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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Phenotypic Heterogeneity and Fertility Potential of Patients with 17-Hydroxylase/17,20-lyase Deficiency.

Clinical Endocrinology

17α-Hydroxylase/17,20-lyase deficiency (17OHD) is caused by a human CYP17A1 gene mutation and has the classical phenotype of hypertension, hypokalemia, sexual infantilism, and primary amenorrhea in females (46,XX) and disorders of sexual development in males (46,XY). To date, few cases of 17OHD have been reported, and the likelihood of pregnancy has rarely been explored.

To study the clinical characteristics, phenotype heterogeneity, genotyping and the likelihood of pregnancy of patients with 17OHD.

Genotype analysis was performed by direct sequencing of the CYP17A1 gene and next-generation sequencing in nonclassical patients. In vitro enzyme activity assays and three-dimensional structure observations were used to assess the function of 3 missense mutations of the CYP17A1 gene. Progestin-primed ovarian stimulation (PPOS) was chosen for ovulation induction in 2 patients.

Eight mutations were identified from 13 patients, including the homozygous mutation p. N395D and p. R496C, compound heterozygous mutation p. Y329fs/p. A421A and p. I332T/p. D487_F489del in 4 nonclassical patients. For the three missense mutations, an in vitro functional study showed mild impairment of 17α-hydroxylase activities 15.3-25.0% but residual 17,20-lyase activities 6.6%-9.4%. Two 46,XX females succeeded in pregnancy by combined PPOS, IVF-ET and the use of low-dose dexamethasone. One patient successfully delivered 1 healthy baby.

Partial 17OHD present nonclassical clinical features, without hypertension and hypokalemia. Successful pregnancy in such 46,XX patients could be attained by the appropriate choice of ovulation induction regimen, precise dose of glucocorticoid to reduce progesterone levels, and the use of IVF-ET.

Relation of Testosterone, Dihydrotestosterone and Estradiol with Changes in Outcomes Measures in the Testosterone Trials.

Clinical Endocrinology

Many effects of testosterone are mediated through dihydrotestosterone (DHT) and estradiol. The relative contributions of each hormone to the observed effects of testosterone remain incompletely understood.

Using data from the Testosterone Trials, we assessed the association of changes in total testosterone, estradiol, and DHT levels over 12-months of testosterone treatment with hemoglobin, HDL cholesterol (HDLC), volumetric bone mineral density (vBMD) of lumbar spine, sexual desire, and prostate-specific antigen (PSA). We used random forests to model the associations of predicted mean changes in outcomes with change in each hormone at low, mean, or high change in the other two hormones. Stepwise regression models were run to confirm the findings of random forests.

Predicted increases in hemoglobin and sexual desire were greater with larger increases in estradiol and were larger with high change in DHT compared to low change in DHT. Greater increases in estradiol were associated with larger decreases in HDLC; this association did not vary according to changes in DHT or testosterone. Change in vBMD was most robustly associated with change in estradiol and was greater with high change in testosterone and DHT. There was no consistent relation between change in PSA and change in any hormone.

Change in estradiol level was the best predictor not only of the change in vBMD and sexual desire but also of the changes in hemoglobin and HDLC. Consideration of testosterone, E2, and DHT together offers a superior prediction of treatment response in older hypogonadal men than testosterone alone.

Circulating levels of microRNA-122 and hepatic fat change in response to weight-loss interventions: CENTRAL Trial.

Clinical Endocrinology

Little is known about the relations between changes in circulating microRNA-122 (miR-122) and liver fat in response to weight-loss interventions. We aimed to investigate the association between miR-122 and changes of hepatic fat content during 18-month diet and physical activity interventions.

The CENTRAL trial is an 18-month randomized, controlled trial among adults with abdominal obesity or dyslipidemia. Subjects were randomly assigned to a low-fat diet or a Mediterranean/low-carbohydrate diet. After six months of dietary intervention, each diet group was further randomized into added physical activity groups or no added physical activity groups for the following 12 months of intervention. The current study included 220 participants at baseline and 134 participants with repeated measurements on serum miR-122 and hepatic fat content over 18 months.

Serum miR-122 significantly increased from baseline to 18 months, while no difference was observed across the four intervention groups. We found a significant association between miR-122 and hepatic fat content at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content (P<0.001). Furthermore, we found that higher elevations in miR-122 were associated with less reductions in hepatic fat percentage during 18-month interventions (β=1.56, P=0.002). We also found a significant interaction between changes in miR-122 and baseline fasting plasma glucose with hepatic fat content changes in 18 months (P interaction=0.02).

