Determinants of Advanced Bone Age in Childhood Obesity

Background: Childhood obesity is associated with advanced bone age (BA). Previous studies suggest that androgens, oestrogens, sex hormone-binding globulin, and insulin are responsible for this phenomenon, but results are contradictory and might be biased by confounders. We aim to elucidate this matter by applying a multivariate approach. Method: We performed a correlation analysis of BA standard deviation score (SDS) with age- and sex-specific SDS for androgens, oestrogens, and with indicators of insulin secretion derived from oral glucose tolerance testing, in a group of obese children. A multivariate analysis was performed to investigate which parameters were independently predictive of BA SDS. Results: In this cohort (n = 101; mean age 10.9 years; mean BA 11.8 years; mean BMI SDS 3.3), BMI SDS was significantly correlated to BA SDS (r = 0.55, p < 0.001). In a regression analysis in the total cohort (B = 0.27, p < 0.001) as well as in females (B = 0.34, p = 0.042), males (B = 0.31, p = 0.006), and pubertal children (B = 0.32, p = 0.046), dehydroepiandrosterone sulphate (DHEAS) showed a positive, independent association with BA SD

Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults.

CONTEXT With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. OBJECTIVE To investigate incidence and determinants of spontaneous normalization of thyroid-stimulating hormone (TSH) levels in older adults with subclinical hypothyroidism. DESIGN Pooled data were used from the (i) pre-trial population, and (ii) in-trial placebo group from two randomized, double-blind, placebo-controlled trials (TRUST and IEMO thyroid 80-plus thyroid trial). SETTING Community-dwelling 65 + adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. PARTICIPANTS The pre-trial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free thyroxine (fT4) within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. MAIN OUTCOME MEASURES Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. RESULTS In the pre-trial phase, TSH levels normalized in 60.8% of participants in a median follow-up of one year. In the in-trial phase, levels normalized in 39.9% of participants after one year follow-up. Younger age, female sex, lower initial TSH level, higher initial fT4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. CONCLUSIONS Since TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment

The heart in sporadic inclusion body myositis: a study in 51 patients

The purpose of this study was to explore the prevalence and nature of cardiac abnormalities in sporadic inclusion body myositis (sIBM). Fifty-one sIBM patients were cross-sectionally studied using history-taking, physical examination, measurements of serum creatine kinase activity, the MB fraction (CK-MB), cardiac troponin T (cTnT) and I (cTnI), a 12-lead electrocardiogram (ECG) and 2-dimensional echocardiography. Present cardiac history was abnormal in 12 (24%) out of 51 patients, 12 (24%) patients had abnormalities on ECG, mostly aspecific, and in 12 (24%) patients the echocardiograph showed abnormalities. Elevated CK-MB was present in 42 (82%) patients and 40 (78%) had an elevated cTnT in the absence of acute cardiac pathology. In contrast, in one patient (2%) cTnI was elevated. There was no apparent association between elevated biomarkers, ECG or echocardiographic abnormalities. The prevalence of cardiac abnormalities in sIBM does not seem to be higher than would be expected in these elderly patients. Elevated CK-MB and cTnT levels are common, in contrast to cTnI, but do not reflect cardiac pathology

Discomfort in children undergoing unsedated MRI

Magnetic resonance imaging (MRI) scans for research purposes usually do not directly benefit the children scanned, so that review boards need to assess whether the risk of harm or discomfort is minimal. This study aimed at providing empirical data on discomfort related to unsedated MRI in children aged 5–12 years. Secondary objectives were to determine whether lower age is associated with higher levels of discomfort and to investigate which other characteristics of subjects and/or procedures may be associated with higher levels of discomfort. Self-report scores, observation scores, heart rate standard deviation scores, and incremental salivary cortisol levels were obtained from 54 children aged 5–12 years with non-acute conditions undergoing diagnostic MRI. Of the 54 children, 10 scored relatively high values on the self-report score and on one or two of the other measures, and another 15 scored relatively high on the self-report score alone. Rather than an age effect, associations were found between parents’ trait anxiety and observation score values and between use of contrast fluid (requiring the insertion of a venous cannula) and high incremental salivary cortisol levels. In conclusion, MRI-related discomfort may be regarded as minimal for more than half of children aged 5–12

Impact of a Public Health Emergency on Behavior, Stress, Anxiety and Glycemic Control in Patients With Pancreas or Islet Transplantation for Type 1 Diabetes

A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (β-cell Tx; n = 51) to control T1D patients (n = 272). Fear of coronavirus infection was higher in those with β-cell Tx than without (Visual Analogue Scale 5.0 (3.0–7.0) vs. 3.0 (2.0–5.0), p = 0.004) and social isolation behavior was more stringent (45.8% vs. 14.0% reported not leaving the house, p &lt; 0.001). A previous β-cell Tx was the most important predictor of at-home isolation. Glycemic control worsened in patients with β-cell Tx, but improved in control patients (ΔHbA1c +1.67 ± 8.74 vs. −1.72 ± 6.15 mmol/mol, p = 0.006; ΔTime-In-Range during continuous glucose monitoring −4.5% (−6.0%–1.5%) vs. +3.0% (−2.0%–6.0%), p = 0.038). Fewer patients with β-cell Tx reported easier glycemic control during lockdown (10.4% vs. 22.6%, p = 0.015). All T1D patients, regardless of transplantation status, experienced stress (33.4%), anxiety (27.9%), decreased physical activity (42.0%), weight gain (40.5%), and increased insulin requirements (29.7%). In conclusion, T1D patients with β-cell Tx are increasingly affected by a viral pandemic lockdown with higher fear of infection, more stringent social isolation behavior and deterioration of glycemic control.This trial has been registered in the clinicaltrials.gov registry under identifying number NCT05977205 (URL: https://clinicaltrials.gov/study/NCT05977205)

