The latest medical research on Endocrinology

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 endocrinology gathered by our medical AI research bot.

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Comparison of normocalcemic versus hypercalcemic primary hyperparathyroidism in a hypercalciuric renal stone population.

Clinical Endocrinology

Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed.

Our objective was to compare hypercalcemic hyperparathyroidism (HPHPT) versus NHPT hypercalciuric renal stone patients.

We took advantage of a routine calcium load test performed in hypercalciuric renal stone patients to assess retrospectively among PHPT patients, prevalence and characteristics of NHPT and HPHPT under a calcium restricted diet.

Among 1671 hypercalciuric patients included, 91 patients have a final diagnosis of PHPT(post load ionized calcium (iCa)>1.31 mmol/L and PTH>30 pg/ml). Prevalence of NHPT is 40% of all PHPT, however according to total serum calcium 4/35 NHPT and 7/56 HPHPT would have been misclassified in the other group. 18/35 NHPT and 40/56 HPHPT underwent parathyroidectomy. No significant characteristics related to parathyroid weight, stone composition or bone remodeling biomarkers is detected between groups. Whereas iCa is higher in HPHPT in fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Of notice, renal calcium excretion (FECa) post load increases by 303% in NHPT but only 176% in HPHPT (p=0.01) likely explained by a lesser PTH decrease (p=0.02). However, a strong negative association (p<0.0001) detected between pooled pre and post load iCa and PTH only in NHPT group suggests a persistent efficient PTH-CaSR control within parathyroid glands in this group.

Our data show the relevance of dynamic tests to unmask NHPT in hypercalciuric renal stone patients.

Impact of Insulin-Induced Relative Hypoglycemia on Vascular Insulin Sensitivity and Central Hemodynamics in Prediabetes.

Clinical Endocrinology

Relative hypoglycemia (RH) is linked to sympathetic responses that can alter vascular function in individuals with type 2 diabetes. However, less is known about the role of RH on hemodynamics or metabolic insulin sensitivity in prediabetes.

Determine if RH alters peripheral endothelial function or central hemodynamics to a greater extent in those with prediabetes (PD) versus normoglycemia (NG).

Seventy adults with obesity were classified using ADA criteria as PD (n=34 (28F); HbA1c=6.02±0.1%) or NG (n=36 (30F); HbA1c=5.4±0.0%). Brachial artery endothelial function, skeletal muscle capillary perfusion, and aortic waveforms were assessed at 0 and 120min of a euglycemic clamp (40 mU/m2/min, 90 mg/dl). Plasma nitrate/nitrite and endothelin-1 (ET-1) were measured as surrogates of nitric oxide-mediated vasodilation and vasoconstriction, respectively. RH was defined as the drop in glucose (%) from fasting to clamp steady state.

There were no differences in age, weight, or VO2max between groups. PD had higher HbA1c (P<0.01) and a greater drop in glucose in response to insulin (14 vs. 8%; P=0.03). Further, heart rate (HR) increased in NG compared to PD (P<0.01), while forward wave (Pf) decreased in PD (P=0.04). Insulin also tended to reduce arterial stiffness (cfPWV) in NG versus PD (P=0.07), despite similar increases in pre-occlusion diameter (P=0.02), blood flow (P=0.02), and lower augmentation index (AIx75) (P≤0.05).

Compared with NG, insulin-induced RH corresponded with a blunted rise in HR and drop in Pf during insulin infusion in adults with PD, independent of changes in peripheral endothelial function.

The impact of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on weight loss following bariatric treatment: a systematic review and meta-analysis.

Clinical Endocrinology

CRD42023450024.

We conducted a systematic review and meta-analysis to evaluate the effect of GLP-1 RA on weight changes in patients who previously underwent MBS.

We examined the impact of GLP-1 RA on weight changes by calculating pooled estimates (random-effects model) of the absolute differences in bodyweight (kg) as compared to baseline for observational studies and as compared to control group for RCTs.

