Effects of Thyroid Function on Phosphodiester Concentrations in Skeletal Muscle and Liver: An In Vivo NMRS Study.

Context: Thyroid function is clinically evaluated by determination of circulating concentrations of thyrotropin (thyroid-stimulating hormone; TSH) and free thyroxine (fT4). However, a tissue-specific effector substrate of thyroid function is lacking. Energy-rich phosphorus-containing metabolites (PM) and phospholipids (PL) might be affected by thyroid hormone action and can be noninvasively measured by 31P nuclear magnetic resonance spectroscopy (NMRS).

Effects of insulin therapy on myocardial lipid content and cardiac geometry in patients with type-2 diabetes mellitus.

Aims/hypothesis: Recent evidence suggests a link between myocardial steatosis and diabetic cardiomyopathy. Insulin, as a lipogenic and growth-promoting hormone, might stimulate intramyocardial lipid (MYCL) deposition and hypertrophy. Therefore, the aim of the present study was to investigate the short-term effects of insulin therapy (IT) on myocardial lipid content and morphology in patients with T2DM.

The impact of type 2 diabetes on circulating adipokines in patients with metabolic syndrome.

Aim: The aim of the study was to investigate, whether type 2 diabetes independently influences adipokines and inflammatory markers in patients with metabolic syndrome.

Methods: 36 patients with metabolic syndrome without type 2 diabetes and 39 patients with metabolic syndrome with type 2 diabetes, carefully matched for age, sex, and BMI, were investigated. Primary outcome measures were circulating adipokines and inflammatory markers (adiponectin, leptin, visfatin, vaspin, resistin, TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), retinol binding protein 4 (RBP-4), growth differentiation factor-15 (GDF-15)).

From metabolic normality to cardiometabolic risk factors in subjects with obesity.

The aim of the study was to evaluate the 3 years incidence of cardiometabolic risk factors, such as impaired fasting glucose, reduced high-density lipoprotein (HDL)-cholesterol, increased plasma triglycerides or blood pressure as well as impaired glucose tolerance in overweight or obese (ow/ob) and normal body weight (nbw) subjects metabolically normal at baseline. Subjects from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study were analyzed. We analyzed 284 nbw and 152 ow/ob subjects who, at baseline, did not show any of the above-mentioned cardiometabolic risk factors.

Influence of hyperinsulinemia and insulin resistance on in vivo β-cell function: their role in human β-cell dysfunction.

Objective: Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the β-cell could cause β-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate β-cell function in subjects with normal glucose tolerance (NGT) and whether they contribute to dysglycemia in impaired glucose regulation (IGR).

Research Design And Methods: Insulin sensitivity (by euglycemic clamp), insulin-induced secretory response at isoglycemia (IISR) (as C-peptide percent change from basal during the clamp), glucose-induced secretory response (GISR) to an intravenous glucose bolus, and β-cell glucose sensitivity (β-GS) (by oral glucose tolerance test [OGTT] modeling) were measured in 1,151 NGT and 163 IGR subjects from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study.

Glucose absorption in gestational diabetes mellitus during an oral glucose tolerance test.

Objective: Women with gestational diabetes mellitus (GDM) show reduced insulin sensitivity and markedly elevated glucose excursions. After delivery, GDM mostly reverts to normal glucose tolerance (NGT), although leaving an increased risk of type 2 diabetes. Because gastrointestinal function changes during pregnancy causing vomiting, constipation, or reduced motility, we thought that gut glucose absorption in GDM or pregnancy might be altered to affect circulating glucose excursions.

A combination of (ω-3) polyunsaturated fatty acids, polyphenols and L-carnitine reduces the plasma lipid levels and increases the expression of genes involved in fatty acid oxidation in human peripheral blood mononuclear cells and HepG2 cells.

Background: Hyperlipidemia and obesity are associated with metabolic syndrome and increased risk in developing diabetes and cardiovascular disease. Nutritional supplements, e.g.

Liver enzymes are associated with hepatic insulin resistance, insulin secretion, and glucagon concentration in healthy men and women.

Objective: The pathophysiological mechanisms to explain the association between risk of type 2 diabetes and elevated concentrations of γ-glutamyltransferase (GGT) and alanineaminotransferase (ALT) remain poorly characterized. We explored the association of liver enzymes with peripheral and hepatic insulin resistance, insulin secretion, insulin clearance, and glucagon concentration.

