Patients with newly diagnosed rheumatoid arthritis are at increased risk of diabetes mellitus: an observational cohort study.

Aims: To reveal the prevalence of Diabetes Mellitus (DM) in patients with newly diagnosed Rheumatoid Arthritis (RA) and evaluate the association between clinical characteristics of RA and DM as well as treatment response in newly diagnosed RA patients with DM.

Methods: Newly diagnosed, adult, RA patients, who were registered in Danish Danbio since 1st January 2010, were included. Patients' demographics, serology results including rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP) and antinuclear antibody (ANA) as well as disease activity score in 28 joints-C-reactive protein (DAS28-CRP) at the time of diagnosis and after 4 months (±1-2 months) of treatment initiation were extracted from Danbio Registry.

Endogenous incretin hormone augmentation of acute insulin secretion in normoglycemic relatives of type 2 diabetic subjects: a 10-year retrospective pathophysiological study.

Aims/hypothesis: The pathophysiological role of gut incretin hormone argumentation on acute insulin release in the genesis of type 2 diabetes (TDM2) is uncertain. We examined retrospectively at 0 year and 10 years the endogenous incretin hormone action (IHA) on acute insulin release and glucose tolerance in normoglycemic relatives (REL) of TDM2 and control (CON) subjects.

Methods: At 0 year and 10 years, glucose tolerance, paired oral glucose tolerance test (OGTT)- and i.

Telemedicine diabetes consultations are cost-effective, and effects on essential diabetes treatment parameters are similar to conventional treatment: 7-year results from the Svendborg Telemedicine Diabetes Project.

Background: The increasing number of patients with diabetes poses a major challenge for the health care system. One instrument to meet these challenges could be the use of telemedicine, which, at the same time, may reduce treatment costs. Since 2005, diabetes patients on the island of Aeroe have been offered expert diabetes care using teleconsultations.

The metabolic responses induced by acute dexamethasone predict glucose tolerance and insulin secretion over 10 years in relatives of type 2 diabetic subjects.

Background: This study aimed to compare the metabolic and insulin secretory responses to dexamethasone with the metabolic responses observed at 10 years in normoglycaemic relatives of type 2 diabetic and healthy control subjects.

Methods: Twenty relatives and 20 matched control subjects were studied twice at 0 year (pre- and post-dexamethasone) and at 10 years, employing a 75-g oral glucose tolerance test (OGTT), with serial measurements of glucose and insulin, for determination of glucose tolerance and calculations of acute insulin release (ΔI30 /ΔG30 ; insulinogenic index) and insulin sensitivity (SIHOMA ).

Results: Following dexamethasone, the relatives group developed varying degrees of glucose intolerance, associated with reduced insulin sensitivity and insulinogenic index.

Novel mutation in the AVPR2 gene in a Danish male with nephrogenic diabetes insipidus caused by ER retention and subsequent lysosomal degradation of the mutant receptor.

Mutations in the arginine vasopressin receptor 2 (AVPR2) gene can cause X-linked nephrogenic diabetes insipidus (NDI) characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel mutation in the AVPR2 gene (L170P) located in the fourth transmembrane domain in a Danish NDI male. Analysis of the mutant receptor in Madin-Darby Canine Kidney cell culture revealed that AVPR2-L170P was retained in the endoplasmic reticulum, and the expression was dramatically downregulated compared to wild-type AVPR2.

Glucose effectiveness and insulin sensitivity measurements derived from the non-insulin-assisted minimal model and the clamp techniques are concordant.

Background: We investigated the concordance between glucose effectiveness (SG) and insulin sensitivity (SI), derived from the unmodified dynamic non-insulin-assisted intravenous glucose tolerance test (IVGTT) implemented by SG(MM) and SI(MM); simulation analysis and modelling/conversational interaction (SAAM/CONSAM) versus the eu/hyperglycaemic basal insulinaemic and the euglycaemic hyperinsulinaemic clamp (SG(CLAMP) and SI(CLAMP)).

Methods: Twenty-seven of 30 normoglycaemic subjects completed a (1) euglycaemic hyperinsulinaemic clamp, (2) 6-h eu/hyperglycaemic near-normoinsulinaemic pancreatic clamp with hyperglycaemia present over the final 2 h of the clamp (Day 2 study), (3) identical clamp to (2) but with euglycaemia maintained over the entire 6 h (Day 3 study) and (4) IVGTT. SG(CLAMP) was calculated in two ways based on data from study (2) alone (Day 2 SG(CLAMP210-240')) or from data from study day (2) and (3) (Day 2-3 SG(CLAMP330-360')).

Oxidation of intramyocellular lipids is dependent on mitochondrial function and the availability of extracellular fatty acids.

Obesity and insulin resistance are related to both enlarged intramyocellular triacylglycerol stores and accumulation of lipid intermediates. We investigated how lipid overflow can change the oxidation of intramyocellular lipids (ICL(OX)) and intramyocellular lipid storage (ICL). These experiments were extended by comparing these processes in primary cultured myotubes established from healthy lean and obese type 2 diabetic (T2D) individuals, two extremes in a range of metabolic phenotypes.

