Association of Dipeptidiyl Peptidase-4 Inhibitors and Bullose Pemphigoid: A Report of Four Cases.

Dipeptidyl-peptidase 4 inhibitors (DPP4i) are commonly used as antidiabetic medications. Although these drugs are generally recognized for their favorable clinical safety profile, emerging evidence points to the potential for adverse events associated with DPP4i. Notably, cases of bullous pemphigoid (BP) linked to DPP4i therapy have recently been documented in the medical literature. This report presents four cases of BP in elderly patients resulting from DPP4i treatment, involving two cases with ligandliptin and two with vildagliptin use. Successful remission was achieved in all cases through discontinuation of the implicated medication and implementation of topical corticosteroid therapy. It is imperative for clinicians to be vigilant about the potential risk of BP development when employing DPP4i drugs, particularly in the context of elderly patients with diabetes.

Groundwater potential assessment based on GIS-based Best-Worst Method (BWM) and Step-Wise Weight Assessment Ratio Analysis (SWARA) Method.

In this study, the most suitable areas in terms of groundwater potential within the borders of the adjacent area of Sivas Municipality (Sivas/Turkey) were determined with the help of Geographic Information System (GIS)-based Best-Worst Method (BWM) and Step-Wise Weight Assessment Ratio Analysis (SWARA) methods. Slope, drainage density, Topographic Position Index (TPI), lineament density, lithology, soil types, land use, geomorphology, and rainfall criteria were selected to determine groundwater potential areas. These criteria were weighted with the help of BWM, SWARA, and BWM-SWARA methods and the Groundwater Potential Index (GPI) was calculated according to the weighted linear combination method. According to the calculated GPI values, the groundwater potential of the study area was represented as "excellent," "very good," "good," "moderately good," "low," and "very low." According to all three methods, areas in the "excellent" class constituted 10.99%, 8.40%, and 11.16% of the study area, respectively, while areas in the "very low" class covered 8.33%, 7.98%, and 9.04% of the study area, respectively. The linear correlation coefficient (R2) values of the BWM, SWARA, and BWM-SWARA methods were calculated as 0.80, 0.82, and 0.75, respectively, while the area under the curve (AUC) values were determined as 0.83, 0.79, and 0.81, respectively. These results showed that the accuracy of the model was "very good" overall. As a result, groundwater potential mapping created for the study area will contribute to better development of groundwater resources and water management planning.

Assessment of subclinical cardiovascular alterations in nonfunctioning adrenal incidentalomas.

BACKGROUND: Adrenal incidentalomas have been associated with increased cardiovascular risk and have a prevalence as high as 10%. This study aims to evaluate carotid- intima media thickness (CIMT), left ventricular mass, and epicardial adipose tissue thickness in nonfunctioning adrenal incidentaloma patients and compare their results with healthy controls. METHODS: Patients who were referred to the endocrinology clinic for adrenal incidentaloma between 2014 and 2019 were assessed with 1 mg dexamethasone suppression test, 24-h urine metanephrines and normetanephrines, plasma aldosterone to renin ratio. Age and gender-matched subjects without an adrenal mass formed the control group. Left ventricular mass, epicardial adipose tissue thickness, and CIMT of both groups were measured. RESULTS: A total of 41 adrenal incidentaloma patients (21 female, 52.5%) and 40 healthy controls (19 female, 46.3%) were included in the study. Patients with adrenal incidentalomas had increased CIMT. No differences were observed in left ventricle mass or epicardial adipose tissue thickness. There was no correlation between CIMT and adenoma size or serum cortisol (p = 0.2 and p = 0.6, respectively). There was a statistically significant correlation between CIMT and age (p = 0.016, r = 0.295). HBA1c (p = 0.001) and age (p = 0.05) were independently associated with CIMT in regression analysis. DISCUSSION: Adrenal incidentaloma patients need to be monitored for cardiac dysfunction. CIMT may be used to evaluate adrenal incidentaloma patients for early cardiovascular risk.

