Long-chain fatty acids (FAs) are the major substrates fueling brown adipose tissue (BAT) thermogenesis. Investigation of mouse models has previously called into question the contribution of brown adipocyte intracellular lipolysis to cold-induced non-shivering thermogenesis. Here, we determined the role of the lipolytic enzymes, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in BAT thermogenesis.
View Article and Find Full Text PDFAim: To evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) initiation according to diabetes duration (DD).
Materials And Methods: We analysed patient-level data from 2381 insulin-naïve individuals with type 2 diabetes (T2D), of whom 2349 (98.7%) were treated with Gla-300 for 24 weeks.
Gut
November 2024
Background: The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity.
Objective: To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues.
Design: Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose).
The major female ovarian hormone, 17β-estradiol (E), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E, but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα.
View Article and Find Full Text PDFGrowth and differentiation factor 15 (GDF15) has recently emerged as a weight loss and insulin-sensitizing factor. Growing evidence also supports a role for GDF15 as a physiological, exercise-induced stress signal. Here, we tested whether GDF15 is required for the insulin-sensitizing effects of exercise in mice and humans.
View Article and Find Full Text PDFIntroduction: Second-generation basal insulins like glargine 300 U/mL (Gla-300) have a longer duration of action and less daily fluctuation and interday variability than first-generation ones, such as glargine 100 U/mL (Gla-100). The EF-BI study, a nationwide observational, retrospective study, was designed to compare persistence, acute care complications, and healthcare costs associated with the initiation of such basal insulins (BI) in a real-life setting in France.
Methods: This study was conducted using the French healthcare claims database (SNDS).
The population of older adults (≥65 years) with type 2 diabetes mellitus (T2DM) is diverse, encompassing individuals with varying functional capabilities, living arrangements, concomitant medical conditions, and life expectancies. Hence, their categorization into different patient profiles (ie, good health, intermediate health, poor health) may aid in clinical decision-making when establishing glycemic goals and pharmacological treatment strategies. Further granularity in assessing each patient profile through interdisciplinary collaboration may also add precision to therapeutic and monitoring decisions.
View Article and Find Full Text PDFAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity in individuals with type 2 diabetes mellitus (T2DM). Accordingly, several scientific societies have released clinical practice guidelines to assist health professionals in ASCVD risk management in patients with T2DM. However, some recommendations differ from each other, contributing to uncertainty about the optimal clinical management of patients with T2DM and established ASCVD or at high risk for ASCVD.
View Article and Find Full Text PDFDietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is largely unknown. We investigate the impact of dietary lipids on human gut microbiota composition and the effects of microbiota-lipid interactions on steatosis in male mice. In humans, low intake of saturated fatty acids (SFA) is associated with increased microbial diversity independent of fiber intake.
View Article and Find Full Text PDFBackground: Estrogen Receptor α (ERα) is a significant modulator of energy balance and lipid/glucose metabolisms. Beyond the classical nuclear actions of the receptor, rapid activation of intracellular signaling pathways is mediated by a sub-fraction of ERα localized to the plasma membrane, known as Membrane Initiated Steroid Signaling (MISS). However, whether membrane ERα is involved in the protective metabolic actions of endogenous estrogens in conditions of nutritional challenge, and thus contributes to sex differences in the susceptibility to metabolic diseases, remains to be clarified.
View Article and Find Full Text PDFDue to their cardiovascular protective effect, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent breakthrough therapies for type 2 diabetes mellitus (T2DM). In this review article, we discuss the mechanistic and clinical synergies that make the combined use of GLP-1RAs and SGLT2is appealing in patients with T2DM. Overall, the presented cumulative evidence supports the benefits of GLP-1RA plus SGLT2i combination therapy on metabolic-cardiovascular-renal disease in patients with T2DM, with a low hypoglycemia risk.
View Article and Find Full Text PDFBackground: There is a lack of real-life data regarding the frequency and predictive factors of hypoglycemia in older patients with type 2 diabetes (T2D). This study aimed to determine the frequency and predictors of hypoglycemia in older patients with insulin-treated T2D.
Methods: This prospective multicenter study included 155 insulin-treated T2D patients aged 75 years and older with ≥2 self-monitoring of blood glucose (SMBG) daily controls.
Introduction: Using pooled data from the REALI European database, we evaluated the impact of previous basal insulin (BI) type on real-life effectiveness and safety of switching to insulin glargine 300 U/ml (Gla-300) in people with suboptimally controlled type 2 diabetes.
Methods: Patient-level data were pooled from 11 prospective, open-label, 24-week studies. Participants were classified according to the type of prior BI.
Introduction: Combining basal insulin (BI) with glucagon-like peptide-1 receptor agonist (GLP-1RA) is recognized as a relevant option to optimize glucose control in type 2 diabetes (T2D). The EASY real-world study aimed to evaluate the modalities of initiation and the effectiveness of the insulin Degludec plus Liraglutide (IDegLira) fixed-ratio combination in the French health care system.
Methods: A retrospective analysis included all patients with T2D and prior injectable therapy (GLP1-RA and/or insulin) who started treatment with IDegLira from September 2016 to December 2017 in 11 French diabetes centers.
Background: It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19.
Methods: We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020-October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization.
Aim: To provide a detailled analysis of the microvascular burden in patients with diabetes hopitalized for COVD-19.
Materials And Methods: We analysed data from the French CORONADO initiative and the UK Association of British Clinical Diabetologists (ABCD) COVID-19 audit, two nationwide multicentre studies, and the AMERICADO, a multicentre study conducted in New York area. We assessed the association between risk of all-cause death during hospital stay and the following microvascular complications in patients with diabetes hospitalized for COVID-19: diabetic retinopathy and/or diabetic kidney disease and/or history of diabetic foot ulcer.
In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This includes the biosynthesis of ketone bodies and of fibroblast growth factor 21 (FGF21). Here we show that in the absence of adipose triglyceride lipase (ATGL) in adipocytes, ketone body and FGF21 production is impaired upon fasting.
View Article and Find Full Text PDFLiver physiology is circadian and sensitive to feeding and insulin. Food intake regulates insulin secretion and is a dominant signal for the liver clock. However, how much insulin contributes to the effect of feeding on the liver clock and rhythmic gene expression remains to be investigated.
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