Seventeen studies (1164 participants) met our inclusion criteria. Pooling the data from the 14 observational studies evaluating the effect of GLP-1 RA post-bariatric treatment demonstrated a reduction of 7.83 kg as compared to pre-treatment (before the use of GLP-1 RA) [weight - 7.83 kg (95%CI: -9.27 to -6.38)]. With respect to tolerability, 23% (95%CI: 10 to 36%) of participants reported any adverse event but only 7% discontinued treatment. Data from RCTs showed that the use of GLP-1 RA induced weight reduction of 4.36 kg (95%CI: -0.42 to -8.30), as compared to placebo with similar safety profile.

Our findings suggest that the use of liraglutide and semaglutide in patients who previously underwent MBS can promote significant weight reduction with acceptable safety profile.

Moderate-Intensity Combined Training Induces Lipidomic Changes in Individuals with Obesity and Type 2 Diabetes.

Clinical Endocrinology

Alterations in the lipid metabolism are linked to metabolic disorders such as insulin resistance (IR), obesity and type 2 diabetes (T2D). Regular exercise, particularly combined training (CT), is a well-known non-pharmacological treatment that combines aerobic (AT) and resistance (RT) training benefits. However, it is unclear whether moderate-intensity exercise without dietary intervention induces changes in lipid metabolism to promote a 'healthy lipidome'.

The study aimed to investigate the effect of 16 weeks of CT on plasma and white adipose tissue in both sexes, middle-aged subjects with normal weight, obesity and T2D using an ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) untargeted lipidomics approach.

Body composition, maximum oxygen consumption (VO2 max), strength, and biochemical markers were evaluated before and after the control/training period and correlated with lipid changes. CT consisted of 8 to 10 RT exercises, followed by 35 min of AT (45 -70% VO2 max), 3 times a week for 16 weeks.

The CT significantly reduced the levels of saturated and monounsaturated fatty acid side-chains (SFA/MUFA) in sphingolipids, glycerolipids (GL) and glycerophospholipids (GP) as well as reducing fat mass, circumferences and IR. Increased levels of polyunsaturated fatty acids in GPs, and GLs were also observed, along with increased fat-free mass, VO2 max, and strength (all p < 0.05) after training.

Our study stated that 16 weeks of moderate-intensity CT remodelled the lipid metabolism in OB, and T2D individuals, even without dietary intervention, establishing a link between exercise-modulated lipid markers and mechanisms that reduce IR and obesity-related comorbidities.

Effects of Supplemental Vitamin D3, Omega-3 Fatty Acids on Physical Performance Measures in VITamin D and OmegA-3 TriaL.

Clinical Endocrinology

Declining muscle strength and performance in older adults are associated with falls, fractures, and premature death.

To determine whether supplementation with vitamin D3 or omega-3 fatty acids vs. placebo for 2 years improves physical performance measures.

2-year changes in physical performance measures of grip strength, walking speed, standing balance, repeated chair stands, and Timed-up and Go (TUG).

At 2 years, all randomized groups showed worsening walking speeds and TUG. There were no differences in changes in grip strength, walking speeds, Short Physical Performance Battery (composite of walking speed, balance, and chair stands), and TUG between the vitamin D3-treated and the placebo-treated groups and between the omega-3-treated and the placebo-treated groups. Effects overall did not vary by sex, age, body mass index, or baseline measures of total or free 25-hydroxyvitamin D (25[OH]D) or plasma n-3 index; TUG slightly worsened with vitamin D supplementation, compared to placebo, in participants with baseline total 25(OH)D levels above the median (p=0.01, p for interaction=0.04).

Neither supplemental vitamin D3 nor marine omega-3 fatty acids for 2 years improved physical performance in this generally healthy adult population.

Age-related curves of AMH using the Gen II, the picoAMH and the Elecsys assays in women with polycystic ovary syndrome.

