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.     

Serum zinc is associated with plasma leptin and Cu–Zn SOD in elite male basketball athletes

This paper investigates the relationship between plasma trace element and plasma leptin, as well as percent fat mass, in 16 male basketball athletes. Blood samples were obtained before intensive training and 24 h after intensive training to measure plasma zinc (Zn), copper (Cu), calcium (Ca), magnesium (Mg), iron (Fe), and leptin levels. High-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride (TG), total and cholesterol (TC) levels were determined using commercially available kits for humans. Subjects presented similar values in terms of age (21.1 ± 2.2 years old), body mass index (23.9 ± 2.00 kg/m²), percent body fat (14.40 ± 1.52%), plasma hemoglobin (150.1 ± 9.4 g/L), plasma Zn (17.47 ± 1.28 μmol/l), plasma Cu (13.42 ± 1.40 μmol/L), plasma Ca (2.41 ± 0.14 mmol/L), and plasma Mg (0.96 ± 0.02 mmol/L). The correlation analysis between degree of plasma leptin and plasma element contents was performed using the SPSS 16.0 software. Plasma Zn correlated positively with plasma leptin (r = 0.746, P < 0.01), Cu–Zn SOD (r = 0.827, P < 0.01), and negatively with percent fat mass (r = –0.598, P < 0.05) under no-training conditions. Meanwhile, plasma Cu, Ca, Mg, and Fe did not correlate with plasma leptin or percent fat mass (P > 0.05). In conclusion, plasma Zn may be involved in the regulation of plasma leptin and may serve as a lipid-mobilizing factor in Chinese men's basketball athletes.     

Correlation between serum trace elements and risk of preeclampsia: A case controlled study in Riyadh,Saudi Arabia

Preeclampsia is a serious medical complication during pregnancy. In response to an increasing number of preeclamptic cases and scarcity of data concerning the interrelation between trace element levels and preeclampsia, we carried out a hospital based case–control study in Riyadh, Saudi Arabia to study the correlation between levels of serum trace elements and risk of preeclampsia. One hundred and twenty pregnant women were enrolled in this study and divided into three groups of 40 each—Control group, HR group (women at high risk of preeclampsia) and PET group (Preeclampsia group). Serum trace element levels were estimated by inductively coupled plasma optical emission spectrophotometer. The analysis found that mean values of Ca, Mg and Zn were 90.08 ± 6.38, 19.33 ± 3.32 and 1.30 ± 0.83 mg/L respectively in normotensive control and 77.85 ± 4.47, 15.44 ± 1.43 and 0.98 ± 0.63 mg/L respectively in the HR group. The mean values of Ca, Mg and Zn in the preeclamptic group were 70.37 ± 4.66, 13.58 ± 1.98 and 0.67 ± 0.59 mg/L, respectively. Interelement analysis reflected a negative correlation between Ca and Mg and between Mg and Zn whereas positive correlation between Ca and Zn in preeclamptic women. However the correlation was not statistically significant. In conclusion, our study suggests that decreased levels of these trace elements in serum may act as predisposing factors in pathogenesis of Preeclampsia.     

Relationship of lead and essential elements in whole blood from school-age children in Nanning,China

ObjectivesThe aim of this study was to investigate blood lead level and its relationship to essential elements (zinc, copper, iron, calcium and magnesium) in school-age children from Nanning, China.MethodsA total of 2457 children aged from 6 to 14 years were enrolled in Nanning, China. The levels of lead (Pb), zinc (Zn), copper (Cu), iron (Fe), calcium (Ca) and magnesium (Mg) were determined by an atomic absorption spectrometer.ResultsThe mean blood lead level (BLL) was 57.21 ± 35.00 μg/L. 188 (7.65%) asymptomatic children had toxic lead level higher than 100 μg/L. The school-age boys had similar lead level among different age groups, while the elder girls had less BLL. The blood Zn and Fe were found to be increased in the boys with elevated BLL, but similar trends were not observed in the girls. Positive correlations between Pb and Fe or Mg (r = 0.112, 0.062, respectively, p < 0.01) and a negative correlation between Pb and Ca (r = −0.047, p < 0.05) were further established in the studied children.ConclusionsLead exposure in school-age children was still prevalent in Nanning. The boys and girls differed in blood levels of lead and other metallic elements. Lead exposure may induce metabolic disorder of other metallic elements in body.     

