Molecular, Metabolic, and Nutritional Changes after Metabolic Surgery in Obese Diabetic Patients (MoMen): A Protocol for a Multicenter Prospective Cohort Study.

Metabolic surgery is an essential option in the treatment of obese patients with type 2 diabetes (T2D). Despite its known advantages, this surgery still needs to be introduced in Malaysia. In this prospective study, the pathophysiological mechanisms at the molecular level will be studied and the metabolomics pathways of diabetes remission will be explored.

Gut Microbiome Associated With Graves Disease and Graves Orbitopathy: The INDIGO Multicenter European Study.

Context: Gut bacteria can influence host immune responses but little is known about their role in tolerance-loss mechanisms in Graves disease (GD; hyperthyroidism caused by autoantibodies, TRAb, to the thyrotropin receptor, TSHR) and its progression to Graves orbitopathy (GO).

Objective: This work aimed to compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HCs).

Methods: Patients were recruited from 4 European countries (105 GD patients, 41 HCs) for an observational study with cross-sectional and longitudinal components.

Orbital Signaling in Graves' Orbitopathy.

Graves' orbitopathy (GO) is a complex and poorly understood disease in which extensive remodeling of orbital tissue is dominated by adipogenesis and hyaluronan production. The resulting proptosis is disfiguring and underpins the majority of GO signs and symptoms. While there is strong evidence for the thyrotropin receptor (TSHR) being a thyroid/orbit shared autoantigen, the insulin-like growth factor 1 receptor (IGF1R) is also likely to play a key role in the disease.

Expression of Endogenous Putative TSH Binding Protein in Orbit.

Thyroid stimulating antibodies (TSAB) cause Graves' disease and contribute to Graves' Orbitopathy (GO) pathogenesis. We hypothesise that the presence of TSH binding proteins (truncated variants ()) and/or nonclassical ligands such as () might provide a mechanism to protect against or exacerbate GO. We analysed primary orbital preadipocyte-fibroblasts (OF) from GO patients and people free of GO (non-GO).

The Role of Mitochondria-Linked Fatty-Acid Uptake-Driven Adipogenesis in Graves Orbitopathy.

Context: Depot-specific expansion of orbital adipose tissue (OAT) in Graves orbitopathy (GO; an autoimmune condition producing proptosis, visual impairment and reduced quality of life) is associated with fatty acid (FA)-uptake-driven adipogenesis in preadipocytes/fibroblasts (PFs).

Objective: This work sought a role for mitochondria in OAT adipogenesis in GO.

Methods: Confluent PFs from healthy OAT (OAT-H), OAT from GO (OAT-GO) and white adipose tissue in culture medium compared with culture medium containing a mixed hormonal cocktail as adipogenic medium (ADM), or culture-medium containing FA-supplementation, oleate:palmitate:linoleate (45:30:25%) with/without different concentration of mitochondrial biosubstrate adenosine 5'-diphosphate/guanosine 5'-diphosphate (ADP/GDP), AICAR (adenosine analogue), or inhibitor oligomycin-A for 17 days.

Distinctive Features of Orbital Adipose Tissue (OAT) in Graves' Orbitopathy.

Depot specific expansion of orbital-adipose-tissue (OAT) in Graves' Orbitopathy (GO) is associated with lipid metabolism signaling defects. We hypothesize that the unique adipocyte biology of OAT facilitates its expansion in GO. A comprehensive comparison of OAT and white-adipose-tissue (WAT) was performed by light/electron-microscopy, lipidomic and transcriptional analysis using ex vivo WAT, healthy OAT (OAT-H) and OAT from GO (OAT-GO).

Prostaglandin F2-Alpha Eye Drops (Bimatoprost) in Graves' Orbitopathy: A Randomized Controlled Double-Masked Crossover Trial (BIMA Trial).

Background: Previous in vitro experiments have demonstrated that prostaglandin F2-alpha (PF) reduced proliferation and adipogenesis in a murine cell line and human orbital fibroblasts derived from subjects with inactive Graves' orbitopathy (GO). The objective of this study was to determine if the PGF analogue bimatoprost is effective at reducing proptosis in this population.

Methods: A randomized controlled double-masked crossover trial was conducted in a single tertiary care academic medical center.

Combining micro-RNA and protein sequencing to detect robust biomarkers for Graves' disease and orbitopathy.

Graves' Disease (GD) is an autoimmune condition in which thyroid-stimulating antibodies (TRAB) mimic thyroid-stimulating hormone function causing hyperthyroidism. 5% of GD patients develop inflammatory Graves' orbitopathy (GO) characterized by proptosis and attendant sight problems. A major challenge is to identify which GD patients are most likely to develop GO and has relied on TRAB measurement.

The Role of Thyrotropin Receptor Activation in Adipogenesis and Modulation of Fat Phenotype.

Evidence from clinical and experimental data suggests that thyrotropin receptor (TSHR) signaling is involved in energy expenditure through its impact on white adipose tissue (WAT) and brown adipose tissue (BAT). TSHR expression increases during mesenchymal stem cell (MSC) differentiation into fat. We hypothesize that TSHR activation [TSHR*, elevated thyroid-stimulating hormone, thyroid-stimulating antibodies (TSAB), or activating mutation] influences MSC differentiation, which contributes to body composition changes seen in hypothyroidism or Graves' disease (GD).

Characterisation of adipocyte-derived extracellular vesicles released pre- and post-adipogenesis.

Extracellular vesicles (EVs) are submicron vesicles released from many cell types, including adipocytes. EVs are implicated in the pathogenesis of obesity-driven cardiovascular disease, although the characteristics of adipocyte-derived EVs are not well described. We sought to define the characteristics of adipocyte-derived EVs before and after adipogenesis, hypothesising that adipogenesis would affect EV structure, molecular composition and function.

TSH levels and risk of miscarriage in women on long-term levothyroxine: a community-based study.

Context: Thyroid dysfunction is associated with adverse obstetric outcomes, but there is limited information on pregnancy outcomes in women established on levothyroxine.

Objective: The objective of the study was to determine the relationship between TSH levels and pregnancy outcomes in levothyroxine-treated women in a large community-based database.

Design: This was a historical cohort analysis.

Effects of prostaglandin F(2α) on adipocyte biology relevant to graves' orbitopathy.

Background: In Graves' orbitopathy (GO), increased proliferation, excess adipogenesis, and hyaluronan overproduction produce GO exophthalmos. Enophthalmos occurs in some glaucoma patients treated with Bimatoprost (prostaglandin F2α, PGF2α) eye drops. We hypothesized that enophthalmos is secondary to reductions in orbital tissue proliferation, adipogenesis, and/or increased lipolysis.

Don't forget your hammer if you want to go to work!

Unlabelled: Bilateral lower limb paraesthesia is a common diabetic neuropathy presentation in any busy diabetic clinics. We present a case of a 28-year-old man with a long history of type 1 diabetes mellitus presented with bilateral paraesthesia of both feet and unsteady gait. The patient was able to feel a 10 g monofilament.