Our data indicate that participants with higher elevation in serum miR-122 may benefit less in reduction of hepatic fat content in response to diet and physical activity interventions.

Surveillance improves outcomes for carriers of SDHB pathogenic variants: a multi-center study.

Clinical Endocrinology

Carriers of succinate dehydrogenase type B (SDHB) pathogenic variants (PV) are at risk of pheochromocytoma and paraganglioma (PPGL) from a young age. It is widely recommended carriers enter a surveillance program to detect tumors but there are limited studies addressing outcomes of surveillance protocols for SDHB PV carriers.

The purpose of this study was to describe surveillance-detected (s-d) tumors in SDHB PV carriers enrolled in a surveillance program and to compare their outcomes to probands.

This was a multi-center study of SDHB PV carriers with at least one surveillance episode (clinical, biochemical, imaging) in Australian genetics clinics. Data were collected by both retrospective and ongoing prospective follow-up. Median duration of follow-up was 6.0 years.

181 SDHB PV carriers (33 probands and 148 non-probands) were assessed. Tumors were detected in 20% of non-probands undergoing surveillance (age range 9-76 years). Estimated 10-year metastasis-free survival was 66% for probands and 84% for non-probands with s-d tumors (p=0.027). S-d tumors were smaller than those in probands (median 27 mm versus 45 mm respectively, p=0.001). Tumor size ≥40 mm was associated with progression to metastatic disease (OR 16.9, 95% CI 2.3-187.9, p=0.001). Patients with s-d tumors had lower mortality compared to probands: 10-year overall survival was 79% for probands and 100% for non-probands (p=0.029).

SDHB carriers with s-d tumors had smaller tumors, reduced risk of metastatic disease and lower mortality compared to probands. Our results suggest that SDHB PV carriers should undertake surveillance to improve clinical outcomes.

Effects of Different Doses of Exercise on Inflammation Markers Among Adolescents with Overweight/Obese: HEPAFIT Study.

Clinical Endocrinology

Obesity-related metabolic risk factors in adolescents with overweight/obesity may be associated with systemic low-grade inflammation, and therefore we investigated whether a 6-month exercise training altered markers of inflammation.

Secondary analyses of a randomized controlled exercise-based intervention trial (September 2017 to December 2018). Adolescents aged 11 to 17 years (Tanner stage II to V), 70% girls, with a body mass index (BMI) z-score at or above the 85 th percentile, and/or with excess of adiposity (body fat >30%). The participants were randomly assigned to the following 4 groups for 6 months: (1) standard physical education lessons, as a control (CTRL); (2) high-intensity physical education class (HIPE); (3) low-to-moderate intensity physical education class (LIPE); (4) a combined group (PLUS group). Inflammatory markers and immune molecules including chemokines, cytokines, and growth factors (n=65 biomarkers) were determined by cytokine antibody array.

Of the 120 randomly assigned participants, 95 were included in the analysis. Considering these 22 proteins, the LIPE group shows statistical significance in 9 proteins with logfold-change (logFC) and p<0.05 was found in BLC, Eotaxin, FGF-6, GCP-2, I-309, IGFBP-4, MCP-4, NAP-2, and PARC), followed by the PLUS group in 9 proteins (BLC, EGF, Eotaxin, FGF-6, MCP-4, NAP-2, Osteopontin, PARC, and RANTES), the HIPE group in 7-proteins (FGF-4, FGF-7, GCP-2, IGF-1, IGFBP-1, IGFBP-4, and MIP-1 delta), the CTRL group in 6 proteins (FGF-4, IP-10, Leptin, MCP-1, MIG, and MIP-1 delta). However, sub-analysis performed to detect differentially expressed proteins at baseline and post-intervention, with significance at an adjusted p value ≤ 0.05 and absolute (logFC) ≥ 1.0, shown three down-regulated proteins in the LIPE group (BLC (logFC)= 1.27, Eotaxin (logFC)= 1.18 and MCP-4 (logFC)= 1.14), and four proteins in the HIPE group (BLC (logFC)= 1.45, FGF-6 (logFC)= 1.20, MCP-4 (logFC)= 1.50, and PARC ​(logFC)= 1.33), supporting that the changes that we observed in the exercise groups were not time-related changes but occurred in response to exercise.

Implementing a 6-month physical exercise program in overweight/obese adolescents, based on LIPE and PLUS groups, significantly change several circulating inflammatory levels. Interventions involving supervised physical exercise may reduce the associated effects of systemic low-grade inflammation, thus preventing the development of obesity-related metabolic diseases in adolescents with overweight/obesity.

