Moderate Red Wine and Grape Juice Consumption Modulates the Hydrolysis of the Adenine Nucleotides and Decreases Platelet Aggregation in Streptozotocin-Induced Diabetic Rats

This study investigated the ex vivo effects of the moderate red wine (RW) and grape juice (GJ) consumption, and the in vitro effects of the resveratrol, caffeic acid, gallic acid, quercetin, and rutin on NTPDase (nucleoside triphosphate diphosphohydrolase), ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP), 5′-nucleotidase, and adenosine deaminase (ADA) activities in platelets and platelet aggregation from streptozotocin-induced diabetic rats. The animals were divided into six groups (n = 10): control/saline, control/GJ, control/RW, diabetic/saline, diabetic/GJ, and diabetic/RW. RW and GJ were administered for 45 days; after this period, the blood was collected for experimental determinations. Results showed that NTPDase, E-NPP, 5′-nucleotidase, and ADA activities as well as platelet aggregation were increased in the diabetic/saline group compared to the control/saline group. Treatment with RW and GJ increased ectonucleotidases activities and prevented the increase in the ADA activity in the diabetic/GJ and diabetic/RW groups. Platelet aggregation was also decreased by the treatment with RW and GJ in the diabetic/GJ and diabetic/RW groups. In the in vitro tests, resveratrol, caffeic acid, and gallic acid increased ATP, ADP, and AMP hydrolysis, while quercetin and rutin decreased the hydrolysis of these nucleotides in platelets of diabetic rats. The ADA activity and platelet aggregation were reduced in platelets of diabetic rats in the presence of all polyphenols tested in vitro. These findings suggest that RW, GJ, and all polyphenols tested were able to modulate the ectoenzymes activities. Moreover, a decrease in the platelet aggregation was observed and it could contribute to the prevention of platelet abnormality, and consequently vascular complications in diabetic state.     

Comparison of Different Diagnostic Criteria for Gestational Diabetes Mellitus Based on the 75-G Oral Glucose Tolerance Test: A Cohort Study

ObjectiveTo compare the different diagnostic criteria for gestational diabetes mellitus (GDM) proposed by the American Diabetes Association (ADA), World Health Organization (WHO), and Australian Diabetes in Pregnancy Society (ADIPS) in a 75-g, 2-hour oral glucose tolerance test (OGTT) and to investigate their effects on neonatal birth weight.MethodsHealthy pregnant women were enrolled in a cohort study to undergo a 75-g OGTT during 24 to 28 weeks of pregnancy and then followed up to delivery. ADA criteria and recommendations were used for the management of patients.ResultsAmong 670 pregnant women, GDM was diagnosed in 41 (6.1%), 81 (12.1%), and 126 (18.8%) on the basis of ADA, WHO, and ADIPS criteria, respectively. The kappa value was 0.38 (P < .0001) for the agreement between ADA and WHO criteria, 0.41 (P < .0001) for agreement between ADA and ADIPS criteria, and 0.64 (P < .0001) for agreement between WHO and ADIPS criteria. WHO-only “positive” women had significantly lower fasting plasma glucose (87.9 versus 102.2 mg/dL; P < .0001) and 1-hour plasma glucose levels (146.4 versus 200.5 mg/dL; P < .0001) but higher 2-hour plasma glucose levels (150.1 versus 109.1 mg/dL; P < .0001) than women diagnosed with GDM by only ADA criteria. The correlation coefficient between 1-hour glucose level and neonatal birth weight was 0.09 (P < .02). The adjusted odds ratio of macrosomia associated with GDM according to ADA criteria was 1.34 (95% confidence interval, 0.15 to 12).ConclusionThe frequency of occurrence of GDM was 6.1% in a 75-g OGTT based on ADA criteria, and there was fair agreement between ADA and WHO criteria, moderate agreement between ADA and ADIPS criteria, and strong agreement between WHO and ADIPS criteria. A modest correlation was found between the 1-hour serum glucose value and neonatal birth weight. (Endocr Pract. 2008;14:312-317)     

Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study

BackgroundChromium is an essential mineral that contributes to normal glucose function and lipid metabolism. This study evaluated the effect of chromium picolinate (CrPic) supplementation in patients with type 2 diabetes mellitus (T2DM).MethodsA four month controlled, single blind, randomized trial was performed with 71 patients with poorly controlled (hemoglobin A1c [HbA1c] > 7%) T2DM divided into 2 groups: Control (n = 39, using placebo), and supplemented (n = 32, using 600 μg/day CrPic). All patients received nutritional guidance according to the American Diabetes Association (ADA), and kept using prescribed medications. Fasting and postprandial glucose, HbA1c, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and serum ferritin were evaluated.ResultsCrPic supplementation significantly reduced the fasting glucose concentration (−31.0 mg/dL supplemented group; −14.0 mg/dL control group; p < 0.05, post- vs. pre-treatment, in each group) and postprandial glucose concentration (−37.0 mg/dL in the supplemented group; −11.5 mg/dL in the control group; p < 0.05). HbA1c values were also significantly reduced in both groups (p < 0.001, comparing post- vs. pre-treatment groups). Post-treatment HbA1c values in supplemented patients were significantly lower than those of control patients. HbA1c lowering in the supplemented group (−1.90), and in the control group (−1.00), was also significant, comparing pre- and post-treatment values, for each group (p < 0.001 and p < 0.05, respectively). CrPic increased serum chromium concentrations (p < 0.001), when comparing the supplemented group before and after supplementation. No significant difference in lipid profile was observed in the supplemented group; however, total cholesterol, HDL-c and LDL-c were significantly lowered, comparing pre- and post-treatment period, in the control group (p < 0.05).ConclusionsCrPic supplementation had a beneficial effect on glycemic control in patients with poorly controlled T2DM, without affecting the lipid profile. Additional studies are necessary to investigate the effect of long-term CrPic supplementation.     

Central visfatin potentiates glucose-stimulated insulin secretion and β-cell mass without increasing serum visfatin levels in diabetic rats

IntroductionOur previous study revealed that plasma visfatin levels were lower in pregnant women with gestational diabetes (GDM) than non-GDM independent of prepreganacy BMI. We examined whether central visfatin modulates energy and glucose homeostasis via altering insulin resistance, insulin secretion or islet morphometry in diabetic rats.MethodsPartial pancreatectomized, type 2 diabetic, rats were interacerbroventricularly infused with visfatin (100 ng/rat/day, Px-VIS), visfatin + visfatin antagonist, CHS-828 (100 μg/rat/day, Px-VIS-ANT), or saline (control, Px-Saline) via osmotic pump, respectively, for 4 weeks.ResultsCentral visfatin improved insulin signaling (pAkt → pFOXO-1) but not pSTAT3 in the hypothalamus. Central visfatin did not alter serum visfatin levels in diabetic rats whereas the levels were higher in non-diabetic rats than diabetic rats. Body weight at the 2nd week was lowered in the Px-VIS group due to decreased food intake in the first two weeks compared to the Px-Saline group and energy expenditure was not significantly different among the treatment groups of diabetic rats. Visfatin antagonist treatment nullified the central visfatin effect. Px-VIS increased whole body glucose disposal rates in euglycemic hyperinsulinemic clamp compared to Px-Saline and lowered hepatic glucose output, whereas Px-VIS-ANT blocked the visfatin effect on insulin resistance (P < 0.05). In hyperglycemic clamp study, the area under the curve of insulin in first and second phase were significantly higher in the Px-VIS group than the Px-Saline group without modifying insulin sensitivity at the hyperglycemic state, whereas the increase in serum insulin levels was blocked in the Px-VIS-ANT group. Central visfatin also increased β-cell mass by increasing β-cell proliferation.ConclusionsCentral visfatin improved glucose homeostasis by increasing insulin secretion and insulin sensitivity at euglycemia through the hypothalamus in diabetic rats. Therefore, visfatin is a positive modulator of glucose homeostasis by delivering the hypothalamic signals into the peripheries.     

