Evaluation of serum Angiopoietin-like protein 2 (ANGPTL-2), Angiopoietin-like protein 8 (ANGPTL-8), and high-sensitivity C-reactive protein (hs-CRP) levels in patients with gestational diabetes mellitus and normoglycemic pregnant women.

OBJECTIVE: In the present study, we aimed to investigate the role of the fasting serum levels of Anjiopoetin 2 - like protein (ANGPTL2), Anjiopoetin 8-like protein (ANGPTL8), and high-sensitivity C-reactive protein (hs-CRP) in the etiopathogenesis of gestational diabetes mellitus (GDM), and analyze the relationships between insulin resistance parameters. MATERIAL AND METHOD: The 90 individuals admitted to Izmir Katip Celebi University Hospital Internal Medicine, Endocrinology and Obstetrics, and gynecology outpatient clinic were included in the study of similar ages and similar demographic characteristics. Forty-five women with diet-controlled GDM and 45 women with normoglycemic pregnancy were enrolled. ANGPTL-2, ANGPTL-8, hs-CRP, creatinine, ALT, GGT, lipid profile, HBA1c(%), and serum insülin, c-peptide levels were studied in the fasting serum samples of research groups. All individuals had 75-g OGTT testing. GDM screening was performed at 24-28 weeks' gestation. Exclusion criteria were as follows: Age <18 years or >40 years, pregestational diabetes (type 1 or 2), drug or alcohol abuse, thyroid dysfunction, Hepatitis B, and other infectious diseases (Herpes virus, Streptococcus B carriers, Chlamydia and Candida), Thalassemia carriers or other significant medical conditions, the use of any medication that interferes with lipid or glucose metabolism that would affect glucose regulation. RESULT: Forty-five women with GDM and for the control group, 45 women with normoglycemic pregnant women were identified. The mean gestational age was 30.7 (18-38) for GDM and 29.6 (24-39) for the control group. Serum ANGPTL-8 (GDM =19.5 ± 93 Control = 0.73 ± 3.78 p = <.001). There was a statistically significant difference between the case and control groups for serum ANGPTL-8 levels. Serum ANGPTL-2 (GDM =19.9 ± 23.1 Control = 26.0 ± 23.4 p = .105) and serum hs-CRP(GDM =106 ± 65.1 Control =98.2 ± 87.3 p = .768). There was no statistically significant difference between the case and control groups for serum ANGPTL-2 and hsCRP levels. Serum ANGPTL8 levels were positively correlated with FPG (r = 0.391, p = <.001), FPI (r = 0.212, p = .045), 1-h PPG (r = 0.514, p = <.001), 2-h PPG (r = 0.502, p = <.001), HOMA-IR) score (r = 0.310, p = .003), TG (r = 0.245, p = .020); they were not except for BMI, hs-CRP levels and ANGPTL2 levels. CONCLUSIONS: ANGPTL8 levels were significantly higher in GDM than in healthy control group. ANGPTL2 levels and hs-CRP levels were similar to the healthy control group. Elevated serum ANGPTL8 levels were correlated significantly with insulin resistance parameters, the main component of GDM pathophysiology. Our data showed that ANGPTL8 could be a new biomarker for diagnosing GDM.

Microwave ablation as an efficient therapy for primary hyperparathyroidism: Efficacy and predictors of treatment success.

BACKGROUND: Microwave ablation (MWA) has great potential for the treatment of primary hyperparathyroidism, but as predictors and therapeutic efficiency have not been fully clarified, further investigations are required. AIM: The purpose of this study was to explore the predictors of MWA efficacy in patients with primary hyperparathyroidism (PHPT) induced by parathyroid adenoma. METHODS: The study included patients with PHPT treated with MWA separated into two groups as response and no response group, according to the efficacy of the treatment. The two groups were compared with respect of possible predictors, such as age, gender, parathyroid adenoma volume, baseline levels of calcium (Ca), phosphorous (P), alkaline phosphate (ALP) and vitamin D, localisation of parathyroid adenoma, and instrumental parameters such as microwave ablation time and power. The statistical significance of possible predictors of MWA efficacy was investigated by using logistic regression analysis. RESULTS: Evaluation was made of 32 patients in respect of analysing predictors of MWA efficacy. In the comparison of the values of the response and no response groups, only baseline Ca level was determined to be a potential predictor of the efficacy of MWA (P < .05). Further logistic regression results showed the baseline Ca level to be insignificant for the construction of a mathematical model to predict the efficacy of MWA (P = .071). The clinical success rate was 87.5%. Compared with pre-MWA, the serum PTH, calcium, phosphorus and ALP levels were significantly improved at 6 months post-MWA (PTH, 99 (86-154) ng/L vs 50 (46-58) ng/L; calcium, 2.94 (2.81-2.98) mmol/L vs 2.38 (2.28-2.50) mmol/L; phosphorus, 0.87 (0.82-1.01) mmol/L vs 1.16 (1.0-1.3) mmol/L; ALP, 82 (73-98) U/L vs 69 (54-84) U/L, respectively; all, P < .01. CONCLUSIONS: Although no predictor of treatment success could be determined, MWA might be an effective treatment in patients with PHPT.

