Circulatory adipocytokines and lipid profile variations in type-2 diabetic subjects: Desirable side-effects of antidiabetic drugs

AimInspite of availability of a variety of drugs to treat type 2 diabetes, little is known about their effects on other systems. Normalization of glucose metabolism by these drugs may consequently affect the secretory function in adipocytes. Secretory adipocytokines like adiponectin and leptin are emerging as novel therapeutic targets for type 2 diabetes mellitus (T2DM). The present study was undertaken to analyze the effects of commonly used Oral Hypoglycemic Agents (OHAs) alone, or in combination with other drugs and/or insulin on circulatory adiponectin and leptin levels, lipid profile, and blood pressure in diabetic subjects.MethodsThe study was undertaken at IRSHA and Bharati Vidyapeeth Medical College and Hospital, MS, India. Clinically diagnosed T2DM subjects and age, gender matched healthy controls were recruited. Fasting blood was collected from each subject and the blood samples were analyzed for circulatory adipocytokines and lipid parameters using commercial kits.ResultsSerum adiponectin levels were significantly increased while leptin significantly decreased in diabetic men (p < 0.05) and women (p < 0.001) on OHA, as compared to healthy controls. Triglyceride levels significantly decreased (p < 0.05) in diabetic men, however, they remained unchanged in women despite same drug treatment. Serum HDL and LDL levels (p < 0.001) were significantly lower in diabetic women as compared to healthy women. Systolic (p < 0.05) and diastolic (p < 0.001) blood pressure was significantly high in diabetic men but remained unchanged in women.ConclusionsFrequently used OHAs significantly improve circulatory levels of adipocytokines. Selecting best treatment option for each patient is a key, and 2012 European Association for the Study of Diabetes (EASD) and ADA guidelines recommend diabetes treatment to be individualized depending on various socioeconomic and lifestyle factors. We recommend regular analysis of circulatory adipocytokines in T2DM patients to help clinicians select the best treatment option to normalize levels of these important therapeutic targets.     

Reduced serum resistin levels in diabetic patients: Study from western India

ObjectiveResistin is an adipocyte-derived peptide that might play a role in obesity and insulin resistance (IR); however, its role in humans is largely unknown. The aim of the study was to elucidate the role of serum resistin and explore its relationship with inflammatory marker C-reactive protein (CRP) and adipocytokine (leptin, adiponectin) in Indian diabetic patients.Design and methodsA total of 171 subjects including 41 controls, 41 obese and 89 Type 2 diabetes mellitus (T2DM) patients were recruited in this cross-sectional study. Fasting serum resistin, leptin, adiponectin, insulin and CRP were measured by enzyme immunoassay. The relation between these variables was studied by univariate and multiple regression analysis.ResultsSerum resistin levels were significantly reduced in non-obese treated T2DM patients. In the correlation analysis after controlling for age and BMI we found that resistin is significantly associated with leptin (0.687, p < 0.002) and CRP (0.549, p < 0.018) in only control females and with CRP (0.642, p < 0.01) in T2DM female patients. In multiple linear regression analysis resistin was independently predicted by the leptin (p < 0.01) and leukocyte (p < 0.004) in controls, treated T2DM patients.ConclusionReduced resistin and leptin levels in non-obese treated T2DM and significant association between these two in control and treated T2DM suggest interplay between these two adipocytokines. In addition, the weak association of resistin with diabetes indicates that it may be playing an indirect role in the pathogenesis of T2DM.     

