Women with polycystic ovary syndrome (PCOS) were treated with the GLP‐1 receptor agonist liraglutide to investigate the effect on liver fat content, visceral adipose tissue (VAT) and the prevalence ...of nonalcoholic fatty liver disease (NAFLD). In a double‐blind, placebo‐controlled, randomized clinical trial 72 women with PCOS, with a BMI > 25 kg/m2 and/or insulin resistance, were treated with liraglutide or received placebo 1.8 mg/d (2:1) for 26 weeks. Liver fat content was assessed by 1
HMR spectroscopy, VAT by MRI, body composition by DXA, and glucose metabolism by oral glucose tolerance test. Compared with placebo, liraglutide treatment reduced body weight by 5.2 kg (5.6%), liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two‐thirds (all P < .01). Sex‐hormone‐binding‐globulin (SHBG) levels increased by 19% (P = .03), and free testosterone decreased by 19% (P = .054). HbA1c, fasting glucose and leptin were reduced (all: P < .05), whereas measures of insulin resistance, adiponectin and glucagon did not change. In conclusion, 26 weeks of liraglutide treatment in PCOS resulted in significant reductions in liver fat content, VAT and the prevalence of NAFLD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Context:
Thyroid dysfunction has been associated with both increased all-cause and cardiovascular mortality, but limited data are available on mild thyroid dysfunction and cause-specific mortality.
...Objective:
The objective of the study was to examine the risk of all-cause mortality, major adverse cardiovascular events (MACEs), and cause-specific events in subjects with overt and subclinical thyroid dysfunction.
Design:
This was a retrospective cohort study.
Setting and Participants:
Participants in the study were subjects who underwent thyroid blood tests, without prior thyroid disease, consulting their general practitioner in 2000–2009 in Copenhagen, Denmark.
Main Outcome Measure:
All-cause mortality, MACEs, and cause-specific events identified in nationwide registries were measured.
Results:
A total of 47 327 (8.4%) deaths occurred among 563 700 included subjects mean age 48.6 (SD ±18.2) y; 39% males. All-cause mortality was increased in overt and subclinical hyperthyroidism age adjusted incidence rates of 16 and 15 per 1000 person-years, respectively; incidence rate ratios (IRRs) 1.25 95% confidence interval (CI) 1.15–1.36 and 1.23 (95% CI 1.16–1.30) compared with euthyroid (incidence rate of 12 per 1000 person-years). Risk of MACEs was elevated in overt and subclinical hyperthyroidism IRRs 1.16 (95% CI 1.05–1.27) and 1.09 (95% CI 1.02–1.16) driven by heart failure IRRs 1.14 (95% CI 0.99–1.32) and 1.20 (95% CI 1.10–1.31). A reduction of all-cause mortality was observed in subclinical hypothyroidism with TSH of 5–10 mIU/L IRR 0.92 (95% CI 0.86–0.98).
Conclusions:
Heart failure is the leading cause of an increased cardiovascular mortality in both overt and subclinical hyperthyroidism. Subclinical hypothyroidism with TSH 5–10 mIU/L might be associated with a lower risk of all-cause mortality.
Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels ...and symptoms suggestive of hypogonadism in current and former AAS abusers.
This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18-50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically.
Former AAS abusers exhibited significantly lower median (25th -75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9-17.7) nmol/l vs. 18.8 (16.6-22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05).
Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation. Current AAS abusers exhibited severely decreased AMH and inhibin B indicative of impaired spermatogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Low energy availability (EA) in female athletes with or without an eating disorder (ED) increases the risk of oligomenorrhoea/functional hypothalamic amenorrhoea and impaired bone health, a syndrome ...called the female athlete triad (Triad). There are validated psychometric instruments developed to detect disordered eating behaviour (DE), but no validated screening tool to detect persistent low EA and Triad conditions, with or without DE/ED, is available.
The aim of this observational study was to develop and test a screening tool designed to identify female athletes at risk for the Triad.
Female athletes (n=84) with 18-39 years of age and training ≥5 times/week filled out the Low Energy Availability in Females Questionnaire (LEAF-Q), which comprised questions regarding injuries and gastrointestinal and reproductive function. Reliability and internal consistency were evaluated in a subsample of female dancers and endurance athletes (n=37). Discriminant as well as concurrent validity was evaluated by testing self-reported data against measured current EA, menstrual function and bone health in endurance athletes from sports such as long distance running and triathlon (n=45).
The 25-item LEAF-Q produced an acceptable sensitivity (78%) and specificity (90%) in order to correctly classify current EA and/or reproductive function and/or bone health.
The LEAF-Q is brief and easy to administer, and relevant as a complement to existing validated DE screening instruments, when screening female athletes at risk for the Triad, in order to enable early detection and intervention.