Associations Between Bioavailable Vitamin D and Remnant Cholesterol in Patients With Type 2 Diabetes Mellitus.

Introduction In circulation, 99% vitamin D is transported by binding to vitamin D binding protein (VDBP) and albumin. Vitamin D at free form and vitamin D binding to albumin are defined as bioavailable vitamin D. Vitamin D deficiency is associated with atherogenic lipid profile and insulin resistance. Remnant cholesterol is defined as the cholesterol component of triglyceride-rich lipoproteins and contributes to the atherosclerotic burden. The aim of this study was to investigate the association between bioavailable vitamin D and remnant cholesterol in patients with type 2 diabetes mellitus (T2DM). Methods A total of 198 T2DM patients and 208 non-diabetic subjects underwent biochemical measurements of lipid profiles, 25(OH)D, VDBP, CRP and albumin levels. Their demographic characteristics (age, sex) were questioned. Subjects with thyroid, kidney and liver dysfunction and using lipid-lowering therapy were not included in the study. The diagnosis of T2DM was made according to the American Diabetes Association ADA 2016 criteria. Classification of vitamin D levels was done according to the Endocrine Society. Bioavailable vitamin D concentrations were calculated. Results High-density lipoprotein cholesterol (HDL), 25(OH)D, free vitamin D and bioavailable vitamin D levels were significantly lower in diabetic patients than in non-diabetic patients while triglyceride, remnant cholesterol and CRP levels were found to be significantly higher. VDBP was positively correlated with CRP and remnant cholesterol in diabetic patients, but not in non-diabetic patients. Cut-off values were determined from non-diabetics as 3.56 ng/mL for bioavailable vitamin D and 26.56 mg/dL for remnant cholesterol. Logistic regression analysis in the control group showed that the odds ratio for increasing remnant cholesterol above the cut-off value was determined as 2.01 for low bioavailable vitamin D and 1.1 for elevated CRP. However, in T2DM there was no significant relationship. In all subjects, low bioavailable vitamin D increased the remnant cholesterol above the cut-off by 2.18-fold independent of the presence of T2DM. However, there was no significant risk to increase remnant cholesterol, considering a total 25(OH) D deficiency in all groups. Conclusions Low bioavailable vitamin D was found to be a risk factor for elevated remnant cholesterol. This relationship was not detected in patients with T2DM. We believe that the inflammation observed in Diabetes Mellitus may increase the concentrations of VDBP and a decrease in bioavailable vitamin D levels. Therefore, measuring VDBP and calculating the bioavailable vitamin D may provide additional information about the actual vitamin D status.

Apelin: A potential novel serum biomarker for early detection of diabetic nephropathy in patients with type 2 diabetes.

OBJECTIVE: Diabetic nephropathy (DN) is the major cause of chronic renal failure, and proteinuria is an independent risk factor for the end stage renal disease. The random urine protein: creatinine ratio (P:C ratio) can accurately predict the amount of 24-hour urinary protein excretion. Apelin is thought to be associated with endothelial dysfunction, angiogenesis, and inflammation. This study investigated the apelin concentration and its association with the urine P:C ratio, and metabolic parameters in subjects with and without type 2 diabetes mellitus (T2D). METHODS: This study involved 86 subjects: 56 with newly diagnosed and untreated T2D and 30 non-diabetic controls. All subjects underwent a complete clinical examination that included anthropometric and laboratory measurements. RESULTS: Twenty-four males and sixty-two females participated in this study, and their mean age was 52.27±11.34 years. There were no differences in age, thyrotropin-stimulating hormone (TSH), creatinine clearance, and apelin levels between groups. As expected, fasting plasma glucose, weight, body mass index, and HbA1C were higher in T2D subjects (p=0.001, p=0.02, p=0.03, and p=0.001, respectively). Although apelin levels were higher in the control group, the differences were not statistically significant (p=0.93). The P:C ratio levels were lower in the control group, and the differences were statistically significant (p=0.006). A Spearman correlation analysis revealed that serum apelin levels were not correlated with the urine P:C ratio. CONCLUSION: Our study demonstrates that T2D is associated with decreased serum apelin levels and increased urine P:C ratios compared to those in non-diabetic subjects. This association may depend on impaired glucose homeostasis. Our results show that the serum apelin levels were not correlated with the urine protein: creatinine ratio and provide further evidence regarding the relationship between apelin and DN.