The effect of glucagon-like peptide-2 on arterial blood flow and cardiac parameters

BackgroundGlucagon-like peptide-2 (GLP-2) is known to increase mesenteric blood flow. The aim of the study was to evaluate the effect of GLP-2 on blood flow in different vascular sites, and dynamic changes in cardiac parameters.Methods10 healthy volunteers were given 450 nmol subcutaneous (SC) GLP-2 or isotonic saline (5 subjects) in a single blinded manner. During the following 90 min, blood flow in the superior mesenteric artery (SMA), celiac artery (CA), renal artery (RA), common carotid artery (CCA) was measured using Doppler ultrasound (US), and cardiovascular variables were measured by impedance cardiography and finger plethysmography. Plasma GLP-2 was measured at times 0, 30 and 60 min.ResultsCompared to the placebo group, GLP-2 elicited a 27% decrease in the resistance index (RI) and a 269.4% increase in Time Averaged Maximal Velocity (TAMV) in the SMA (P < 0.01). CA, RA and CCA: There were no significant changes in RI or TAMV in the GLP-2 or placebo group, and no change in CA diameter.Cardiac parameters: GLP-2 increased cardiac output (CO), stroke volume (SV) and heart rate (HR) compared to baseline (respectively: 15.3, 4.81 and 8.2% (P < 0.001, P < 0.01 and P < 0.01)). The CO, SV and HR changes were not significantly different from the placebo group.Mean plasma GLP-2 serum levels in the placebo group at times 0, 30 and 60 min were 22.8, 23.4 and 23.2 pmol/l. In the GLP-2 group 20.3, 1273 and 1725 pmol/l.ConclusionSC GLP-2 increased SMA blood flow, as previously shown, but elicited no changes in other vascular sites. CO and HR increased significantly, presumably due to the increased mesenteric blood flow.     

Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes

Introduction/objectivesThe role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic.The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls.MethodsPRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n = 8) at delivery and compared to controls (n = 5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n = 5) or nicotinamide (NCT) plus STZ (n = 9) or vehicle (n = 9). Placental whole-genome gene expression and PRL western blots were performed at birth.ResultsIn human placentas, PRL (p < 0.05) and BMP-1 (p < 0.01) gene expressions were increased with a higher amount of cleaved PRL (p < 0.05) in T1D than controls. In rats, diabetes was more pronounced in STZ than in NCT–STZ group with intra-uterine growth restriction. Decidual prolactin-related protein (Dprp) (p < 0.01) and Bmp-1 (p < 0.001) genes were up-regulated in both diabetic groups, with an increased cleaved PRL amount in the STZ (p < 0.05) and NCT–STZ (p < 0.05) groups compared to controls. No difference in CTSD gene expression was observed in rats or women.ConclusionsAlterations in the levels of the PRL family are associated with maternal diabetes in both rats and T1D women suggesting that placental changes in these hormones impact on fetal development.     

Metabolic control and chronic complications during a 3-year follow-up period in a cohort of type 2 diabetic patients attended in primary care in the Community of Madrid (Spain)

BackgroundOur aim was to analyze both metabolic control and chronic complications of type 2 diabetes mellitus (T2D) patients regularly attended in primary care during a 3 years of follow-up in the Community of Madrid (Spain).MethodsFrom 2007 to 2010 we prospectively included 3268 patients with T2D attended by 153 primary care physicians from 51 family health centers. An prospective cohort study with annual evaluation over 3 years to the same population was performed. We measured the goals of control in diabetic patients and the incidence of chronic complications of diabetes during the study period.ResultsA significant decrease in serum glucose levels (143 ± 42 mg/dl vs 137 ± 43 mg/dl, p < 0.00), HbA1c (7.09 ± 1.2% vs 7.02 ± 1.2%, p < 0.00), total cholesterol (191.4 ± 38 mg/dl vs 181.5 ± 36 mg/dl, p < 0.00), LDL cholesterol (114.7 ± 31 mg/dl vs 105.5 ± 30 mg/dl, p < 0.00) and triglyceride levels (144.5 ± 93 mg/dl vs 138 ± 84 mg/dl, p < 0.00) during study period was documented. On the contrary, a significant elevation in HDL cholesterol levels was observed (49.2 ± 14 mg/dl vs 49.9 ± 16 mg/dl, p < 0.00). The incidence of diabetic complications throughout the study period was low, with a incidence of coronary heart disease of 6.2%, peripheral arterial disease 3%, ischemic stroke 2.8%, diabetic foot 11.2%, nephropathy 5.9%, retinopathy 4.5%, and neuropathy 3%.ConclusionMetabolic control in T2D patients attended in primary care in the Community of Madrid throughout 3 years is adequate and is accompanied by low percent of chronic diabetic complications during this period of follow-up.     