Aims
Among patients with type 2 diabetes and albuminuria, cardiorenal morbidity and mortality are high despite multifactorial treatment. Short‐term reduction in albuminuria is considered suggestive ...of long‐term renoprotective effects. We evaluated the renal effects of the glucagon‐like peptide‐1 (GLP‐1) receptor agonist liraglutide on top of multifactorial care, including renin‐angiotensin‐system (RAS)‐inhibition.
Materials and methods
Randomized, double‐blind, placebo‐controlled, cross‐over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin‐to‐creatinine ratio >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in a random order. The primary endpoint was change in 24‐h urinary albumin excretion rate (UAER).
Results
A total of 32 patients were randomized and 27 completed the study. After placebo treatment, geometric mean (IQR) UAER was 199 (81‐531) mg/24‐h, mean (SD) measured GFR (mGFR) 75 (36) mL/min/1.73 m2, 24‐h blood pressure 145/80 (15/8) mm Hg and HbA1c 61 (11) mmol/mol. Liraglutide reduced HbA1c by 8 (95% CI: 5; 11) mmol/mol (P
< .001) and weight by 1.8 (95% CI: 0.2; 3.4) kg (P
= .032) compared to placebo. Furthermore, liraglutide reduced UAER by 32 (95% CI: 7; 50)% (
P
= .017) compared with placebo. The change in mGFR was −5 (95% CI: −11; 2) mL/min/1.73 m2 (
P
= .15), and change in 24‐h systolic blood pressure was −5 (95% CI: −10; 0) mm Hg (
P
= .07). In multivariate regression models, change in UAER was associated with change in 24‐h systolic blood pressure (
P
= .025) but not with change in HbA1c, weight or mGFR (
P
≥ .14), overall model
R
2
= .39.
Conclusions
Our placebo‐controlled randomized trial suggests that liraglutide has renoprotective effects on top of multifactorial treatment, including RAS‐inhibition, in patients with type 2 diabetes and albuminuria.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neocortical demyelination in the forebrain has recently been identified as an important pathological feature of multiple sclerosis (MS). Here we describe that the cerebellar cortex is a major ...predilection site for demyelination, in particular in patients with primary and secondary progressive MS. In these patients, on average, 38.7% of cerebellar cortical area is affected, reaching in extreme examples up to 92%. Cerebellar cortical demyelination occurs mainly in a band‐like manner, affecting multiple folia. The lesions are characterized by primary demyelination with relative axonal and neuronal preservation, although some axonal spheroids and a moderate reduction of Purkinje cells are present. Although cortical demyelination sometimes occurs together with demyelination in the adjacent white matter (leukocortical lesions), in most instances, the cortex was affected independently from white matter lesions. We found no correlation between demyelination in the cortex and the white matter, and in some cases, extensive cortical demyelination was present in the near absence of white matter lesions. Our data identify cortical demyelination as a potential substrate of cerebellar dysfunction in MS.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
An exceptionally deep upper-air sounding launched from Kiruna
airport (67.82∘ N, 20.33∘ E) on 30 January 2016 stimulated
the current investigation of internal gravity waves excited during a minor
...sudden stratospheric warming (SSW) in the Arctic winter 2015/16. The analysis
of the radiosonde profile revealed large kinetic and potential energies in
the upper stratosphere without any simultaneous enhancement of upper
tropospheric and lower stratospheric values. Upward-propagating
inertia-gravity waves in the upper stratosphere and downward-propagating
modes in the lower stratosphere indicated a region of gravity wave generation
in the stratosphere. Two-dimensional wavelet analysis was applied to vertical
time series of temperature fluctuations in order to determine the vertical
propagation direction of the stratospheric gravity waves in 1-hourly
high-resolution meteorological analyses and short-term forecasts. The
separation of upward- and downward-propagating waves provided further evidence
for a stratospheric source of gravity waves. The scale-dependent
decomposition of the flow into a balanced component and inertia-gravity waves
showed that coherent wave packets preferentially occurred at the inner edge
of the Arctic polar vortex where a sub-vortex formed during the minor SSW.
Glucose-dependent insulinotropic polypeptide (GIP) is glucagonotropic, and glucagon-like peptide-1 (GLP-1) is glucagonostatic. We studied the effects of GIP and GLP-1 on glucagon responses to ...insulin-induced hypoglycemia in patients with type 1 diabetes mellitus (T1DM). Ten male subjects with T1DM (C-peptide negative, age mean ± SEM 26 ± 1 years, BMI 24 ± 0.5 kg/m(2), HbA1c 7.3 ± 0.2%) were studied in a randomized, double-blinded, crossover study, with 2-h intravenous administration of saline, GIP, or GLP-1. The first hour, plasma glucose was lowered by insulin infusion, and the second hour constituted a "recovery phase." During the recovery phase, GIP infusions elicited larger glucagon responses (164 ± 50 GIP vs. 23 ± 25 GLP-1 vs. 17 ± 46 saline min ⋅ pmol/L, P < 0.03) and endogenous glucose production was higher with GIP and lower with GLP-1 compared with saline (P < 0.02). On the GIP days, significantly less exogenous glucose was needed to keep plasma glucose above 2 mmol/L (155 ± 36 GIP vs. 232 ± 40 GLP-1 vs. 212 ± 56 saline mg ⋅ kg(-1), P < 0.05). Levels of insulin, cortisol, growth hormone, and noradrenaline, as well as hypoglycemic symptoms and cognitive function, were similar on all days. Our results suggest that during hypoglycemia in patients with T1DM, exogenous GIP increases glucagon responses during the recovery phase after hypoglycemia and reduces the need for glucose administration.