Association of Epicardial Adipose Tissue Thickness with Cardiovascular Risk in Acromegaly.

Objective: Acromegaly is a rare disease associated with increased mortality. Reports on coronary artery disease in acromegaly are controversial. This study aimed to investigate the possible association of epicardial adipose tissue thickness with cardiovascular risk in patients with acromegaly. Methods: The study included 38 patients followed up with the diagnosis of acromegaly and 29 healthy controls. Patients with acromegaly were divided into controlled and uncontrolled acromegaly groups based on insulin-like growth factor-1 levels. Epicardial adipose tissue thickness measurements were obtained from chest computed tomography, and laboratory data were extracted from patient files. Results: Twenty-nine patients (76.3%) had controlled acromegaly. Eleven patients with acromegaly had diabetes mellitus (28.9%), 18 (47.4%) had hypertension, and 27 (71%) had a concomitant chronic disease. Epicardial adipose tissue thickness was significantly increased in the acromegaly group (p<0.001). No significant difference was observed between the controlled and uncontrolled acromegaly groups in terms of the epicardial adipose tissue thickness. Age was the only parameter that was significantly correlated with the epicardial adipose tissue thickness. When the Framingham risk score was calculated, the 10-year cardiovascular risk of patients with acromegaly was 5.63%. Conclusions: The epicardial adipose tissue thickness is increased in acromegaly. However, this increase may not have clinical relevance in terms of cardiovascular risk.

Status of Weight Change, Lifestyle Behaviors, Depression, Anxiety, and Diabetes Mellitus in a Cohort with Obesity during the COVID-19 Lockdown: Turk-Com Study Group.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to a lockdown period. Confinement periods have been related to unhealthy lifestyle behaviors. Our study aimed to determine weight change, changes in eating and exercise habits, the presence of depression and anxiety, and diabetes mellitus (DM) status in a cohort of patients with obesity. METHODS: The study was undertaken in nine centers of Collaborative Obesity Management (COM) of the European Association for the Study of Obesity (EASO) in Turkey. An e-survey about weight change, eating habits, physical activity status, DM status, depression, and anxiety was completed by patients. The International Physical Activity Questionnaire (IPAQ) score was used to determine physical activity in terms of metabolic equivalents (METs). A healthy nutrition coefficient was calculated from the different categories of food consumption. The Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) Questionnaire  were used for determining depression and anxiety, respectively. RESULTS: Four hundred twenty-two patients (age 45 ± 12.7 years, W/M = 350/72) were included. The healthy nutrition coefficient before the pandemic was 38.9 ± 6.2 and decreased to 38.1 ± 6.4 during the pandemic (p < 0.001). Two hundred twenty-nine (54.8%) patients gained weight, 54 (12.9%) were weight neutral, and 135 (32.3%) lost weight. Patients in the weight loss group had higher MET scores and higher healthy nutrition coefficients compared with the weight gain and weight-neutral groups (p < 0.001). The PHQ and GAD scores were not different between the groups. Percent weight loss was related to healthy nutrition coefficient (CI: 0.884 [0.821-0.951], p = 0.001) and MET categories (CI: 0.408 [0.222-0.748], p = 0.004). One hundred seventy patients had DM. Considering glycemic control, only 12 (8.4%) had fasting blood glucose <100 mg/dL and 36 (25.2%) had postprandial BG <160 mg/dL. When patients with and without DM were compared in terms of dietary compliance, MET category, weight loss status, PHQ-9 scores, and GAD-7 scores, only MET categories were different; 29 (11.7%) of patients in the nondiabetic group were in the highly active group compared with 5 (2.9%) in the diabetic group. CONCLUSION: The COVID-19 lockdown resulted in weight gain in about half of our patients, which was related to changes in physical activity and eating habits. Patients with DM who had moderate glycemic control were similar to the general population in terms of weight loss but were less active.

Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients.