Glycemic Control and Outcomes of Hospitalization in Noncritically Ill Patients With Type 2 Diabetes Admitted With Cardiac Problems or Infections

ObjectiveAlthough the importance of glycemic control is well established for patients with diabetes hospitalized for surgical problems, it has not been supported by clinical studies for patients with diabetes hospitalized on the medical floors.MethodsWe conducted a retrospective study of 378 patients with type 2 diabetes admitted for cardiac or infectious disease (ID) diagnosis between September 1, 2011, and August 1, 2012. Exclusion criteria included type 1 diabetes, admission to the intensive care unit (ICU), hospital stay shorter than 3 days, and daily glucocorticoid dose > 20 mg of methylprednisolone. The primary composite outcome included death during hospitalization, ICU transfer, initiation of enteral or parenteral nutrition, line infection, deep vein thrombosis, pulmonary embolism, rise in plasma creatinine by 1 or > 2 mg/dL, new infection, an infection lasting for more than 20 days, and readmission within 30 days and between 1 and 10 months after discharge.ResultsPatients were stratified by mean blood glucose (BG) level: group 1 had mean BG of < 180 mg/dL (n = 286; mean BG, 142 ± 23 mg/dL), whereas group 2 had mean BG levels > 181 mg/dL (n = 92; mean BG, 218 ± 34 mg/dL; P < .0001). Group 2 had a 46% higher occurrence of the primary outcome (P < .0004). The rate of unfavorable events was greater in cardiac and ID patients with worse glycemic control (group 2).ConclusionOur data strongly support a positive influence of better glycemic control (average glycemia < 180 mg/dL or 10 mmol/L) on outcomes of hospitaliza-tion in patients with type 2 diabetes. (Endocr Pract. 2014; 20:1303-1308)     

Effect of sophora japonica total flavonoids on pancreas,kidney tissue morphology of streptozotocin-induced diabetic mice model

To observe effect of sophora japonica total flavonoids on pancreas, kidney tissue morphology of streptozotocin-induced diabetic mice model. Mice received tail vein injection of streptozotocin (60 mg/kg) for diabetes modeling. The model mice were divided into five groups, to be respectively fed with high, middle and small doses of sophora japonica total flavonoids solution, metformin solution and saline of the same volume. Another blank control group was set to be fed with saline of the same volume. The mice were administered once a day for 30 consecutive days, to be euthanatized after fasting blood glucose level testing on 30th day with pancreas, kidney taken out for pathological section and microscopic examination. The mice chain streptozotocin diabetes modeling was successful, with significant pathological changes (P < 0.01) in pancreas, kidney. Compared with model group, high, middle and small doses of sophora japonica total flavonoids could significantly alleviate streptozotocin-induced pancreas, kidney damage (P < 0.01). Conclusion: Sophora japonica total flavonoids can effectively alleviate pancreas, kidney injury of streptozotocin-induced diabetic mice model.     

The protective effect of montelukast sodium on carbon tetrachloride induced hepatopathy in rat

AimThis study investigates the effects of montelukast sodium (MK) (CysLTLT1 receptor antagonist) on CCl₄induced hepatopathy on rat.Material and methodsWe worked on 4 groups of 10 Wistar male rats each. The groups received as follows: group I (control group) – saline, group II – MK 5 mg/kg/day i.p. for 5 days, group III – MK 5 mg/kg/day i.p., 1 day prior to and 4 days concomitantly with CCl₄ p.o., 0.3 ml/Kg/day and group IV – CCl₄, p.o., 0.3 ml/Kg/day for 4 days. One day after the last administration, samples of blood were taken and alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), malondialdehyde (MDA), catalase (CAT) as well as total antioxidant capacity (TAC) were determined. The histopathological exam was performed. We also determined superoxide dismutase (SOD), MDA, CAT and GSH in liver homogenate.ResultsCompared to group IV, group III exhibited statistically significant lower levels of ALT (318 ± 15.75 versus 203.14 ± 10.28 UI, p < 0.0001), TB (3.16 ± 0.30 versus 1.99 ± 0.08 mg/dl, p < 0.0001), MDA in blood and in liver homogenate (4.98 ± 1.71 versus 2.15 ± 1.18 nmol/ml, p = 0.0004) and higher levels of SOD and CAT. Histopathologically, group IV presented important macro- and micro-vesicular hepatic steatosis and group III preserved lobular histoarchitecture and had less severe cellular lesions.ConclusionMK exhibits a partial hepatoprotective effect on rats treated with CCl₄.     