Effect of salinity and seawater calcite saturation state on Mg and Sr incorporation in cultured planktonic foraminifera

Trace elements incorporated in planktonic foraminiferal test carbonate are commonly used as paleoproxies. For instance, Mg/Ca ratios are frequently used for reconstructing sea surface temperature and, together with the foraminiferal stable oxygen isotope ratios, are also used as paleosalinity proxy. Foraminiferal Sr/Ca ratios constitute another example of the application of trace elements in paleostudies since they may reflect the Sr/Ca values of seawater. However, over the past few decades it has been proven that the incorporation of trace elements in foraminiferal calcite is controlled by more than one environmental parameter. To quantify the effect of salinity on Mg and Sr incorporation planktonic foraminifera Globigerinoides sacculifer (sensu stricto) were grown in the laboratory under different environmental conditions. Laboratory experiments allowed us to separate a direct salinity effect from a possible independent impact through differences in the calcite saturation state of the seawater (Ω). Although the temperature effect is more important than the salinity effect, a change of 4 salinity units is equivalent to a 1 °C bias on Mg/Ca-based temperatures. This effect of salinity on Mg incorporation is minor. However, when using Mg/Ca-based temperatures in combination with foraminiferal δ¹⁸O to calculate salinity, it cannot be neglected. The present study shows salinity as the overriding control on Mg incorporation within the range of Ω studied (Ω between 5.25 and 6.50; [CO₃²⁻] between 218 and 270 μmol/kg) at a constant temperature of 26 °C. In contrast, Ω appears to be the main control on foraminiferal Sr incorporation (0.10 mmol/mol per 100 µmol/kg rise in [CO₃²⁻]), whereas salinity has a non significant influence on Sr/Ca.     

Premicroalbuminuria in Women with Polycystic Ovary Syndrome: A Metabolic Risk Marker

ObjectiveTo determine the relationship between urinary albumin excretion and features of the metabolic syndrome in women with polycystic ovary syndrome (PCOS).MethodsWe retrospectively analyzed the medical records of 189 premenopausal women (mean age ± SD, 28.9 ± 7.7 years) with PCOS and 81 control patients (mean age ± SD, 37.9 ± 8.6 years) from a single endocrinology practice. Exclusion criteria were diabetes, heart disease, kidney disease, use of lipid-lowering agents, and use of antihypertensive agents (except spironolactone). The urine albumin-to-creatinine ratio (ACR) was measured in a random single-voided urine sample. Premicroalbuminuria was defined as an ACR > 7 mg/g.ResultsThe prevalence of ACR > 7 mg/g was 31.2% in the PCOS group (N = 189) and 35.8% in the control group (N = 81). The metabolic syndrome was noted in 16.3% (27 of 166) of patients with PCOS and in 2.9% (2 of 69) of control subjects. Nine percent of patients with PCOS who had an ACR ≤ 7 mg/g but 30.9% of those with an ACR > 7 mg/g had the metabolic syndrome. Patients with PCOS who had an ACR > 7 mg/g had significantly higher blood pressure and alanine aminotransferase levels than did those with an ACR ≤ 7 mg/g. In the patients with PCOS who had an ACR ≤ 7 mg/g versus those who had an ACR > 7 mg/g, no significant difference was found in frequency of use of metformin, spironolactone, or oral contraceptives.ConclusionIn women with PCOS, an ACR > 7 mg/g was strongly associated with the metabolic syndrome, high blood pressure, and elevated alanine aminotransferase levels. It may be useful to consider ACR > 7 mg/g as an associated sign of the presence of metabolic syndrome in women with PCOS. (Endocr Pract. 2008;14: 193-200)     

Associations of soil iron with citrus tree decline and variability of sand,soil water,pH, magnesium and Diaprepes abbreviatus root weevil: Two-site study