Dysregulation of glycogen synthase COOH- and NH2-terminal phosphorylation by insulin in obesity and type 2 diabetes mellitus.

Context: Insulin-stimulated glucose disposal is impaired in obesity and type 2 diabetes mellitus (T2DM) and is tightly linked to impaired skeletal muscle glucose uptake and storage. Impaired activation of glycogen synthase (GS) by insulin is a well-established defect in both obesity and T2DM, but the underlying mechanisms remain unclear.

Design And Participants: Insulin action was investigated in a matched cohort of lean healthy, obese nondiabetic, and obese type 2 diabetic subjects by the euglycemic-hyperinsulinemic clamp technique combined with muscle biopsies.

Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma: a novel marker of insulin resistance.

Background: Macrophage CD36 scavenges oxidized low-density lipoprotein, leading to foam cell formation, and appears to be a key proatherogenic molecule. Increased expression of CD36 has been attributed to hyperglycemia and to defective macrophage insulin signaling in insulin resistance. Premature atherosclerosis is the major cause of morbidity and mortality in type 2 diabetes.

Reduced insulin-mediated citrate synthase activity in cultured skeletal muscle cells from patients with type 2 diabetes: evidence for an intrinsic oxidative enzyme defect.

In myotubes established from patients with type 2 diabetes (T2D), lipid oxidation and insulin-mediated glucose oxidation are reduced, whereas in myotubes from obese non-diabetic subjects, exposure to palmitate impairs insulin-mediated glucose oxidation. To determine the underlying mechanisms of these metabolic malfunctions, we studied mitochondrial respiration, uncoupled respiration and oxidative enzyme activities (citrate synthase (CS), 3-hydroxy-acyl-CoA-dehydrogenase activity (HAD)) before and after acute exposure to insulin and/or palmitate in myotubes established from healthy lean and obese subjects and T2D patients. Basal CS activity was lower (14%) in diabetic myotubes compared with myotubes from lean controls (P=0.

Skeletal muscle lipid accumulation in type 2 diabetes may involve the liver X receptor pathway.

Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism and are also involved in glucose metabolism. However, the functional role of LXRs in human skeletal muscle is at present unknown. This study demonstrates that chronic ligand activation of LXRs by a synthetic LXR agonist increases the uptake, distribution into complex cellular lipids, and oxidation of palmitate as well as the uptake and oxidation of glucose in cultured human skeletal muscle cells.

Heritability of insulin secretion, peripheral and hepatic insulin action, and intracellular glucose partitioning in young and old Danish twins.

The etiology of type 2 diabetes is multifactorial, including genetic as well as pre- and postnatal factors that influence several different defects of glucose homeostasis, primarily in muscle, beta-cells, and liver. In the present twin study, we report heritability estimates (h(2)) for measures of insulin secretion, insulin resistance, hepatic glucose production (HGP), and intracellular glucose partitioning using gold standard methods (euglycemic-hyperinsulinemic clamp technique, tritiated glucose infusion, indirect calorimetry, and intravenous glucose tolerance testing) among 110 younger (22-31 years of age) and 86 older (57-66 years of age) twins. To obtain a valid estimate of beta-cell function, insulin secretion was adjusted for the individual degree of insulin action (disposition index).

A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene.

Recently, various subtypes of familial hyperinsulinemic hypoglycemia with an autosomal-dominant inheritance have been etiologically characterized. In the present study, we have delineated the genetics and metabolic phenotype of a novel form of hypoglycemia in a large pedigree with an apparent autosomal-dominant transmission. After initial investigations of the proband, her mother, and a sister, the study was extended to 19 family members in three generations.

Effects of troglitazone in young first-degree relatives of patients with type 2 diabetes.

Objective: Insulin resistance is a key characteristic of first-degree relatives of patients with type 2 diabetes. We therefore treated young, glucose-tolerant relatives with the insulin action enhancer troglitazone in order to determine the effects on insulin sensitivity, glucose metabolism, and glycogen synthase activity.

Research Design And Methods: Relatives were randomized in a double-blind manner and treated for 12 weeks with either 200 mg troglitazone or placebo.

Troglitazone treatment increases protein kinase B phosphorylation in skeletal muscle of normoglycemic subjects at risk for the development of type 2 diabetes.

We investigated whether the effect of troglitazone on glucose disposal is associated with altered insulin signaling. Nondiabetic first-degree relatives of type 2 diabetic patients (age 30 +/- 2 years, BMI 30 +/- 1 kg/m(2); n = 20) were randomized in a double-blind manner to 3 months of troglitazone (200 mg/day) or placebo treatment. Before and after treatment, 3-h euglycemic-hyperinsulinemic glucose clamps (40 mU.

Muscle fiber type distribution and nonlinear .VO(2)-power output relationship in cycling.

Purpose: We examined whether reported deviations from linearity of the oxygen uptake (.VO(2))-to-power output (W) relationship during intense cycling exercise correlated with the percentage Type II fibers in the exercising muscle.

Methods: Twelve trained young men with known fiber type distribution in the vastus lateralis muscle performed step-increment exercise (40 W.