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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Approach to the patient: Diagnosis of Cushing's syndrome.

Clinical Endocrinology

Cushing's syndrome results from supraphysiological exposure to glucocorticoids and is associated with significant morbidity and mortality. The path...

Inflammatory cytokines rewire the proinsulin interaction in human islets.

Clinical Endocrinology

Aberrant biosynthesis and secretion of the insulin precursor proinsulin occurs in both Type I and Type II diabetes (T1D, T2D). Inflammatory cytokines are implicated in pancreatic islet stress and dysfunction in both forms of diabetes but the mechanisms remain unclear.

We sought to determine the effect of the diabetes associated cytokines on proinsulin folding, trafficking, secretion, and b-cell function.

Human islets were treated with interleukin-1β and interferon-γ for forty-eight hours, followed by analysis of IL6, nitrite, proinsulin and insulin release, RNAseq, and unbiased profiling of the proinsulin interactome by Affinity Purification-Mass Spectrometry (AP-MS).

Cytokine treatment induced secretion of IL6, nitrites, and insulin, as well as aberrant release of proinsulin. RNAseq showed that cytokines upregulated genes involved in ER stress and consistent with this, AP-MS revealed cytokine induced proinsulin binding to multiple ER chaperones and oxidoreductases. Moreover, increased binding to the chaperone BiP was required to maintain proper proinsulin folding in the inflammatory environment. Cytokines also regulated novel interactions between proinsulin and T1D and T2D GWAS candidate proteins not previously known to interact with proinsulin (e.g., Ataxin-2). Finally, cytokines induced proinsulin interactions with a cluster of microtubule motor proteins and chemical destabilization of microtubules with Nocodazole exacerbated cytokine induced proinsulin secretion.

Together, the data shed new light on mechanisms by which diabetes associated cytokines dysregulate β-cell function. For the first time we show that even short term exposure to an inflammatory environment reshapes proinsulin interactions with critical chaperones and regulators of the secretory pathway.

The androgen metabolome of preterm infants reflects fetal adrenal gland involution.

Clinical Endocrinology

The human adrenal cortex changes with fetal-neonatal transition from the fetal to the adult organ, accompanied by changes in the steroid metabolome.

As it is unclear how the observed developmental changes differ between preterm and full-term neonates, we investigated whether the involution of the fetal adrenals is following a fixed time course related to postmenstrual age or whether it is triggered by birth. Furthermore, the fetal and postnatal androgen metabolome of preterm infants was characterized in comparison to term babies.

Steroid metabolites were measured from spot urines by gas chromatography-mass spectrometry. Data relating were modelled according to established pre- and postnatal pathways.

Fetal adrenal involution occurs around term-equivalent age in preterm infants and is not triggered by premature birth. Testosterone levels are higher in preterm infants at birth and decline slower till term compared to full-term babies. Dihydrotestosterone levels and the activity of the classic androgen biosynthesis pathway are lower in premature infants as is 5α-reductase activity. No difference was found in the activity of the alternate backdoor pathway for androgen synthesis.

Human adrenal involution follows a strict timing that is not affected by premature birth. By contrast, prematurity is associated with an altered androgen metabolome after birth. Whether this reflects altered androgen biosynthesis in utero remains to be investigated.

Approach to Hypophosphatemic Rickets.

Clinical Endocrinology

Hypophosphatemic rickets typically presents in infancy or early childhood with skeletal deformities and growth plate abnormalities. The most common...

Targeted therapies in Pheochromocytoma and Paraganglioma.

Clinical Endocrinology

Molecular targeted therapy plays an increasingly important role in the treatment of metastatic pheochromocytomas and paragangliomas (PPGLs), which ...

Metabolic and genetic markers improve prediction of incident type 2 diabetes: A nested case-control study in Chinese.

Clinical Endocrinology

To identify novel metabolic markers for future type 2 diabetes (T2D) in Chinese individuals of Han ethnicity and to determine whether the combined effect of metabolic and genetic markers improves the accuracy of prediction models containing clinical factors.

A nested case-control study containing 220 incident T2D and 220 age- and sex- matched controls from normoglycemic Chinese individuals of Han ethnicity was conducted within the Wuxi Non-Communicable Disease cohort with a 12-year follow-up. Metabolic profiling detection was performed by high-performance liquid chromatography‒mass spectrometry (HPLC‒MS) by an untargeted strategy. Twenty single nucleotide polymorphisms (SNPs) associated with type 2 diabetes were genotyped using the Iplex Sequenom MassARRAY platform. Machine learning methods were used to identify metabolites associated with future T2D risk.

