disease (PAD), nephropathy, retinopathy, and composite complications. All cases were diagnosed together with diabetes. We performed follow-up analyses by conducting seven sensitivity analyses and comparing the present MR with results in general population, and clinical trials.
Genetic predisposition of each 10-mmHg SBP decrease was significantly associated with 28% decreased risk of CAD (Odd Ratio [OR]: 0.72, 95% Confidence Interval [CI]: 0.59-0.89, p =0.002), 34% decreased risk of nephropathy (OR: 0.66, 95% CI: 0.54-0.81, p <0.001), and 34% decreased risk of the composite complications (OR: 0.66, 95% CI: 0.58-0.76, p <0.001); while nominally associated with decreased risk of PAD (OR: 0.69, 95% CI: 0.48-0.99) and retinopathy (OR: 0.90, 95% CI: 0.81-0.99). The MR results in diabetes were similar with that in general population and clinical trials.
SBP lowering was causally associated with an attenuated risk of diabetic CAD and nephropathy. It provided genetic evidence for the beneficial effect of lifelong SBP control in preventing diabetes-related vascular outcomes.
Metabolomic changes upon conjugated linoleic acid supplementation and predictions of body composition responsiveness.Clinical Endocrinology
Conjugated linoleic acid (CLA) may optimize body composition, yet mechanisms underlining its benefits were not clear in human.
To reveal the CLA-induced changes in plasma metabolome associated with body composition improvement and the predictive performance of baseline metabolome on intervention responsiveness.
Plasma metabolome from overnight fasted samples at pre- and post-intervention of 65 participants in a 12-week randomized, placebo-controlled trial (3.2 g/day CLA vs. 3.2 g/day sunflower oil) were analyzed using untargeted LC-MS metabolomics. Mixed linear model and machine learning were applied to assess differential metabolites between treatments, and to identify optimal panel (based on baseline conventional variables vs. metabolites) predicting responders of CLA-derived body composition improvement (increased muscle variables or decreased adiposity variables) based on dual-energy X-ray absorptiometry.
Compared to placebo, CLA altered 57 metabolites (P < 0.10) enriched in lipids/lipid-like molecules including glycerophospholipids (n=7), fatty acyls (n=6), sphingolipids (n=3). CLA-upregulated cholic acid (or downregulated aminopyrrolnitrin) was inversely correlated with changes in muscle and adiposity variables. Inter-individual variability in response to CLA-derived body composition change. The areas under the receiver operator characteristics curves of optimal metabolite panels were higher than that of optimal conventional panels in predicting favorable responders of waist circumference (0.93 [0.82-1.00] vs 0.64 [0.43-0.85]), visceral adiposity index (0.95 [0.88-1.00] vs 0.58 [0.35-0.80]), appendicular fat mass (0.97 [0.92-1.00] vs 0.73 [0.55-0.91]) upon CLA supplementation (all FDR P<0.05).
Post-intervention metabolite alterations were identified, involving in lipid/energy metabolism, associated with body composition changes. Baseline metabolite profiling enhanced the prediction accuracy on responsiveness of CLA-induced body composition benefits.
A Biphasic Pattern of Reproductive Hormones in Healthy Female Infants -The COPENHAGEN Minipuberty Study.Clinical Endocrinology
Minipuberty, a period of a transient activation of the hypothalamic-pituitary-gonadal (HPG) axis in both sexes, enables evaluation of gonadal function in infants suspected of hypogonadism. However, female minipuberty remains poorly elucidated.
We aimed to establish continuous reference ranges for the most commonly used reproductive hormones and to evaluate the dynamics of the HPG axis in females aged 0-1 year.
Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin B, anti-Müllerian hormone (AMH), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were quantified using highly sensitive methods in 266 serum samples.
Reference ranges were established for LH, FSH, inhibin B, AMH, E1, E2, and SHBG. Two peaks were observed in normalized mean curves for all hormones. The first peaks were timed around postnatal days 15-27 followed by a general nadir for all hormones around days 58-92. The second peaks occurred around days 107-125 for inhibin B, AMH, E1, E2, and SHBG and day 164-165 for LH and FSH.
We present age-related, continuous reference ranges of the most commonly used reproductive hormones and present novel data revealing a biphasic and prolonged female minipuberty.
The changing face of drug-induced adrenal insufficiency in the Food and Drug Administration Adverse Event Reporting System.Clinical Endocrinology
Adrenal insufficiency (AI) is a life-threatening condition complicating heterogenous disorders across various disciplines, with challenging diagnosis and notable drug-induced component.