Growth hormone/insulin-like growth factor axis in patients with subclinical thyroid dysfunction

ObjectiveOur aim was to evaluate serum concentrations of GH, IGF-I, and insulin-like growth factor-binding protein-3 (IGFBP-3) in patients with subclinical thyroid dysfunction before and after normalization of thyroid function.Design and methodsThe study included 51 patients (mean age 42.2 ± 1.8 years) with subclinical hypothyroidism and 30 patients (mean age 44.3 ± 2.4 years) with subclinical hyperthyroidism. A group of 37 euthyroid healthy subjects were studied as controls. Serum concentrations of TSH, FT4, FT3, GH, insulin, IGF-I, and IGFBP-3 were measured in all patients before starting therapy and after normalization of thyroid function. The dosage of levothyroxine (LT4) and antithyroid drugs was adjusted in attempt to keep the serum-free thyroxine (FT4) and thyrotropin (TSH) concentrations within the normal range.Main outcomeBaseline growth hormone levels were similar with hypothyroid group and hyperthyroid group in relation to euthyroid control subjects. Fasting serum IGF-I levels were significantly lower in the subclinical hypothyroid group compared with the control group. On the other hand, IGF-I levels of subclinical hyperthyroid patients and control group were similar. After normalization of thyroid function tests, IGF-I concentrations were increased in subclinical hypothyroid subjects, but unchanged in subclinical hyperthyroid subjects. Patients with subclinical hyperthyroidism showed slightly lower mean serum IGFBP-3 concentrations than those found in control group, but the difference was not statistically significant. Serum GH and IGFBP-3 levels were unaltered by treatment.ConclusionsIn this study, it was shown that GH–IGF axis was not affected in patients with subclinical hyperthyroidism, while it was affected in patients with subclinical hypothyroidism. That is, investigation of the axis in subclinical hyperthyroidism would not bring any extra advantages, but LT4 replacement therapy could prevent abnormalities related to GH–IGF axis in patients with subclinical hypothyroidism.     

The relationship of serum leptin levels with disease activity in Egyptian patients with rheumatoid arthritis

Aim of the workTo investigate whether serum leptin levels are elevated in patients with rheumatoid arthritis (RA) and whether these levels correlate with disease activity.Patients and methodsA case-control study was made on 37 patients with RA and 34 healthy control subjects. The following values were assessed for each patient: erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF), swollen and tender joint counts, disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), visual analog scale (VAS) of pain and serum leptin concentrations.ResultsPatients with RA had mild to moderate (DAS28 < 5.1) disease activity. The mean serum leptin in patients with RA (12.15 ± 11.48 ng/mL) was significantly higher (p < 0.001) than controls (3.99 ± 1.84 ng/mL). Serum leptin levels were significantly (p < 0.001) higher in female RA patients than in female controls. A nonsignificant difference (p = 0.41) was found between male patients with RA and male controls. Serum leptin levels were significantly (p < 0.001) higher in women than in men in both patients and controls. Serum leptin levels did not show correlation with age, disease duration, duration of morning stiffness, VAS, number of swollen and tender joints, DAS28, HAQ, ESR or CRP in patients with RA. Serum leptin levels were correlated positively with BMI in RA patients. The BMI was significantly higher (p < 0.001) in female than in male patients with RA.ConclusionAlthough leptin levels were higher in RA patients, there was no correlation with disease activity parameters, therefore, leptin levels cannot be used to reflect disease activity.     

Serum leptin level and its association with fatigue in patients with chronic hepatitis C virus infection

Background and study aimFatigue is one of the most common presenting symptoms of chronic hepatitis C virus (HCV) infection. Its pathogenesis has been poorly investigated. Serum leptin levels are increased in cirrhosis and are suggested to have a role in the mediation of fatigue. This study was designed to assess possible association of serum leptin levels with fatigue and severity of liver disease in Egyptian patients with chronic hepatitis C infection.Patients and methodsSeventy patients and 20 control subjects participated in the study. They were subjected to clinical and laboratory assessment, the determination of serum leptin level by ELISA and the assessment of fatigue using the multidimensional assessment of fatigue (MAF) scale. Respondents are asked to reflect on fatigue patterns for the past week. The MAF is a revision of the Piper Fatigue Scale.ResultsFatigue was present in all patients (100%) and 13 subjects of the control group (65%). There was a highly significant statistical difference between cases and controls regarding the presence and severity of fatigue. Serum leptin level was significantly higher in cases (24.9 ± 28) in comparison to the control subjects (14.8 ± 8). Serum leptin was not related to severity of liver disease as assessed by the Child Pugh classification. Serum leptin levels were directly correlated to the severity of fatigue (p < 0.01) in patients but not in the control subjects.ConclusionFatigue is highly prevalent in Egyptian patients with chronic HCV infection. Leptin might play a role in the mediation of fatigue in those patients drawing attention to biological basis of one of the most common symptoms facing clinician dealing with this problem.     