OBJECTIVE: Thyroid-stimulating hormone (TSH) suppression treatment can induce signs and symptoms of hyperthyroidism and hypothyroidism due to inappropriate treatment or poor compliance to the treatment. The current study aimed to investigate TSH levels, frequency of being on target TSH, adherence to levothyroxine (LT4) suppression treatment in differentiated thyroid cancer (DTC) patients after surgery in a multicentric setting. DESIGN AND PATIENTS: This multicentric cross-sectional study was conducted at 21 medical centres from 12 cities in Turkey. DTC patients followed at least one year in the same center included in the study. Clinical data, serum TSH, free thyroxine (FT4), thyroglobulin (Tg) and anti-Tg levels were recorded during the most recent visit. Body mass index, systolic and diastolic blood pressures, pulse rate were measured. LT4 doses were recorded and doses per kilogram of bodyweight were calculated. Pill ingestion habits recorded and adherence to the therapy were evaluated using the Morisky Medication Adherence Scale and categorized as good, moderate or poor compliant based on their scores. Risk stratification forpredicting the disease persistance and/or reccurence was assessed using the American Joint Committee on Cancer-7th edition thyroid cancer staging calculator. TSH serum concentrations were classified as severe suppression (TSH < 0.01 mU/L), moderate suppression (TSH: 0.01-0.1 mU/L), mild suppression (TSHL 0.1-0.5 mU/L), euthyroid (TSH: 0.5-4 mU/L) and hypothyroid (TSH > 4 mU/L). TSH levels can also be classified as on being on target, under the target, or beyond over the target, according to the American Thyroid Association recommendations. RESULTS: A group of 1125 patients (F/M: 941/184, 50.7 ± 11.7 years) were included in the study. The mean LT4 daily dosage was 132.4 ± 39.6 mcg/day. TSH levels showed severe suppression in 99 (%8.8) patients, moderate suppression in 277 (%24.6) patients and mild suppression in 315 (%28) patients and euthyroid range in 332 (%29.5) patients and hypothyroid range in 97 (8.6%). TSH levels were in target in 29.2% of the patients 20.4% of the patients were undertreated, 50.4% overtreated. The daily LT4 dose and LT4 dose/kg were significantly higher in the severe suppression group (p < .001, p < .001). According to the Morisky scale, 564 patients (50.1%) were good compliant, 368 patients (32.7%) were moderate compliant, and 193 patients (17.1%) were noncompliant. Patients with poor compliance need a higher dose of LT4 compared to the good compliance group (p < .001). TSH levels of patients with good compliance were 0.67 ± 1.96 mU/L and TSH with poor compliance was 2.74 ± 7.47 mU/L (p < .001). TSH levels were similar in patients on fixed and alternating dosages. CONCLUSION: In 29.2% of the DTC patients, serum TSH levels were at target levels. Remaining of the study group have TSH levels under or over treatment range, exposing the patient to medication side effects. Majorty of the study group 82.8% have good or moderate adherence to LT4 therapy. Reaching TSH targets requires simplified and applicable guidelines and following the guideline recommendations.

The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.

Inflammatory markers are associated with the progression of gestational diabetes to metabolic syndrome.

The progression of gestational diabetes mellitus (GDM) to metabolic syndrome (MetS) is associated with systemic inflammation. The aim of this study was to compare the levels of inflammatory markers in former GDM patients with and without MetS. Medical records were screened retrospectively for patients who were diagnosed with GDM 10 (±2) years ago. Former GDM patients were invited to the hospital for an assessment of their current health status. Of 52 women with former GDM, 27 (52%) had MetS. C-reactive protein (CRP), interleukin-6 and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in the MetS group while adiponectin was significantly lower (p < .001, p = .037, p = .002 and p = .013, respectively). There was no significant difference in plasma levels of visfatin and tumour necrosis factor-α. Interleukin-6, CRP, PAI-1 and adiponectin may be used as biomarkers to detect MetS in the pre-clinical phase. With timely diagnosis, early interventions can be implemented. IMPACT STATEMENTWhat is already known on this subject? The progression of 'gestational diabetes mellitus' to 'metabolic syndrome' is associated with systemic inflammation. Up to half of cases with former gestational diabetes mellitus (GDM) eventually progress to metabolic syndrome (MetS).What do the results of this study add? Interleukin-6, C-reactive protein, plasminogen activator inhibitor-1 and adiponectin may be used as biomarkers to detect MetS in the pre-clinical phase.What are the implications of these findings from clinical practice and/or further research? The progression of GDM to MetS is associated with systemic inflammation. Potential therapies should therefore target this inflammatory state. Interleukin-6, C-reactive protein, plasminogen activator inhibitor-1 and adiponectin may be used as biomarkers to detect MetS in the pre-clinical phase. With timely diagnosis, early interventions and lifestyle changes can be implemented to prevent morbidity and mortality associated with full-blown MetS.