To describe the spectrum of drug-induced AI through adverse drug event reports received by the Food and Drug Administration (FDA).
Reporting trend of drug-induced AI.
We identified 8,496 cases of AI, 97.5% serious, 41.1% requiring hospitalization. AI showed an exponential increase throughout the years, with 5,282 (62.2%) cases in 2015-2020. We identified 56 compounds associated with significant disproportionality: glucocorticoids (N=1971), monoclonal antibodies (N=1644, of which N=1330 associated with immune checkpoint inhibitors - ICIs), hormone therapy (N=291), anti-infectives (N=252), drugs for hypercortisolism or adrenocortical cancer diagnosis/treatment (N=169), protein kinase inhibitors (N=138). Cases of AI by glucocorticoids were stable in each 5-year period (22-27%), whereas those by monoclonal antibodies, largely ICIs, peaked from 13% in 2010-2015 to 33% in 2015-2020.
We provided a comprehensive insight into the evolution of drug-induced AI, highlighting the heterogeneous spectrum of culprit drug classes and the emerging increased reporting of ICIs. We claim for urgent identification of predictive factors for drug-induced AI, and establishment of screening and educational protocols for patients and caregivers.
A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline for the Management of Hyperglycemia in Adults Hospitalized for Noncritical Illness or Undergoing Elective Surgical Procedures.Clinical Endocrinology
Individuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these patients is challenging.
To support development of the Endocrine Society Clinical Practice Guideline for management of hyperglycemia in adults hospitalized for noncritical illness or undergoing elective surgical procedures.
We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence.
We included 94 studies reporting on 135 553 patients. Compared with capillary blood glucose, continuous glucose monitoring increased the number of patients identified with hypoglycemia and decreased mean daily blood glucose (BG) (very low certainty). Data on continuation of insulin pump therapy in hospitalized adults were sparse. In hospitalized patients receiving glucocorticoids, combination neutral protamine hagedorn (NPH) and basal-bolus insulin was associated with lower mean BG compared to basal-bolus insulin alone (very low certainty). Data on NPH insulin vs basal-bolus insulin in hospitalized adults receiving enteral nutrition were inconclusive. Inpatient diabetes education was associated with lower HbA1c at 3 and 6 months after discharge (moderate certainty) and reduced hospital readmissions (very low certainty). Preoperative HbA1c level < 7% was associated with shorter length of stay, lower postoperative BG and a lower number of neurological complications and infections, but a higher number of reoperations (very low certainty). Treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors in hospitalized patients with type 2 diabetes and mild hyperglycemia was associated with lower frequency of hypoglycemic events than insulin therapy (low certainty). Caloric oral fluids before surgery in adults with diabetes undergoing surgical procedures did not affect outcomes (very low certainty). Counting carbohydrates for prandial insulin dosing did not affect outcomes (very low certainty). Compared with scheduled insulin (basal-bolus or basal insulin + correctional insulin), correctional insulin was associated with higher mean daily BG and fewer hypoglycemic events (low certainty).
The certainty of evidence supporting many hyperglycemia management decisions is low, emphasizing importance of shared decision-making and consideration of other decisional factors.
Management of Hyperglycemia in Hospitalized Adult Patients in Non-Critical Care Settings: An Endocrine Society Clinical Practice Guideline.Clinical Endocrinology
Adult patients with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. These patients are at increased risk for adverse clinical outcomes in the absence of defined approaches to glycemic management.
To review and update the 2012 Management of Hyperglycemia in Hospitalized Patients in Non-Critical Care Settings: An Endocrine Society Clinical Practice Guideline and to address emerging areas specific to the target population of noncritically ill hospitalized patients with diabetes or newly recognized or stress-induced hyperglycemia.
A multidisciplinary panel of clinician experts, together with a patient representative and experts in systematic reviews and guideline development, identified and prioritized 10 clinical questions related to inpatient management of patients with diabetes and/or hyperglycemia. The systematic reviews queried electronic databases for studies relevant to the selected questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations.
The panel agreed on 10 frequently encountered areas specific to glycemic management in the hospital for which 15 recommendations were made. The guideline includes conditional recommendations for hospital use of emerging diabetes technologies including continuous glucose monitoring and insulin pump therapy; insulin regimens for prandial insulin dosing, glucocorticoid, and enteral nutrition-associated hyperglycemia; and use of noninsulin therapies. Recommendations were also made for issues relating to preoperative glycemic measures, appropriate use of correctional insulin, and diabetes self-management education in the hospital. A conditional recommendation was made against preoperative use of caloric beverages in patients with diabetes.