Retinopathy is a Strong Determinant of Atherosclerosis in Type 2 Diabetes: Correlation with Carotid Intima Media Thickness

ObjectiveWe investigated the correlation between the severity of diabetic retinopathy (DR) and carotid intima media thickness (IMT) as a marker of atherosclerosis in patients with type 2 diabetes.MethodsThe study group consisted of 140 normo-tensive Egyptian patients (68 males and 72 females) with type 2 diabetes and DR. Carotid IMT was evaluated using high-resolution B-mode ultrasonography. DR was assessed and graded using colored fundus photography and fundus fluorescein angiography, as either nonproliferative DR (NPDR) or proliferative DR (PDR).ResultsCarotid IMT was greater in patients with PDR compared to those with NPDR (1.094 ± 0.142 mm vs. 0.842 ± 0.134 mm; P < .001). Carotid IMT showed positive correlation with diabetes duration (P < .01), systolic blood pressure (P < .001), diastolic blood pressure (P < .01), fasting blood glucose (P < .01), postprandial blood glucose (PPBG) (P < .001), glycated hemoglobin (P < .01), total cholesterol (P < .01), triglycerides (TGs) (P < .001), and DR (P < .0001). No significant difference was found between males and females in any of the studied parameters. Multiple regression analysis revealed that the determinants of carotid IMT in the studied group were age (P < .01), PPBG (P < .01), TGs (P < .001), and DR (P < .0001).ConclusionOur study proves that both NPDR and PDR are strong determinants of carotid IMT and atherosclerosis in patients with type 2 diabetes. (Endocr Pract. 2015;21:226-230)     

Hypoglycemic,antiperoxidative and antihyperlipidemic effects of saponins from Solanum anguivi Lam. fruits in alloxan-induced diabetic rats

The present study evaluates the hypoglycemic, antiperoxidative and antihyperlipidemic activities of saponins from Solanum anguivi fruits in alloxan induced diabetes rats. Diabetic rats were treated with saponin (20–100 mg/kg) for 21 days. Results indicated that administration of saponins significantly reduced the elevated levels of glucose, decreased total cholesterol (TC), total triglycerides (TG), low density lipoprotein (LDL) and increased high density lipoprotein (HDL) in the serum towards normalcy when compared to the diabetic control (p < 0.05). In addition, saponins exhibited strong inhibition of lipid peroxidation and increased the levels of antioxidant enzymes (superoxide dismutase and catalase) in the serum, liver and pancreas when compared to the diabetic control (p < 0.05). Our results suggest that saponins from S. anguivi fruit can enhance the hypoglycemic, hypolipidemic and antioxidant properties in alloxan-induced diabetic rats, and may have the potential to be used in the prevention or in the management of diabetes.     

Marcadores bioquímicos,nutricionales y actividad antioxidante en el síndrome metabólico

Background and objectives1) Nutritional assessment of the diet followed by patients with metabolic syndrome, and 2) biochemical analysis of the oxidation-reduction level in patients with metabolic syndrome.Material and methodsA cross-sectional study was conducted in patients with metabolic syndrome in Murcia. Fifty-three patients, 33 with and 20 without (control group) metabolic syndrome, were selected. The intervention consisted of completion of a recall survey and a test to nutritionally assess dietary intake. Anthropometric and laboratory variables, including those related to antioxidant activity, were also tested.ResultsAntioxidant activity was within normal limits in both groups (1.7 ± 0.2 mmol/L in the control group and 1.8 ± 0.1 mmol/L in the metabolic syndrome group) (NS). Superoxide dismutase levels were not significantly different between the groups. Mean glutathione reductase levels (U/L) were higher in the control group as compared to patients with metabolic syndrome (P < .05). As regards oxidative stress biomarkers, mean isoprostane levels were higher in the control group (4.9 ± 6.2 ng/mL) than in metabolic syndrome patients (3.5 ± 3.9 ng/mL) (P < .05). Oxidized LDL values tended to be higher in metabolic syndrome patients (96 ± 23.2 U/L) as compared to the control group (86.2 ± 17.3  U/L), but differences were not significant.ConclusionsThere is a trend to a poorer nutritional and biochemical profile in patients with metabolic syndrome, who also tend to have a greater degree of oxidative stress.     

