SERUM CARBOXYMETHYL-LYSINE AND SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS IN HYPERTHYROID AND HYPOTHYROID PATIENTS.

Purpose: The formation and accumulation of advanced glycation end products (AGEs) are enhanced with increased oxidative stress and inflammatory conditions. A hyperthyroid and hypothyroid state is associated with oxidative stress. This study aimed to evaluate skin AGE deposition, serum carboxymethyl-lysine (CML), and serum soluble receptor for AGEs (sRAGE) levels in hypothyroid and hyperthyroid patients. Methods: A total of 203 subjects were included in this cross-sectional study. After excluding diabetes mellitus, 103 newly diagnosed hypothyroid patients, 50 newly diagnosed hyperthyroid patients, and 50 control (euthyroid) subjects were enrolled. All tests were done before beginning the appropriate treatment. Accumulated AGEs in the skin collagen were measured by skin autofluorescence (SAF) using an AGE Reader. Results: SAF measurements were 1.82 ± 0.04, 1.80 ± 0.40, and 1.63 ± 0.30 arbitrary units for the hypothyroid, hyperthyroid, and euthyroid groups, respectively (p = 0.04). Serum CML levels were 8.2 ± 2.8, 10.2 ± 2.0, and 8.0 ± 3.3 ng/mL for the hypothyroid, hyperthyroid, and euthyroid groups, respectively (p = 0.01). sRAGE levels were similar between the groups. Serum thyroid-stimulating hormone and SAF measurements were positively correlated (r = 0.25, p = 0.02) in the hypothyroid group and negatively correlated in the hyperthyroid group (r = -0.36, p = 0.04). There was no correlation between CML and sRAGE levels. Conclusion: SAF measurements are increased in both hypo- and hyperthyroid normoglycemic patients. Serum CML levels are increased in hyperthyroid patients. Hypo and hyperthyroid states might be associated with acceleration of AGE accumulation and may have a long term effect on metabolic memory.

Assessment of non-traumatic vertebral fractures in Cushing's syndrome patients.

PURPOSE: Hypercortisolism has detrimental effects on bone metabolism with the consequences of bone loss and bone fractures. We aimed to evaluate the frequency of vertebral fragility fractures and to determine the factors associated with Cushing's syndrome (CS). METHODS: A total of 135 patients diagnosed with Cushing's syndrome [108 patients with Cushing's disease and 27 patients with adrenocortical adenoma] and 107 healthy controls were included in this cross-sectional study. The available clinical, laboratory, and radiologic data of patients with CS were recorded, retrospectively. Lateral vertebral radiograms were evaluated for vertebral fragility fractures according to Genant's semi-quantitative method. Bone mineral density (BMD) was determined using a Dual-energy X-ray absorptiometry (DEXA). RESULTS: Vertebral fragility fractures (VFs) were observed in 75.3% (n = 61) of the patients. The median number of VFs was six (min-max: 2-12). All patients with vertebral fractures had thoracic VF, and 50.7% of the patients had lumbar fragility fractures. Thirty-three (40.7%) patients with vertebral fractures had normal bone densitometry values. Osteoporosis and osteopenia were observed in 16.2% and 40.7% of the patients, respectively. The duration of active disease, the presence of ACTH-secreting pituitary adenoma, and 24-h urinary cortisol did not influence the presence of vertebral fractures. Vertebral fractures were independently associated with age, FSH, LH levels, and lumbar BMD (R2 = 68.18%, p = 0.028). The femoral neck BMD (but not lumbar BMD) was independently associated with age, BMI, and PTH levels (R2 = 48.48%, p < 0.001). CONCLUSION: Vertebral fracture frequency was higher in CS patients. Most of the patients with vertebral fractures had multiple fractures. Although low lumbar BMD was associated with VF, patients with CS with normal bone densitometry could experience VF. Vertebral radiograph evaluations as a part of routine evaluation for silent vertebral fractures may help to prevent further fractures in patients with CS.

Thyroid disease in the perimenopause and postmenopause period.

The interpretation of thyroid function tests should be cautiously made during the perimenopause and postmenopause period bearing in mind that physiologic changes do exist in this group of women in terms of secretion and metabolism of thyrotropin and thyroid hormones. Moreover the incidence of thyroid disorders increases in postmenopausal and elderly women. There is no consensus for screening postmenopausal women even though there is well-known evidence about the effect of thyroid status on cognitive function, cardiovascular risk, bone turnover, and longevity. The diagnosis of any thyroid disorder is challenging in these patients because the symptoms are more subtle and attributed to menopausal symptoms. Management requires more attention in this population than that of younger groups, because high doses of L-thyroxine can lead to cardiac complications and increased bone turnover. Furthermore radio-iodine is preferred in treatment of hyperthyroidism in older patients. The risk of nodular thyroid disease and thyroid cancers increases in this group. Although the diagnostic approach is the same as for young patients, the risk of surgery is high and disease prognosis is worse. Women with any form of thyroid disease should be treated according to the current guidelines. Decision for menopausal hormonal therapy should be individualized regardless of the concomitant presence of thyroid disorders.

Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes.

BACKGROUND/OBJECTIVE: Artificial sweeteners were thought to be metabolically inactive, but after demonstrating that the gustatory mechanism was also localized in the small intestine, suspicions about the metabolic effects of artificial sweeteners have emerged. The objective of this study was to determine the effect of artificial sweeteners (aspartame and sucralose) on blood glucose, insulin, c-peptide and glucagon-like peptide-1 (GLP-1) levels. SUBJECTS/METHODS: Eight newly diagnosed drug-naive type 2 diabetic patients (mean age 51.5±9.2 years; F/M: 4/4) and eight healthy subjects (mean age 45.0±4.1 years; F/M: 4/4) underwent 75 g oral glucose tolerance test (OGTT). During OGTT, glucose, insulin, c-peptide and GLP-1 were measured at 15- min intervals for 120 min. The OGTTs were performed at three settings on different days, where subjects were given 72 mg of aspartame and 24 mg of sucralose in 200 ml of water or 200 ml of water alone 15 min before OGTT in a single-blinded randomized order. RESULTS: In healthy subjects, the total area under the curve (AUC) of glucose was statistically significantly lower in the sucralose setting than in the water setting (P=0.002). There was no difference between the aspartame setting and the water setting (P=0.53). Total AUC of insulin and c-peptide was similar in aspartame, sucralose and water settings. Total AUC of GLP-1 was significantly higher in the sucralose setting than in the water setting (P=0.04). Total AUC values of glucose, insulin, c-peptide and GLP-1 were not statistically different in three settings in type 2 diabetic patients. CONCLUSIONS: Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in newly diagnosed type 2 diabetic patients.

Association of serum paraoxonase concentration with serum lipid levels and bone mineral density measurements in early postmenopausal women.

OBJECTIVE: To determine the association of serum paraoxonase concentration with serum lipid levels and bone mineral density in early postmenopausal Turkish women. DESIGN: One hundred healthy postmenopausal women were included in a cross-sectional study in a University hospital clinic. Blood was drawn from women who had bone mineral density (BMD) measurements during routine visits. BMD of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry. The serum paraoxonase concentration and serum lipid levels were measured. Women were divided into two groups: those with normal lumbar vertebrae BMD and those with osteopenic lumbar vertebrae. Serum paraoxonase concentration was compared between the groups. The correlation between serum paraoxonase concentration and bone mass parameters was performed using Pearson's test. RESULTS: The paraoxonase concentration in the osteopenic group was significantly lower than in the group with normal lumbar vertebrae BMD. The paraoxonase concentration was moderately correlated with total cholesterol, low density lipoprotein cholesterol and triglyceride levels among early postmenopausal Turkish women. CONCLUSIONS: Early postmenopausal women with osteopenic lumbar vertebrae have significantly lower paraoxonase concentration than those with normal lumbar vertebrae BMD. Further studies are needed to clarify the associations between the osteoporosis risk factors and paraoxonase concentration during late postmenopausal years.

The association of osteopenia with levels of serum 25-hydroxyvitamin D and HOMA-IR values.

OBJECTIVE: To determine the association of osteopenia with levels of serum 25-hydroxyvitamin D and HOMA-IR values in postmenopausal women. Methods One hundred healthy postmenopausal women were included in a cross-sectional study. Venous blood was collected after an overnight fast and 25-hydroxyvitamin D, glucose and insulin levels were measured. HOMA-IR was calculated. Bone mineral density was measured with a dual X-ray absorptiometer. RESULTS: There was no difference in serum 25-hydroxyvitamin D levels and HOMA-IR values between the two groups. A weak positive correlation between serum 25-hydroxyvitamin D levels and osteopenia was detected. Insulin resistance had a weak negative association with osteopenia. CONCLUSIONS: The correlations between osteopenia and serum 25-hydroxyvitamin D levels and HOMA-IR values were weak among early postmenopausal women.

Effect of vitamin D deficiency and replacement on endothelial functions in Behçet's disease.