Effects of three antidiabetics on insulin and leptin in Chinese type 2 diabetes

AimsThis study was to investigate the effects of some different antidiabetics on circulating insulin and leptin levels in type 2 diabetes with or without overweight in a Chinese population.Methods80 type 2 diabetes men with overweight (body mass index BMI > 24 kg/m²) and 35 type 2 diabetes men with normal body weight (BMI ≤ 24 kg/m²) and 56 control subjects were enrolled in the study. We measured blood glucose, insulin, leptin, total cholesterol, LDL-C, HDL-C, triglycerides, fasting glucose, postprandial glycose, HbA1c and BMI before and after the administration of antidiabetic drugs.ResultsCompared with normal body weight, the levels of plasma insulin and leptin in overweight type 2 diabetes men were higher, after 3 months treatment, a significant increase in insulin and leptin levels was observed in overweight type 2 diabetes men in gliclazide group. Levels of leptin and insulin decreased in metformin and rosiglitazone groups, respectively.ConclusionsWe conclude that surfonylureas treatment leads to increased insulin and leptin levels in overweight type 2 diabetes men, metformin, or rosiglitazone treatment can reduce insulin and leptin levels, respectively, and effect of metformin on plasma leptin and insulin levels is more significant than that of rosiglitazone.     

The TSH levels and risk of hypothyroidism: Results from a population based prospective cohort study in an Iranian adult's population

ObjectiveThe aim of current study was to assess the relationship between serum TSH levels and hypothyroidism risk in the euthyroid population.MethodsIn a population-based cohort study, a total of 615 individuals with a normal baseline TSH, from of total population (n = 2254) in 2006, were followed up for 6 years. TSH, total T4, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured. The relative risk (RR) and 95% confidence interval (95%CI) were calculated based on logistic regression. The Receiver Operating Characteristic (ROC) analysis along with area under the curve (AUC) was used to prediction of future hypothyroidism.ResultsTSH level in 2006 was a significant predictor for overt hypothyroidism, in the total population (RR = 3.5) and female (RR = 1.37) (all, P value < 0.05). A cutoff value of TSH at 2.05 mIU/L [AUC: (CI95 %), 0.68 (0.44–0.92; P = 0.05)] was obtained for differentiating the patients with overt hypothyroidism from euthyroid. However, this cut off was not observed when we included only negative TPO and TgAbs people in 2006. The RR of hypothyroidism increased gradually when TSH level increased from 2.06–3.6 mIU/L to > 3.6 mIU/L in the total population and both sexes. In women, the risk of overt hypothyroidism was significantly higher in subjects with TSH above 3.6 than those subject with THS levels ≤ 2.05 [RR: (CI95 %), 20.57(2.− 207.04), P value < 0.05].ConclusionA cutoff value of TSH at 2.05 mIU/L could predict the development of overt hypothyroidism in future. However, it was not applicable for people with negative TPOAb and negative TgAb.     

Serum levels of adiponectin and leptin in asthmatic patients and its relation with asthma severity,lung function and BMI