Increased Atherogenic Low-Density Lipoprotein Cholesterol in Untreated Subclinical Hypothyroidism

ObjectiveTo evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with subclinical hypothyroidism (SCH).MethodsIn a prospective, double-blind, placebo- controlled study, we enrolled 120 patients—mostly, but not exclusively, premenopausal women—with SCH. Patients were randomly assigned to either a levothyroxine- treated group (n = 60) or a placebo (control) group (n = 60). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured before and 52 weeks after assignment to either group.ResultsIn the levothyroxine-treated group, the lipoprotein mean values before and after the 52-week study were as follows: TC, 5.05 ± 0.98 mmol/L versus 4.74 ± 0.87 mmol/L (P < .0001); LDL-C, 3.30 ± 0.90 mmol/L versus 2.89 ± 0.59 mmol/L (P < .01); TG, 1.18 ± 0.71 mmol/L versus 0.95 ± 0.53 mmol/L (P < .002); and HDL-C, 1.20 ± 0.33 mmol/L versus 1.19 ± 0.32 mmol/L (P = .29). In the control group, TC, HDL-C, and TG values remained unchanged after 52 weeks in comparison with baseline, but LDL-C mean values increased from 2.79 ± 0.60 mmol/L to 3.11 ± 0.77 mmol/L, a change that was statistically significant (P < .001). At the end of the study, the lipid profile changes between levothyroxine- treated and control groups were compared. Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group (P < .029 and P < .0001, respectively) in comparison with the control group. The difference did not reach statistical significance for TG and HDL-C values.ConclusionIn premenopausal women, SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated. (Endocr Pract. 2008;14:570-575)     

Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

AimImbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T-cells (Tregs) is suggested to contribute to the pathogenesis of Systemic lupus erythematosus (SLE). Therefore, we evaluated their cytokine secretion profile in SLE patients and their possible association with disease activity.MethodsSixty SLE patients, 24 rheumatoid arthritis (RA) patients and 24 healthy volunteers were included in this study. Demographic, clinical, disease activity and serological data were prospectively assessed. Plasma cytokines levels of TH1 (IL-12, IFN-γ), TH2 (IL-4, IL-6, IL-10), TH17 (IL-17, IL-23) and Treg (IL-10 and TGF-β) were measured by enzyme linked immunosorbent assays (ELISA).ResultsSLE patients were found to have significantly higher levels of IL-17 (p < 0.001), IL-6 (p < 0.01), IL-12 (p < 0.001) and IL-10 (p < 0.05) but comparable levels of IL-23 and IL-4 and slight reduction (but statistically insignificant) of TGF-β levels compared to controls. IL-6, IL-10 and IL-17 were significantly increased (p < 0.05) with disease activity. The RA group exhibited significantly higher levels of plasma IL-4 (p < 0.01), IL-6 (p < 0.05), IL-17 (p < 0.001), IL-23 (p < 0.01) and TGF-β (p < 0.5) and lower IFN-γ (p < 0.001) and IL-10 (p < 0.01) than those of healthy subjects.ConclusionOur study showed a distinct profile of cytokine imbalance in SLE patients. Reduction in IFN-γ (TH1) and TGF-β1 (Treg) with the elevation in IL-6 and IL-17 (TH17) could imply skewing of T-cells toward TH17 cells. Breaking TH17/Treg balance in peripheral blood may play an important role in the development of SLE and could be responsible for an increased pro-inflammatory response especially in the active form of the disease.     

Assay of Free Thyroxine and Free Triiodothyronine in Fine-Needle Aspiration of Thyroid Nodules: a Useful and Low-Cost Assessment