Cyclists often apply block periodization to high training volumes in meso- and macrocycles to optimize training adaptation and to prepare for competition. Body mass influences performance in many ...sports, including endurance disciplines, and conditions related to the syndrome Relative Energy Deficiency in Sports (RED-S) such as metabolic adaptations and premature osteoporosis have also been reported in male cyclists. This study aimed to determine how a 4-week mesocycle of intensified endurance training designed to increase performance, would affect markers of RED-S in well-trained male cyclists. Twenty-two participants (age: 33.5 ± 6.6 years, height: 181.4 ± 5.2 cm, weight: 76.5 ± 7.4 kg, peak oxygen uptake (VO
): 63.5 ± 6.6 mL·kg
·min
) were recruited and instructed to maintain their background training load and to follow a supervised training protocol consisting of three high-intensity interval training sessions per week with a work duration of 32 min per session. Protocols included pre- and postintervention assessment of resting metabolic rate (RMR) using a ventilated hood, body composition and bone health by dual-energy X-ray absorptiometry (DXA), blood samples, energy intake, and aerobic performance. The interval training increased participants' aerobic performance-peak power output 4.8%,
< 0.001, VO
2.4%,
= 0.005, and functional threshold power 6.5%,
< 0.001 as well as total testosterone levels 8.1%,
= 0.011-while no changes were observed in free testosterone 4.1%,
= 0.326. Bodyweight, body composition, and energy intake were unchanged from pre- to post-test. Triiodothyronine (T
) 4.8%,
= 0.008, absolute RMR 3.0%,
= 0.010, relative RMR 2.6%,
= 0.013, and RMR
3.3%,
= 0.011 decreased, and cortisol levels increased 12.9%,
= 0.021, while no change were observed in the total testosterone:cortisol ratio 1.6%,
= 0.789 or the free testosterone:cortisol (fT:cor) ratio 3.2%,
= 0.556. A subgroup analysis of the five participants with the largest increase in fT:cor ratio, revealed a greater improvement in functional threshold power (9.5 vs. 2.5%,
= 0.037), and higher relative RMR (0.6 vs. -4.2%
= 0.039, respectively). In conclusion, 4 weeks of intensified endurance interval training increased the athletes' aerobic performance and testosterone levels. However, negative changes in markers related to RED-S, such as a reduction in RMR and T
, and an increase in cortisol were observed. These results indicate the complexity involved, and that male athletes are at risk of developing clinical indications of RED-S even during a short 4-week endurance training mesocycle.
The autonomic nervous system (ANS) maintains glucose homeostasis. While higher than normal glucose levels stimulate the ANS toward reduction, previous findings suggest an association between ...sensitivity to, or pain from, pressure at the chest bone (pressure or pain sensitivity, PPS) and activity of the ANS. A recent randomized controlled trial (RCT) of type 2 diabetes (T2DM) suggested that addition of an experimental, non-pharmacological intervention more effectively than conventional treatment lowered the levels of both PPS and HbA1c.
We tested the null hypothesis that conventional treatment (
= 60) would reveal no association between baseline HbA1c and normalization of HbA1c in 6 months, related to change of PPS. We compared the changes of HbA1c in PPS reverters who experienced a minimum reduction of 15 units of PPS and in PPS non-reverters who experienced no reduction. Depending on the result, we tested the association in a second group of participants with addition of the experimental program (
= 52).
In the conventional group, PPS reverters experienced normalization of HbA1c that corrected the basal increase, thus disproving the null hypothesis. With the addition of the experimental program, PPS reverters experienced similar reduction. The reduction of HbA1c among reverters averaged 0.62 mmol/mol per mmol/mol increase of baseline HbA1c (
< 0.0001 compared to non-reverters). For baseline HbA1c ≥ 64 mmol/mol, reverters averaged 22% reduction of HbA1c (
< 0.01).
In consecutive analyses of two different populations of individuals with T2DM, we demonstrated that the higher the baseline HbA1c, the greater the reduction of HbA1c but only in individuals with a concomitant reduction of sensitivity to PPS, suggesting a homeostatic effect of the autonomic nervous system on glucose metabolism. As such, ANS function, measured as PPS, is an objective measure of HbA1c homeostasis. This observation may be of great clinical importance.
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