Clinical Endocrinology

Several challenges still exist to adopt the anti-Müllerian hormone (AMH) as a marker of polycystic ovary morphology (PCOM), as included in the recently updated international guideline. Although different evaluations of age- and assay-specific reference ranges have been published in the last years, these studies have mainly been conducted in normo-ovulatory or infertile women.

To develop an age-specific percentile distribution of AMH in patients with polycystic ovary syndrome (PCOS) measured by three different assays.

Serum AMH measurement by the Gen II (Beckman Coulter), the picoAMH (Ansh Labs), and the Elecsys (Roche) assays.

Age-specific centile curves for all the assays and correlations between AMH, clinical, hormonal, and ultrasound characteristics.

Age-related nomograms for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of AMH were calculated using the LMS method for all the assays. AMH levels were significantly different between PCOS phenotypes. AMH levels were positive correlated to luteinizing hormone (LH), LH/follicular stimulating hormone (FSH) ratio, testosterone, androstenedione, free androgen index, mean follicular number, and mean ovarian volume.

To our knowledge this is the first study reporting age specific percentile nomograms of serum AMH levels measured by the Gen II, the picoAMH and the Elecsys assays in a large population of PCOS women. These findings may help to interpret AMH levels in PCOS patients and facilitate the use of AMH as a diagnostic tool across age ranges.

Impact of breastfeeding duration on coagulation in women with and without history of gestational diabetes mellitus.

Clinical Endocrinology

Breastfeeding is associated with a reduced maternal risk for cardiovascular diseases. Since the underlying mechanisms are still poorly understood, we here examined the impact of breastfeeding on the plasmatic coagulation system in women with and without history of gestational diabetes mellitus (GDM).

76 participants of the German Gestational Diabetes Study (PREG; NCT04270578) were examined 14 [interquartile range: 12-26] months after delivery with a 5-point oral glucose tolerance test. Global coagulation tests, prothrombotic coagulation proteins (FII/FVII/FVIII/FIX), antithrombotic proteins (antithrombin, protein C/S) and endothelial markers (von-Willebrand-factor and PAI-1) were determined. The Framingham Risk Score was used to estimate the 10-year cardiovascular risk. The impact of breastfeeding duration on coagulation was analyzed using multivariable linear models.

The mean duration of breastfeeding was 11 [7-14] months. Overall, longer duration of breastfeeding was associated with lower cardiovascular risk (Framingham Risk Score, p=0.05) and was negatively associated with FIX (p=0.018). We detected an interaction between previous GDM and breastfeeding duration for FIX (pInteraction=0.017): only in women with GDM history was the duration of breastfeeding negatively associated with FIX activity (p=0.016). This association persisted in statistical models adjusted for age, body-mass index, insulin sensitivity, and C-reactive protein. The duration of breastfeeding was not associated with anticoagulant proteins and endothelial markers.

Longer duration of breastfeeding is associated with lower cardiovascular risk and an improved coagulation profile. Women with GDM history appear to benefit particularly from prolonged breastfeeding.

The 13C glucose breath test accurately identifies insulin resistance in people with type 1 diabetes.

Clinical Endocrinology

This study investigated whether the delta-over-baseline of exhaled 13CO2 (Δ13CO2), generated from a 13C glucose breath test (13C-GBT), measured insulin resistance (IR) in people with type 1 diabetes, using the hyperinsulinemic-euglycemic clamp (HEC) as reference method. Secondary objective was to compare the 13C-GBT with the estimated glucose disposal rate (eGDR).

A 40 mU/m2/min HEC and two separate 13C-GBTs (euglycemic with insulin bolus and hyperglycemic without bolus) were consecutively performed in 44 adults with type 1 diabetes with varying body compositions. eGDR was calculated based on HbA1c, presence of hypertension and waist circumference.