Fetuin-A levels in hyperthyroidism.

OBJECTIVE: Fetuin-A is a protein secreted from the liver that inhibits arterial calcification deposition and can contribute to insulin resistance. Hyperthyroidism is also associated with insulin resistance. It is not known whether hyperthyroidism has an effect on fetuin-A levels. METHODS: We measured fetuin-A levels and homeostasis model of assessment-insulin resistance before hyperthyroidism treatment was initiated and after euthyroidism was achieved. A total of 42 patients diagnosed with hyperthyroidism were enrolled in this study. Fetuin-A, insulin, high-sensitivity C-reactive protein, fasting blood glucose, free T3 (fT3), free T4 (fT4), and thyrotropin were measured before and after euthyroidism was established. RESULTS: Basal fasting blood glucose, high-sensitivity C-reactive protein, insulin, c-peptide, homeostasis model of assessment-insulin resistance, fT3, fT4 and fetuin-A levels were significantly decreased after euthyroidism was achieved (Table 1). Basal fasting blood glucose (r:0.407, p:0.008), high-sensitivity C-reactive protein (r:0.523, p<0.0001), insulin (r:0.479, p:0.001), homeostasis model of assessment-insulin resistance (r:0.541, p<0.0001), fT3 (r:0.492, p:0.001) and fT4 (r:0.473, p:0.002) were positively correlated with basal fetuin-A levels. Basal thyrotropin levels were significantly negatively correlated (r:-0.553, p<0.0001) with basal fetuin-A levels. CONCLUSION: Our findings suggest that hyperthyroidism influences fetuin-A levels.

Evaluation of circulating endothelial biomarkers in familial Mediterranean fever.

The aim of this was to evaluate some of the vascular biomarkers and cytokines related with atherosclerosis in regularly treated and attack-free familial Mediterranean fever (FMF) patients. Forty (21 males [M] and 19 females [F], 31 [15-58] years) FMF patients and eighteen healthy controls (11 M and 7 F, 35.5 [19-46] years) with no known cardiovascular (CV) risk factors were included. All patients were receiving regular colchicine treatment, and examinations were performed during attack-free periods. Serum samples were used for the determination of high-sensitive C-reactive protein (hs-CRP), tissue factor (TF), tissue plasminogen activator (t-PA), osteoprotegerin (OPG), interleukin-6 (IL-6), IL-17, and IL-23. Plasma samples were used for the determination of asymmetric dimethylarginine (ADMA) and thrombomodulin (TM). Age, sex distribution, waist circumference, body mass index, smoking status, and serum lipids were similar between the patients and controls (P > 0.05). The concentrations of (hs-CRP) and IL-17 were significantly higher in FMF patients compared with controls (P < 0.05). On the other hand, IL-6 and IL-23 levels were not different between the groups (P > 0.05). ADMA, OPG, and TM concentrations were significantly lower in the patients' group compared to those of controls (P < 0.05). However, vWF, TF, and t-PA levels were similar between the groups (P > 0.05). FMF patients receiving regular colchicine therapy during inactive disease state had significantly lower levels of vascular injury parameters.

Effect of family history of type-2 diabetes on coronary flow reserve and it's relationship with insulin resistance: an observational study.

