Chronic systemic inflammation is associated with increased cardiovascular mortality in patients with rheumatoid arthritis (RA). The aim of our study was to investigate association of glucose metabolism and inflammatory markers in a group of patients with rheumatoid arthritis free of other metabolic risk factors. Twenty-two premenopausal RA females (11 patients on low-dose GC (<8.5 mg/day of prednisone or equivalent), 11 patients without glucocorticoid therapy) and 15 age- and BMImatched healthy females underwent the oral glucose tolerance test. The insulin sensitivity indices according Matsuda (ISIMAT) and Cederholm (ISICED) as well as HOMA2 %S were calculated. Cytokines, lipid profile, non-esterified fatty acids (NEFA) and plasminogen activator inhibitor-1 (PAI-1) were measured in baseline blood samples. Despite elevated interleukin IL-6 and TNF alpha, glucose, insulin and C-peptide responses to oral glucose load as well as ISIMAT, ISICED, PAI-1 and NEFA were comparable in both RA groups and healthy controls. HOMA 2 %S correlated with disease activity. In conclusions, low-dose glucocorticoid treatment does not lead to glucose metabolism impairment in RA patients without other metabolic risk factors. Increased cardiovascular mortality and morbidity is probably due to a direct effect of systemic inflammation on myocardium and/or blood vessels., A. Penesová, ... [et al.]., and Obsahuje seznam literatury
Obesity in T1DM patients is associated with the components of metabolic syndrome. The influence of controlled fasting and low calorie diet (LCD) on insulin sensitivity and glucose metabolism was studied in 14 obese patients with type 1 diabetes mellitus (T1DM) (42.6±9.4 years, BMI 32.4±2.1 kg m−2). Insulin sensitivity in obese T1DM patients was measured using a hyperinsulinemic-euglycemic clamp before fasting, immediately after 7 days of fasting, and after 21 days of LCD. Glucose oxidation and non-oxidative glucose disposal were measured before and during the clamp by indirect calorimetry. In the control group of 13 of non-obese T1DM patients (36.9±13.9 years, BMI 22.6±2.1 kg m−2), only one hyperinsulinemiceuglycemic clamp was performed. Obese T1DM patients lost 6.1±1.1 kg after fasting and maintained reduction in body weight after 21 days of LCD. Fasting transiently reduced insulinmediated glucose disposal in the clamp (from 9.69±1.48 to 6.78±1.21 mg min−1 kg−1, P<0.001). This was caused by reduced glucose oxidation after the fasting period (from 2.81±0.52 to 0.88±0.98 mg min−1 kg−1, P<0.001). We conclude that one week of fasting transiently decreased insulin-mediated glucose disposal in T1DM patients. This was caused by reduced glucose oxidation., F. Musil, ... [et al.]., and Obsahuje seznam literatury
The insulin-like growth factor (IGF) is involved in the regulation of growth and metabolism. The aim of this study was to determine selected parameters of IGF system at systemic and local levels [subcutaneous (SAT) and visceral adipose tissue (VAT)] to assess its possible role in gestational diabetes mellitus (GDM). 37 pregnant women (21 with GDM and 16 without GDM) and 15 age-matched non-pregnant females were included in the study. Blood samples were taken in 28-32 and 36-38 weeks of gestation and 6-12 months after delivery. SAT and VAT samples were obtained during delivery or surgery. Compared with nonpregnant women, serum IGF-1 and IGFBP-3 were increased in both groups of pregnant women. IGF-2 was elevated only in GDM women from 36 weeks of gestation culminating 6 months after delivery (p=0.003). Serum IGFBP-3 was increased and IGFBP-4 decreased in GDM women vs. pregnant women without GDM during the whole study (IGFBP-3: p˂0.001 for GDM vs. non-GDM; IGFBP-4: p=0.004 for GDM vs. non-GDM). Pregnant women with GDM had decreased mRNA expression of IGF-1, IGF-1R and IGF-2R and IGFBP-4 in VAT and IGF-1R in SAT compared to pregnant women without GDM. Changes in local activity of IGF are associated with the development of GDM.