Endogenous sex hormones and risk of venous thromboembolism in young women

Background: The risk of venous thromboembolism (VTE) in young women can predominantly be attributed to exogenous hormone use. The influence of (abnormalities in) endogenous sex hormones, as in polycystic ovary syndrome (PCOS) or primary ovarian insufficiency (POI), on VTE risk is uncertain. Objectives: Th assess the association between endogenous sex hormone levels and VTE risk. Methods: Women aged ≤45 years from the MEGA case-control study who provided a blood sample in the absence of exogenous hormone exposure or pregnancy were included. Sex hormone–binding globulin (SHBG), estradiol, follicle-stimulating hormone (FSH) and testosterone were measured. The free androgen index (FAI) and estradiol to testosterone ratio (E:T) were calculated. VTE risk was assessed according to quartiles (Qs) of levels and clinical cut-offs as proxies for PCOS (FAI > 4.5) and POI (FSH > 40 U/L). Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results: Six hundred and sixty-five women (369 cases; 296 controls) were eligible for the analyses. Testosterone and FSH levels, E:T and POI (FSH > 40 U/L vs FSH ≤ 40 U/L) were not associated with VTE risk. For estradiol, VTE risk was increased with levels in Q4 vs Q1 (OR 1.6; 95% CI 1.0-2.5). There was a dose-response relationship between SHBG levels and VTE risk, with the highest OR at Q4 vs Q1: 2.0 (95% CI 1.2-3.3). FAI > 4.5 (PCOS proxy) vs FAI ≤ 4.5 was associated with increased VTE risk (OR 3.3; 95% CI 0.9-11.8). Conclusions: Estradiol, SHBG and FAI were associated with VTE risk, suggesting a role for endogenous sex hormones in the pathophysiology of VTE in young women

Effects of dehydroepiandrostenedione, superimposed on growth hormone substitution, on quality of life and insulin-like growth factor I in patients with secondary adrenal insufficiency: a randomized, placebo-controlled, cross-over trial

To assess whether dehydroepiandrostenedione (DHEA) substitution, superimposed on GH substitution, improves quality of life of patients with secondary adrenal failure, we studied the effects of DHEA (50 mg/d, 16 wk) vs. placebo (16 wk) in GH- and ACTH-deficient men (n = 15; age, 52 +/- 3 yr), and postmenopausal women (n = 16; age, 61 +/- 2 yr) in a double-blind, placebo-controlled, crossover study. All patients were receiving stable hormone replacement therapy, including a fixed dose of human recombinant GH during the study. The men received testosterone substitution. The female patients did not receive estrogen substitution. At baseline, multiple parameters of quality of life were impaired compared with age- and sex-matched controls, especially in female patients. These parameters were not improved by DHEA treatment. DHEA only slightly improved the depression score (women) and health perception (women and men), although these parameters were not abnormal at baseline. DHEA increased serum IGF-I concentrations in female patients (by approximately 18%; P <0.001), but not in male patients. In neither group did DHEA affect IGF-binding protein-3 levels. We conclude that DHEA, superimposed on GH substitution, does not substantially improve quality of life in patients with secondary adrenal insufficiency regardless of gender. In addition, DHEA increases IGF-I levels only in estrogen-depleted females, but not in testosterone-treated males, with secondary adrenal insufficienc

Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term effects on pancreatic endocrine cells are unknown. In this study we investigate the effects of long-term KD on glucose tolerance and β- and α-cell mass in mice. Despite an initial weight loss, KD did not result in weight loss after 22 wk. Plasma markers associated with dyslipidemia and inflammation (cholesterol, triglycerides, leptin, monocyte chemotactic protein-1, IL-1β, and IL-6) were increased, and KD-fed mice showed signs of hepatic steatosis after 22 wk of diet. Long-term KD resulted in glucose intolerance that was associated with insufficient insulin secretion from β-cells. After 22 wk, insulin-stimulated glucose uptake was reduced. A reduction in β-cell mass was observed in KD-fed mice together with an increased number of smaller islets. Also α-cell mass was markedly decreased, resulting in a lower α- to β-cell ratio. Our data show that long-term KD causes dyslipidemia, a proinflammatory state, signs of hepatic steatosis, glucose intolerance, and a reduction in β- and α-cell mass, but no weight loss. This indicates that long-term high-fat, low-carbohydrate KD lead to features that are also associated with the metabolic syndrome and an increased risk for type 2 diabetes in humans

Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic

Introduction Lockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes.Research design and methods We performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes ≥18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown.Results In total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: −0.39% (−4.3 mmol/mol) (p&lt;0.0001 and type 2 diabetes: −0.62% (−6.8 mmol/mol) (p=0.0036). Perceived stress was associated with difficulty with glycemic control (p&lt;0.0001).Conclusions An increase in perceived stress and anxiety, weight gain and less exercise but no deterioration of glycemic control occurs in both people with relatively well-controlled type 1 and type 2 diabetes during short-term lockdown measures. As perceived stress showed to be associated with glycemic control, this provides opportunities for healthcare professionals to put more emphasis on psychological aspects during diabetes care consultations