The hypothesis of associations of environmental soil heterogeneity with citrus tree decline and Diaprepes abbreviatus (L.) root weevil variability was tested in two flatwoods fields of ‘Hamlin’ orange trees (Citrus sinensis (L.) Osb.). Studies were conducted on a loamy, poorly drained Mollisol in Osceola County, central Florida in 2002, and on a sandy, poorly drained Spodosol in DeSoto County, south-west Florida during 2001–2003. Adult weevils were monitored using 50 Tedders traps arranged in a 34 m × 25 m grid at the Osceola site, and using 100 identical traps in a 30 m × 15 m grid at the DeSoto site. Soil water content (SWC), texture, pH, Ca, Mg, Fe, Cu and other nutrients were measured at each trap. Soil was strongly acidic (pH 4.9 ± 0.4) at the Osceola site but near neutral (pH 6.6 ± 0.4) at the DeSoto site. The Mehlich-I extractable soil Mg and Ca were correlated to soil pH and SWC in both soils, and extractable Fe was related to pH, SWC and Mg in the Spodosol (0.30 < R² < 0.65, P < 0.01). The weevil density was high in areas low in soil Mg and Ca in the acidic Mollisol, but high in areas with high soil pH, and Mg and low sand content in the near neutral Spodosol (P < 0.05). Tree decline was associated with soil Fe concentrations >40 mg kg⁻¹ in the Mollisol (P < 0.01). Weevil density was low at a soil pH between 5.7 and 6.2. The range of spatial dependence of weevil population, soil pH, SWC, Fe, Mg and sand varied between 60 and 100 m in the Mollisol and the Spodosol. Soil-weevil-tree simple and multivariate linear models were established to put into practices for predicting and controlling the weevil population and tree decline in the future. Differences in site characteristics suggested the need for site-specific weevil and citrus tree management.     

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.     

Renal GLUT1 reduction depends on angiotensin-converting enzyme inhibition in diabetic hypertensive rats

AimsAngiotensin-converting enzyme (ACE) inhibitors are used in diabetic kidney disease to reduce systemic/intra-glomerular pressure. The objective of this study was to investigate whether reducing blood pressure (BP) could modulate renal glucose transporter expression, and urinary markers of diabetic nephropathy in diabetic hypertensive rats treated with ramipril or amlodipine.Main methodsDiabetes was induced in spontaneously-hypertensive rats (~ 210 g) by streptozotocin (50 mg/kg). Thirty days later, animals received ramipril 15 μg/kg/day (R, n = 10), or amlodipine 10 mg/kg/day (A, n = 8,) or water (C, n = 10) by gavage. After 30-day treatment, body weight, glycaemia, urinary albumin and TGF-β1 (enzyme-linked immunosorbent assay) and BP (tail-cuff pressure method) were evaluated. Kidneys were removed for evaluation of renal cortex glucose transporters (Western blotting) and renal tissue ACE activity (fluorometric assay).Key findingsAfter treatments, body weight (p = 0.77) and glycaemia (p = 0.22) were similar among the groups. Systolic BP was similarly reduced (p < 0.001) in A and R vs. C (172.4 ± 3.2; 186.7 ± 3.7 and 202.2 ± 4.3 mm Hg; respectively). ACE activity (C: 0.903 ± 0.086; A: 0.654 ± 0.025, and R: 0.389 ± 0.057 mU/mg), albuminuria (C: 264.8 ± 15.4; A: 140.8 ± 13.5 and R: 102.8 ± 6.7 mg/24 h), and renal cortex GLUT1 content (C: 46.81 ± 4.54; A: 40.30 ± 5.39 and R: 26.89 ± 0.79 AU) decreased only in R (p < 0.001, p < 0.05 and p < 0.001; respectively).SignificanceWe concluded that the blockade of the renin–angiotensin system with ramipril reduced early markers of diabetic nephropathy, a phenomenon that cannot be specifically related to decreased BP levels.     