Thermally processed food contains advanced glycation end
products (AGEs) including Nε
-(carboxymethyl)lysine (CML).
Higher AGEs or circulating CML were shown to be associated with
pregnancy complications such as preeclampsia and gestational
diabetes. It is unclear whether this association is causal. The aim
of our study was to analyze the effects of dietary CML and
CML-containing thermally processed food on metabolism in
pregnant rats. Animals were fed with standard or with AGE-rich
diet from gestation day 1. Third group received standard diet and
CML via gavage. On gestation day 18, blood pressure was
measured, urine and blood were collected and the oral glucose
tolerance test was performed. Plasma AGEs were slightly higher
in pregnant rats fed with the AGE-rich diet (p=0.09).
A non-significant trend towards higher CML in plasma was found
in the CML group (p=0.06). No significant differences between
groups were revealed in glucose metabolism or markers of renal
functions like proteinuria and creatinine clearance. In conclusion,
this study does not support the hypothesis that dietary AGEs
such as CML might induce harmful metabolic changes or
contribute to the pathogenesis of pregnancy complications. The
short duration of the rodent gestation warrants further studies
analyzing long-term effects of AGEs/CML in preconception
nutrition.
Free fatty acids (FFAs) are natural ligands of the PPARγ2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32±11 years; BMI 23.9±4.0 kg/m2) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels – the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARγ2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes., B. Bendlová, D. Vejražková, J. Včelák, P. Lukášová, D. Burkoňová, M. Kunešová, J. Vrbíková, K. Dvořáková, K. Vondra, M. Vaňková., and Obsahuje bibliografii a bibliografické odkazy
Recent studies have demonstrated that adipocyte fatty acid binding proteins (FABP) may play a role in the etiopathogenesis of insulin resistance. The aim of our study was to assess serum FABP levels in obese patients with type 2 diabetes mellitus (T2DM) before and after 3 months of treatment with PPAR-α agonist fenofibrate (F) and to explore the relationship of FABP to biochemical parameters and measures of insulin sensitivity assessed by hyperinsulinemic-isoglycemic clamp. We measured biochemical parameters by standard laboratory methods, insulin sensitivity by hyperinsulinemic-isoglycemic clamp and serum concentrations of FABP by commercial ELISA kit in 11 obese females with T2DM before and after three months of treatment with PPAR-α agonist fenofibrate and in 10 lean healthy control women (C). Serum FABP levels were 2.5-fold higher in T2DM group relative to C and were not affected by fenofibrate treatment (C: 20.6±2.1 μg/l, T2DM before F: 55.6±5.7 μg/l, T2DM after F: 54.2±5.4 μg/l, p<0.0001 for C vs. T2DM before F). Hyperinsulinemia during the clamp significantly suppressed FABP levels in both C and T2DM group. FABP levels positively correlated with BMI, triglyceride levels, blood glucose, glycated hemoglobin, atherogenic index and insulin levels. An inverse relationship was found between FABP and HDL levels, metabolic clearance rate of glucose, M/I and MCRglc/I sensitivity indexes. We conclude that FABP levels are closely related to BMI, parameters of insulin sensitivity, HDL levels and measures of diabetes compensation. This combination makes FABP a valuable marker of metabolic disturbances in patients with type 2 diabetes mellitus., M. M. Haluzík ... [et al.]., and Obsahuje seznam literatury
Women with a positive history of gestational diabetes mellitus (GDM) face a higher risk of developing type 2 diabetes mellitus (T2DM) and metabolic syndrome later in life. The higher risk of these metabolic complications is closely associated with adipose tissue. In this review, the importance of adipose tissue is discussed in relation to GDM, focusing on both the quantity of fat deposits and the metabolic activity of adipose tissue in particular periods of life: neonatal age, childhood, adolescence, and pregnancy followed by nursing. Preventive measures based on body composition and lifestyle habits with special attention to the beneficial effects of breastfeeding are also discussed., D. Vejrazkova, M. Vankova, P. Lukasova, J. Vcelak, V. Cirmanova, M. Haluzik, B. Bendlova., and Obsahuje bibliografii
