Could phthalates exposure contribute to the development of metabolic syndrome and liver disease in humans?

In the study, 305 patients of both genders were enrolled and divided into three groups: obese (BMI > 30 kg/m2), patients who were diagnosed type 2 diabetes mellitus (T2DM), and control, normal weight healthy volunteers. At least one of ten different phthalate metabolites was determined in the urine samples of 49.84% all enrolled participants. In the obese subgroup, the sum of all urinary phthalate metabolites was positively associated with TG levels (p = 0.031) together with derived TC/HDL and TG/HDL ratios (p = 0.023 and 0.015), respectively. Urinary MEP concentration was positively correlated with the HOMA-IR in T2DM subgroup (p = 0.016) while in the control subgroup, log10MEP levels were negatively correlated with total cholesterol (p = 0.0051), and LDL serum levels (p = 0.0015), respectively. Also, in the control subgroup, positive linear correlations between urinary log10MEP levels and TyG and TYG-BMI values (p = 0.028 and p = 0.027), respectively, were determined. Urinary MEHP levels were associated with glucose serum levels (p = 0.02) in T2DM subgroup, while in the control HDL values were negatively associated with log10MEHP (p = 0.0035). Healthy volunteers exposed to phthalates had elevated AST levels in comparison to non-exposed ones (p = 0.023). In control subgroup, ALT and AST values were increased (p = 0.02 and p = 0.01, respectively) in MEP exposed while GGT levels were enhanced (p = 0.017) in MEHP exposed in comparison with non-exposed. Combined phthalates influence on glucose and lipid metabolism may increase the possibility for NAFLD and insulin resistance development among exposed individuals.

Fecal pancreatic elastase-1 and erythrocyte magnesium levels in diabetes type 1 and type 2.

In both types of diabetes mellitus (DM), type 1 and type 2 (T1DM and T2DM), there are both endocrine and exocrine dysfunctions of the pancreas (PED), as well as disturbances in serum magnesium levels. The aim of this study was to examine the frequency of PED according to the level of fecal elastase-1 (FE-1) in patients with T1DM and T2DM, determining the correlation of the level of FE-1 with certain anthropometric parameters, certain indicators of metabolic regulation of diabetes, and certain nutritive markers of PED. MATERIALS AND METHODS: In the examinees, (56 with T1DM (F = 35 and M = 21), 62 with T2DM (F = 30 and M = 32), and 40 in the control group (F = 19 and M = 21)), we examined anthropometric parameters, and using standard biochemical methods, we measured the level of FE-1, magnesium concentration in blood and erythrocytes, and selected blood parameters. RESULTS: FE-1 concentration < 200 µg/g was present in 14.2% of the examinees with T1DM, 20.9% with T2DM, and 2.5% in the control group. In all examinees with DM, there was a statistically significant correlation (P < 0.05) between the level of FE-1 and Mg concentration in the erythrocytes (R = 0.40). CONCLUSIONS: Prevalence of pancreatic exocrine insufficiency (PEI), according to the level of FE-1, is significantly higher in patients with DM than in the control group, while it is a bit higher in patients with T2DM than the ones with T1DM. In both types of DM, Mg concentration in erythrocytes is in a significant correlation with the level of FE-1.

The Wnt/ß-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity.

BACKGROUND: Sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/ß-catenin signalling pathway (WßcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WßcSP in vascular cells. Nevertheless, results of studies analyzing association between circulating sclerostin level (CSL) and atherosclerotic diseases (AD) are showing conflicting results. The aim of this study is to test the value of CSL as a biomarker of subclinical carotid atherosclerosis (SCA) in obese persons. METHODS: The cross-sectional study included 50 obese persons without previous history of diabetes and AD. Participants underwent adequate anthropometrical, ultrasound and laboratory examinations, including 2h 75 g oral glucose tolerance test (OGTT). RESULTS: Only the presence of SCA significantly indirectly correlated with CSL (p<0.05). Based on the median value of CSL, we formed two groups: low CSL (CSL<7.9 pmol/l) and high CSL (CSL>7.9 pmol/l). There were no statistically significant differences in general (gender, age and current smoking) and anthropometrical characteristics (body mass index, waist circumference, systolic and diastolic blood pressure), inflammatory (total white blood cell count, erythrocyte sedimentation rate, fibrinogen, C-reactive protein and uric acid), glucose metabolism (fasting and 2h OGTT blood glucose, glycated hemoglobin and presence of dysglycemia) and lipid metabolism (low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B and lipoprotein (a)) parameters between low and high CSL groups. Low CSL group had significantly higher incidence of SCA (p<0.05). CONCLUSION: CSL could serve as a useful biomarker of early atherosclerosis in obese persons without previous history of cardiometabolic disorders but the final conclusion requires further testing.