IntroductionAsthma is one of the diseases which has a high prevalence in developed and developing countries. The relationship between asthma and obesity has always been focused by researchers. In this field, adipokines, especially adiponectin and leptin have highly attended by the scientist. The aim of this study was to determine the serum level of adiponectin, leptin and the leptin/adiponectin ratio in asthmatic patients and its relationship with disease severity, lung function and BMI (body mass index).MethodsIn this cross-sectional study, 90 asthmatic women admitted to the tertiary referral hospital in Kurdistan province – Iran, were examined. First, BMI was measured and then pulmonary function tests were performed in all asthmatics patient. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC, were measured. At the end, blood samples were collected and serum level of adiponectin and leptin were measured by ELISA method.ResultSerum leptin and leptin/adiponectin levels correlated positively with asthma severity and BMI (p = 0.0001), but there was no correlation between adiponectin level with asthma severity and BMI (p > 0.05), also serum leptin and leptin/adiponectin levels inversely correlated with FEV1 and FVC in patient (p = 0.0001).ConclusionAsthma is linked with obesity, and there is an association between asthma severity and BMI with serum leptin and leptin/adiponectin levels, but our results do not support a significant role of adiponectin in obesity or asthma.     

NO levels in diabetes mellitus: Effects of l-NAME and insulin on LCAT,Na+/K+ ATPase activity and lipid profile

ObjectivesDiabetes mellitus (DM) is a chronic disease and one of the most important health problems. Several factors may be responsible for the complications of diabetes mellitus including alterations in the activities of sodium–potassium adenosine triphosphatase (Na⁺/K⁺ ATPase) and lecithin:cholesterol acyltransferase (LCAT) and also levels of nitric oxide (NO). We have investigated the effects of alterations in serum NO levels on activities of erythrocyte membran Na/K ATPase and serum LCAT enzymes.Materials and methodsThe experiments were performed on male rats divided into four groups: group 1, control (standart diet); group 2, diabetic control (single dose of 65 mg/kg of streptozotocin (STZ), i.p); group 3, STZ + insulin (8 IU/kg/day s.c.); group 4 (STZ + l-NAME 5 mg/kg/day orally).ResultStreptozotocin-induced diabetic rats, showed a significant increase in blood glucose and serum cholesterol (C) and triglyceride (TG). Compared to the control group with diabetic group plasma LCAT concentrations and erythrocyte membrane Na⁺/K⁺ ATPase were found to be decreased. Activities of Na⁺/K⁺ ATPase and serum NO level were decreased with the administration of l-NAME. We observed that insulin was ameliorated in all parameters.ConclusionsSerum NO levels is related to erythrocyte membrane Na⁺/K⁺ ATPase activity. But serum NO levels did not affect the plasma LCAT activity and serum lipid profiles.     

Levothyroxine treatment restored the decreased circulating fibroblast growth factor 21 levels in patients with hypothyroidism

Background and aimsFibroblast growth factor 21 (FGF21) is an important endogenous regulator of energy metabolism. Thyroid hormone has been shown to regulate hepatic FGF21 expression in rodents. The goal of this study was to evaluate the plasma FGF21 levels in participants with normal thyroid function, subclinical hypothyroidism, or overt hypothyroidism and to investigate the change of plasma FGF21 levels in patients with overt hypothyroidism after levothyroxine treatment.MethodsA total of 473 drug-naive participants were recruited, including 250 healthy control subjects, 116 patients with subclinical hypothyroidism, and 107 patients with overt hypothyroidism. Thirty-eight patients with overt hypothyroidism were assigned to receive levothyroxine treatment.ResultsThe overt hypothyroidism group had decreased FGF21 levels compared with the control and subclinical hypothyroidism groups (P < 0.01). Levothyroxine treatment markedly attenuated the increased circulating levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hsCRP), and homeostasis model assessment index of insulin resistance (HOMA-IR) in patients with overt hypothyroidism. A significant increase in plasma FGF21 levels was observed after levothyroxine treatment (P < 0.01). The change in FGF21 levels was correlated with the increase of FT3 and FT4 after levothyroxine treatment (FT3: r = 0.44; FT4: r = 0.53; all P < 0.05).ConclusionsLevothyroxine treatment ameliorated metabolic disorders and restored the decreased circulating FGF21 levels in patients with overt hypothyroidism. The increase in FGF21 levels after levothyroxine treatment might be partly associated with the amelioration of metabolic disorders in patients with hypothyroidism.     