Glucose tolerance, serum insulin, insulin receptors in epididymal fat tissue, circulating total cholesterol and triglyceride concentrations as well as serum prolactin were studied in obese and lean spontaneously hypertensive rats (SHR) of both sexes. Obese animals displayed insulin resistance and elevated insulin and triglyceride concentrations. Moreover, in obese rats the increased mass of epididymal fat tissue was accompanied with decreased capacity of high affinity binding sites of insulin receptors in the tissue plasma membranes. Terguride treatment lowered prolactin serum levels which was accompanied by ameliorated insulin sensitivity in obese animals of both sexes. In addition, terguride treatment decreased serum insulin and triglyceride concentrations in obese females and at the same time enhanced the affinity of high affinity insulin binding sites. Our results show that obesity in SHR is associated with a decreased capacity of insulin receptors and that prolactin may play a role in obesity-induced insulin resistance, particularly in female rats., V. Golda +, M. Ficková, L. Pinterová, J. Jurčovičová, L. Macho, Š. Zórad., and Obsahuje bibliografii
Bradykinin can enhance skeletal muscle glucose uptake (GU), and exercise increases both br adykinin production and muscle insulin sensitivity, but bradykinin’s relationship with post-exercise insulin action is uncertain. Our primary aim was to determine if the B2 receptor of bradykinin (B2R) is essential for the post- exercise increase in GU by insulin-stimulated mouse soleus muscles. Wildtype (WT) and B2 R knockout (B2RKO) mice were sedentary or performed 60 minutes of treadmill exercise. Isolated soleus muscles were incubated with [ 3 H]-2-deoxyglucose ±insulin (60 or 100 μ U/ml). GU tended to be greater for WT vs. B2RKO soleus with 60 μ U/ml insulin (P=0.166) and was significantly greater for muscles with 100 μ U/ml insulin (P<0.05). Both genotypes had significant exercise-induced reductions (P<0.05) in glycemia and insulinemia, and the decrements for glucose (~14 %) and insulin (~55 %) were similar between genotypes. GU tended to be greater for exercised vs. sedentary soleus with 60 μ U/ml insulin (P=0.063) and wa s significantly greater for muscles with 100 μ U/ml insulin (P<0.05). There were no significant interactions between genotype and exercise for blood glucose, plasma insulin or GU. These results indicate that the B2R is not essential for the exerci se-induced decrements in blood glucose or plasma insulin or for the post-exercise increase in GU by insulin-stimulated mouse soleus muscle., G. G. Schweitzer ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
This mini-review aims to introduce the association between Secretory clusterin/apolipoprotein J (sCLU) and diverse musculoskeletal diseases. A comprehensive review of the literature was performed to identify basic science and clinical studies, which implied the therapeutic and prognostic role of sCLU in diverse musculoskeletal diseases. sCLU is a multifunctional glycoprotein that is ubiquitously expressed in various tissues and is implicated in many pathophysiological processes. Dysregulated expression of sCLU had been reported to be assocaited with proliferative or apoptotic molecular processes and inflammatory responses, which participated in many pathophysiological processes such as degenerative musculoskeletal diseases including ischemic osteonecrosis, osteoarthritis (OA) and degenerative cervical myelopathy (spinal cord injury), neoplastic musculoskeletal diseases, inflammatory and autoimmune musculoskeletal diseases including Rheumatoid arthritis (RA), joint damage induced by Brucella abortus, Sjogren's syndrome, idiopathic inflammatory myopathies, muscle glucose metabolism, insulin sensitivity and traumatic musculoskeletal diseases. Recent findings of sCLU in these musculoskeletal diseases provides insights on the therapeutic and prognostic role of sCLU in these musculoskeletal diseases. sCLU may serve as a promising therapeutic target for ischemic osteonecrosis, OA and spinal cord injury as well as a potential prognostic biomarker for OA and RA. Moreover, sCLU could act as a prognostic biomarker for osteosarcoma (OS) and a promising therapeutic target for OS resistance. Although many studies support the potential therapeutic and prognostic role of sCLU in some inflammatory and autoimmune-mediated musculoskeletal diseases, more future researches are needed to explore the molecular pathogenic mechanism mediated by sCLU implied in these musculoskeletal diseases.