Optical coherence tomography angiography characteristics of the retinal and optic disc morphology in prolactinoma.

PURPOSE: To investigate changes in the retinal and optic disc (OD) morphology in prolactinoma patients without optical chiasmal compression and/or visual field defects using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional imaging study, 16 consecutive prolactinoma patients (group 1, 32 eyes) and 15 age- and gender-matched healthy subjects (group 2, 30 eyes) underwent a thorough neuro-ophthalmological examination, which included testing for the presence of any intracranial compressive lesion that could cause optic neuropathy. Retinal morphological parameters, outer retinal and choriocapillaris flow areas, as well as OD vessel density (VD) and retinal nerve fiber layer (RNFL) thickness in for quadrants were then measured using OCTA. RESULTS: Mean age (p = 0.537) and gender (p = 0.385) of participants in groups 1 and 2 did not differ significantly. The mean BCVA for both groups was 0.00 ± 0.00 logMAR. Microadenomas made up the majority of prolactinomas (87.1 %). All retinal morphological parameters in deep capillary plexus (excluding foveal VD) differed significantly between groups 1 and 2 (whole: p < 0.001, parafoveal: p = 0.021, and perifoveal: p < 0.001). Peripapillary RNFL thickness in temporal (p < 0.001), nasal (p = 0.010), and inferior (p = 0.007) quadrants also differed significantly between the two groups. Foveal deep (r = -0.304, p = 0.035) and choriocapillaris flow (r = -0.511, p = 0.008) were negatively correlated with tumor size at diagnosis. CONCLUSIONS: Significant microvascular morphological changes, particularly in the deep retinal layer, as well as in the peripapillary RNFL thickness, were observed in prolactinoma patients. OCTA appears to be capable of detecting non-manifest circumpapillary and even intra-retinal microvascular changes even when there are no obvious signs of prolactinoma-related ocular complications caused by chiasmal compression.

HNF1A gene p.I27L is associated with co-existing preeclampsia in gestational diabetes mellitus.

The association of the FTO gene and HNF1α gene on gestational diabetes mellitus (GDM) and preeclampsia remains unclear. This is the first study to examine whether HNF1α gene and FTO gene were associated with having GDM and preeclampsia in Turkish women. Healthy pregnant women (n = 101) and women with GDM (n = 169) were included. GDM was divided into two groups as GDM-only (n = 90) and GDM-preeclampsia (n = 79). Genotyping of HNF1α gene p.I27L, p.A98V, and p.S487N, and FTO gene rs9939609 SNPs were performed using RT-PCR. The frequency of p.S487N, p.A98V, and FTO genotype were similar between the groups (p > .05). p.I27L GG-wild, GT, and TT genotype were 56.5%, 36.6%, and 6.9% in controls; 40.0%, 51.1%, and 8.9% in GDM-only; and 26.6%, 51.9%, and 21.5% in GDM-preeclampsia (p = .034). TT and GT genotype was more frequent in GDM-preeclampsia than in controls (p < .05). GT genotype was increased in GDM-only compared with controls (p < .05). TT genotype was more frequent in GDM-preeclampsia than in GDM-only (p < .05). p.I27L TT genotype was independently associated with increased blood pressure (BP) and urinary protein. p.I27L TT genotype was associated with increased preeclampsia risk in patients with GDM by increasing BP and urinary protein.

Clinical evaluation of pituitary insufficiency in adult population

Background/aim: This retrospective study aimed to investigate the clinical profile of pituitary insufficiency (PI) in adult population. Materials and methods: One hundred and fifty patients who were diagnosed as having PI between 2012 and 2018 (53.3% female, mean age 48.13 ± 15.83 years) were retrospectively analyzed. Results: Age at diagnosis was higher in females as compared with males (51.13 ± 15.95 vs. 44.70 ± 15.08 years, P = 0.012). The most frequent presenting signs were headache (29.4%) and visual disturbance (19.6%) in general. Females frequently presented with headache (33.3%), whereas males presented with sexual dysfunction (34.4%). The most frequent cause of PI was nonfunctional pituitary adenoma (28.8%) in general population. A frequent cause of PI was Sheehan's syndrome (33.8%) among females and nonfunctional pituitary adenoma (38.6%) among males. Pituitary macroadenoma (75.8%) was frequent in pituitary tumors with PI. 55.3 % of the patients had 4 pituitary hormones deficiencies and 26.0% of patients had 3 pituitary hormones deficiencies. Gonadotropin deficiency was the leading pituitary hormone deficiency. The frequency of posttraumatic PI was 4.7% in the general population. Conclusion: Nonfunctional pituitary adenoma was the most common cause of PI among males and Sheehan's syndrome was a major etiologic factor in females. Sheehan's syndrome remains an important health problem in Turkey although obstetric care has improved. Posttraumatic PI should be considered in the differential diagnosis of idiopathic PI.