Serum phospholipid omega-3 polyunsaturated fatty acids and insulin resistance in type 2 diabetes mellitus and non-alcoholic fatty liver disease

AimsTo investigate the relationship between serum phospholipid omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).Methods51 patients with T2DM and NAFLD (T2DM + NAFLD group), 50 with T2DM alone (T2DM group), 45 with NAFLD alone (NAFLD group), and 42 healthy control subjects (NC group) were studied. Serum ω-3 PUFA profiles were analyzed by gas chromatography, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and serum lipid concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment method (HOMA-IR).ResultsHOMA-IR levels were higher in the T2DM + NAFLD group than in the T2DM, NAFLD and NC groups (p < 0.05), as were ALT, AST, GGT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) concentrations (p < 0.05). Conversely, serum ω-3 PUFA levels were significantly lower in the T2DM + NAFLD group than in the other groups (p < 0.05). The ω-3 PUFA level was negatively correlated with HOMA-IR, TC, LDL-C and TG.ConclusionsSerum phospholipid ω-3 PUFA levels were significantly decreased in patients with T2DM and NAFLD, and were negatively related with insulin resistance. Thus, reduced ω-3 PUFAs may play an important role in the development of T2DM and NAFLD.     

Clinical significance of serum interleukin-6 and −174 G/C promoter polymorphism in Rheumatoid arthritis patients

Aim of the workTo evaluate the clinical significance of serum levels of interleukin-6 (IL-6) and ?174 G/C promoter polymorphism in Rheumatoid arthritis (RA) patients.Patients and methodsWe studied 37 RA patients and 10 age and gender matched healthy controls. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) were assessed. Serum IL-6 level was measured and promoter (?174G/C) genotyped.ResultsSerum IL-6 levels were significantly higher in RA patients compared to control (p = 0.04), especially those with CC promoter polymorphism. Twenty-four patients had GG IL-6 (?174 G/C) gene promoter polymorphism, 11 were GC and 2 CC. Nine controls were GG and 1 GC. In patients with more advanced polymorphism (?174 CC) there was a significantly increased functional impairment (HAQ score) (p = 0.029) and platelet count (p = 0.049). In those with GG genotype, there was a significant correlation between IL-6 and Morning stiffness duration (r = 0.44,p = 0.03), while those with GC genotype had a significant negative correlation of the IL-6 level with the parameters of disease activity and the DAS28 (r = ?0.69,p = 0.019). None of the studied parameters would predict the IL-6 promoter polymorphism.ConclusionSerum IL-6 levels and ?174 G/C promoter polymorphism were higher in RA patients than in healthy controls. The inverse relation of IL-6 with the DAS28 in those with an increased IL-6 promoter polymorphism may confirm its increased involvement in the pathogenesis of RA and in the increased disease activity which may point to the need for considering of anti-IL-6 agents in their management plan.     

Abnormal levels of adipokines in adolescent offspring of women with type 1 diabetes – Results from the EPICOM study

Aims/HypothesisTo investigate long-term consequences of diabetes during pregnancy, we determined adiponectin and leptin levels in adolescents born by women with type 1 diabetic (T1D) or non-diabetic mothers, and determined associations between adiponectin and leptin levels in adolescence and the magnitude of intrauterine hyperglycemia.Research design and methodsWe measured serum adiponectin and leptin and calculated leptin to adiponectin ratio (LAR) in 271 offspring of T1D women (index offspring) (13–20 years), and 297 matched control offspring. Anthropometry included total body fat (TBF) by dual-energy X-ray absorptiometry and an oral glucose tolerance test.ResultsAdiponectin levels were lower in index females (− 8.0% (95% CI; − 13.9, − 1.6)), but not in index males (0.4% (95% CI; − 7.3, 8.6)). Leptin levels were approximately 30% higher in index than control offspring, irrespective of gender. In males, this was seen despite similar TBF in index and control offspring. LAR was increased in index offspring (both males and females) compared with control offspring. There were no association between offspring adiponectin and maternal HbA1c levels in pregnancy. Leptin and LAR seemed to be associated with third trimester HbA1c levels in females in unadjusted, but not adjusted analyses.ConclusionMale and female offspring of women with T1D demonstrated increased serum leptin and LAR, whereas serum adiponectin was reduced in females only. These results suggest that abnormal regulation of adipokines is a consequence of being born to mothers with T1D. No direct association between maternal glycemic control and adiponectin and leptin levels or LAR in the adolescence was found.Clinical Trial Registration number: NCT01559181     

