Time-restricted eating alters the 24-hour profile of adipose tissue transcriptome in men with obesity.

OBJECTIVE: Time-restricted eating (TRE) restores circadian rhythms in mice, but the evidence to support this in humans is limited. The objective of this study was to investigate the effects of TRE on 24-hour profiles of plasma metabolites, glucoregulatory hormones, and the subcutaneous adipose tissue (SAT) transcriptome in humans. METHODS: Men (n = 15, age = 63 [4] years, BMI 30.5 [2.4] kg/m2 ) were recruited. A 35-hour metabolic ward stay was conducted at baseline and after 8 weeks of 10-hour TRE. Assessment included 24-hour profiles of plasma glucose, nonesterified fatty acid (NEFA), triglyceride, glucoregulatory hormones, and the SAT transcriptome. Dim light melatonin onset and cortisol area under the curve were calculated. RESULTS: TRE did not alter dim light melatonin onset but reduced morning cortisol area under the curve. TRE altered 24-hour profiles of insulin, NEFA, triglyceride, and glucose-dependent insulinotropic peptide and increased transcripts of circadian locomotor output cycles protein kaput (CLOCK) and nuclear receptor subfamily 1 group D member 2 (NR1D2) and decreased period circadian regulator 1 (PER1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) at 12:00 am. The rhythmicity of 450 genes was altered by TRE, which enriched in transcripts for transcription corepressor activity, DNA-binding transcription factor binding, regulation of chromatin organization, and small GTPase binding pathways. Weighted gene coexpression network analysis revealed eigengenes that were correlated with BMI, insulin, and NEFA. CONCLUSIONS: TRE restored 24-hour profiles in hormones, metabolites, and genes controlling transcriptional regulation in SAT, which could underpin its metabolic health benefit.

Time-restricted eating improves glycemic control and dampens energy-consuming pathways in human adipose tissue.

OBJECTIVE: We sought to examine the effects of 8 wk of time-restricted eating (TRE) on glucose metabolism and the adipose tissue transcriptome during a metabolic ward stay in men with obesity. METHODS: In a single-arm, pre-post trial, 15 men (ages 63 ± 4 y, body mass index = 30.5 ± 2.4 kg/m2, waist circumference = 113 ± 4 cm) with obesity but no history of diabetes were enrolled and underwent 2 wk of baseline monitoring before they were instructed to eat their regular diets within a contiguous 10-h time frame each day for 8 wk. Metabolic testing was performed at baseline and week 8 during a 35-h metabolic ward stay, during which all food intake was strictly timed and controlled. Identical meal-tolerance tests were performed at breakfast and dinner. Blood glucose, glucoregulatory hormones, and subjective appetite score were measured. Subcutaneous adipose tissue biopsies were performed and the transcriptome was assessed. RESULTS: The primary outcome, plasma glucose area under the curve, was altered by TRE, being unchanged at breakfast but increased at dinner. However, TRE reduced fasting glucose, glycated hemoglobin, body weight, and body fat, and increased glucose-dependent insulinotropic peptide area under the curve at dinner. In subcutaneous adipose tissue, 117 genes were up-regulated and 202 genes down-regulated by TRE. Pathway analysis revealed down-regulation of genes involved in proteasome function and mitochondrial regulation. CONCLUSIONS: TRE had a net effect of reducing glycemia and dampening energy-consuming pathways in adipose tissue.

Efficacy of methotrexate in polymyalgia rheumatica in routine rheumatology clinical care.

BACKGROUND: Current guidelines recommend methotrexate (MTX) as a glucocorticoid-sparing agent in patients with polymyalgia rheumatica (PMR) who relapse or suffer glucocorticoid adverse effects, although there is no level 1 evidence to support this recommendation. AIMS: To review the effect of MTX in PMR on inflammation and glucocorticoid dose. METHODS: Patients with PMR from rheumatology outpatient clinics at two tertiary centres were identified. A structured case note review was conducted for patient characteristics at diagnosis and medications including glucocorticoid and MTX use. RESULTS: There were 70 patients, 61% female; mean (range) age of 70 (51-87) years. At the time of diagnosis, median (±interquartile range) erythrocyte sedimentation rate (ESR) was 38.5 (26-74) mm/h and C-reactive protein (CRP) 34.5 (6-74 mg/L) with median initiating prednisolone dose of 15 mg (range 5-60 mg). MTX was prescribed in 22 (31%) patients. Mean disease duration at MTX initiation was 2.5 years (1-7 years), with median (range) MTX dose of 10 mg (5-20 mg). At MTX initiation, median (interquartile range) (±standard deviation) ESR was 33 (13-60 mm/h) and CRP 19 (8-42 mg/L). Reasons for commencing MTX were disease relapse (34%) or inability to wean prednisolone dose (66%). Six months after MTX initiation, there was significant reduction in ESR (P = 0.012), CRP (P = 0.0003) and prednisolone dose (P < 0.0001). Eleven (50%) patients stopped MTX, five due to controlled PMR, and six due to adverse effects. CONCLUSIONS: In this study of PMR patients in tertiary care, 31% were co-prescribed MTX, after prolonged disease duration. MTX was associated with improved inflammatory activity and reduced prednisolone dose, with a relatively high risk of adverse events.

Risk of mortality in patients with giant cell arteritis: A systematic review and meta-analysis.

BACKGROUND: Previous studies of mortality associated with GCA have shown conflicting results. We conducted a systematic review and meta-analysis to determine the mortality risk in GCA patients compared to the general population. METHODS: We searched for published studies indexed in MEDLINE and EMBASE and the Cochrane database from inception to June 18, 2015 using the terms "giant cell arteritis" and "temporal arteritis" combined with the terms for death, mortality, and survival. A manual search of citations from retrieved articles was also performed. The inclusion criteria were as follows: (1) observational studies of mortality in GCA and (2) comparison of mortality to the general population. Studies published only in abstract form were excluded. Study eligibility and quality (Newcastle-Ottawa scale) were independently assessed by at least two investigators. Random effects meta-analysis of the mortality ratio (MR) was performed by the inverse variance method. RESULTS: Out of 435 potentially relevant articles, 64 studies were reviewed, 19 studies were included in the review and 17 studies were included in the meta-analysis. Mortality was not increased in GCA patients ascertained from a population base (MR = 1.03, 95% CI: 0.96-1.10), but was increased in patients ascertained from a hospital setting (MR = 1.61, 95% CI: 1.19-2.19). There was no difference in MR by gender, and two studies provided evidence that mortality was increased in the early years following diagnosis. CONCLUSION: At a population level, long-term mortality is not increased in GCA. However, mortality risk may be increased in some patients, and may vary over time.

Acute red eye (non-ulcerative keratitis) associated with mini-scleral contact lens wear for keratoconus.

Mini-scleral lenses are an increasingly popular contact lens modality; however, there are relatively few reports regarding the unique aspects of their fitting and potential complications. We report a complication of mini-scleral lens wear in a 44-year-old female patient using the lenses for keratoconus. Her mini-scleral contact lenses were non-fenestrated and fitted to vault over the cornea and seal at the periphery. The patient presented with an acute red eye (non-ulcerative keratitis), characterised by unilateral severe conjunctival and limbal hyperaemia, corneal infiltration and pain. Refitting the lens to increase the corneal vault clearance did not prevent recurrence of the keratitis, some five months later. Successful prevention of further episodes of the acute red eye was achieved through improved patient compliance with lens cleaning, disinfection and lens case procedures. Lens hygiene may be particularly important for mini-scleral lenses with a sealed fitting.