The VDR gene FokI polymorphism is associated with gestational diabetes mellitus in Turkish women.

BACKGROUND: The association between the vitamin D receptor (VDR) gene and gestational diabetes mellitus (GDM) has not been investigated in Turkish pregnant women. We aimed to investigate associations between VDR gene BsmI (rs15444410), ApaI (rs7975232), FokI (rs19735810), and TaqI (rs731236) single nucleotide polymorphisms (SNPs) and GDM. MATERIAL-METHODS: This case-control study comprised 100 women with GDM and 135 pregnant women without GDM. The VDR polymorphism was evaluated using Sanger-based DNA sequencing. RESULT: VDR gene ApaI, BsmI, and TaqI SNPs did not differ between women with and without GDM (each, p > 0.05). ApaI, BsmI, and TaqI were not associated with GDM risk. The VDR gene FokI CT/TT genotype was associated with an increased GDM risk (CT vs. CC, OR = 1.84, 95% CI: [1.05-3.23], p = 0.031; TT vs. CC, OR = 3.95, 95% CI: [1.56-9.96], p = 0.002; CT/TT vs. CC, OR = 2.29, 95% CI: [1.35-3.89], p = 0.002; and CT/CC vs. TT, OR = 3.02, 95% CI: [1.23-7.38], p = 0.012). The FokI-TT genotype was more associated with younger age and higher glucose, HbA1c, and HOMA-IR than the CC and CT genotype. FokI-T was positively correlated with log-HOMA-IR (r = 0.326, p = 0.004). FokI SNPs were independently associated with GDM after adjusting for BMI and age (ß = 1.63, 95% CI: [1. 2-4.2], p = 0.012). There were no associations between the FokI, ApaI, BsmI and TaqI haplotypes and GDM. CONCLUSION: VDR gene FokI SNPs were independently associated with having GDM in Turkish women. VDR gene FokI SNPs might contribute to insulin resistance of developing GDM.

HNF1A gene p.I27L is associated with early-onset, maturity-onset diabetes of the young-like diabetes in Turkey.

BACKGROUND: The molecular basis of the Turkish population with suspected maturity-onset diabetes of the young (MODY) has not been identified. This is the first study to investigate the association between HNF1A-gene single-nucleotide polymorphisms (SNPs) and having early-onset, MODY-like diabetes mellitus in the Turkish population. METHODS: All diabetic patients (N = 565) who presented to our clinic between 2012 and 2015 with a clinical suspicion of MODY were included in the study. Analysis of HNF1A, HNFB, HNF4A, GCK gene mutations was performed using real-time polymerase chain reaction sequencing. After genetic analysis, diabetics (n = 46) with HNF1A, HNF1B, HNF4A, GCK gene mutations (diagnosed as MODY) and diabetics (n = 30) with HNF1B, HNF4A, GCK gene SNPs were excluded. Patients with early-onset, MODY-like diabetes (n = 486) and non-diabetic controls (n = 263) were included. Genetic analyses for the HNF1A gene p.S487 N (rs2464196), p.A98V (rs1800574) and p.I27L (rs1169288) SNPs were performed using Sanger-based DNA sequencing among the control group. RESULTS: p.S487 N and p.A98V was similar between the diabetics and controls in dominant and recessive models with no association (each, p > 0.05). p.I27L GT/TT carriers (GT/TT vs. GG, OR = 1.68, 95% CI: [1. 21-2.13]; p = 0.035) and p.I27L TT carriers had increased risk of having MODY-like diabetes (GT/GG vs. TT, OR = 1.56, 95% CI: [1. 14-2.57]; p = 0.048). Family inheritance of diabetes was significantly more common in patients with the p.I27L TT genotype. The p.I27L SNP was modestly associated with having diabetes after adjusting for body mass index and age (ß = 1.45, 95% CI: [1. 2-4.2]; p = 0.036). CONCLUSIONS: The HNF1A gene p.I27L SNP was modestly associated with having early-onset, MODY-like diabetes in the Turkish population. HNF1A gene p.I27L SNP might contribute to age at diabetes diagnosis and family inheritance.

Parathyroidectomy improves cardiovascular risk factors in normocalcemic and hypercalcemic primary hyperparathyroidism.