Modulation of methylglyoxal and glutathione by soybean isoflavones in mild streptozotocin-induced diabetic rats

Background and aimsEvidence shows that methylglyoxal (MG), a very reactive metabolite of glucose, plays a critical role in the pathogenesis of diabetes and diabetic complications. Although soy isoflavones have beneficial effects in diabetes, the role of soy isoflavones in regulating MG levels is unknown. The present study investigates the effects of soy protein isoflavones on MG and reduced glutathione (GSH).Methods and resultsMild diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 35 mg/kg streptozotocin (STZ). The diabetic rats were then randomly divided into three groups and received a special diet supplemented with casein (control), low-isoflavone soy protein (LIS), or high-isoflavone soy protein (HIS) for eight weeks, respectively. Compared to the control or LIS group, HIS diet significantly increased serum insulin levels (p < 0.01 or 0.05) and reduced serum glucose and MG levels (p < 0.05). Serum GSH levels were increased in HIS-fed rats compared with the control or LIS group (p < 0.01). Serum total cholesterol and homocysteine levels were significantly lower in HIS and LIS rats than those of the control rats.ConclusionsBoth LIS and HIS diets can lower serum lipid and homocysteine levels in this mild diabetic model. HIS diet enhances insulin secretion and reduces glucose level. Moreover, the HIS diet has potential in reducing MG and increasing GSH levels. In addition to its hypoglycemic effect, the antioxidant protection may provide beneficial effects in preventing the development of diabetic complications.     

Influence of adipocytokines and IL-6 on ankylosing spondylitis disease activity and functional status

Aim of the workThis study aimed to assess serum levels of some adipocytokines (leptin, adiponectin and resistin) and IL-6 in patients with ankylosing spondylitis (AS) to evaluate their relationship to disease activity and functional capacity.Patient and methodTwenty-five AS patients were enrolled. Body mass index (BMI), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) and acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were assessed. Serum leptin, adiponectin, resistin and interleukin (IL)-6 levels were determined using enzyme-linked immunosorbent assay (ELISA).ResultsThe mean levels of leptin (9.1 ± 3.9 ng/ml), resistin (2.27 ± 1.15 ng/ml) and IL-6 (9.2 ± 5.8 pg/ml); were significantly elevated in patients with AS compared to the controls (p = 0.000, p = 0.0028 and p = 0.000, respectively). Only serum leptin levels correlated significantly with IL-6 (p = 0.004), and both serum leptin and IL-6 levels correlated significantly with BASDAI (p = 0.02 and p = 0.005, respectively), ESR (p = 0.04) and CRP (p = 0.01 and p = 0.006, respectively) in AS patients. Serum resistin did not correlate with any of the AS disease parameters, whereas, serum adiponectin neither significantly elevated nor correlated with any of these parameters.ConclusionThe associations of significantly increased levels of serum leptin and IL-6 with AS disease activity parameters give clues to their role in the inflammatory process of the disease. Failure to find any correlation between high serum resistin levels and AS disease activity parameters is suggestive of its role in the pathogenesis rather than disease activity.     

