Vitamin D Supplementation as a Therapeutic Strategy in Autoimmune Diabetes: Insights and Implications for LADA Management.

Latent autoimmune diabetes of adults (LADA) is the most prevalent form of autoimmune diabetes (AI-D) in adulthood; however, its accurate diagnosis and optimal treatment remain challenging. Vitamin D deficiency (VDD) is commonly observed in LADA patients, while increased vitamin D exposure through supplementation and dietary intake is associated with a reduced incidence of LADA. Although limited, case reports, case-control studies, and randomized clinical trials have examined the effects of vitamin D supplementation-alone or combined with dipeptidyl peptidase-4 inhibitors (DPP4-is)-on glucose regulation, residual β-cell function, and glutamic acid decarboxylase antibody (GADA65) levels.

Anti-Diabetic Therapies and Cancer: From Bench to Bedside.

Diabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention for its potential anti-cancer effects, primarily through modulation of the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway and the induction of autophagy. Beyond metformin, other conventional anti-diabetic treatments, such as insulin, sulfonylureas (SUs), pioglitazone, and dipeptidyl peptidase-4 (DPP-4) inhibitors, have also been examined for their roles in cancer biology, though findings are often inconclusive.

l-Securinine Induces ROS-Dependent Apoptosis on Pancreatic Cancer Cells via the PI3K/AKT/mTOR Signaling Pathway.

Accumulating evidence has shown that l-securinine can, in certain circumstances, suppress tumor development by elevating reactive oxygen species (ROS) levels. The current work set out to examine l-securinine's apoptotic effects on HuP-T3 cells as well as any potential underlying molecular mechanism(s) that could explain its action as an anticancer agent. In this study, we used 1.

The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies.

Atherosclerotic cardiovascular disease poses a significant global health issue, with dyslipidemia standing out as a major risk factor. In recent decades, lipid-lowering therapies have evolved significantly, with statins emerging as the cornerstone treatment. These interventions play a crucial role in both primary and secondary prevention by effectively reducing cardiovascular risk through lipid profile enhancements.

SGLT2 Inhibitor Dapagliflozin Increases Skeletal Muscle and Brain Fatty Acid Uptake in Individuals With Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Positron Emission Tomography Study.

Objective: The aim of this study was to investigate the impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET).

Research Design And Methods: In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid.

Role of endogenous GLP-1 on arterial stiffness and renal haemodynamics following bariatric surgery.

Background: Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response post-bariatric surgery on arterial stiffness and renal haemodynamic.

Charcot Foot: An Update on Diagnosis, Treatment, and Areas of Uncertainty.

Background And Aims: Charcot neuroosteoarthropathy (CN) is considered a rare complication of diabetic neuropathy. Due to its insidious mode of presentation, CN may be difficult to diagnose timely and a high index of suspicion is required from both, the diabetic patient (especially those with neuropathy) and their physicians for the early diagnosis and treatment to prevent major complications.

Methods: We planned a narrative review and searched MEDLINE database to identify evidence regarding CN incidence, treatment options, and recent guidelines.

Long-Term effects of physical activity on weight loss, metabolic parameters and blood pressure in subjects undergoing bariatric surgery: A 5-year follow-up study.

Background: bariatric surgery stands as an effective intervention for weight loss and improved metabolic control in obesity, although over time there is a proportion of weight regain and type-2-diabetes (T2D) relapse.

Aims: to explore the role of physical activity (PA) after surgery and its impact on metabolic parameters during a 5-year follow-up.

Methods: 148 individuals who underwent bariatric surgery completed scheduled examinations over 5-years.

Effects of hypertriglyceridemia with or without NEFA elevation on β-cell function and insulin clearance and sensitivity.

Aims: Hypertriglyceridemia is a risk factor for developing type 2 diabetes (T2D) and might contribute to its pathogenesis either directly or through elevation of non-esterified fatty acids (NEFAs). This study aimed at comparing the glucometabolic effects of acute hypertriglyceridemia alone or combined with NEFA elevation in non-diabetic subjects.

Methods: Twenty-two healthy lean volunteers underwent two 5-h intravenous infusions of either saline or Intralipid, without (n=12) or with heparin (I+H; n=10) to activate the release of NEFAs.

What is New on Diabetic Neuropathy? Insights from the 2023 ADA and EASD Conferences.

Diabetic neuropathy is a common complication of diabetes; yet its pathophysiology is still incompletely understood and until today, there is no specific treatment against it. In the two 2023 large congresses on diabetes (American Diabetes Association, ADA, European Association for the Study of Diabetes, EASD), several high-level studies have been presented. They have attempted to delineate the pathophysiology of DN, the characteristics of affected patients, and future potential treatments.

Kinetic Modeling of Brain [F]FDG Positron Emission Tomography Time Activity Curves with Input Function Recovery (IR) Method.

Accurate positron emission tomography (PET) data quantification relies on high-quality input plasma curves, but venous blood sampling may yield poor-quality data, jeopardizing modeling outcomes. In this study, we aimed to recover sub-optimal input functions by using information from the tail (5th-100th min) of curves obtained through the frequent sampling protocol and an input recovery (IR) model trained with reference curves of optimal shape. Initially, we included 170 plasma input curves from eight published studies with clamp [F]-fluorodeoxyglucose PET exams.