BACKGROUND: Parathyroidectomy has ameliorated cardiovascular risk factors in patients with hypercalcemic primary hyperparathyroidism (PHPT), but the effect of parathyroidectomy on normocalcemic PHPT is not exactly known. This case-controlled study aimed to investigate the effect of parathyroidectomy on cardiovascular risk factors in patients with normocalcemic and hypercalcemic PHPT. METHODS: Subjects with normocalcemic PHPT (n = 35), age- and sex-matched hypercalcemic PHPT (n = 60) and age- and sex-matched control (n = 60) were included. Cardiometabolic disorders were investigated with traditional cardiometabolic risk factors and the Framingham cardiovascular risk score (CRS) before and 6 months after parathyroidectomy. RESULTS: Diabetes, dyslipidemia, hypertension, obesity, insulin resistance, osteoporosis, having fractures were similarly increased in the hypercalcemic and normocalcemic PHPT groups (p > 0.05) compared with the controls (p < 0.05). Blood pressures, glucose metabolism (glucose, insulin, HOMA-IR) and lipid profiles were similarly increased in the PHPT groups (p > 0.05) compared with the controls (p < 0.05). After parathyroidectomy, blood pressures, serum total cholesterol, and HOMA-IR were decreased in both PHPT groups (p < 0.05). CRS was lower in the controls (5.74 ± 3.24, p < 0.05). After parathyroidectomy, CRS was decreased in the normocalcemic (11.98 ± 10.11 vs. 7.37 ± 4.48) and hypercalcemic (14.62 ± 11.06 vs. 8.05 ± 7.72) PHPT groups. Increased blood pressures were independent predictors of serum iPTH. CONCLUSION: The normocalcemic and hypercalcemic PHPT groups had similarly increased cardiovascular risk factors, even independently of serum calcium. Parathyroidectomy ameliorated the increased cardiovascular risk factors in both normocalcemic and hypercalcemic PHPT.

The effect of disease activity on thyroid nodules in patients with acromegaly.

Nodular thyroid disease is a very common disorder in patients with acromegaly. Insulin-like growth factor-1 (IGF-1) is a thyroid growth factor, and there is a correlation between IGF-1 levels and thyroid volume (TV) in patients with acromegaly. There is no study investigating the impact of somatostatin analog (SSA) treatment on thyroid nodule volume in patients with acromegaly. We aimed to assess thyroid nodule volume change with SSA treatment in patients with persistent acromegaly. We retrospectively analyzed data from 108 consecutive patients with acromegaly who were followed up by our clinic after undergoing surgery between 2002 and 2014. Patients who were cured after surgery were excluded. We only selected 43 patients (21 males, 22 females, mean age 52.8 ± 11.9 years) who did not meet the criteria of remission postoperatively, who were treated with SSA for at least six months and had normal thyroid function. Patients were divided into three groups (well-controlled, controlled, and active) according to their IGF-1 and growth hormone (GH) levels. All patients underwent an evaluation of TV and total thyroid nodule volume (TTNV) by ultrasound. TTNV decreased significantly in patients with well-controlled acromegaly (0.44 [0.75] to 0.23 [0.73], p < 0.001). TTNV did not change in controlled patients (0.18 [1.28] to 0.13 [1.54], p = 0.959); however TTNV increased in patients with active acromegaly (0.77 [1.46] to 1.03 [1.88], p = 0.028). Successful medical treatment of patients with active acromegaly decreases thyroid nodule volume. Sustained exposure to IGF-1 may cause an increase in thyroid nodule volume in patients with acromegaly.

Melanocortin 3 receptor gene polymorphism is associated with polycystic ovary syndrome in Turkish population.

Polycystic ovary syndrome (PCOS) is a frequent complex disorder with an ill-defined etiology. Genetic factors seem rather effective at the occurrence of the disease, however, the evidence of established various studies results are unsatisfied. We aimed to make a contribution to the genetic baseline of the disease by investigating melanocortin 3 receptor gene polymorphism in affected patients. 101 PCOS patients and 162 age-matched healthy volunteered control subjects recruited to the study. PCOS patients classified according to their BMI class and insulin resistance situation. Anthropometric measurements, physical examination results, laboratory findings, and hormone levels were recorded for each participant and analysis of two SNPs on the MC3R gene; rs3746619 and rs3827103 were performed. Although no significant difference was observed in rs3827103 polymorphism between PCOS patients and controls; rs3746619 polymorphism was determined associated with PCOS in the heritage of dominant (AA + AC) and co-dominant (AA) genotypes. Two polymorphisms did not found related to obesity and insulin resistance in PCOS subgroups analysis. MC3R gene rs 3746619 polymorphism was found associated with PCOS in the Turkish population and may make a contribution to the genetic baseline of the disease.