OBJECTIVES: Endothelial dysfunction is previously demonstrated in Behçet's disease (BD) and vitamin D is implicated to affect endothelial functions. We aimed to evaluate the status of serum 25(OH)Vit D3 levels and its association with disease activity, endothelial function and carotis intima media thickness (CIMT) in patients with BD. METHODS: Thirty-six BD (F/M: 22/14, mean age: 39.6 years) patients and 51 healthy controls (F/M: 28/23, mean age: 34.5 years) were studied. Rheumatoid arthritis (RA) (n=33) patients (F/M: 26/7, mean age: 50.82 years) were also enrolled, as a disease control group. Endothelial function was evaluated by brachial artery flow mediated dilatation (FMD) and CIMT with B-Mode ultrasound. The vitamin D-deficient BD patients received 1000 IU Vitamin D3 daily for 3 months. RESULTS: Less than 50 nmol/L levels of 25(OH) Vit D3 were present in 61.1% (n=22) of BD and 35.3% (n=18) of HC (serum 25(OH)Vit D3 levels: BD: 44.5 (9-112) vs HC: 56 (14-125) nmol/lt, p=0.01). CIMT and FMD were also significantly different between BD and HC [0.56 (0.35-9.26) vs. 0.39 (0-0.52) and 5.20 (0.56-30.58) vs. 9.04 (-6.9-34.17), p=0.001 and p=0.02, respectively]. However, no correlation was observed between 25(OH)VitD3 levels and CIMT or FMD (r=0.6, p=0.7 and r=0.03, p=0.8, respectively) at baseline. CIMT measurements improved after replacement therapy (0.56 vs. 0.49, p=0.02), FMD measurements also improved, but not reaching statistical significance (5.2 vs. 8.28, p=0.06). CONCLUSIONS: A high presence of vitamin D deficiency was observed in BD patients from Turkey and replacement of vitamin D had favourable effects on endothelial function.

Estrogen receptor gene polymorphisms in a group of postmenopausal Turkish women: association with bone mineral density.

OBJECTIVE: To evaluate the frequency of the estrogen receptor (ER) gene PvuII and XbaI polymorphisms and their associations with bone mineral density (BMD) in a group of postmenopausal Turkish women. DESIGN: A total of 125 healthy postmenopausal women and 125 premenopausal healthy young women as controls were included in the study. The PvuII and XbaI polymorphisms in the ER gene were studied by the polymerase chain reaction-restriction fragment length polymorphism method. The BMD of the lumbar vertebrae and femoral neck were measured by dual-energy X-ray absorptiometry. RESULTS: The frequencies of the ERα PVuII genotypes PP, Pp and pp were 20%, 54.4% and 25.6% in premenopausal and 24.8%, 44.8% and 30.4% in postmenopausal women, respectively. The frequencies of the ER XbaI genotypes XX, Xx, xx were 16.8%, 48.8% and 34.4% in premenopausal and 16.8%, 48% and 35.2% in postmenopausal women, respectively. There was no difference in the frequencies of ER gene polymorphisms between premenopausal and postmenopausal women. BMD measurements were not different between ER PvuII and XbaI genotypes in premenopausal and postmenopausal women. CONCLUSIONS: ER gene PvuII and XbaI polymorphisms have no major influence on bone mineral density in our group of postmenopausal women.

Vitamin D receptor gene polymorphisms in a group of postmenopausal Turkish women: association with bone mineral density.

OBJECTIVE: To determine the frequency of the vitamin D receptor (VDR) gene polymorphisms BsmI, ApaI, TaqI and FokI and their associations with bone mineral density (BMD) in postmenopausal Turkish women. DESIGN: One hundred and thirty healthy postmenopausal women and 130 premenopausal healthy women acting as controls were included in the study. The BsmI, FokI, ApaI and TaqI polymorphisms in the VDR gene were studied by polymerase chain reaction-restriction fragment length polymorphism method. The BMD of the lumbar vertebrae and femur neck were measured by dual-energy X-ray absorptiometry. Comparisons between the groups were performed using the paired t-test and ANOVA. χ (2) or contingency tables were used to analyze qualitative results. RESULTS: Genotypes BB, Bb and bb occurred in premenopausal women with frequencies of 16.92%, 50% and 33.08% and in postmenopausal women with frequencies of 16.92%, 56.15% and 26.92%, respectively. Genotypes FF, Ff, ff occurred in premenopausal women with frequencies of 47.69%, 42.31% and 10% and in postmenopausal women with frequencies of 50.77%, 42.31% and 6.92%, respectively. Genotypes AA, Aa, aa occurred in premenopausal women with frequencies of 23.85%, 56.15% and 20% and in postmenopausal women with frequencies of 26.15%, 46.15% and 27.70%, respectively. Genotypes TT, Tt and tt occurred in premenopausal women with frequencies of 37.69%, 45.38% and 16.92% and in postmenopausal women with frequencies of 39.23%, 45% and 15.38%, respectively. There was no difference in the frequencies of VDR gene polymorphisms between premenopausal and postmenopausal women. BMD measurements were not different between genotypes in premenopausal and postmenopausal women. CONCLUSIONS: The VDR gene BsmI, FokI, ApaI and TaqI polymorphisms have no major influence on bone mineral density in our group of postmenopausal women.