Comparative analysis of serum zinc,copper, magnesium,calcium and iron level in acute and chronic patients of visceral leishmaniasis

ProjectChronic visceral leishmaniasis (VL) is an increasingly common problem in disease endemic states of India. Identification of prognosis risk factor in patients with VL may lead to preventive actions, toward decreasing its mortality in chronic individuals. Though serum Zinc levels are decreased in patients of VL, limited information is available regarding trace elements status in acute and chronic VL patients. The present study was undertaken to compare serum trace elements concentrations in acute and chronic VL patients.ProcedureAcute (mean age = 28.64 years), chronic (mean age = 23.68 years) VL patients and healthy controls (mean age = 23.05 years) who agreed to provide blood specimens for laboratory investigations participated in this study. Serum zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg) and calcium (Ca) were measured spectrophotometrically using chemistry analyzer.ResultsSerum Zn concentration was comparatively much decreased in chronic VL than to acute ones (p = 0.007) while serum Mg was higher in chronic VL than acute (p = 0.002) ones. There was no statistically significant difference between acute and chronic VL in serum concentrations of Cu, Fe and Ca.ConclusionsSerum Zn levels were much decreased and serum Mg were increased in chronic VL as compared to acute cases. The serum concentrations of Fe and Ca did not show any difference between two groups. The serum Cu was increased in both groups but more in chronic ones. Serum Zn and Mg could be a potential prognosis factor for chronic VL patients. We hypothesize zinc supplementation as a chemo preventive agent for chronic VL cases, particularly in endemic areas.     

Phytochemical characterization of potential nutraceutical ingredients from Evening Primrose oil (Oenothera biennis L.)

Evening Primrose oil (EPO) is a natural product extracted by cold-pressed from Oenothera biennis L. seeds. EPO is widely used as a dietary supplement from which beneficial effects have been reported in rheumatic and arthritic conditions, atopic dermatitis, psoriasis, premenstrual and menopausal syndrome, and diabetic neuropathy. The beneficial effects of EPO are thought to be due to its γ-linolenic acid content; in contrast, little effort has been expended to characterize the non-triglyceridic constituents of EPO. In order to evaluate its potential as source of functional food ingredients our aim in this work has been identified and quantified the different components of EPO by different techniques (GC–MS and HPLC). The lipid profile showed that oleic (7%), linoleic (74%) and γ-linolenic (9%) were the most abundance fatty acids. Unsaponifiable matter and subfractions were obtained by CEE/2568/91. Separation of the compounds under study was achieved giving a reasonable analysis time and good resolution. A yield (1.82–1.95%) of unsaponifiable matter was obtained and levels of saturated hydrocarbons (0.291.97 ± 14.85 mg) were noticed. β-Sitosterol (7952.00 ± 342.25 mg/kg oil) and campesterol (883.32 ± 0.45 mg/kg oil) were predominant in phytosterol fraction (9573 mg/kg oil), while tetracosanol (236.93 ± 2.32 mg/kg oil) and hexacosanol (289.92 ± 3.41 mg/kg oil) in linear aliphatic alcohol fraction (798.04 ± 5.66 mg/kg oil). In the phenolic fraction (55.49 ± 2.76 mg/kg oil), ferulic acid (25.23 ± 2.64 mg/kg oil) was the major component. From the results obtained, it can be suggested that the Evening Primrose oil can be considered an interesting alimentary source of substances of nutraceutical value.     

Clinical Profile of Nonalcoholic Fatty Liver Disease Among Young Patients With Type 1 Diabetes Mellitus Seen at a Diabetes Speciality Center in India