The recommendations are based on the consideration of important outcomes, practicality, feasibility, and patient values and preferences. These recommendations can be used to inform system improvement and clinical practice for this frequently encountered inpatient population.
Enhancing the Trustworthiness of the Endocrine Society's Clinical Practice Guidelines.Clinical Endocrinology
In an effort to enhance the trustworthiness of its clinical practice guidelines, the Endocrine Society has recently adopted new policies and more r...
Excess 11-Oxygenated androgens in women with severe insulin resistance are mediated by adrenal insulin receptor signaling.Clinical Endocrinology
Syndromes of severe insulin resistance (SIR) include insulin receptoropathy, in which all signaling downstream of the insulin receptor is lost, and lipodystrophy, in which some signaling pathways are impaired and others preserved. Women with SIR commonly have ovarian hyperandrogenemia; adrenal-derived 11-oxygenated androgens, produced by CYP11B1, have not been studied.
To evaluate classic pathway androgens (androstenedione, testosterone) and 11-oxygenated androgens in women with SIR and hyperandrogenemia, and to elucidate the role of insulin receptor signaling for 11-oxygenated androgen production by comparing lipodystrophy and receptoropathy.
Steroid hormones were quantified using LC-MS/MS in a cross-sectional study of 18 women with hyperandrogenemia and SIR (11 lipodystrophy, 7 receptoropathy) and 23 controls. To assess ovarian versus adrenal origin, steroids were compared in receptoropathy patients with (Ovary+) versus without (Ovary-) ovarian function.
Compared to controls, classic androgens were elevated in both lipodystrophy and receptoropathy, and 11-oxygenated androgens were increased in lipodystrophy (2.9-fold higher 11OHA4, 2.4-fold higher 11KA4, 3.6-fold higher 11KT; p<0.01), but not receptoropathy. Product-to-precursor ratios for CYP11B1 conversion of androstenedione to 11OHA4 were similar in lipodystrophy and controls, but decreased in receptoropathy (6.5-fold lower than control; p=0.001). Classic androgens were elevated in Ovary+ but not Ovary- patients.
11-Oxygenated androgens are elevated in lipodystrophy but not receptoropathy. In SIR, insulin receptor signaling is necessary for adrenal hyperandrogenemia, but not ovarian hyperandrogenemia; excess classic androgens are derived from the ovaries. Insulin receptor signaling increases adrenal 19-carbon steroid production, which may have implications for more common disorders of mild IR.
Peptic ulcer disease and risk of hip fracture: a general population-based cohort study.Clinical Endocrinology
Previous studies reported proton pump inhibitors (PPIs) use may increase the risk of fracture; however, the findings may be susceptible to indication bias since peptic ulcer disease (PUD), one major indication for PPIs, may affect skeletal health. Determining whether PUD would increase hip fracture risk may help identify high risk population and explore risk factors.
We conducted a cohort study using data from The Health Improvement Network (THIN) in the UK. THIN contains patient information such as disease diagnosis and medicine prescriptions. Up to five non-PUD individuals (n=138,265) were matched to each case of incident PUD (n=27,653) by age, sex, and body mass index. We examined the association between PUD and hip fracture by a multivariable Cox-proportional hazard model. We repeated the same analysis among individuals with incident PUD and gastroesophageal reflux disease (GERD) (n=27,160), another disease with similar indication for PPIs, as a positive control exposure.
Over a mean of 5.6 years follow-up, hip fracture occurred in 589 individuals with PUD and 2,015 individuals without PUD (3.8 vs 2.6/1000 person-years), with a multivariable-adjusted hazard ratio (HR) being 1.44 (95%CI: 1.31 to 1.58). The association persisted among subgroups stratified by sex and age. In positive control exposure analysis, the hip fracture risk was also higher in PUD than GERD (3.8 vs 2.4/1000 person-years; multivariable-adjusted HR=1.65, 95%CI: 1.45 to 1.7).
This general population-based cohort study suggests, after controlling for acid-lowering medication and other potential risk factors, PUD is independently associated with an increased risk of hip fracture.
Changes in sex steroids and enteric peptides after sleeve gastrectomy in youth in relation to changes in bone parameters.Clinical Endocrinology
Sleeve gastrectomy (SG) improves metabolic endpoints but is associated with impaired bone outcomes.
To determine mechanisms contributing to impaired bone health in youth following SG.
Fasting blood for enteric peptides, sex steroids, sclerostin, and bone turnover markers [N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide (CTX)]; DXA measures of areal bone mineral density (aBMD) and body composition; high resolution peripheral quantitative CT measures of volumetric BMD (vBMD); microfinite element analysis of strength estimates (distal radius and tibia).