Renal Cortical Glucose Uptake Is Decreased in Insulin Resistance and Correlates Inversely With Serum Free-fatty Acids.

Context: Studies on human renal metabolism are scanty. Nowadays, functional imaging allows the characterization of renal metabolism in a noninvasive manner. We have recently demonstrated that fluorodeoxyglucose F18 (18F FDG) positron emission tomography can be used to analyze renal glucose uptake (GU) rates, and that the renal cortex is an insulin-sensitive tissue.

Insulin-stimulated brain glucose uptake correlates with brain metabolites in severe obesity: A combined neuroimaging study.

The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy (H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with F-fluorodeoxyglucose positron emission tomography (F-FDG-PET)) was also performed in a subset of subjects during clamp.

Renal Perfusion, Oxygenation and Metabolism: The Role of Imaging.

Thanks to technical advances in the field of medical imaging, it is now possible to study key features of renal anatomy and physiology, but so far poorly explored due to the inherent difficulties in studying both the metabolism and vasculature of the human kidney. In this narrative review, we provide an overview of recent research findings on renal perfusion, oxygenation, and substrate uptake. Most studies evaluating renal perfusion with positron emission tomography (PET) have been performed in healthy controls, and specific target populations like obese individuals or patients with renovascular disease and chronic kidney disease (CKD) have rarely been assessed.

Near-Infrared Spectroscopy: A Free-Living Neuroscience Tool to Better Understand Diabetes and Obesity.

The human brain is the least accessible of all organs and attempts to study it in vivo rely predominantly on neuroimaging. Functional near-infrared spectroscopy (fNIRS) allows for the study of cortical neural activity in a non-invasive manner that may resemble free-living conditions. Moreover, compared to other neuroimaging tools, fNIRS is less expensive, it does not require the use of ionizing radiation, and can be applied to all study populations (patients suffering from claustrophobia, or neonates).

The Role of Vitamin D in Health and Disease: A Narrative Review on the Mechanisms Linking Vitamin D with Disease and the Effects of Supplementation.

Vitamin D insufficiency or deficiency (VDD) is a very prevalent condition in the general population. Vitamin D is necessary for optimal bone mineralization, but apart from the bone effects, preclinical and observational studies have suggested that vitamin D may have pleiotropic actions, whereas VDD has been linked to several diseases and higher all-cause mortality. Thus, supplementing vitamin D has been considered a safe and inexpensive approach to generate better health outcomes-and especially so in frail populations.

Thermogenic Capacity of Human Supraclavicular Brown Fat and Cold-Stimulated Brain Glucose Metabolism.

Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation in the expression of , which represents the thermogenic capacity of the supraclavicular BAT, is linked with brain metabolism during cold stress.

Secretin modulates appetite via brown adipose tissue-brain axis.

Purpose: Secretin activates brown adipose tissue (BAT) and induces satiation in both mice and humans. However, the exact brain mechanism of this satiety inducing, secretin-mediated gut-BAT-brain axis is largely unknown.

Methods And Results: In this placebo-controlled, single-blinded neuroimaging study, firstly using [F]-fluorodeoxyglucose (FDG) PET measures (n = 15), we established that secretin modulated brain glucose consumption through the BAT-brain axis.

Evaluation of renal glucose uptake with [F]FDG-PET: Methodological advancements and metabolic outcomes.

Background/purpose: Studying renal glucose metabolism non-invasively in humans is an unmet need. Positron emission tomography (PET) is the current gold standard for measuring regional tissue glucose uptake rates, but the most widely used glucose analog ([F]FDG) is not a good substrate for sodium-glucose cotransporters (SGLTs). As a consequence, [F]FDG spills over into the urine and [F]FDG-PET considerably underestimates published rates of whole renal glucose uptake obtained using the arterial-venous difference technique.

Decreased Weight Loss Following Bariatric Surgery in Patients with Type 2 Diabetes.

Background: Bariatric surgery represents the most effective treatment for achieving significant and sustained weight loss. We aimed to assess whether presence of type 2 diabetes (T2D) at baseline, and T2D remission following bariatric surgery affect the weight loss outcome.

Methods: Data of 312 consecutive morbidly obese subjects who underwent bariatric surgery were analysed.

The Beneficial Effects of Bariatric-Surgery-Induced Weight Loss on Renal Function.

Obesity represents an independent risk factor for the development of chronic kidney disease (CKD), leading to specific histopathological alterations, known as obesity-related glomerulopathy. Bariatric surgery is the most effective means of inducing and maintaining sustained weight loss. Furthermore, in the context of bariatric-surgery-induced weight loss, a reduction in the proinflammatory state and an improvement in the adipokine profile occur, which may also contribute to the improvement of renal function following bariatric surgery.

Obesity risk is associated with brain glucose uptake and insulin resistance.

Objective: To investigate whether alterations in brain glucose uptake (BGU), insulin action in the brain-liver axis and whole-body insulin sensitivity occur in young adults in pre-obese state.

Methods: Healthy males with either high risk (HR; n = 19) or low risk (LR; n = 22) for developing obesity were studied with [18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography during hyperinsulinemic-euglycemic clamp. Obesity risk was assessed according to BMI, physical activity and parental overweight/obesity and type 2 diabetes.