ObjectiveTo estimate the prevalence and clinical profile of nonalcoholic fatty liver disease (NAFLD) among young type 1 diabetes mellitus (T1DM) patients at a tertiary care diabetes center in India.MethodsElectronic medical records of T1DM patients (age at first diagnosis of T1DM ≤ 25 years) registered between January 1992 and May 2013 who had undergone ultrasonography and denied history of any alcohol intake (n = 736) were reviewed. NAFLD was diagnosed if there was any degree of fatty liver. Retinopathy was initially assessed by direct and indirect ophthalmoscopy and later by retinal photography. Nephropathy was diagnosed if urine protein excretion was > 500 mg/day, and neuropathy was diagnosed if a patient’s vibration perception threshold on biothesiometry was ≥ 20 V.ResultsA total of 204/736 (27.7%) T1DM patients had NAFLD. Compared to T1DM subjects without NAFLD those with NAFLD had higher body mass index (BMI) (18.9 ± 4.2 vs. 20.2 ± 4.7 kg/m², P < .001), waist circumference (67.9 ± 13.2 vs. 71.9 ± 13.3 cm, P < .05), systolic blood pressure (110 ± 15 vs. 116 ± 18 mm Hg, P < .001) and diastolic blood pressure (72 ± 9 vs. 74 ± 10 mm Hg, P < .05), while fasting blood glucose (201 ± 101 vs. 183 ± 101 mg/dL, P < .05) and alkaline phosphatase (419 [12.5] vs. 315 [15.8], P < .001) levels were lower in patients with T1DM with NAFLD. Multiple logistic regression analysis showed a significant association between NAFLD and retinopathy (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.13-3.43; P = .017, after adjusting for sex, duration of diabetes, overweight/obesity, hypertension, fasting plasma glucose, nephropathy, and nephropathy (OR: 1.89, 95% CI: 1.02-3.50; P = .042), after adjusting for sex and fasting plasma glucose.ConclusionsThis study suggests that NAFLD is also seen among T1DM patients and that it has an independent and significant association with retinopathy and nephropathy. (Endocr Pract. 2014;20:1249-1257)     

Hair cortisol determination in sows in two consecutive reproductive cycles

Hair analysis has been proposed as a minimally invasive technique capable of furnishing information regarding the stress response during medium- and long-term periods. Bristle samples were collected from the rump region of sows at three key physiological phases (before delivery – BD; weaning time – WT; pregnancy diagnosis – PD) during consecutive reproductive cycles in order to test swine hair as a reliable matrix of cortisol evaluation. Cortisol was extracted from the bristles and assayed using radioimmunoassay. The highest mean hair cortisol concentrations were demonstrated (p < 0.001) at the PD time points (20.1 ± .95 and 16.29 ± 2.15 pg/mg). Moreover, cortisol was significantly higher (p < 0.001) at BD2 (10.48 ± 0.96 pg/mg) as compared to BD1 (5.17 ± 0.51 pg/mg) and WT1 (6.01 ± 0.47 pg/mg). The various physiological phases had a significant effect on cortisol concentration (p < 0.00001) with a higher cortisol concentration found during late pregnancy and lactation than in early-mid pregnancy. This could be due not only to the physiological hormonal status, but also to the different housing conditions (single crates vs. group housing). The season of the year was also observed to have an effect (p < 0.005), with the lowest cortisol concentration recorded during the hot season.     

EPA,DHA, cholesterol and phospholipid content in Pagrus pagrus (cultured and wild), Trachinus draco and Trigla lyra from Mediterranean Sea

EPA, DHA, cholesterol and phospholipid content were determined in the Trachinus draco, Trigla lyra and (wild and cultured) Pagrus pagrus muscles.The EPA and DHA levels – as determined by GC-GC/MS – in the cultured P. pagrus muscles (233.20 ± 16.3 and 399.39 ± 31.1 mg/100 g of the wet tissue respectively) were found to be significantly higher compared to the ones in the wild P. pagrus, T. draco and T. lyra (26.31 ± 2.26, 158.24 ± 10.92 mg/100 g, 28.65 ± 1.68, 155.97 ± 2.63 mg/100 g 35.66 ± 0.66 and 102.52 ± 1.71 mg/100 g of the wet muscles respectively). The amounts of cholesterol (determined by GC on a capillary column) and phospholipids in the cultured P. pagrus muscles were significantly higher (149.3 mg/100 g and 0.80 g/100 g of the wet tissue respectively) compared to the ones in the wild P. pagrus (8.73 mg/100 g and 0.40 g/100 g), T. draco (41.72 mg/100 g and 0.59 g/100 g) and T. lyra muscles (38.63 mg/100 g and 0.40 g/100 g of the wet tissue respectively).The highest DHA/EPA and ω-3/ω-6 ratios were 6.00 and 5.93 in wild P. pagrus and T. draco muscles respectively, while the lowest in cultured P. pagrus (1.71 and 1.48 respectively).     

