Endocrinology

Plasma and urine metabolic profiles are reflective of altered beta-oxidation in non-diabetic obese subjects and patients with type 2 diabetes mellitus
The two primary pathophysiological characteristics of patients with type 2 diabetes mellitus (T2DM) are insulin resistance (IR) and beta cell dysfunction. It has been proposed that the development of IR is secondary to the accumulation of triacylglycerols and fatty acids in the muscle and liver, which is in turn thought to be secondary to an enzymatic defect in mitochondrial beta-oxidation. The...


Ten-year improvement of insulin resistance and growth with recombinant human insulin-like growth factor 1 in a patient with insulin receptor mutations resulting in leprechaunism
Leprechaunism, a rare genetic disease resulting from mutations in two alleles of the insulin receptor gene, is characterized by severe insulin resistance, retarded growth and, usually, premature death. The ability of treatment with recombinant human insulin-like growth factor 1 (rhIGF1) to improve metabolic and clinical parameters in the long-term is still controversial. Mutations were looked f...
Usefulness of bovine and porcine IVM/IVF models for reproductive toxicology
Women presenting fertility problems are often helped by Assisted Reproductive Techniques (ART), such as in vitro fertilization (IVF) programs. However, in many cases the etiology of the in/subfertility remains unknown even after treatment. Although several aspects should be considered when assisting a woman with problems to conceive, a survey on the patients' exposure to contaminants would help...


Flexible Lifestyles for Youth (FL3X) behavioural intervention for at-risk adolescents with Type 1 diabetes: a randomized pilot and feasibility trial
To determine the potential effect sizes for the Flexible Lifestyle for Youth (FL3X) behavioural intervention to improve glycaemic control (HbA1c) and quality of life for at-risk adolescents with Type 1 diabetes. Participants [n=61; age 12–16 years, HbA1c 64–119 mmol/mol (8–13%)] were randomized to FL3X (minimum three sessions) or usual care. Effect sizes (Cohen's d), comparing the mean di...
Diabetes and hyperlipidemia induced dysfunction of VSMC: contribution of metabolic inflammation-miRNA pathway
Vascular endothelial cell injury was considered the major factor that induced vascular complications in metabolic diseases, and played an important role in other organ damage. With diabetic and hyperlipidemic rat and cultured VSMC, the present study aimed to investigate if the early damage of VSMC during metabolic diseases plays a critical role in vascular dysfunction and will be a promising tr...


The vitamin D receptor in the proximal renal tubule is a key regulator of serum 1alpha,25-dihydroxyvitamin D3
It is well established that the mitochondria of proximal convoluted tubule cells of the kidney are the site of production of circulating 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The production of 1,25(OH)2D3 at this site is tightly regulated. Parathyroid hormone markedly stimulates 1,25(OH)2D3 production, while 1,25(OH)2D3 itself suppresses production. The mechanism of suppression by 1,25...
Pregestational Diabetes Induces Fetal Coronary Artery Malformation via Reactive Oxygen Species Signaling
Hypoplastic coronary artery disease is a congenital coronary artery malformation associated with a high risk of sudden cardiac death. However, the etiology and pathogenesis of hypoplastic coronary artery disease remain undefined. Pregestational diabetes increases reactive oxygen species (ROS) levels and the risk of congenital heart defects. Here we show that pregestational diabetes in mice indu...

Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance
Accumulation evidence links obesity-induced inflammation as an important contributor to the development of insulin resistance which plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes mellitus and non- alcoholic fatty liver disease. Cyclooxygenase (COX)-1 and -2 catalyze the first step in prostanoid biosynthesis. Since adult hepatocytes fail to induce COX...
Role of Type 1 diabetes associated SNPs on risk of autoantibody positivity in the TEDDY Study
The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,677 children enrolled from birth, who carry HLA-susceptibility genotypes for development of islet autoantibodies (IA) and type 1 diabetes (T1D). During the median follow-up time of 57 months, 350 children developed at least one persistent IA (GADA, IA-2A or mIAA) and 84 of them progressed to T1D. We ge...

Detection of a low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes
The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3-9 weeks after onset of type 1 diabetes in 6 adult patients (age 24-35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunoh...
Regardless of the Degree of Glycaemic Control, Linagliptin has Lower Hypoglycaemia Risk Than All Doses of Glimepiride, at All Time Points Over a 2-Year Trial
To evaluate the risk for documented hypoglycaemia with glimepiride versus linagliptin. This was an exploratory analysis of data from a 2-year, randomised, double-blind study of the dipeptidyl peptidase-4 inhibitor linagliptin 5 mg qd (n = 764) versus the sulphonylurea glimepiride 1–4 mg qd (n = 755) in patients uncontrolled by metformin. Patients randomised to glimepiride started ...

Single-dose new insulin glargine 300 U.mL−1 provides prolonged, stable glycaemic control in Japanese and European people with type 1 diabetes
Two single-dose studies were conducted in Japan and Europe to compare pharmacokinetic (PK) and pharmacodynamic (PD) profiles of new insulin glargine 300 U.mL−1 (Gla-300) and insulin glargine 100 U.mL−1 (Gla-100) in people with type 1 diabetes mellitus (T1DM). In two double-blind, randomised, crossover studies, 18 Japanese participants (aged 20–65 years) and 24 European participants (aged ...
A Post Hoc Analysis of HbA1c, Hypoglycemia, and Weight Change Outcomes with Alogliptin vs Glipizide in Older Patients with Type 2 Diabetes
Adverse events and complications limit the long-term use of current antidiabetic treatment options for patients with type 2 diabetes mellitus (T2DM), particularly for older adults who are often receiving therapy for other comorbid conditions. The aim of this study was to evaluate the benefits of the dipeptidyl peptidase-4 inhibitor, alogliptin, versus glipizide, a sulfonylurea, in achieving gly...
Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their Basic and Clinical Pharmacology
Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a newly developed class of oral anti-diabetic drugs (OADs) with a unique mechanism of action. This review describes the biochemistry and physiology underlying the use of SGLT2 inhibitors, and their clinical pharmacology, including mechanism of action and posology. The pragmatic placement of these molecules in the existing OAD arena is also ...
Phenotypic heterogeneity of latent autoimmune diabetes in adults identified by body composition analysis
In patients with Latent Autoimmune Diabetes in Adults (LADA) a lower body mass index was reported compared with classical type 2 diabetes (T2D), and it appears to be associated with faster progression to insulin-dependence. In this study we determined the body composition in a cohort of LADA patients from Sardinia, Italy, and compared it with age- and gender-matched patients diagnosed as having...