The value of parathyroid scintigraphy on lesion detection in patients with normocalcemic primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine diseases. Most of the patients with PHPT are asymptomatic, and only 20% of them become symptomatic with increasing levels of calcium. It has been reported that normocalcemic primary hyperparathyroidism (NPHPT) may be the incipient period of PHPT where calcium (Ca) levels are in normal range, and it may advance to overt PHPT. Early diagnosis of PHPT is important in order to prevent its complications. In this retrospective study, we aimed to evaluate the role of 99mTc-MIBI parathyroid scintigraphy on lesion detection in patients with NPHPT. MATERIAL AND METHODS: The parathyroid scintigraphy database was reviewed retrospectively in patients with PHPT. 117 patients who underwent 99mTc-MIBI scintigraphy were recruited to the study. Serum calcium level above 10.5mg/dl was considered as hypercalcemia. RESULTS: A total of 117 patients (female/male:98/19) mean serum PTH levels (mean±SD) were 149±97pg/ml in normocalcemic group (Ca:9.6±0.6mg/dl, n:38) and 189±135pg/ml in hypercalcemic group (Ca:11.4±0.6mg/dl, n:79) (p:0.072). The sex and ages were not different between the scintigraphy positive and negative groups, but the lesion detection rates with parathyroid scintigraphy were 42% in normocalcemic group and 81% in hypercalcemic group (p<0.0001). CONCLUSIONS: Several factors including serum Ca, the imaging protocol, existence of multiglandular disease, the size and MIBI biokinetics of the adenoma may influence lesion detectability in parathyroid scintigraphy. Although high serum Ca level is an important parameter in predicting its success, parathyroid scintigraphy remains a valuable diagnostic method even in patients with NPHPT.

Effects of androgen deprivation therapy on metabolic markers and bioelectrical impedance analyze in prostate cancer patients.

INTRODUCTION AND OBJECTIVES: Prostate cancer (PCa) is the most widespread malignancy within men. Androgen deprivation therapy (ADT), which is the central component of advanced PCa treatment, causes side effects. The goal of this study was to examine the metabolic changes and bioelectrical impedance analysis differences in PCa patients who received ADT. MATERIALS AND METHODS: After age-related match-pair analysis, a total of 519 patients with PCa and control group who had benign disease were enrolled in the study. Biochemical blood parameters and TANITA measurements were recorded for all patients. Patients were categorized into three groups, ADT group (Group 1, n=124) and non-ADT group (Group 2, n=248), control group (Group 3, n=147). RESULTS: The mean age of groups was similar. Body mass index, waist circumference, body fat mass and fat ratio, which were among the TANITA parameters, were higher in group 1 (p<0.05). Total cholesterol, high density lipoprotein, non- high density lipoprotein, triglycerids and fasting blood glucose values were also higher in group 1 (p<0.05). Myocardial infarction and metabolic syndrome rates were also higher in this group. CONCLUSIONS: While the use of ADT is manifested by an increase in fat mass and fat ratio in body composition, it negatively affects waist circumference measurements. It is associated with metabolically unfit body composition changes that predispose to diabetes mellitus and may increase cardio-vascular disease. For this reason, it is necessary to be careful about metabolic and endocrinological diseases in long-term therapy.