Interrelations of serum leptin levels with adrenocorticotropic hormone,basal cortisol and dehydroepiandrosterone sulphate levels in patients with metabolic syndrome

ObjectivesThe aim of this study was to determine serum leptin levels, adrenocorticotropic hormone, basal cortisol and dehydroepiandrosterone sulphate levels in patients with metabolic syndrome.Material and methodsThe study was comprised of 35 female patients and who applied to Eskisehir Osmangazi University Medicine Faculty Endocrinology polyclinic due to the symptoms of obesity and diagnosed as having metabolic syndrome.ResultsPlasma adrenocorticotropic hormone and dehydroepiandrosterone sulphate levels of metabolic syndrome group were lower than controls (P < 0.001, P < 0.05, respectively). Serum basal cortisol, resistin and leptin levels of metabolic syndrome group were higher than control (P < 005, P < 0.01, P < 0.001, respectively).ConclusionsOur data suggest that hormonal changes in metabolic syndrome pathogenesis may be related with increased leptin levels and for that reason leptin may be an important marker in metabolic syndrome.     

The changes of serum sKlotho and NGAL levels and their correlation in type 2 diabetes mellitus patients with different stages of urinary albumin

ObjectiveTo investigate the changes of serum anti-aging protein Klotho and neutrophil gelatinase-associated lipocalin (NGAL) levels and their correlation in type 2 diabetes mellitus (T2DM) patients at different stages of diabetic kidney disease (DKD) determined by urinary albuminuria.Methods462 cases with T2DM were divided into three groups: normoalbuminuric [N-UAlb; urinary albumin to creatinine ratio (UACR) < 30 mg/g, n = 180], microalbuminuric [M-UAlb; UACR 30–300 mg/g, n = 158], macroalbuminuric [L-UAlb; UACR > 300 mg/g, n = 124]. The levels of serum soluble-Klotho (sKlotho), NGAL, 8-isoprostane prostaglandin F2α (8-iso-PGF2α), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) were determined by enzyme-linked immunosorbent assay (ELISA) in all cases and 160 control subjects.ResultsCompared with control, serum sKlotho levels were significantly decreased (P < 0.001), and serum NGAL levels increased significantly (P < 0.001) in T2DM patients. Furthermore, serum sKlotho and NGAL levels were significantly negatively correlated (P < 0.001). Serum sKlotho levels negatively correlated with UACR, TG, CHO, LDL, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001), but positively correlated with LDL (P < 0.001). Serum NGAL levels positively correlated with UACR, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001). In addition, serum NGAL levels and LDL were significantly positively correlated (P = 0.005), and HDL was significantly negatively correlated (P < 0.001).ConclusionSerum Klotho and NGAL levels may become new biomarkers of the early diagnosis of DKD in T2DM. Klotho may participate in the development of DKD pathological mechanism such as oxidative stress related to inflammation, renal fibrosis, lipid metabolic disorders, modulating the pathological process of diabetic kidney tissue. NGAL may play a part in these mechanisms.     

Serum leptin levels and lipid profiles in patients with allergic rhinitis and mild asthma

BackgroundDespite improved understanding of the pathophysiology of allergic rhinitis and asthma, the effect of serum leptin level is still controversial. Only a few studies have been performed to investigate the serum leptin levels in allergic rhinitis and asthma, and contradictory results have been observed.ObjectiveWe aimed to investigate the association between leptin, lipid profiles and allergic rhinitis and mild asthma, and to determine whether inhaled and/or intranasal steroids affect the leptin levels.Patients and methodsWe studied 43 patients with allergic rhinitis (10 of with mild asthma) (mean age 29.81, range 18-45 yr) and 32 volunteers as a control group (mean age 30.53, range 20-45 yr).ResultsSerum leptin levels in patients were 8.49 ± 10.76 μg/ml, and did not differ from volunteers 5.42 ± 6.63 μg/ml. (p > 0.05). We found a direct link between increased body mass index (BMI) and serum leptin levels (p = 0.008). No association was seen between leptin and triglyceride, HDL-cholesterol, VLDL-cholesterol, eosinophil, total IgE (p > 0.05); except for total cholesterol and LDL-cholesterol (p < 0.05). Although, no correlation between allergic rhinitis and mild asthma and serum level of leptin was shown, these parameters and age correlations were stronger in female than in male (p = 0.39 for male and p = 0.011 for female), and also found direct link between increased BMI and sex and patients group (p = 0.008 for male and p = 0.0001 for female). We also determined that there was no effect of inhaled and/or intranasal steroids statistically on serum leptin levels.ConclusionOur data demonstrate that the serum levels of leptin and lipid profiles on allergic rhinitis and mild asthma were not different than those in controls.     