We found that abnormal levels of five metabolites were associated with an increased risk of future type 2 diabetes: riboflavin, cnidioside A, 2-methoxy-5-(1H-1, 2, 4- triazol-5- yl)- 4-(trifluoromethyl) pyridine, 7-methylxanthine and mestranol. The genetic risk score (GRS) based on 20 SNPs was significantly associated with T2D risk (OR = 1.35, 95% CI: 1.08-1.70 per SD). The area under the receiver operating characteristic curve (AUC) was greater for the model containing metabolites, GRS, and clinical traits than for the model containing clinical traits only (0.960 vs. 0.798, P = 7.91×10-16).

In individuals with normal fasting glucose levels, abnormal levels of 5 metabolites were associated with future T2D. The combination of newly discovered metabolic markers and genetic markers could improve the prediction of incident T2D.

Abaloparatide Increases Lumbar Spine and Hip BMD in Japanese Patients With Osteoporosis: The Phase 3 ACTIVE-J Study.

Clinical Endocrinology

Abaloparatide reduced fracture risk in postmenopausal women with osteoporosis in the ACTIVE study. Its effect in Japanese patients remains unexamined.

To determine the efficacy and safety of abaloparatide in increasing bone mineral density (BMD) in Japanese patients with osteoporosis at high fracture risk.

Randomized, double-blind, placebo-controlled study in Japan. Postmenopausal women and men with osteoporosis with high fracture risk were given daily subcutaneous 80 µg abaloparatide or placebo for 78 weeks (18 months). The primary endpoint was percent change in lumbar spine (LS) BMD from baseline at the last visit. Secondary endpoints included time-course changes in LS, total hip (TH), and femoral neck (FN) BMDs and bone turnover markers, and cumulative number of fractures.

Abaloparatide increased LS, TH, and FN BMDs (mean [95% CI]) by 12.5% (10.3%-14.8%; p<0.001), 4.3% (3.3%-5.3%), and 4.3% (2.9%-5.6%), respectively, vs placebo. Serum PINP increased rapidly to ~140% above baseline at 6 weeks and gradually decreased but was ~25% higher than baseline at 78 weeks. Serum CTX gradually increased to 50% above baseline at 24 weeks and decreased gradually to the placebo-group level from 60 weeks. Four vertebras of three participants in the placebo group, but none in the abaloparatide group, developed new vertebral fractures. The safety profile was similar to that in the ACTIVE study.

In Japanese patients with postmenopausal and male osteoporosis with high fracture risk, abaloparatide for 78 weeks robustly increased LS, TH, and FN BMDs, suggesting a similar efficacy in Japanese patients vs the ACTIVE study population.

Effect of Degarelix administration on bone health in prostate cancer patients without bone metastases. The Blade study.

Clinical Endocrinology

To characterize the changes in bone mineral density (BMD) and bone turnover markers after degarelix administration in prostate cancer patients without bone metastases. To explore the predictive role of body composition on treatment induced bone loss.

BMD and body composition [lean body mass (LBM), fat body mass (FBM) and appendicular mass index (ALMI)] were assessed by dual X-ray absorptiometry (DXA) on study entry and after 12 months of degarelix therapy. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) were assessed at baseline, 6 and 12 months.

Twenty-nine patients entered the study. Degarelix administration was associated with a significant decrease in BMD after 12 months (2.4% reduction from baseline at lumbar spine). Serum CTX and ALP increased significantly (median increase from baseline 99% and 19.3%, respectively). An inverse correlation was observed between ALMI and CTX, but not ALP, at both baseline (Pearson R -0.62, p<0.0001) and month 12 (Pearson R -0.41, p=0.032). Moreover, a significant inverse correlation between changes in ALMI and CTX at 12 months (Pearson R -0.43, p= 0.019) and a direct relationship between changes of ALMI and ALP (Pearson R 0.44, p= 0.016) during degarelix therapy were observed.

Degarelix administration is associated with a significant decrease in BMD and increase in bone turnover markers. ALMI is a promising predictor of bone loss in prostate cancer patients receiving androgen deprivation therapy and ALMI changes during therapy are associated with bone turnover derangement favouring bone quality alterations.

Longitudinal sex steroid data in relation to birth weight in preterm boys.

Clinical Endocrinology

There is a lack of knowledge on longitudinal sex steroid patterns during infancy, especially for boys born preterm, or with low birth weight (LBW).

To find out whether LBW boys have a disturbed sex steroid profile during infancy.

Serum androgen and estrogen concentrations were analyzed by gas chromatography-tandem mass spectrometry and IGF-I was determined with radioimmunoassay in umbilical cord and at 0, 2, 5, and 10 months corrected age.