The contribution of deleterious rare alleles in ENPP1 and osteomalacia causative genes to atypical femoral fracture.

Clinical Endocrinology

Atypical femoral fractures (AFFs) are very rare atraumatic or mild-trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incident of AFFs is higher in Asian. Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes were not reported, we investigated rare variants in genes causing abnormal mineralization.

Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese AFF patients (n=42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n=4773).

The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P=0.0012, corrected P [Pc]=0.0155, odds ratio [OR] 4.73, 95% confidence interval [CI] 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P=0.0025, OR 2.72, 95%CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of AFF patients with higher frequencies of deleterious rare alleles in ENPP1 (P=4.69X10 -5, Pc=0.0006, OR 8.47, 95%CI 3.76-19.09) and the candidate genes (P=1.08X10 -5, OR 5.21, 95%CI 2.76-9.86).

AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1.

National Hospital Organization.

Steroid hormone profiles and molecular diagnostic tools in pediatric patients with non-CAH primary adrenal insufficiency.

Clinical Endocrinology

There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology.

Investigation of the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin.

Forty-one patients (17 females, median age: 3 months, range: 0-8 years) with non-CAH PAI of unknown etiology.

A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to healthy control group, patients showed lower steroid concentrations, most significantly in cortisone, cortisol, and corticosterone (p<0.0001, area under the ROC curve: 0.96, 0.88, 0.87, respectively). Plasma cortisol<4 ng/mL, cortisone<11 ng/mL, and corticosterone<0.11 ng/mL had >95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology.

Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, while they are unlikely to point out a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, while little additional benefit is expected from WES.

Intra-trial mean 25(OH)D and PTH levels and risk of falling in older men and women in the Boston STOP IT trial.

Clinical Endocrinology

Supplementation with vitamin D has the potential to both reduce and increase risk of falling, and parathyroid hormone (PTH) may contribute to fall risk.

To assess the associations of intra-trial mean circulating levels of 25-hydroxyvitamin D [25(OH)D] and PTH on incident falls in healthy older adults.

410 men and women age 65 years and older who participated in the 3-year Boston STOP IT trial to determine the effect of supplementation with 700 IU of vitamin D3 plus calcium on incident falls (secondary endpoint). Intra-trial exposures of 25(OH)D and PTH were calculated as the mean of biannual measures up to and including the first fall.Main outcome measures: incidence of first fall.

Intra-trial mean 25(OH)D was significantly associated with risk of falling in a U-shaped pattern; the range associated with minimal risk of falling was approximately 20-40 ng/ml. PTH was not significantly associated with risk of falling.

The findings highlight the importance of maintaining the circulating 25(OH)D level between 20 and 40 ng/ml, the range that is also recommended for bone health. At PTH levels within the normal range, there was no detectible independent association of PTH with fall risk.

Hyperthyroidism in Graves' disease causes sleep disorders related to sympathetic hypertonia.

Clinical Endocrinology

It is well known that Graves' disease (GD) causes sleep disorders (SD). However, the characteristics and associated factors of SD and its clinical course post-hyperthyroidism normalization remain unclear.

To clarify the characteristics and associated factors of subjective SD and its clinical course after GD treatment.

From November 2017 to October 2020, we enrolled 72 participants (22 newly diagnosed with GD with untreated hyperthyroidism, 20 previously diagnosed with GD with normal thyroid function, and 30 normal controls) with no other underlying sleep disorder-related diseases. We compared the groups at enrollment and conducted prospective observations after 12 months of treatment on participants with newly diagnosed GD.

Differences and changes in the Pittsburgh Sleep Quality Index (PSQI) global and component sleep quality scores.

PSQI global sleep quality scores (p = 0.036) and sleep disturbance scores (p = 0.011) were significantly different among the three groups, and were highest in the untreated hyperthyroidism group. Multiple regression analysis demonstrated that free thyroxine level, which was positively correlated with sympathetic tone (ST) as evaluated by pulse rate and urinary total metanephrines, was associated with poorer PSQI global sleep quality scores independently of other factors (p = 0.006). Prospective observation showed that PSQI global sleep quality scores (p = 0.018) and sleep disturbance scores (p = 0.011) significantly improved with thyroid function normalization and ST attenuation.

Hyperthyroidism caused by GD augmented ST and exacerbated subjective SD. Normalization of hyperthyroidism caused by GD improved subjective SD.

Circulating MicroRNA Profiles as Potential Biomarkers for differentiated thyroid cancer recurrence.