Effect of parathyroidectomy on epicardial fat thickness as a cardiovascular risk factor in patients with primary hyperparathyroidism

Background/aim: Several studies demonstrated that primary hyperparathyroidism is related to increased risk for cardiovascular diseases (CVDs), and risk is decreased by parathyroidectomy. Epicardial fat thickness (EFT) has been postulated as a new marker of CVD risk. We evaluated the impact of parathyroidectomy on EFT in patients with primary hyperparathyroidism (PHPT). Materials and methods: Thirty-four PHPT patients (29 female, 5 male) and 28 age- and sex-matched controls (19 female, 9 male) were included in the study. Demographic, anthropometric, and biochemical data were recorded both before parathyroidectomy and 6 months after the procedure. Epicardial fat thickness was measured by transthoracic echocardiography. Results: Mean age was 53.15 ± 8.44 years. Mean preoperative EFT was higher than mean EFT in the control group (0.49 ± 0.07 cm to 0.46 ± 0.08 cm, P: 0.0005), and EFT decreased after parathyroidectomy (0.49 ± 0.07 cm to 0.44 ± 0.08 cm, P: 0.0005). Systolic blood pressure and calcium, parathormone, and hsCRP levels decreased after parathyroidectomy (P < 0.05). Vitamin D levels increased (P < 0.05). Diastolic blood pressure, body mass index, carotid intima-media thickness, and HOMA-IR, fasting plasma glucose, and phosphorus levels were unchanged after parathyroidectomy (P > 0.05). Preoperatively, EFT was correlated with SBP (r: 0.360, P: 0.0285) and age (r: 0.466, P: 0.0036). Multiple linear regression used to identify independent predictors of change in epicardial fat did not find any predictor of change in epicardial fat (P > 0.05). Conclusion: EFT was decreased by parathyroidectomy in patients with primary hyperparathyroidism.However, the decrease in EFT was not correlated with any of the cardiovascular risk factors. More comprehensive studies evaluating the potential relation between PHPT and EFT need to be conducted.

The effect of parathyroidectomy on bone mineral density in primary hyperparathyroidism

Background/aim: This study aimed to investigate the change in bone mineral density (BMD) before and 1 year after parathyroidectomy in patients with primary hyperparathyroidism (PHPT). Materials and methods: The clinical and biochemical parameters and DEXA screening of patients with symptomatic PHPT (n = 28) and asymptomatic PHPT (n = 63) were investigated before and 1 year after parathyroidectomy. Results: Patients with symptomatic PHPT had a higher prevalence of nephrolithiasis (18.2% vs. 4.6%, P = 0.032) when compared to the prevalence in patients with asymptomatic PHPT. The prevalence of osteoporosis in the lumbar spine (63.0% vs. 37.5%, P = 0.026) and femoral neck (40.7% vs. 20.6%, P = 0.048) was higher in symptomatic PHPT when compared to the prevalence in asymptomatic PHPT. After parathyroidectomy, the decreases in the prevalence of osteoporosis in the lumbar spine (25.8% vs. 9.4%, P = 0.014), femoral neck (22.1% vs. 8.2%, P =0.009), and total hip (22.4% vs. 5.3%, P = 0.007) were higher in symptomatic PHPT compared to the asymptomatic PHPT group. A higher BMD gain (g/cm2) was seen in the lumbar spine (10.83% vs. 4.65%, P=0.016) and femoral neck (12.61% vs. 4.37%, P=0.005) in symptomatic PHPT compared to the asymptomatic PHPT group. Conclusion: Parathyroidectomy provided more BMD gain in the lumbar spine and femoral neck in patients with symptomatic PHPT when compared to patients with asymptomatic PHPT 1 year after parathyroidectomy.

Factors associated with glomerular filtration rate variation in primary hyperparathyroidism after parathyroidectomy

Background/aim: Prolonged hypercalcemia impairs renal function, and a reduced glomerular filtration rate (GFR) is typical in advanced primary hyperparathyroidism (PHPT). There are scarce data related to predictors of renal impairment in patients with PHPT. Hence, we aimed to evaluate changes in kidney function in PHPT patients after parathyroidectomy (PTX) and identify factors associated with GFR variation in these patients. Materials and methods: One hundred and twenty-five patients with PHPT who underwent surgery between 2012 and 2014 were enrolled in the study. Patients were divided into two groups according to GFR values: patients whose GFR was lower than 60 mL/min/1.73 m2 and higher than 60 mL/min/1.73 m2. Demographic and laboratory parameters were compared before and 6 months after parathyroidectomy. Results: Prevalence of antihypertensive drug users and patients with renal cysts and parathormone (PTH) and alkaline phosphatase levels were higher in patients with GFR of ≥60 than in GFR of <60 mL/min/1.73 m2 (P < 0.05). Systolic BP, uric acid, and magnesium were decreased in patients with GFR of ≥60, but GFR did not change in the two groups after parathyroidectomy. After parathyroidectomy, calcium and PTH decreased but 25(OH)D3 and phosphorus increased in the two groups. In multiple regression analysis, age, calcium, and baseline GFR were independent predictors of GFR variation. Parathyroid adenoma volume and urinary calcium were not independent predictors of GFR change. Conclusion: Olderage, higher preoperative calcium, and GFR were factors associated with GFR increase in PHPT patients after parathyroidectomy. Further renal impairment was prevented by parathyroidectomy in PHPT patients

VDR gene FokI polymorphism as a poor prognostic factor for papillary thyroid cancer.