Mean M-value was 5.9 ± 3.1 mg/kg/min, mean euglycemic Δ13CO2 was 6.4 ± 2.1 δ‰, while median eGDR was 5.9 [4.3 - 9.8] mg/kg/min. The hyperglycemic Δ13CO2 did not correlate with the M-value, while the euglycemic Δ13CO2 and the M-value correlated strongly (r = 0.74, p < 0.001). Correlation between M-value and eGDR was more moderate (Spearman's rho = 0.63, p < 0.001). Linear regression showed an association between Δ13CO2 and M-value, adjusted for age, sex and HbA1c (adjusted R² = 0.52, B = 1.16, 95% CI 0.80 - 1.52, p < 0.001). The AUROC for Δ13CO2 to identify subjects with IR (M-value < 4.9 mg/kg/min) was 0.81 (95% CI 0.68 - 0.94, p < 0.001). The optimal cut-off for Δ13CO2 to identify subjects with IR was ≤ 5.8 δ‰.

Under euglycemic conditions, the 13C-GBT accurately identified individuals with type 1 diabetes and concurrent IR, suggesting its potential as a valuable non-invasive index.

Critical Role for 24-Hydroxylation in Homeostatic Regulation of Vitamin D Metabolism.

Clinical Endocrinology

The body has evolved homeostatic mechanisms to maintain free levels of Ca+2 and 1,25-dihydroxyvitamin D [1,25(OH)2D] within narrow physiological ranges. Clinical guidelines emphasize important contributions of PTH in maintaining this homeostasis.

To investigate mechanisms of homeostatic regulation of vitamin D (VitD) metabolism and to apply mechanistic insights to improve clinical assessment of VitD status.

VitD3-supplements (50,000 IU once or twice a week depending on BMI, for 4-6 weeks) were administered to achieve 25(OH)D≥30 ng/mL.

VitD3-supplementation significantly increased mean 25(OH)D by 2.7-fold and 24,25-dihydroxyvitamin D [24,25(OH)2D] by 4.3-fold. In contrast, mean levels of PTH, FGF23, and 1,25(OH)2D did not change. Mathematical modeling suggested that 24-hydroxylase activity was maximal for 25(OH)D≥50 ng/mL and achieved a minimum (∼90% suppression) with 25(OH)D<10-20 ng/mL. The 1,25(OH)2D/24,25(OH)2D ratio better predicted modeled 24-hydroxylase activity (h) (ρ=-0.85; p=0.001) compared to total plasma 25(OH)D (ρ=0.51; p=0.01) and the 24,25(OH)2D/25(OH)D ratio (ρ=0.37; p=0.3).

Suppression of 24-hydroxylase provides a first line of defense against symptomatic VitD-deficiency by decreasing metabolic clearance of 1,25(OH)2D. The 1,25(OH)2D/24,25(OH)2D ratio provides a useful index of VitD status since it incorporates 24,25(OH)2D levels and therefore, provides insight into 24-hydroxylase activity. When VitD availability is limited, this suppresses 24-hydroxylase activity - thereby decreasing the level of 24,25(OH)2D and increasing the 1,25(OH)2D/24,25(OH)2D ratio. Thus, an increased 1,25(OH)2D/24,25(OH)2D ratio signifies triggering of homeostatic regulation, which occurs at early stages of VitD-deficiency.

Elagolix Represents a Less Invasive and Cheaper Option than Injectable GnRH Antagonist for Ovulation Suppression in IVF.

Clinical Endocrinology

The injectable GnRH antagonists have traditionally been used for ovulation suppression during controlled ovarian hyperstimulation in IVF, leading to increased painful daily injections and cost. The use of the oral GnRH antagonist elagolix for ovulation suppression in IVF has not been studied.

A retrospective cohort study of patients undergoing IVF received either oral elagolix 50 mg every other day or ganirelix/cetrotide injection daily for ovulation suppression during controlled ovarian hyperstimulation. A total of 269 patients, 173 in the elagolix group and 96 in the ganirelix/cetrotide group, were included. The main outcome was the suppression of luteinizing hormone (LH) blood levels reflecting ovulation suppression.