Research Design And Methods: We studied 1,309 nondiabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study; all had a euglycemic-hyperinsulinemic clamp and an oral glucose tolerance test (OGTT) with assessment of insulin secretion and hepatic insulin extraction.

Effects of gastric bypass surgery on insulin resistance and insulin secretion in nondiabetic obese patients.

Roux-en-Y-Gastric-Bypass (RYGB) reduces overall and diabetes-specific mortality by 40% and over 90%. This study aims to gain insight into the underlying mechanisms of this effect. We evaluated time-courses of glucose, insulin, C-peptide, and the incretin glucagon like peptide-1 (GLP-1) following an oral glucose load.

Insulin infusion during normoglycemia modulates insulin secretion according to whole-body insulin sensitivity.

Objective: Glucose is the major stimulus for insulin release. Time course and amount of insulin secreted after glycemic stimulus are different between type 2 diabetes mellitus (T2DM) patients and healthy subjects. In rodents, it was demonstrated that insulin can modulate its own release.

Sex-specific differences in glycemic control and cardiovascular risk factors in older patients with insulin-treated type 2 diabetes mellitus.

Background: Because women have been excluded from many study populations in investigations of diabetes care, there is insufficient information on sex-specific differences in glycemic control.

Objective: The aim of the present study was to assess whether treatment goals for glycemic and cardiovascular risk factor control are achieved equally in older, Central European, female and male patients with type 2 diabetes mellitus (T2DM).

Methods: In a retrospective cross-sectional study, data were analyzed from consecutive older (aged ≥60 years) female and male patients with insulin-treated T2DM who attended a diabetes outpatient clinic between January 2007 and April 2008 at the Medical University of Vienna, Austria.

The relationship between insulin resistance and the cardiovascular biomarker growth differentiation factor-15 in obese patients.

Background: Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events.

Methods: We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.

Mechanism and effects of glucose absorption during an oral glucose tolerance test among females and males.

Background: Several epidemiological studies revealed sex-specific differences during oral glucose tolerance tests (OGTTs), such as higher prevalence of glucose intolerance (i.e. increased glucose at the end of the OGTT) in females, which was not yet explained.

Insulin sensitivity and beta-cell function in the offspring of type 2 diabetic patients: impact of line of inheritance.

Context: What defects in glucose metabolism are present in offspring of type 2 diabetic patients (FHD(+) with a positive family history of diabetes) and to what extent they depend on line of inheritance are uncertain.

Objective: The objective of this study was to assess clinical phenotype, insulin sensitivity, and β-cell function in FHD(+) by line of inheritance.

Subjects: The subjects included 1221 nondiabetic men and women aged 30-60 yr, of whom 343 were FHD(+), who participated to the Relationship between Insulin Sensitivity and Cardiovascular Disease Investigators study, a multicenter European collaboration.

Impact of family history on relations between insulin resistance, LDL cholesterol and carotid IMT in healthy adults.

Background: Insulin resistance (IR) is implicated as an independent risk factor for vascular disease. The aim of this study was to assess the impact of family history (FH) of type 2 diabetes (T2DM) and/or cardiovascular disease (CVD) on the associations between IR, low-density-lipoprotein cholesterol (LDL-C) and subclinical atherosclerosis (common and internal carotid artery intima media thickness (IMT)) in healthy European adults.

Methods: Participants (n=1048) in the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study were grouped according to family history of: (i) type 2 diabetes (FH-T2DM); (ii) cardiovascular disease (FH-CVD); (iii) both (FH-BOTH); or (iv) neither (CON).

Thyrotropin serum concentrations in patients with papillary thyroid microcancers.

Background: Recent studies have shown that elevated serum thyrotropin (thyroid-stimulating hormone [TSH]) concentrations are associated with an increased risk of differentiated thyroid cancers in patients with nodular goiter. Therefore, the measurement of TSH concentrations might support the clinical estimation of cancer risk, especially in patients with thyroid nodules that are too small for fine-needle aspiration biopsies. Thus, the objective of this study was to compare preoperative serum TSH concentrations in patients with papillary thyroid microcarcinoma (PTMC) and individuals in whom the presence of even small differentiated thyroid cancers was excluded by thorough histological examination of the thyroid after total thyroidectomy because of medullary thyroid carcinoma or c-cell hyperplasia.