This is the first study to investigate the effect of vitamin D receptor ( VDR) gene single-nucleotide polymorphisms on the clinicopathologic features of papillary thyroid cancer in Turkey. A total of 165 patients with papillary thyroid cancer and 172 controls were included in this case-control study. VDR gene single-nucleotide polymorphisms FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) were evaluated using reverse-transcription polymerase chain reaction. VDR gene polymorphisms BsmI, ApaI, and TaqI did not differ between the papillary thyroid cancer group and control group (p > 0.05, each). BsmI, ApaI, and TaqI were not associated with papillary thyroid cancer risk. The VDR gene FokI CT/TT genotype was associated with an increased papillary thyroid cancer risk (CT vs CC: odds ratio = 1.71, 95% confidence interval = 1.15-2.76, p = 0.028; TT vs CC: odds ratio = 2.44, 95% confidence interval = 1.29-4.62, p = 0.005; CT/TT vs CC: odds ratio = 1.88, 95% confidence interval = 1.20-2.96, p = 0.006; CT/CC vs TT: odds ratio = 1.80, 95% confidence interval = 1.05-3.20, p = 0.041). VDR gene polymorphisms were not in linkage disequilibrium. The FokI TT genotype was associated with having T3 and T4, stage III/IV, extra-thyroidal invasion. The FokI CT/TT or TT genotype was associated with developing N1 status, multifocality, tumor size ≥10 mm, and treatment with radioiodine therapy. Persistence/recurrence did not differ between the FokI genotypes. Carriers of the FokI T allele were at an increased risk of more advanced tumor-node-metastasis stage, greater tumor size, multifocality, and extra-thyroidal invasion of papillary thyroid cancer compared with the CC genotype. VDR gene FokI T allele and TT genotype correlated with aggressiveness of papillary thyroid cancer; thus, FokI could be useful as a poor prognostic factor to assess the high risk of papillary thyroid cancer.

The effects of metformin in type 1 diabetes mellitus.

BACKGROUND: This retrospective study investigated the effect of adding metformin to pharmacologic insulin dosing in type 1 diabetics on insulin therapy 1 year after treatment compared with patients on insulin therapy alone. METHODS: Twenty-nine adults with type 1 diabetes who had metformin added to their insulin therapy for 12 months were compared with 29 adults with type 1 diabetes who remained on insulin-alone therapy. RESULTS: Fifty-eight patients with C peptide negative-type 1 diabetics (26 females, mean age: 29.01 ± 7.03 years, BMI: 24.18 ± 3.16 kg/m2) were analyzed. Age, sex, body weight, insulin dose requirement, plasma glucose (PG), blood pressure (BP), and lipids did not differ between groups before treatment (p > 0.05). Metabolic syndrome (44.8 vs 41.4%, p > 0.05) did not differ between the metformin-insulin and insulin alone groups before treatment. Metabolic syndrome was more decreased in the metformin-insulin group than in the insulin alone group after treatment (-8.9 ± 1.3 vs. 2.5 ± 0.6%, p = 0.028). Insulin dose requirement was lower in the metformin-insulin group than in the insulin alone group (-0.03 vs. 0.11 IU/kg/d, p = 0.006). Fasting PG (-26.9 ± 54.2 vs. 0.7 ± 29.5 mg/dL, p = 0.022) and postprandial PG (-43.1 ± 61.8 mg/dL vs. -3.1 ± 40.1 mg/dL, p = 0.010) was more decreased in the metformin-insulin group than in the insulin alone group. Body weight, lipids, and HbA1c did not differ between the groups (p > 0.05). CONCLUSIONS: Metformin decreased glucose concentrations, reduced metabolic syndrome, as well as insulin dose requirement more than insulin therapy alone, 1 year after treatment. These results were independent of blood lipid improvement or weight loss, although on average weight remained decreased with metformin-insulin therapy, whereas the average weight increased with insulin therapy alone.

The effects of single high-dose or daily low-dosage oral colecalciferol treatment on vitamin D levels and muscle strength in postmenopausal women.