Serum levels of androstenedione, estrone, and estradiol declined gradually from birth to 10 months corrected age. In both LBW boys and their counterparts, a surge was seen at 2 months corrected age (3 months chronological age) for testosterone, median (range) 6.5 (2.0 - 18.9) nmol/L, and in dihydrotestosterone 1.2 (0.4 - 4.3) nmol/L. At birth, LBW boys had higher median testosterone (0.7 versus 0.4 nmol/L, p=0.019), and at 0 months corrected age, both higher testosterone (5.7 versus 3.5 nmol/L, p=0.003) and dihydrotestosterone (1.2 versus 0.9 nmol/L, p=0.006) than their counterparts. At 10 months corrected age, catch-up in weight SDS from birth correlated with testosterone (rho=0.27, p=0.044), and androstenedione (rho=0.29, p=0.027).

Moderately to late preterm LBW boys showed a disturbed sex hormone profile, with elevated concentrations of androgens in early infancy.

A shifting relationship between sex hormone-binding globulin and total testosterone across puberty in boys.

Clinical Endocrinology

We aimed to clarify the nature of the relationship between testosterone and sex hormone binding globulin (SHBG) and improve our understanding of th...

Metabolic factors predict changes in endothelial function during the early course of type 1 and type 2 diabetes.

Clinical Endocrinology

Endothelial dysfunction may occur early in the development of cardiovascular and metabolic diseases, however, it remains often underestimated and studies rarely discriminate between diabetes types. Here, we examined endothelial function and its determinants during the early course of type 1 and type 2 diabetes.

Caucasian participants of the prospective German Diabetes Study (GDS) with known diabetes duration <1 year (n=398) or without diabetes, but of similar age, BMI and sex distribution (n=109), underwent measurements of flow-mediated dilation (FMD) and nitroglycerin-mediated dilatation (NMD). Whole-body insulin sensitivity (M-value) was assessed by hyperinsulinemic-euglycemic clamps and physical fitness (VO2max) by spiroergometry. A subset of individuals with type 1 or type 2 diabetes (n=108) was re-evaluated after 5 years.

At baseline, neither FMD nor NMD differed between people with diabetes and the matched glucose-tolerant groups. At the 5-year follow-up, decline in FMD (-13.9%, p=0.013) of persons with type 2 diabetes was independent of age, sex and BMI, but associated with baseline adipose tissue insulin resistance and indices of liver fibrosis. M-value decreased in both type 1 and type 2 diabetes groups by 24% and 15% (both p<0.001, respectively) over 5 years. Higher HbA1c, lower M-value and lower VO2max at baseline associated with lower FMD in both, type 1 and type 2 diabetes.

Endothelial function decreases during the early course of type 2 diabetes. In addition to age and BMI, insulin sensitivity at diagnosis was the best predictor of progressive impairment in endothelial function in type 2 diabetes.

The Risks of Cardiovascular Disease Following Weight Change in Adults with Diabetes: A Cohort Study and Meta-analysis.

Clinical Endocrinology

Weight management is recognized as critical in reducing cardio-metabolic risk factors for adults with diabetes, but the effects of weight change on cardiovascular disease in patients with diabetes are unknown.

To evaluate 18-month weight change and subsequent risk of macrovascular and microvascular complications in established individuals with type 2 diabetes.

This study consisted of a cohort study and a meta-analysis. In the cohort study, weight change over 18 months was divided into: gain ≥5%, gain 1%-5%, stable (-1%-1%), loss 1%-5%, and loss ≥5%. Cox regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). We then used random-effect models to pool the results combing our study with other relevant studies.

In the cohort study, 8920 participants with valid weight measurements were included. Compared with patients with stable weight, higher risks were seen in those with weight change for total vascular complications (gain ≥5%: HR=1.43, 95% CI: 1.10-1.85; gain 1-5%: HR=1.44, 95% CI: 1.02-2.03; loss ≥5%: HR=1.58, 95% CI: 1.20-2.08), macrovascular complications (gain ≥5%: HR=1.84, 95% CI: 1.16-2.91; loss 1-5%: HR=1.91, 95% CI: 1.06-3.43; loss ≥5%: HR=2.18, 95% CI: 1.36-3.49) and microvascular complications (loss ≥5%: HR=1.48, 95% CI: 1.06-2.06). Meta-analysis also showed similar results.

Weight gain and loss over 18 months among patients with type 2 diabetes, especially weight change ≥5%, may be a warning sign of adverse cardiovascular outcomes.