Clinical Endocrinology

Circulating microRNAs (miRNAs) are emerging biomarkers of thyroid cancer.

This study sought to identify the profile of circulating miRNAs and its response to human recombinant TSH (rhTSH) in thyroid cancer patients with recurrent/persistent disease.

We obtained serum samples from 30 patients with differentiated thyroid cancer, 14 with recurrent/persistent disease and 16 with complete remission. We used next generation sequencing to define the miRnomes along with a comprehensive qPCR validation using two different platforms. We made a transversal study by comparing serum miRNA profiles of patients with or without recurrent/persistent disease and a longitudinal study looking at differences before and after rhTSH stimulation. Selected miRNAs were then studied in human thyroid cancer cell lines TPC-1, FTC-133 and OCUT-2 in response to TSH stimulation.

We could not demonstrate any consistent differences in serum profiles of known miRNAs between patients with and without recurrent/persistent disease or before and after rhTSH stimulation. However, our sequencing data revealed two putative novel miRNAs that rise with rhTSH stimulation in the serums of patients with recurrent/persistent disease. We further confirmed by qPCR the upregulation of these putative miRNAs both in serums and in TSH-stimulated cells. We also show miRNAs that are good candidates for housekeeping genes in the serum of patients independently of the levels of TSH.

The present study does not provide evidence that known miRNAs can be used as circulating markers for recurrence of thyroid cancer. However, we suggest that novel miRNA molecules may be related to thyroid cancer pathogenesis.

Salt sensitivity of blood pressure and aldosterone: interaction between Lysine-specific demethylase 1 gene, sex, and age.

Clinical Endocrinology

Salt sensitivity of blood pressure (SSBP) is associated with increased cardiovascular risk, especially in individuals of African descent, although underlying mechanisms remain obscure. Lysine-specific demethylase 1 (LSD1) is a salt-sensitive epigenetic regulator associated with SSBP and aldosterone dysfunction. An LSD1 risk allele in humans is associated with SSBP and lower aldosterone levels in hypertensive African but not European descent. Heterozygous knockout LSD1 mice display SSBP and aldosterone dysregulation, but this effect is modified by age and biological sex. This might explain differences in cardiovascular risk with aging and biological sex in humans.

To determine if LSD1 risk allele (rs587618) carriers of African descent display a sex-by-age interaction with SSBP and aldosterone regulation.

We analyzed 297 individuals of African and European descent from the HyperPATH cohort. We performed multiple regression analyses for outcome variables related to SSBP and aldosterone.

LSD1 risk allele carriers of African (but not European) descent had greater SSBP than non-risk homozygotes. Female LSD1 risk allele carriers of African descent had greater SSBP, mainly relationship-driven by women of low estrogen (postmenopausal). There was a significant LSD1 genotype-sex interaction in aldosterone response to angiotensin II stimulation in individuals ≤50 years, with female carriers displaying decreased aldosterone responsiveness.

SSBP associated with LSD1 risk allele status is driven by women of deplete estrogen state. Mechanisms related to a resistance to develop SSBP in females are uncertain but may relate to an estrogen modulating effect on mineralocorticoid receptor activation and/or LSD1 epigenetic regulation of the mineralocorticoid receptor.

Variability, mean, and baseline values of metabolic parameters in predicting the risk of type 2 diabetes.

Clinical Endocrinology

Impact of baseline and alteration of metabolic parameters (MPs), including plasma glucose (PGs) testing, insulin resistance surrogates, and lipid profile and their mutual interactions on the development of type 2 diabetes (T2DM) has not been investigated systematically.

To access the association of the past variability (V), past mean (M), and the baseline (B) values of various MPs and their mutual interaction with the risk of T2DM.

3829 non-diabetic participants with completed MPs measurements during three biannually visits were followed up over the next 10 years.

Among predictors, PG concentrations measured during the oral glucose tolerance test were the most prominent T2DM determinants, in which the M of the average value of fasting PG, 1-h, and 2-h PGs had the strongest discriminative power (hazard ratios and 95% CI for an increment of SD: 3.00 (2.5-3.26), AUC: 0.82). The M values of MPs were superior to their B and V values in predicting T2DM, especially among post-load PGs. Various mutual interactions between indices and among MPs were found. The most consistent interactants were the M values of high-density lipoprotein cholesterol and the M and V values of fasting PG. The findings were similar in normal tolerance glucose participants and were confirmed by sensitivity analyses.

The post-load PGs, past alteration of measurements, and mutual interactions among indices of MPs are important risk factors for T2DM development.