INTRODUCTION: Vitamin D deficiency is a common health problem. Vitamin D supplements are used to improve vitamin D status; however, there are contradictory data related to what doses to give and how often they should be given. Many studies have investigated the effects of vitamin D supplementation on muscle strength, but the results remain controversial. We aimed to compare the effects and safety of single high-dose with daily low-dose oral colecalciferol on 25(OH)D levels and muscle strength in postmenopausal women with vitamin D deficiency or insufficiency. METHODS AND DESIGN: Sixty healthy postmenopausal women who had serum vitamin D levels < 20 ng/mL (50 nmol/L) were enrolled in the study. Group 1 (n = 32) was given daily oral dosages of 800 IU vitamin D3, and group 2 (n = 28) was given a single oral dose of 300,000 IU vitamin D3. Serum vitamin D levels and muscle strengths were measured at the beginning, 4th, and 12th week. Muscle strength tests were performed at 60° using a Biodex system 3 isokinetic dynamometer. RESULTS: Pretreatment vitamin D levels did not differ between the two groups (10.2 ± 4.4 ng/mL (25,4 ± 10,9 nmol/L); 9.7 ± 4.4 ng/mL (24,2 ± 10,9 nmol/L), p > 0.05). A significant increase in vitamin D levels was observed in both groups at 4 and 12 weeks after vitamin D3 treatment. The increase in the single-dose group was significantly higher than the daily low-dosage group at the 4th week (35.9 ± 9.6 ng/mL (89,6 ± 23,9 nmol/L), 16.9 ± 5.8 ng/mL (42,1 ± 14,4 nmol/L), p = 0.01). The increase in the single-dose group was significantly higher than in the daily low dosage group at the 12th week (23.4 ± 4.7 ng/mL (58,4 ± 11,7 nmol/L), 19.8 ± 7.2 ng/mL (49,4 ± 17,9 nmol/L), p = 0.049). The quadriceps muscle strength score increased significantly in the daily group at the 4th week (p = 0.038). The hamstring muscle strength score increased significantly in the daily group at the 12th week (p = 0.037). CONCLUSION: Although daily administration routes are more effective in improving muscle strength, a single administration is more effective in increasing vitamin D levels. TRIAL REGISTRATION NUMBER: ISRCTN14226530 (04.07.2018), Name of the registry: ISRCTN registry, The study was retrospectively registered.

Screening for celiac disease in poorly controlled type 2 diabetes mellitus: worth it or not?

BACKGROUND: Recent studies have demonstrated that immune factors might have a role in the pathophysiology of insulin resistance and type 2 diabetes mellitus (T2DM). Inappropriate glycemic control in patients with T2DM is an important risk factor for the occurrence of diabetes complications. The prevalence of celiac disease (CD) is high in type 1 diabetes mellitus however, there are scarce data about its prevalence in T2DM. Our aim was to investigate the prevalence of celiac disease among insulin-using type 2 diabetes patients with inappropriate glycemic control. METHODS: IgA tissue transglutaminase antibodies (tTGA IgA) test was performed as a screening test. A total of 135 patients with T2DM whose control of glycemia is inappropriate (HbAlc value >7%) in spite of using insulin treatment for at least 3-months (only insulin or insulin with oral antidiabetic drugs) and 115 healthy controls were enrolled in the study. Upper gastrointestinal endoscopy with duodenal biopsy was performed to all patients with raised tTGA IgA or selective lgA deficiency. RESULTS: Gender, age, body mass index (BMI) and tTGA IgA, kreatinin, calcium, LDL-cholesterol (LDL-C), total cholesterol, 25-OH vitamin D3 levels were similar between groups. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, postprandial plasma glucose, urea, sodium, HbA1c, LDL-C, triglyceride, vitamin B12 levels were significantly higher in DM group (p < 0.0001). BMI, high-sensitive CRP, microalbuminuria, and AST, ALT, potassium, phosphorus levels were significantly higher in the T2DM group (p < 0.05). HDL-cholesterol and parathormone levels were significantly lower in the T2DM group (p < 0.05). Two of the 135 patients with T2DM were diagnosed with CD (1.45%). CONCLUSIONS: The prevalence of celiac disease among patients with type 2 diabetes, with poor glycemic control despite insulin therapy, is slightly higher than the actual CD prevalence in general population. Type 2 diabetic patients with inappropriate control of glycemia in spite of insulin treatment might be additionally tested for Celiac disease especially if they have low C-peptide levels.

PENTRAXIN 3 AS A NEW CARDIOVASCULAR MARKER IN ADRENAL ADENOMAS.