1h Post-load Blood Glucose in the Identification of Proatherogenic Cardiometabolic Profile in Obesity.

BACKGROUND AND AIM: Current data show that 1h oral glucose tolerance test (OGTT) blood glucose (1h-BG) might identify persons at increased risk of developing type 2 diabetes and cardiovascular diseases more precisely than fasting blood glucose (FBG) and 2h OGTT blood glucose (2h-BG). The aim of study was to determine whether is justified to use 1h-BG over traditional blood glucose measurements, in cardiometabolic profiling of obese individuals. METHOD: Cross-sectional study enrolled 60 obese individuals without previous history of diabetes and other cardiometabolic disorders. Anthropometrical, ultrasound and laboratory examinations were conducted. RESULTS: All three parameters significantly directly correlated with age, body mass index, waist circumference, erythrocyte sedimentation rate, C-reactive protein, triglycerides and glycated hemoglobin. FBG and 1h-BG significantly directly correlated with alanine transaminase, gammaglutamyltransferase and total cholesterol. FBG significantly directly correlated with fibrinogen and aspartate transaminase, 1h-BG with systolic blood pressure and 2h-BG with diastolic blood pressure. None of parameters significantly correlated with gender, total white blood cell count, uric acid, 25-hydroxyvitamin D, high density lipoprotein cholesterol, low density lipoprotein cholesterol, serum adiponectin and albuminuria. Differences in correlation coefficients were not statistically significant. Individuals with 1h-BG >8.6 mmol/l had much more proatherogenic cardiometabolic profile, as well as higher incidence of dysglycemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) than ones with 1h-BG <8.6 mmol/l, but all differences were driven by the average value of glycemia. There were no statistically significant differences in ability of predicting MetS, NAFLD and pathologically increased carotid artery intima media thickness among analyzed glucose metabolism parameters. CONCLUSION: 1h-BG is not superior to FBG and 2h-BG in the identification of proatherogenic cardiometabolic profile in obesity.

Multiple Causes of Hyponatremia: A Case Report.

OBJECTIVE: To present a case with 4 different potential causes of hyponatremia. CLINICAL PRESENTATION AND INTERVENTION: The patient presented with the following symptoms: nausea, vomiting, diarrhea, and dark urine after drinking large amounts of fluids that included alcohol and caffeine. Laboratory, microbiological, and morphological examinations revealed the existence of severe hyponatremia and acute poststreptococcal glomerulonephritis. The patient developed acute symptomatic seizures and coma. Gradual normalization of the sodium level led to a recovery of consciousness. CONCLUSION: Treatment with hypertonic sodium, fluid restriction, and antibiotics led to a complete recovery. In the case of multiple causes of hyponatremia, it is necessary to treat all causes.

Surrogates of Insulin Sensitivity and Indices of Cardiometabolic Profile in Obesity.

BACKGROUND AND OBJECTIVES: Obesity is often associated with insulin resistance (IR). We considered different IR indexes: the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, the two specimen (0 and 120 min) oral glucose tolerance test Matsuda Index (MI) and the Homeostasis Model Assessment-Adiponectin (HOMA-AD) index. These IR indexes were compared with indicators of the cardiometabolic profile. METHOD: This cross-sectional study enrolled 60 obese individuals without previous history of diabetes. Anthropometrical, ultrasound and laboratory examinations were conducted. RESULTS: All 3 indexes significantly correlated with indicators of central obesity, systolic and diastolic blood pressure, inflammation parameters, liver enzymes, HbA1c and some lipid parameters. The majority of correlation coefficients were the highest for HOMA-AD, but only the difference in correlation with waist circumference comparing with MI was statistically significant. HOMA-IR directly, and MI indirectly, significantly correlated with age, while HOMA-AD significantly directly correlated with the mean carotid artery intima media thickness (CAIMT). MI showed the best performances in predicting non-alcoholic fatty liver disease and pathologically increased CAIMT; HOMA-AD was the best in predicting metabolic syndrome, while HOMA-IR demonstrated the poorest performances in the prediction of all 3 conditions. There were no statistically significant differences in predicting performances of the analysed indexes. CONCLUSION: The HOMA-AD and MI are not superior compared with the HOMA-IR, in the identification of obese individuals with a proatherogenic cardiometabolic profile.