Angiotension converting enzyme inhibition and calcium channel blockage improves cyclosporine induced glucose intolerance in rats.

The aim of this study was to evaluate the effects of quinapril, valsartan, and amlodipin on glucose tolerance in cyclosporine (CsA)-toxic rats. Among 40 male Wistar rats 32 were administered cyclosporine (CsA) (15 mg/kg) intraperitoneally for 6 weeks. Quinapril (10 mg/kg per day) (group Q), valsartan (40 mg/kg per day) (group V), and amlodipine (10mg/kg per day) (group A) were administered to individual sets of eight CsA-treated animals via the drinking water with the remaining untreated hosts followed as a control group (group C) and 8 healthy controls (group H). A Glucose-tolerance test was performed by administering oral glucose (2 g/kg) followed by blood samples obtained from the tail vein at baseline as well as 30,60,90, and 120 minutes after the glucose load. Glucose area under the curve (AUC) was calculated according to the trapezoidal rule. CsA levels were determined using an immunofluorescence method. Kruskal Wallis ANOVA test was used for statistical analysis. Median CsA levels were 1968 ng/mL, 1982 ng/mL, 1580 ng/mL, 1600 ng/mL; and glucose AUC, 232.4 +/- 130 mg/min per dL, 63.1 +/- 25 mg/min per dL, 115.0 +/- 90 mg/min per dL, 47.4 +/- 34 mg/min per dL 53.4 +/- 38 mg/min per dL for groups C,Q,V,A and H, respectively. Quinapril-treated and amilodipine-treated rats displayed a lower glucose AUC than group C (P <.01), which had higher glucose levels than healthy controls (P <.001). In summary, CsA treated rats show impaired glucose tolerance, which is improved by quinapril or amlodipine treatment. Angiotensin converting enzymes inhibitors and calcium channel blockers affect beta cell function rather than insulin sensitivity.

Effects of aminoguanidine on glomerular basement membrane thickness and anionic charge in a diabetic rat model.

We investigated the effect of aminoguanidine (AG) administration on GBM thickness, glomerular heparan sulfate (HS) content, and urinary albumin and HS excretion in diabetic rats. After induction of diabetes, female Wistar rats were divided into 2 groups: Group AGDM (n = 11) received 1 g/L aminoguanidine bicarbonate in drinking water, group DC (n = 12) was given only tap water. Control rats received AG (group AGH, n = 8) or tap water (group HC, n = 8). At the end of a period of 8 weeks, urinary albumin and glycosaminoglycan (GAG) excretion was detected. GBM heparan sulfate distribution and count was determined under the electron microscope. The AGDM group had lower urinary albumin and GAG excretion than diabetic controls. GBM thickness was increased in diabetic rats compared to groups of AGDM and HC. In AGDM group alcian blue stained particle distribution and count in the GBM was similar to healthy controls. In conclusion AG prevents the decrease of anionic charged molecules in the GBM and GBM thickening. This can be one of the mechanisms by which AG decreases albuminuria in diabetic rats.

The effect of losartan and captopril on glomerular basement membrane anionic charge in a diabetic rat model.

OBJECTIVE: Although angiotensin-converting enzyme inhibitors are known to reduce albuminuria by preserving glomerular basement membrane anionic content, the effects of angiotensin II receptor blockage are currently not known. The aim of this study was to evaluate the effects of captopril and losartan on glomerular basement membrane anionic charges in a diabetic rat model. DESIGN: After diabetes induction with streptozotocin, female Wistar rats were divided into three groups: group A, losartan 10 mg/kg by gavage (n = 8); group B, captopril 50 mg/l in drinking water (n = 6); group C, diabetic control rats (n = 8) given only tap water. Group D (eight rats) served as non-diabetic controls. At the end of 8 weeks, erythrocyte membrane charge, serum sialic acid, urinary glycosaminoglycan and albumin were measured and kidney specimens stained with Alcian blue in order to assess basement membrane glycosaminoglycans. RESULTS: Red blood cell anionic charges (ng Alcian blue/ 10(6) red blood cells) were 371.5+/-9.9 for group A, 443.5+/-7.1 for group B, 400.1+/-14.7 for group C, 468.7+/-4 for group D (AD, P<0.01; A>B P<0.01). Albuminuria (microg/day) was 778+/-221 for group A, 719+/-314 for group B, 1724+/-945 for group C, 393+/-263 for group D (A, B