Activities of cyclooxygenases,and levels of prostaglandins E2 And F2α, in fetopathy associated with experimental diabetic gestation

AimThe present study investigated the cyclooxygenase (COX) pathway to elucidate any changes that may be involved in the mechanism(s) underlying diabetic fetopathy.MethodsDiabetes was induced in female rats (n = 12) by two successive daily injections of 55 mg/kg streptozotocin, while control animals (n = 10) were injected with a buffer solution; hyperglycaemia was confirmed by blood glucose levels greater than 11 mmol/L. The study female rats were made pregnant and, on day 15 of gestation, the rats were sacrificed, and the fetuses, placentas and membranes dissected out of the uterine horns. Following morphological examination, the fetuses, placentas and membranes were homogenized, and used to measure COX activities and prostaglandin (PG) E₂ and PGF_2α levels.ResultsFetuses from diabetic mothers exhibited significantly (P < 0.05) shorter crown-to-rump lengths, lower body weights and heavier placental weights. The activity of COX-1 in the fetuses, placentas and membranes from diabetic mothers represented a small percentage of total COX activity compared with that of COX-2. The presence of a COX-1 inhibitor in the control and diabetic rats was investigated and found to be negative. The activity of COX-2 in malformed fetuses from diabetic mothers was significantly lower (P < 0.05) compared with non-malformed fetuses from control and diabetic mothers. The mean level of PGE₂ in fetuses from diabetic mothers was significantly (P < 0.05) lower than that in controls. In contrast, the biggest increases in PGF_2α were observed in the malformed diabetic fetuses, placentas and membranes.ConclusionThe increased production of PGF_2α probably proceeds, at least in part, independently of the COX pathway and via the isoprostane route. However, it is unclear whether the relatively high levels of PGF_2α are causally related to, or simply coincidental with, fetal malformation.     

The effects of hypothyroidism in rats on serum leptin concentrations and leptin mRNA levels in adipose tissue and relationship with body fat composition

Both thyroid hormones and leptin affect sympathetic nervous system activity, basal metabolic rate, body fat mass, food intake, and thermogenesis, and each one also affects the actions of the other. We examined the alterations in serum leptin concentrations and leptin mRNA expression in hypothyroid rats and investigated the relation between serum leptin and leptin mRNA levels with the total adipose tissue mass and total body weight. Twenty male Wistar rats were divided into 2 groups, euthyroid and hypothyroid. Their body compositions were examined by Dual Energy X-ray Absorptiometry at the beginning and end of the study. Serum leptin concentrations and levels of leptin mRNA in the retroperitoneal white adipose tissue were measured at the end of the study. Serum leptin concentrations did not show any difference between the two groups (1.9 +/- 0.2 ng/ml in the hypo and euthyroid group, P > 0.05), but the fat mass of the hypothyroid rats were lower than the euthyroid rats (21.1 +/- 2.5 g in the euthyroid group and 14.2 +/- 1.9 g in the hypothyroid group, P > 0.05 between groups at the end of the study) although the difference between the groups was statistically not significant. Leptin mRNA level was significantly higher in the hypothyroid group than in the euthyroid group (21.6 +/- 1.6 vs. 15.1 +/- 1.2 ng respectively, P = 0.002) although the dissected retroperitoneal fat weight was significantly lower in the hypothyroid group versus the euthyroid group (1.0 +/- 0.2 vs. 1.8 +/- 0.2 g respectively, P = 0.013). In conclusion, the change of leptin mRNA expression in white adipocytes was thought to be the direct result of hypothyroidism or a compensatory response to metabolic changes caused by hypothyroidism.