Levothyroxine Replacement In Obese Hypothyroid Females After Total Thyroidectomy

Objective: Levothyroxine (LT4) replacement in hypothyroid obese patients is poorly understood. We assessed whether the LT4 regimen required to achieve euthyroidism differs between nonobese and obese hypothyroid females.Methods: We retrospectively identified nonobese and obese females who received LT4 starting with a standard dose of 1.6 μg/kg after total thyroidectomy for preoperative diagnosis of benign goiter. We examined the association between LT4 dosage required to achieve euthyroid state (thyroid-stimulating hormone [TSH] 0.4–2.5 mIU/L) and patient characteristics using linear regression models with and without adjustment for age, ethnicity, medication use, and postoperative hypoparathyroidism.Results: We identified 32 females (15 nonobese/17 obese) who achieved euthyroid state. Obese patients weighed more (104.1 ± 22.5 vs. 64.9 ± 10.0 kg, P<.0001) and required a higher final LT4 than nonobese (146 ± 38 vs. 102 ± 12 μg, P = .0002) but LT4 requirements per kg total body weight (TBW) were similar (1.60 ± 0.29 vs. 1.42 ± 0.38 μg/kg, P = .15). LT4 dose per kg ideal body weight (IBW) was higher in obese than in nonobese females (2.62 ± 0.67 vs. 1.88 ± 0.28 μg/kg, P = .0004) and this difference persisted after adjustments (P<.05). During LT4 titration, 47% and 20% of obese and nonobese patients had subnormal TSH episodes, respectively (P = .11). After taking LT4 compliance, malabsorption, and competing medication use into consideration, we found marked LT4 dose variability in obese patients. Patients who needed a mean daily LT4 dose ≤150 mg (124 ± 16 μg/day) compared with >150 μg (198 ± 4 μg/day) demonstrated lower LT4 per TBW (1.25 ± 0.18 vs. 1.84 ± 0.43 μg/kg, P = .03) and IBW (2.28 ± 0.47 vs. 3.44 ± 0.18 μg/kg, P<.0001), respectively.Conclusion: The standard approach to LT4 replacement in obese and nonobese females after thyroidectomy is imprecise. Mean daily LT4 doses in obese and nonobese patients were similar if expressed per kg TBW, though there was variability in the final LT4 among obese patients. We suggest initiating LT4 at a dose lower than that routinely recommended in obese females.Abbreviations:AACE = American Association of Clinical EndocrinologistsATA = American Thyroid AssociationBMI = body mass indexIBW = ideal body weightLT4 = levothyroxineTBW = total body weightTSH = thyroid-stimulating hormone     

Validation of a free software for unsupervised assessment of abdominal fat in MRI

PurposeTo demonstrate the accuracy of an unsupervised (fully automated) software for fat segmentation in magnetic resonance imaging. The proposed software is a freeware solution developed in ImageJ that enables the quantification of metabolically different adipose tissues in large cohort studies.MethodsThe lumbar part of the abdomen (19 cm in craniocaudal direction, centered in L3) of eleven healthy volunteers (age range: 21–46 years, BMI range: 21.7–31.6 kg/m²) was examined in a breath hold on expiration with a GE T1 Dixon sequence. Single-slice and volumetric data were considered for each subject. The results of the visceral and subcutaneous adipose tissue assessments obtained by the unsupervised software were compared to supervised segmentations of reference. The associated statistical analysis included Pearson correlations, Bland-Altman plots and volumetric differences (VD_%).ResultsValues calculated by the unsupervised software significantly correlated with corresponding supervised segmentations of reference for both subcutaneous adipose tissue – SAT (R = 0.9996, p < 0.001) and visceral adipose tissue – VAT (R = 0.995, p < 0.001). Bland-Altman plots showed the absence of systematic errors and a limited spread of the differences. In the single-slice analysis, VD_% were (1.6 ± 2.9)% for SAT and (4.9 ± 6.9)% for VAT. In the volumetric analysis, VD_% were (1.3 ± 0.9)% for SAT and (2.9 ± 2.7)% for VAT.ConclusionsThe developed software is capable of segmenting the metabolically different adipose tissues with a high degree of accuracy. This free add-on software for ImageJ can easily have a widespread and enable large-scale population studies regarding the adipose tissue and its related diseases.     