OBJECTIVE: Coronary microvascular function among offspring of patients with diabetes mellitus might be compromised when compared to persons with no first-degree relative with diabetes mellitus. The aim of the study was to evaluate effect of family history of type-2 diabetes on coronary flow reserve. METHODS: In this observational study, we evaluated coronary flow reserve (CFR) via echocardiography of 95 subjects having a biological parent with type-2 diabetes and 34 healthy volunteers without any biological parent with type-2 diabetes. We have analyzed possible association with CFR and homeostasis model assessment - insulin resistance (HOMA-IR). Comparison analyses were made using independent samples t test, Chi-square test and one-way ANOVA. Association of independent variables with CFR was obtained by correlation analysis and stepwise linear regression model including potential confounders. RESULTS: CFR was significantly lower in the positive family history group than in the controls. Moreover, when compared with controls, the subgroup of insulin-sensitive subjects in the positive family history group also had significantly reduced CFR (2.67±0.28 vs. 2.83±0.19; p=0.01). Correlation analysis revealed that CFR was inversely correlated with HOMA-IR, (r=-0.433), fasting glucose (r=-0.331), fasting insulin (r=-0.396), and hemoglobin (Hb)A1c (r=-0.405). When the positive family history group was divided into tertiles of insulin resistance (HOMA-IR <1.3, 1.3-2.6, and >2.6; Groups 1-2, and 3), there was a significant difference in CFR between Groups 1 and 2 and between Groups 1 and 3 (p<0.05 for all). Though statistically not significant, there was also a difference in CFR between Groups 2 and 3. In a linear regression model, only fasting glucose level was independent predictor of CFR (ß=-677; p value =0.001, 95% CI: -0.061 and -0.019). CONCLUSION: Nondiabetic first-degree relatives of patients with type-2 diabetes are at increased risk of developing coronary microvascular dysfunction.

Serum lipid levels in women with premature ovarian failure.

OBJECTIVE: The aim of this study was to investigate serum lipid and hormone levels in women with premature ovarian failure (POF) and compare them with those of healthy women of similar age. METHODS: We measured fasting total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), high-density lipoprotein, estradiol (E2), follicle-stimulating hormone (FSH), progesterone, and testosterone levels in 47 women with POF not using any hormone therapy and 60 healthy women of the same age range not using oral contraceptives or any other hormonal medication. RESULTS: There were no statistically significant differences between the groups in terms of age, body mass index (BMI) and smoking status (P = 0.054, 0.250, and 0.656, respectively). The mean E2 levels of the POF and control groups were 27.9 ± 2.3 and 87.8 ± 75.2 pg/mL, respectively (P < 0.001). Women with POF presented with significantly higher TC and LDL levels (P = 0.006 and 0.040, respectively). However, no difference was found between the groups with regard to triglyceride and high-density lipoprotein levels (P = 0.128 and 0.062, respectively). We determined that there was a significant negative correlation between E2 and TC levels (r = -0.291, P = 0.047) in the POF group. However, no correlation could be identified between E2 and lipids in the control group. Likewise, no correlation was present between FSH and lipids in both groups. We divided the control group according to basal FSH level. Group A consisted of the women with a serum FSH level lower than 7 IU/L, and group B consisted of the women with a serum FSH level of 7 IU/L or higher. There was no difference between the groups in age, body mass index, E2 concentration, and smoking status. The FSH level of group A was significantly lower than that of group B (P < 0.001). We found no difference between groups A and B with regard to lipid levels. CONCLUSIONS: Higher TC and LDL levels in women with POF compared with the control group suggest that estrogen deprivation in women with POF leads to unfavorable lipid changes.

Frequency of Thyroid Nodules among Patients with Colonic Polyps.

Aim. Colonic polyps and thyroid nodules are common diseases and their frequency increases with age. In the literature, there is no study investigating the coexistence of colonic polyps and thyroid nodules. Therefore, this study was designed to investigate thyroid nodule prevalence in patients with colonic polyps. Material and Methods. Sixty-six patients with colonic polyps and 146 patients without colonic polyps enrolled into the study. Age and sex matched control group was composed from patients without colonic polyps. Colonoscopic examinations, thyroid ultrasonographies were performed in all patients, and TSH were measured. Results. Male/female ratio in polyp and control groups were 40/26 versus 68/78, respectively (P = 0.058). Mean ages were similar in both groups (53.3 ± 11.4 versus, 51.8 ± 11.4, P = 0.373). Thyroid nodule was detected in 44 (66.7%) patients with polyps and in 61 (41.8%) controls (P = 0.001). Patients with adenomatous polyps had 5 or more thyroid nodules compared to patients with hyperplastic polyps (P = 0.03). Thyroid nodules were more prevalent among patients aged 50 or older compared to 50 years or less (P = 0.023). Conclusion. Thyroid nodules were detected more common in patients with colonic polyps. Further studies are needed to clarify this coexistence.

Asymmetric dimethylarginine levels and carotid intima-media thickness in obese patients with polycystic ovary syndrome and their relationship to metabolic parameters.