ObjectiveTo evaluate whether analysis of thyroid hormones in fine-needle aspiration (FNA) of thyroid nodules can provide information about the functional status and the nature of the nodules.MethodsWe studied 4 groups of patients: group 1, 17 patients with autonomous hyperfunctioning thyroid nodules; group 2, 52 patients with cold nonfunctioning thyroid nodules; group 3, 12 patients with malignant thyroid nodules; and group 4 (control group), 10 patients with nonthyroid nodular lesions (enlarged parathyroid glands or lymph nodes). The assay of thyroid hormones was performed in FNA after the washing of needles and, with patient consent, also in normal thyroid parenchyma.ResultsThe free thyroxine (FT₄) and free triiodothyronine (FT₃) values were remarkably high in group 1 (mean, 5.5 ± 0.53 ng/dL and 27.6 ± 3.1 pg/mL, respectively; P < 0.05 versus group 2 and group 4, the control group). The levels of FT₄ and FT₃ were very low in group 3 (< 0.2 ng/dL and < 1.0 pg/mL, respectively; P < 0.05 versus group 2). Thyroglobulin values in FNA specimens were much higher than the normal range in human serum, but no significant differences were found between the various groups. The control group had low levels of FT₄ and FT₃ (< 0.2 ng/dL and < 1.0 pg/mL, respectively) in conjunction with low levels of thyroglobulin, whereas parathyroid hormone levels were high in parathyroid nodules.ConclusionThese results show that assay of FT₄ and FT₃ in FNA can yield information about the functional status of thyroid nodules and, indirectly, about the nature of nodules. In this era of sophisticated new molecular markers in FNA cytology, this low-cost diagnostic method can be readily performed in every laboratory. (Endocr Pract. 2004;10:311-316)     

Relationship of Prostate -Specific Antigen to Age and Testosterone in Men With Type 2 Diabetes Mellitus

ObjectiveTo determine whether prostate-specific antigen (PSA) concentrations in type 2 diabetic men with hypogonadotrophic hypogonadism are lower than those in eugonadal men with type 2 diabetes and whether PSA concentrations are related to plasma testosterone concentrations.MethodsIn this cross-sectional study, we measured serum total testosterone, sex hormone–binding globulin, free testosterone, PSA, hematocrit, and hemoglobin A_1c in consecutive type 2 diabetic men who presented to 2 endocrinology referral centers between January 2006 and January 2007. We collected other clinical and demographic data including age, height, weight, and ethnicity.ResultsOf 400 eligible patients, 280 men met inclusion criteria. Plasma PSA concentrations were lower in type 2 diabetic men with low free testosterone concentrations than in those with normal free testosterone concentrations (25.65 ± 2.02 ng/dL vs 31.70 ± 2.31 ng/dL, P = .011). PSA concentrations were positively related to age (r = 0.34, P < .001), total testosterone (r = 0.29, P < .001), free testosterone (r = 0.17, P = .02), and sex hormone– binding globulin (r = 0.22, P < .001) and negatively related to body mass index (r = –0.28, P < .001). In stepwise backward regression analysis, PSA concentration was predicted by age (P < .001) and free testosterone (P < .001), but not by body mass index or sex hormone–binding globulin.ConclusionsPlasma PSA concentrations are lower in type 2 diabetic men with hypogonadism than in eugonadal men with type 2 diabetes, and plasma PSA is related to age, plasma total testosterone concentrations, and free testosterone concentrations in patients with type 2 diabetes. (Endocr Pract. 2008;14:1000-1005)     

Effects of Canarium odontophyllum leaves on plasma glucose and T lymphocyte population in streptozotocin-induced diabetic rats

Type 1 diabetes mellitus is a chronic disease characterized by lack of insulin production. Immune mechanisms are implicated in the pathogenesis of Type 1 diabetes. Canarium odontophyllum (CO) fruits and leaves have been shown to possess high antioxidant activity. This study was conducted to evaluate the effects of CO leaves aqueous extract on the blood glucose and T lymphocyte population in the spleen of streptozotocin (STZ)-induced diabetic rats. Nineteen male Sprague–Dawley rats were randomly divided into three groups: normal, diabetic control and CO treated diabetic groups. Diabetes was induced by a single intraperitoneal injection of 65 mg STZ/kg body weight. The extract of CO leaves was administered orally by force feeding daily at the dose of 300 mg/kg for 28 days. The rats were sacrificed at the end of the study and the spleen was harvested for flow cytometry analysis. The results showed a significant decrease in body weight of diabetic and CO treated diabetic groups compared with the normal group (p < 0.05). The fasting blood glucose level of CO treated diabetic group was significantly lower than the diabetic group (p < 0.05). Diabetic and CO treated diabetic groups showed a significant increase in the percentage of spleen CD3⁺ CD4⁺ T lymphocytes (p < 0.05) when compared with the normal group. However, there was no significant difference in the percentage of spleen CD3⁺ CD8⁺ T lymphocytes among all experimental groups. The finding suggested that an aqueous extract of CO leaves has the ability to reduce blood glucose levels in diabetic rats.     