OBJECTIVE: Pentraxin 3 (PTX3) is an acute-phase glycoprotein, which is increased in patients with cardiovascular disease (CVD) and considered as a predictor of CVD in the general population. Both functional and nonfunctional adrenal tumors are associated with a higher risk of cardiovascular events and mortality. We aimed to investigate plasma PTX3 levels in patients with functioning and nonfunctioning adrenal tumors and determine its relationship with cardiovascular risk factors. METHODS: Twenty-one patients with functional adrenal tumors (11 pheochromocytomas, 9 Cushing syndrome, and 1 primary hyperaldosteronism), 28 patients with nonfunctional adrenal incidentalomas, and 40 healthy controls were enrolled in the study. Serum PTX3 levels were measured using a human PTX3 enzyme-linked immunosorbent assay. RESULTS: PTX3 concentrations were significantly higher in the adrenal tumor group compared with the control group (3,001.64 ± 374.64 pg/mL vs. 1,173.59 ± 168.89 pg/mL; P<.001). PTX3 concentrations were positively correlated with carotid intima media thickness (CIMT) (r2, 0.464; P<.001), high-sensitivity C-reactive protein (hsCRP) (r2, 0.551; P<.001), diastolic blood pressure (r2, 0.334; P = .003), systolic blood pressure (r2, 0.312; P = .006), and urinary metanephrine concentrations (r2, 0.320; P = .041). Serum PTX3 concentrations in patients with functional adrenal tumors and comorbidities including hypertension, diabetes mellitus, or CVD were higher than in those without comorbidities (3,654.54 ± 447 pg/mL vs. 1,026.96 ± 447.97 pg/mL; P = .008). CONCLUSION: We found that serum PTX3 concentrations increased in both functional and nonfunctional adrenal tumors. PTX3 levels were correlated with cardiovascular risk factors such as CIMT, hsCRP, and blood pressure. ABBREVIATIONS: BMI = body mass index; CIMT = carotid intima-media thickness; CRP = C-reactive protein; CT = computed tomography; CVD = cardiovascular disease; FGF2 = fibroblast growth factor 2; hsCRP = high-sensitivity C-reactive protein; PA = primary hyperaldosteronism; PTX3 = pentraxin 3.

Metabolic syndrome and Visceral Adiposity Index in non-functional adrenal adenomas.

Objective: We aimed to identify metabolic dysfunction in non-functioning adrenal adenomas (NFAAs) and Visceral Adiposity Index (VAI) predictability in the practical estimation of metabolic syndrome (MetS) in NFAAs. Subjects and methods: 134 NFAA patients and 68 control subjects matched for age, sex, and body mass index (BMI) were included in the study. After physical, biochemical, and endocrine evaluation, IDF and NCEP ATP III criteria were used to determine MetS. HOMA-IR and VAI were calculated for both study group subjects. Results: MetS was significantly higher in the NFAA patients. The incidence of MetS by IDF and NCEP criteria was 52.9%,48.5% in the NFAI and 32.3%,30.8% in the control group (p < 0.01, p = 0.02). The risk of MetS was increased in NFAA (75.6 vs. 24.4%, p = 0.017, OR = 1.34, 95% CI = 1.06-1.68). Glucose, HOMA IR, hypertension, and VAI were significantly increased in NFAA patients. The risk of MetS was independently associated with high VAI (79.2 vs. 20.8%, p = 0.001, OR = 2.22; 95% CI = 1.70-2.91). Conclusion: MetS, insulin resistance, and VAI are more prevalant in NFAA patients than in healthy individuals. VAI can be used with high specificity to estimate MetS in NFAA patients.

Visceral Adiposity Index, Triglyceride/High-Density Lipoprotein Ratio, and Lipid Accumulation Product Index to Discriminate Metabolic Syndrome Among Adult Type 1 Diabetes Patients.

Background: Obesity and metabolic syndrome (MetS) are growing problems in type 1 diabetic patients; these can influence clinical complications and also treatment regimens. Visceral adipose tissue inflammation plays an important role in cardiovascular complications. Visceral adiposity index (VAI), lipid accumulation product index (LAP), and triglyceride (TG)/high-density lipoprotein (HDL) ratio have been strongly correlated with insulin resistance and visceral adipose tissue amount in previous studies. Therefore, this study aimed to investigate and compare the usefulness of these indices to detect MetS in patients with type 1 diabetes mellitus (T1DM). Materials and Methods: Patients with T1DM and gender- and age-matched controls were included in this cross-sectional study. MetS was defined using both International Diabetes Federation (IDF), World Health Organization (WHO), and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. T1DM patients were divided into two groups according to the IDF criteria. VAI, LAP, and TG/HDL ratio were calculated for all patients. Groups were compared accordingly. Results: One hundred twenty-six patients with T1DM were included in the study. Increased VAI was observed in association with MetS. Patients with MetS (32.2%) had the highest VAI than healthy controls (8.21 ± 8.86; 3.49 ± 2.73, respectively, P < 0.01). For determining MetS in type 1 diabetes, the cutoff value of VAI was 2.65 [area under the curve (AUC) = 0.837, sensitivity 80.0%, specificity 72.8%], LAP was 27.57 (AUC = 0.842, sensitivity 80.0%, specificity74.0%), TG/HDL ratio was 2.18 (AUC = 0.826, sensitivity 75.0%, specificity 74.0%), each P < 0.001. Conclusions: MetS becomes increasingly common in T1DM. VAI, LAP, and TG/HDL ratio were useful for predicting MetS in patients with T1DM.