OBJECTIVE: To evaluate the plasma asymmetric dimethyl arginine (ADMA) levels and carotid intima-media thickness (IMT) in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective study. SETTING: University medical center. PATIENT(S): Thirty-five patients with PCOS and 31 healthy controls. INTERVENTION(S): Peripheral venous puncture, ultrasonography, oral glucose tolerance test (OGTT). MAIN OUTCOME MEASURE(S): Plasma ADMA, serum FSH, LH, dehydroepiandrosterone sulfate (DHEAS), free T and total T, insulin, fasting plasma glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, homocysteine, fibrinogen, C-reactive protein, and carotid IMT. RESULT(S): The PCOS group had higher levels of androgens, triglycerides, homocysteine, insulin, and homeostasis model assessment of insulin resistance when compared with controls. There were no significant differences in ADMA levels and IMT between the two groups. The fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, fibrinogen, and C-reactive protein levels were not different among the groups. Intima-media thickness was significantly correlated with DHEAS, but there was no association between IMT and ADMA. CONCLUSION(S): Results of our study revealed that ADMA levels and carotid IMT in patients with PCOS are not different from healthy controls.

49,XXXXY syndrome with autoimmune diabetes and ocular manifestations.

OBJECTIVE: We report a rare case of 49,XXXXY syndrome with autoimmune diabetes (requiring insulin therapy), bilateral cataracts and unilateral glaucoma. CLINICAL PRESENTATION AND INTERVENTION: A 25-year-old man with mental retardation presented with multiple skeletal abnormalities, polyuria and polydipsia. He had high glucose concentrations, without ketonuria, and hypergonadotropic hypogonadism. Ophthalmic examination revealed a polar cataract in both eyes and increased intraocular pressure in the left eye. The anti-islet cell antibody test was positive, and anti-glutamic acid decarboxylase autoantibody levels were elevated. Karyotype analysis revealed 49,XXXXY. Intensive insulin therapy and testosterone replacements were started. CONCLUSION: The autoimmune nature of diabetes that we observed in our patient seems to be predisposed by hypogonadism. Cataract and glaucoma in this case seem to be the result of diabetes, and an association of these ocular manifestations with the syndrome 49,XXXXY seems unlikely.

Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism.

BACKGROUND: Mitochondria are the main production site of free oxygen radicals, which can cause organ dysfunction by oxidation of cellular macromolecules such as carbohydrates, lipids and proteins. Oxidative stress may result from either overproduction of these species or from failure of the antioxidant defence systems. Thyroid hormones have well-known effects on mitochondrial oxygen consumption, but data about how hypothyroidism affects oxidative stress are controversial, and little is known about oxidative stress in subclinical hypothyroidism. Total antioxidant status (TAS) gives information about all of the antioxidants in the organism, while malondialdehyde (MDA) is a lipid peroxidation marker used to assess lipid peroxidation due to increased oxidative stress. We aimed to determine how hypothyroidism and subclinical hypothyroidism affect serum MDA and TAS. SUBJECTS AND METHODS: Serum TAS, MDA, C-reactive protein levels and lipid compositions were studied in 20 hypothyroid, 40 subclinical hypothyroid and 40 healthy subjects. RESULTS: MDA was elevated in both hypothyroid and subclinical hypothyroid patients compared with controls, while TAS levels show no significant differences between groups. Low-density lipoprotein (LDL) cholesterol levels were significantly high in both hypothyroid and subclinical hypothyroid patients. Triglyceride levels were high only in hypothyroid patients when compared with the controls. MDA showed a correlation with LDL cholesterol, total cholesterol and triglyceride. CONCLUSIONS: These results suggest an increased oxidative stress in both hypothyroid and subclinical hypothyroidism states, which can be explained by both the insufficient increase in the antioxidant status and the altered lipid metabolism in these cases.

Coronary flow reserve is impaired in subclinical hypothyroidism.

OBJECTIVE: Although the cardiovascular system is highly sensitive to thyroid hormones, the cardiovascular effects of subtle thyroid dysfunction such as subclinical hypothyroidism (SHT) remain unclear. Therefore, we investigated coronary flow reserve (CFR) reflecting coronary microvascular function in patients with SHT. METHODS: Fifty subjects with SHT and 30 control subjects with normal serum thyroid hormones and TSH levels were included in this study. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocity. RESULTS: Age, gender, diastolic and systolic blood pressure, body mass index (BMI), serum lipid parameters, and thyroid hormone levels were similar between the groups. Heart rate was significantly lower in the SHT group. Left ventricular diastolic filling parameters were significantly different in the SHT group while other echocardiographic parameters were similar. CFR values were significantly lower in subjects with SHT than in the control group (2.38 +/- 0.44 vs. 2.98 +/- 0.47, p < 0.0001). CONCLUSIONS: These findings suggest that CFR, which reflects coronary microvascular function, is impaired in patients with SHT.