The age, body mass index, AMH levels, baseline FSH, antral follicles count, the dose of medications used, the number of days of ovarian stimulation, and peak estradiol (E2) levels were similar in both groups. When blood LH and E2 levels were measured before the intake and the day after intake of either elagolix or ganirelix/cetrotide, both groups had significant and similar drop in LH levels and increase in E2 levels. When comparing the IVF cycle outcomes in both groups, the number of oocytes retrieved, the number of mature oocytes, the fertilization rate, the blastocyst formation rate, the euploidy rate and the endometrial lining thickness at the time of the trigger were all similar.

Oral GnRH antagonist, a much cheaper and less invasive medication that is used at a lower frequency, showed comparable ovulation suppression to the costly injectable GnRH antagonist. Further studies are required to evaluate the effect of oral GnRH antagonist on endometrial lining receptivity and pregnancy outcomes especially when using fresh embryo transfer IVF protocols.

Genetic Links Between Metabolic Syndrome and Osteoarthritis: Insights from Cross-Trait Analysis.

Clinical Endocrinology

Previous observational studies have indicated a bidirectional association between metabolic syndrome (MetS) and osteoarthritis (OA). However, it remains unclear whether these bidirectional associations reflect causal relationships or shared genetic factors, and the underlying biological mechanisms of this association are not fully understood.

Leveraging summary statistics from genome-wide association studies (GWASs) conducted by the UK Biobank and the Glucose and Insulin-related Traits Consortium (MAGIC), we performed global genetic correlation analyses, genome-wide cross-trait meta-analyses, and a bidirectional two-sample Mendelian randomization analyses using summary statistics from GWASs to comprehensively assess the relationship of MetS and OA.

We first detected an extensive genetic correlation between MetS and OA (rg=0.393, P=1.52×10-18), which was consistent in four MetS components, including waist circumference, triglycerides, hypertension and high-density lipoprotein cholesterol and OA with rg ranging from -0.229 to 0.490. We then discovered 32 variants jointly associated with MetS and OA through multi-trait Analysis of GWAS. Co-localization analysis founded 12 genes shared between MetS and OA, with functional implications in several biological pathways. Finally, MR analysis suggested genetic liability to MetS significantly increased the risk of OA, but no reverse causality was found.

Our results illustrate a common genetic architecture, pleiotropic loci, as well as causality between MetS and OA, potentially enhancing our knowledge of high comorbidity and genetic processes that overlap between the two disorders.

Cardiovascular Safety of Romosozumab vs. PTH Analogs for Osteoporosis Treatment: a Propensity Score Matched Cohort Study.

Clinical Endocrinology

Romosozumab, a monoclonal sclerostin antibody, is a recently approved highly potent anti-osteoporotic agent with osteoanabolic properties. Clinical use of Romosozumab is hindered by the fear of adverse cardiovascular (CV) events raised following the pivotal ARCH-trial.

To assess real-world CV safety of romosozumab vs. alternative osteoanabolic therapies used for treatment of severe osteoporosis.

Data was obtained from TriNetX, a global federated health research network including real-time electronic medical records from 113 healthcare organizations with a total of 136,460,930 patients across 16 countries at time of analysis. Inclusion criteria were age ≥ 40 years, a diagnosis of osteoporosis and prescription of romosozumab or a PTH analog (teriparatide/abaloparatide) during 8.2019-8.2022. 1:1 propensity score matched cohorts were created using demographic variables, comorbidities, and medications. Kaplan-Meier analysis was used to estimate the probability of the outcomes.

5,626 and 15,986 patients met the criteria for romosozumab and PTH analog cohorts, respectively, with 5,610 patients per group following propensity score matching. 3P-MACE was significantly less frequent in the romosozumab vs. PTH analog cohort (158 vs 211 patients with an outcome, p=0.003) with reductions in the individual components of the composite outcome: myocardial ischemic events (31 vs 58, p=0.003); cerebrovascular events 56 vs 79, p=0.037; deaths (83 vs 104, p=0.099).

In a diverse real-world setting, prescription of romosozumab for osteoporosis is associated with less adverse CV events when compared to PTH analog therapy.