Impact of lockdown COVID-19 on metabolic control in type 2 diabetes mellitus and healthy people.

AIMS: The impact of prolonged COVID-19 lockdown on metabolic control in type 2 diabetes patients and healthy individuals has not exactly been known. We aimed to evaluate the change in body weight and metabolic control in type 2 diabetic and non-diabetic healthy subjects during the prolonged lockdown period. METHODS: Diabetic (n = 85), and age-and sex-matched non-diabetic subjects (n = 55) were included in this prospective study. Body mass index and metabolic parameters were compared between before and 6th months of lockdown. Changes in values were evaluated using the difference before and after lockdown. RESULTS: Age (54.81 ± 10.53 vs. 52.61 ± 4.88 years), gender (female, 68.2% vs. 56.4%) and, BMI (33.44 ± 6.48 vs. 31.63 ± 3.57 kg/m2) were similar between groups (p > 0.05). Before and after lockdown, BMI increased both in non-diabetic (0.54 ± 0.95 kg) and diabetic groups (1.91 ± 5.48 kg) (p > 0.05). Increase in HbA1c was more in diabetic than in non-diabetic groups (0.71 ± 1.35 vs. 0.02 ± 0.19%, p = 0.002). Glucose, LDL-C, and TG increased in diabetic (39.69 ± 74.69, 7.60 ± 34.33, and 58.21 ± 133.54 mg/dl, p < 0.05) whereas non significantly decreased in non-diabetic group (-0.51 ± 4.40, -3.52 ± 14.53, and -6.47 ± 41.77 mg/dl, respectively. After adjusting BMI, increase in blood glucose (p = 0.021), HbA1c (p = 0.018), and TG (p = 0.041) levels were more in diabetic than non-diabetic group. Duration of diabetes was an independent predictor of the change in HbA1c (OR: 1.2, 95% CI = 1.1-1.8, p = 0.032). CONCLUSIONS: Body weight gain was observed in type 2 diabetic patients and healthy subjects. This is the first study to show that prolonged lockdown COVID-19 pandemic worsened glucose regulation and increased TG level in diabetes mellitus independent of weight gain.

Circulating sTweak is associated with visceral adiposity and severity in patients with obstructive sleep apnea syndrome.

Hypoxia is linked to an inflammatory imbalance in obstructive sleep apnea syndrome (OSAS). Circulating soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) is a cytokine that regulates inflammation and insulin resistance in adipose tissue. This study first investigated sTWEAK concentrations in patients OSAS and evaluated associations between sTWEAK concentrations and visceral adiposity, metabolic dysfunction, and hypoxia observed in OSAS. Forty age, sex, and body mass index-matched patients with simple habitual snoring (HSS) and 70 patients with OSAS were included. Patients were divided according to OSAS severity: mild-moderate (apnea-hypopnea index, AHI 5-30 events/h) and severe (AHI ≥ 30 events/h). Anthropometric data, glucose metabolism, visceral fat (VF) ratio, and sTWEAK levels were compared. sTWEAK levels were higher in the OSAS group than in the HSS group (931.23 ± 136.48 vs. 735.22 ± 102.84 ng/L, p = 0.001). sTWEAK levels were higher in severe OSAS than in mild-moderate OSAS (1031.83 ± 146.69 vs. 891.01 ± 110.01 ng/L, p = 0.002. When we evaluated the sTWEAK value and AHI, VF ratio, total cholesterol, blood pressure, homeostasis model of assessment-insulin resistance, and high-sensitivity C-reactive protein using multiple regression analysis, a significant correlation was found between sTWEAK levels and AHI (p < 0.001). It was found that sTWEAK levels were not correlated with glucose metabolism and VF ratio. Increased circulating sTWEAK levels were associated with the severity of OSAS. High sTWEAK levels were correlated with increased AHI. sTWEAK concentrations are linked to severe OSAS.