Possible influence of the environmental pollutant bisphenol A on the cardiometabolic risk factors.

Bisphenol A (BPA) is a ubiquitous environmental pollutant which is often associated with various health issues. In this study 103 healthy female volunteers in reproductive age from Serbian north province Vojvodina were enrolled and examined for the BPA exposure in the urine samples after 12 h of fasting. BPA was found in 35.92 % (37/103) of subjects. Statistically significant increment in waist circumference (p = 0.045) and waist-to-height ratio (p = 0.037) was observed among the BPA positive women in comparison with the women who had the same energetic balance and had not been exposed to BPA. Linear correlation was obtained between the BPA concentration in urine samples and body mass index (r2 = 0.35, p = 0.003) waist circumference (r2 = 0.21, p = 0.02) and waist-to-height ratio (r2 = 0.25, p = 0.01) among the obese. High energetic intake and reduced physical activity additionally pronounced BPA positive association with obesity. No statistically significant difference was observed in triglycerides, HDL and LDL cholesterol levels between the BPA exposed and BPA non-exposed female volunteers.

Pituitary Abscess with Unusual Clinical Course

The aim is to present unusual clinical course and magnetic resonance imaging (MRI) features of pituitary abscess. A 59-year-old man presented with fever, polyuria, polydipsia and marked weight loss within the last two months. Basic endocrinology tests revealed the presence of anterior pituitary dysfunction, associated with central diabetes insipidus and increased levels of inflammatory markers. The presence of expansile sellar lesion, showing restricted diffusion signal pattern compatible with acute pituitary pyogenic abscess was found on MRI. Regression of pituitary abscess was obvious during the next few weeks of parenteral antibiotic treatment. Adequate substitution treatment with L thyroxine, hydrocortisone, testosterone and desmopressin was achieved. Seventeen months later, clinical deterioration associated with recurrent pituitary abscess was confirmed on MRI. Abscess regression was obvious again after conservative treatment. However, control MRI study performed three years after initial scanning revealed the presence of pituitary tumor, most consistent with macroadenoma. Surgical intervention was ordered. Histologic evaluation indicated the presence of fibrotic changes, associated with granulation tissue and rare cellular elements, compatible with chronic inflammation. To the best of our knowledge, there are no studies in the literature describing such a pattern of chronic evolution of pyogenic pituitary abscess with consequent chronic inflammatory changes with granulation tissue proliferation, mimicking macroadenoma.

Do diethyl phthalate (DEP) and di-2-ethylhexyl phthalate (DEHP) influence the metabolic syndrome parameters? Pilot study.

The study objective was to determine if the healthy participants were exposed to diethyl phthalate (DEP) and di (2-ethylhexyl) phthalate (DEHP) and if this exposure could be linked to the development of metabolic syndrome. The study included 103 healthy volunteers of similar age with normal BMI values, waist circumference, total cholesterol, HDL, LDL, and triglycerides. DEP and DEHP were measured in the morning urine samples to detect monoethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Two phthalate groups and a control group were formed. Both MEP group and control group had similar results. The correlations between MEP and the measured parameters were insignificant. The correlation between the MEHP group and the age was significantly negative, but between the MHEP group and the waist circumference the correlation was significantly positive. Lipids and lipoproteins were within the reference values and equal in both groups. The significant negative correlation was observed only between MEHP and HDL. Our population is exposed to DEP and DEHP. There was only a significant correlation between DEHP and the observed metabolic syndrome components. Its negative impact was higher as the participants were younger.