The Relationship of Thyroid Functions with ADMA, IMA, and Metabolic Laboratory Parameters in Euthyroid Adults with and without Autoimmune Thyroiditis.

OBJECTIVE: To investigate the relationship between thyroid functions and asymmetric dimethylarginine (ADMA), ischemia-modified albumin (IMA), and other metabolic laboratory markers in euthyroid adults and whether narrower thyroidal targets are required for lower metabolic risk. MATERIALS AND METHODS: Thyroid functions, antithyroid autoantibodies, and metabolic parameters were measured for 115 patients. Forty-seven had autoimmune thyroiditis (AIT). Analyses were performed according to cutoff values of 1, 2, 2.5, and 3 mIU/L for thyrotropin, 0.84 ng/dL for free thyroxine (fT4), and 3.59 ng/dL for free tri-iodothyronine (fT3). RESULTS: There was no relationship between thyrotropin and fT3 cutoff values and metabolic parameters. Only C-reactive protein was lower in the group with thyrotropin ≤2.5 µIU/L. A weak positive correlation was found between fT4 with IMA and IMA corrected for albumin (r = 0.187, P = .05; r = 0.204, P = .034, respectively). There was no difference between AIT and the metabolic laboratory parameters examined in the study. CONCLUSION: This study is the first to evaluate ADMA in AIT. Narrower thyroid function targets are not required for better metabolic control in euthyroid adults.

Risk factors predicting the development of diabetes mellitus and metabolic syndrome following gestational diabetes mellitus

Background/aim: To determine risk factors associated with the development of insulin resistance, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) in gestational diabetes mellitus (GDM) patients 10 years after giving birth. Materials and methods: Medical records of patients with former GDM were screened. Eligible patients were invited to the hospital to obtain information about their present health status. Patients with pregestational diabetes and patients with multiple pregnancies were excluded. A total of 67 women formed the study group. American Diabetes Association (ADA) and International Diabetes Federation (IDF) criteria were used to define T2DM and MetS, respectively. Results: A total of 27 patients developed diabetes (40.3%) and 35 patients (52%) developed MetS. T2DM developed, on average, 4.8 years after delivery. There was a significant difference between diabetic and nondiabetic patients in terms of insulin use during pregnancy (P < 0.001). Women who developed diabetes within 10 years after giving birth were observed to have significantly higher fasting plasma glucose on oral glucose tolerance test during their pregnancy (P = 0.007). Current and pregestational body mass indices had a significant effect on the development of MetS (P = 0.003 and P = 0.027, respectively). Conclusion: In this long-term study, we found that patients with high fasting plasma glucose (FPG) and insulin requirement during pregnancy are at an increased risk of developing T2DM, while pregestational obesity is predictive of progression to MetS. Identifying and targeting high-risk individuals may delay and possibly prevent T2DM and MetS.

Serum zonulin level is not elevated in patients with polycystic ovary syndrome without metabolic syndrome.

AIM: Polycystic ovary syndrome (PCOS) is a complex disorder with gynecological, metabolic and carcinogenic effects. Increased intestinal permeability is related with obesity, insulin resistance, type 1 and 2 diabetes mellitus. The existence of such a relationship between PCOS and intestinal permeability has come to an end. Zonulin can change intestinal permeability, and this effect is reversible. We studied the relation between zonulin and the hormonal and metabolic parameters of PCOS. METHOD: A total of 45 women with PCOS and 17 healthy women were included in the study. Histories were taken from all the participants, body mass indexes were calculated, and biochemical tests and suprapubic over ultrasonography were made. Zonulin was studied with enzyme-linked immunosorbent assay. RESULTS: Serum zonulin levels were similar between PCOS and control groups (p = 0.893). In all participants, there were negative correlations between zonulin and the total cholesterol, LDL-cholesterol, triglycerides and non-HDL-cholesterol (respectively, p = 0.00, 0.018, 0.004, 0.002), there were boundary correlations with age and total cholesterol/HDL-cholesterol (respectively, p = 0.052 and 0.058). No statistically significant was detected in the PCOS group except negative correlation between zonulin and age (p = 0.046), boundary correlation between zonulin and total cholesterol/HDL-cholesterol (p = 0.064). CONCLUSION: PCOS patients did not have metabolic syndrome. Zonulin was not higher in PCOS then controls, and it had only negative relation with age. The negative relation between zonulin and some metabolic parameters in all participants was not detected in PCOS group. So zonulin is not a useful molecule for the diagnosis of PCOS without metabolic syndrome.