Effect of Astragalus polysaccharides on expression of TNF-α, IL-1β and NFATc4 in a rat model of experimental colitis

AimAstragalus membranaceus is a Chinese medicinal herb and has been shown to improve hapten-induced experimental colitis. One of its major components is polysaccharides. We investigated the effect of Astragalus polysaccharides (APS) on expression of TNF-α, IL-1β and NFATc4 in a rat model of experimental colitis.MethodsThe experimental colitis model was induced by TNBS. Forty five rats were divided into five groups (n = 9): Normal control group, receiving ethanol vehicle with no TNBS during induction and IP saline injection during treatment; TNBS colitis model group (TNBS + IP saline), receiving only IP saline vehicle treatment; APS low dose group (TNBS + L-APS), receiving APS 100 mg/kg; APS high dose group (TNBS + H-APS), receiving APS 200 mg/kg; and positive control group (TNBS + Dexm), receiving dexamethasone 0.3 mg/kg. The clinical features, macroscopic and microscopic scores were assessed. The expressions of TNF-α, IL-1β and NFATc4 were measured by real-time PCR and ELISA assays.ResultsCompared to normal control rats, TNBS + IP saline had significant weight loss, increased macroscopic and microscopic scores, higher disease activity index (DAI) up-regulation of TNF-α, IL-1β and NFATc4 mRNA expression and up-regulation of TNF-α and IL-1β protein expression. Compared to TNBS + IP saline, treatment with APS or dexamethasone significantly reduced DAI, partially but significantly prevented TNBS colitis-induced weight loss and improved both macroscopic and microscopic scores; high dose APS or dexamethasone significantly down-regulated TNF-α and IL-1β expressions (both mRNA and protein) and up-regulated NFATc4 mRNA and protein expression. The effect of high dose APS and dexamethasone is comparable.ConclusionsAPS significantly improved experimental TNBS-induced colitis in rats through regulation of TNF-α, IL-1β and NFATc4 expression.     

A Comparison of Twice-Daily Biphasic Insulin Aspart 70/30 and Once-Daily Insulin Glargine in Persons With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Therapy: A Randomized,Open-Label Study

ObjectiveTo compare efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) with insulin (glargine) in type 2 diabetic patients who were not maintaining glycemic control on basal insulin and oral antidiabetic drugs.MethodsIn a 24-week, open-label, parallel-group trial, type 2 diabetic patients who were not maintaining glycemic control on basal insulin (glargine or neutral protamine Hagedorn) + oral antidiabetic drugs were randomly assigned to twice-daily BIAsp 30 + metformin or oncedaily glargine + metformin + secretagogues (secretagogues were discontinued in the BIAsp 30 arm).ResultsOne hundred thirty-seven patients were randomly assigned to the BIAsp 30 group and 143 patients were randomly assigned to the glargine group. Of 280 patients randomized, 229 (81.8%) completed the study. End-of-trial hemoglobin A_1c reductions were − 1.3% (BIAsp 30) vs − 1.2% (glargine) (treatment difference: 95% confidence interval, − 0.06 [− 0.32 to 0.20]; P = .657). Of patients taking BIAsp 30, 27.3% reached a hemoglobin A_1c level < 7.0% compared with 22.0% of patients taking glargine (treatment difference: P = .388). Glucose increment averaged over 3 meals was lower in the BIAsp 30 arm (treatment difference: − 17.8 mg/dL, P = .001). Fasting plasma glucose reductions from baseline were − 13.8 mg/ dL (BIAsp 30) vs − 42.5 mg/dL (glargine) (P = .0002). Final minor hypoglycemia rate, insulin dose, and weight change were higher in the BIAsp 30 arm (6.5 vs 3.4 events/patient per year, P <.05; 1.19 vs 0.63 U/kg; and 3.1 vs 1.4 kg, P = .0004, respectively).ConclusionsDespite not receiving secretagogues, patients taking BIAsp 30 + metformin achieved similar hemoglobin A_1c levels and lower postprandial plasma glucose compared with those receiving glargine + metformin + secretagogues. The large improvement in the glargine group suggests the patients were not true basal failures at randomization. While switching to BIAsp 30 improves glycemic control in this patient population, remaining on basal insulin and optimizing the dose may be equally effective in the short term. (Endocr Pract. 2011;17:41-50)