SG had greater reductions in BMI z-scores, serum estrone and the free androgen index (FAI) (p≤0.046) and greater increases in sclerostin, P1NP and CTX (p≤0.010) than NS. Fasting ghrelin decreased in SG vs. NS (p<0.0001); fasting PYY did not change. Most changes were driven by female SG participants. Among females (majority of study participants), after controlling for baseline age and race, reductions in aBMD Z-scores were positively associated with changes in BMI, lean mass, estrone, FAI, and ghrelin, and inversely with changes in sclerostin. Decreases in total vBMD of the radius and tibia were associated positively with decreases in BMI. Increases in CTX were associated with decreases in BMI, lean mass, and ghrelin, and increases in sclerostin.
Bone loss after SG in youth is associated with changes in body composition, sex steroids, sclerostin and enteric peptides. These are potential targets for future preventative or therapeutic strategies.
Clinically symptomatic resistance to thyroid hormone β syndrome due to THRB gene mosaicism.Clinical Endocrinology
Resistance to thyroid hormone β syndrome (RTHβ) is caused by pathogenic variants in the THRB gene, but such variants are found in only 85% of cases. We report the case of a patient with RTHβ phenotype but for whom we found a pathogenic variant of the THRB gene in a mosaic state.
Patient is a 52-year-old woman with clinical and biological signs of RTHβ. Symptoms included asthenia, cardiac palpitations and diarrhoea. Repeated thyroid function tests showed an elevated serum TSH, elevated serum fT4 and variably normal or slightly elevated serum fT3. Pituitary MRI was normal and the TRH test result was compatible with the diagnosis of RTHβ syndrome. Initial Sanger sequencing on blood samples could not highlight the presence of a mosaic variant due to insufficient sensitivity. When NGS sequencing became accessible, blood samples were retested and we found a known pathogenic variant: c.949G>A ; p.(ala317Thr), with an allelic frequency of 12%. Other samples from tissues of different embryological origin were also tested and found an allelic frequency of 5.7%, 17.9%, 9.9%, 6.4% and 0% on urines, oral swab, nasal mucosa swab, skin biopsy and conjunctival swab, respectively. Cloning confirmed the allelic frequency observed.
We highlight that a pathogenic variant in a mosaic state in the THRB gene may be the cause of an authentic RTHβ syndrome. High-throughput sequencing of multiple tissues eases the detection of pathogenic variant in a mosaic state and allows the correct diagnosis of patients with true RTHβ, thus avoiding patient mismanagement.
A novel germline deletion of p.C630 in RET causes MTC and promotes cell proliferation and sensitivity to pralsetinib.Clinical Endocrinology
Medullary thyroid cancer (MTC) is usually caused by gain-of-function mutations in the proto-oncogene RET.
This study aimed to determine the underlying mechanism in a male patient diagnosed with the MTC at age 51 years.
Genomic DNA extracted from leukocytes or tumor tissues of patients was used for next-generation sequencing-based (NGS) panel sequencing and Sanger sequencing. Wild-type (WT RET) and p.C630 deletion RET were expressed in HEK 293T cells. Activation of phosphorylation of the crucial tyrosine 905 of RET and MAPK/ERK was analyzed by Western blotting. The effect of RET mutants on cell viability and colony formation ability was determined by CCK8 assay and a colony forming assay.
NGS-Panel sequencing revealed a 3-nucleotide/1-amino acid C630 in-frame deletion in exon 11 of RET (c.1887_1889delGTG p.C630del). In vitro expression showed that phosphorylation of the crucial tyrosine 905 was much stronger in the p.C630del RET mutant than in WT RET, indicating ligand-independent activation of the Ret protein tyrosine kinase. Furthermore, p.C630del RET mutant induced strong activation of the MAPK/ERK pathway. In addition, p.C630del RET mutant cells exhibited increased HEK 293T cell viability and colony formation compared with WT RET cells. Pralsetinib (BLU-667), a highly selective RET inhibitor, inhibited the viability of WT RET and p.C630del RET mutant-transfected HEK 293T cells (IC50s: 18.54 and 16.49 µM after treatment for 24 h), followed by inhibition of the RET-induced MAPK/ERK pathway.
The finding in our patient with MTC was reported to be a 3-base-pair deletion in exon 11 of RET, a p.C630 deletion not yet reported. The p.C630del RET stimulates cell proliferation by increasing ligand-independent phosphorylation and activation of MAPK/ERK pathway, demonstrating pathogenic nature of the mutation. We therefore recommend screening panel sequence of RET in MTC patients with indications of a genetic cause.