Clinical Outcomes Using Long-Term Combination Therapy with Insulin Glargine and Exenatide in Patients with Type 2 Diabetes Mellitus

ObjectiveTo examine the long-term effects of combination insulin glargine/exenatide treatment on glycemic control.MethodsWe conducted a 24-month retrospective US chart review of patients with inadequately controlled type 2 diabetes (T2DM) and hemoglobin A_1c (A1C) levels > 7.0% for whom glargine and exenatide were coprescribed in differing order (glargine added after exenatide [exenatide/glargine]; exenatide added after glargine [glargine/exenatide]). Treatment order groups were combined to form a pooled treatment group. Changes from baseline in A1C, patients with A1C ≤ 7.0%, body weight, glargine/exenatide daily dose, oral antidiabetic drug (OAD) use, and hypoglycemia were evaluated.ResultsTreatment groups were similar at baseline; however, patients in the glargine/exenatide group (n = 121) (vs exenatide/glargine group [n = 44]) had longer disease duration (11.8 vs 8.0 years) and took fewer OADs (1.7 vs 2.3). Overall, baseline A1C was 8.8 ± 1.3% and weight was 109.5 ± 25.3 kg. Significant A1C reductions emerged at month 6 and persisted throughout 24 months (vs baseline) in both treatment groups (pooled: –0.7 ± 1.6; P < .001), and 33.0% of patients achieved an A1C level ≤ 7.0%. After 24 months of exenatide/glargine, body weight remained unchanged (0.7 ± 8.3 kg; P = .640). With glargine/exenatide, body weight decreased (–2.5 ± 6.7 kg; P = .001). At month 24, daily glargine dose was 0.40 ± 0.23 units/kg for the exenatide/glargine group and 0.47 ± 0.30 units/kg for the glargine/exenatide group. Hypoglycemia frequency was similar in both treatment groups.ConclusionsRegardless of treatment order, long-term combined therapy with glargine and exenatide for up to 24 months in patients with inadequately controlled T2DM suggests reduction of A1C without significant weight gain or increased hypoglycemia risk. (Endocr Pract. 2012;18:17-25)     

Improvement in Pancreatic β-Cell Function with Vitamin D and Calcium Supplementation in Vitamin D-Deficient Nondiabetic Subjects

ObjectiveThere are varied reports on the effect of vitamin D supplementation on β-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on β-cell function and plasma glucose levels in subjects with vitamin D deficiency.MethodsNondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented.ResultsThirty-seven patients with 25-OHD deficiency participated in the study. The baseline and postvitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (− 0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (− 20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (− 4.88 ± 10.65 mg/dL); and homeostasis model assessment-2–percent β-cell function C-peptide secretion (HOMA-2–%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, − 3.751; P < .0001), 25-OHD (Z, − 4.9; P < .0001), intact PTH (Z, − 4.04; P < .0001), fasting plasma glucose (Z, − 2.7; P < .007), and HOMA-2–%B C-PEP (Z, − 1.923; P < .05) as determined by Wilcoxon signed rank test. Insulin resistance as measured by HOMA was unchanged.ConclusionOptimizing serum 25-OHD concentrations and supplementation with calcium improves fasting plasma glucose levels and β-cell secretory reserve. Larger randomized control studies are needed to determine if correction of 25-OHD deficiency will improve insulin secretion and prevent abnormalities of glucose homeostasis. (Endocr Pract. 2014;20:129-138)