Chronic peripheral hyperinsulinemia in type 1 diabetic patients after successful combined pancreas-kidney transplantation does not affect ectopic lipid accumulation in skeletal muscle and liver.

Objective: So far it is unclear whether chronic peripheral hyperinsulinemia per se might contribute to ectopic lipid accumulation and consequently insulin resistance. We investigated the effects of systemic instead of portal insulin release in type 1 diabetic patients after successful pancreas-kidney transplantation (PKT) with systemic venous drainage on the intracellular lipid content in liver and soleus muscle, endogenous glucose production (EGP), and insulin sensitivity.

Research Design And Methods: In nine PKT patients and nine matching nondiabetic control subjects, intrahepatocellular lipids (IHCLs) and intramyocellular lipids (IMCLs) were measured using (1)H nuclear magnetic resonance spectroscopy.

Adipokines in type 1 diabetes after successful pancreas transplantation: normal visfatin and retinol-binding-protein-4, but increased total adiponectin fasting concentrations.

Objective: In type 1 diabetes mellitus (T1DM), the release of many hormones, not only from beta-cells, but also from adipocytes (adipokines) may be altered. After successful pancreas-kidney-transplantation (PKTx), T1DM patients can revert to a nondiabetic metabolism, but it is unclear whether alterations of adipokines are still present after PKTx.

Design, Patients And Measurements: Concentrations of adipokines [visfatin, retinol-binding protein-4 (RBP-4), adiponectin, high molecular weight (HMW) adiponectin] were measured at fasting in 10 PKTx and in 19 T1DM.

Effects of high-dose simvastatin therapy on glucose metabolism and ectopic lipid deposition in nonobese type 2 diabetic patients.

Objective: Statins may exert pleiotropic effects on insulin action that are still controversial. We assessed effects of high-dose simvastatin therapy on peripheral and hepatic insulin sensitivity, as well as on ectopic lipid deposition in patients with hypercholesterolemia and type 2 diabetes.

Research Design And Methods: We performed a randomized, double-blind, placebo-controlled, single-center study.

Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans.

Obestatin, a recently discovered 23-amino acid peptide, is involved in the regulation of appetite and body weight in antagonistic fashion to ghrelin, both deriving from a common precursor peptide. Ghrelin was shown to be associated with insulin resistance, which may also affect obestatin. We investigated the association between insulin resistance and plasma concentrations of obestatin and ghrelin in nondiabetic individuals with high (IS; n = 18, 13 females and 5 males, age 47 +/- 2 yr, BMI = 25.

Insulin resistance is unrelated to circulating retinol binding protein and protein C inhibitor.

Context: Recent data suggest that circulating retinol-binding protein (RBP) might be involved in the pathogenesis of insulin resistance. Moreover, protein C inhibitor (PCI), which specifically binds retinoic acid, was found to be increased in myocardial infarction survivors who are also insulin resistant.

Objective: The objective of this study was to investigate the association of insulin resistance with RBP factors and PCI active antigen.

The Clamp-Like Index: a novel and highly sensitive insulin sensitivity index to calculate hyperinsulinemic clamp glucose infusion rates from oral glucose tolerance tests in nondiabetic subjects.

Objective: Insulin resistance, the underlying pathophysiological mechanism of the metabolic syndrome, can not only predict type 2 diabetes development but also cardiovascular disease. Thus, precise insulin resistance measurement in individuals at risk for metabolic diseases would support clinical risk stratification. However, the gold standard for measuring insulin resistance, the hyperinsulinemic clamp test, is too labor intensive to be performed in large clinical studies/settings.

The Mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man.

The nutrient-sensitive kinase mammalian target of rapamycin (mTOR) and its downstream target S6 kinase (S6K) are involved in amino acid-induced insulin resistance. Whether the mTOR/S6K pathway directly modulates glucose metabolism in humans is unknown. We studied 11 healthy men (29 years old, BMI 23 kg/m(2)) twice in random order after oral administration of 6 mg rapamycin, a specific mTOR inhibitor, or placebo.

Severity of insulin resistance in critically ill medical patients.

Critical illness is characterized by a hypermetabolic state associated with increased mortality, which is partly ascribed to the occurrence of hyperglycemia caused by enhanced endogenous glucose production and insulin resistance (IR). Insulin resistance is well described in patients after surgery and trauma. However, it is less clearly quantified in critically ill medical patients.