Evaluation of groundwater quality in Sivas province (Turkey) using water quality index and GIS-based analytic hierarchy process.

The main purpose of the research was to evaluate the groundwater quality in wet and dry seasons of the study area and determine the areas with high water quality. First, diagrams commonly used in groundwater quality assessment were prepared. Water quality index (WQI) values were calculated by using water quality parameters, spatial distribution maps of WQI and water quality parameters were created by using Geographical Information System (GIS). Groundwater quality mapping was performed with the help of GIS-based analytic hierarchy process. The obtained findings showed that, 91.66% and 77.07% of groundwater samples respectively received at wet and dry seasons have been suitable for drinking. Groundwater quality of around Sivas city center has been rated with 'excellent' water quality. The most important factors affecting the water quality of the research area were the lithological characteristics of the area and agricultural uses. TDS, NO3, SO4, Cr and As are the parameters that negatively affect water quality.

Novel spatial filter for SSVEP-based BCI: A generated reference filter approach.

Steady state visual evoked potential (SSVEP)-based brain computer interface (BCI) systems can be realised using only one electrode; however, due to the inter-user and inter-trial differences, the handling of multiple electrode is preferred. This raises the problem of evaluating information from multiple electrode signals. To solve this problem, we developed a novel spatial filtering method (Generated Reference Filter) for SSVEP-based BCIs. In our method an artificial reference signal is generated by a combination of reference electrode signals. Multiple regression analysis (MRA) was used to determine the optimal weight coefficients for signal combination. The filtered signal was obtained by subtraction. The method was tested on a SSVEP dataset and compared with minimum energy combination and common reference methods, namely the surface Laplacian technique and common average referencing. The newly developed method provided more effective filtering and therefore higher SSVEP detection accuracy was obtained. It was also more robust against subject-to-subject and trial-to-trial variability as the artificial reference signal was recalculated for each detection round. No special preparation is required, and the method is easy to implement. These experimental results indicate that the proposed method can be used confidently with SSVEP-based BCI systems.

The effects of three regimens of cholecalciferol (vitamin D3) supplementation on vitamin D deficiency in non-obese and obese females.

INTRODUCTION: Vitamin D deficiency is a common health problem worldwide and tends to be a risk factor for all-cause mortality. We evaluated the effect of continuous low-dose oral daily and loading dose of oral weekly and loading monthly intramuscular (IM) vitamin D3 regimens on circulating levels of total 25(OH)D and in vitamin D deficient females, and between non-obese and obese subgroups. MATERIAL AND METHODS: A total of 231 vitamin D deficient females were included to the study. According to treatment regimen, patients were divided into three groups: daily continuous oral, loading dose of weekly oral and monthly intramuscular. All patients in treatment groups were divided into non-obese (105) and obese (126) groups. Serum 25(OH)D and parathormone (PTH) levels were evaluated at baseline and at the third and sixth month. RESULTS: In obese patients oral weekly loading regimen and in non-obese patients oral daily continuous regimens were found to be more potent. Baseline PTH levels decreased when compared with the third and sixth months (p < 0.001), but between the third and sixth months it was not changed (p = 0.783). CONCLUSIONS: Oral daily regimen in non-obese patients and loading weekly oral regimen in obese patients were more effective in achieving the target levels of 25(OH)D concentration above 30 ng/ml and provided a stable plasma vitamin D concentration over a long period of time.