Search

It has been demonstrated that bone mineral density (BMD) loss is substantial within the first 12 months after allogeneic hematopoietic stem cell transplantation (alloHSCT). Declines in BMD showed a disproportionate cortical bone loss even though trabecular bone is metabolically more active than cortical bone. This finding suggests a unique mechanism. However, the structural bone deficits after alloHSCT have not been well characterized. The trabecular bone score (TBS) has emerged as a method to assess bone microarchitecture. The aim of this study was to evaluate the changes in BMD and TBS in patients who received alloHSCT with follow-up of two years. All patients 18 years and older who received alloHSCT between 2009 and 2015 at Seoul St. Mary's Hospital, Korea were included. They were segregated into a first group (A, n = 24) that was evaluated for BMD at the time of alloHSCT and 12 months posttransplant and a second group (B, n = 44) that was evaluated for BMD at 12 and 24 months following alloHSCT. Subjects in group A experienced a decrease in BMD at the femoral neck and total hip between the time of transplantation and 12 months posttransplantation: 0.056 ± 0.057 (5.48%) and 0.072 ± 0.063 (6.84%), respectively. Subjects in group B experienced an increase in BMD at the lumbar spine and total hip between 12 and 24 months post-alloHSCT: 0.047 ± 0.064 (4.90%) and 0.017 ± 0.045 (2.16%), respectively. In group A, TBS at 12 months post-alloHSCT decreased 0.028 ± 0.067 (1.92%) from the baseline (p = 0.086). In group B, TBS at 24 months post-alloHSCT increased 0.010 ± 0.049 (0.78%) from the 12 months post-alloHSCT evaluation (p = 0.149). TBS change was positively associated with BMD changes at all measured sites. The cumulative dose of glucocorticoid therapy was associated with loss of BMD at all measured sites and TBS. In addition, the dose of total body irradiation (TBI) was negatively associated with TBS. In summary, this study delineated longitudinal microarchitectural changes in bone structure occurring in the context of alloHSCT. TBS change per 12 months was insignificant during the two years following alloHSCT. Therefore, our data represented disproportionate cortical bone loss in the context of the microarchitecture. • Before alloHSCT, 29% of patients had a partially degraded TBS. • TBS at 12 and 24 months post-alloHSCT insignificantly changed -1.92% and +0.78% from the baseline and 12 months post-alloHSCT, respectively. • TBS change was associated with BMD changes at all measured sites, cumulative dose of glucocorticoids, and TBI. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We aim to investigate erythropoietin (EPO) response to anemia and its association with autonomic neuropathy in type 2 diabetic patients without advanced renal failure. Methods: A cross-sectional study was conducted on 211 type 2 diabetes mellitus patients without advanced renal failure [estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m2]. The response of EPO to anemia of type 2 diabetic patients without advanced renal failure was compared with those of nondiabetic control subjects. Autonomic nerve function was assessed using three cardiovascular tests (deep breathing, the Valsalva maneuver, and lying-to-standing). The results of each test were scored as 0 if normal, 1 if borderline, and 2 if abnormal. Autonomic neuropathy was diagnosed when a total score of the tests was 2 or more. Results: Fifty-eight patients were anemic; compared with nonanemic patients, they had a longer duration of diabetes (16.69±10.11 vs. 10.67±8.41 years, P<.001), lower eGFR (66.43±16.30 vs. 81.74±19.49 ml/min/1.73 m2, P<.001), and higher cardiovascular autonomic neuropathy score (3.17±1.95 vs. 1.79±1.72, P<.001). Serum EPO level was weakly correlated with hemoglobin (Hb) level (r=−.085, P<.001). However, the slopes of regression lines between EPO and Hb levels differed significantly between type 2 diabetic patients and nondiabetic control subjects (−0.0085 vs. −0.255, P=.008). Multiple linear regression analysis revealed that cardiovascular autonomic neuropathy score was independently related to Hb (P<.001) or EPO level (P=.052). Conclusions: Autonomic neuropathy is associated with a blunted EPO response to anemia in type 2 diabetic patients without advanced renal failure. [Copyright &y& Elsevier]

Abstract: Changes in bone and mineral metabolism that occur after gastrectomy have long been recognized. Gastrectomy has been identified as a risk factor for decreased bone mass and the increased fracture incidence. Previous investigations concerning postgastrectomy bone disease have been observational studies. No prospective studies have been reported that quantify the amount of bone loss after gastrectomy within the same patients. This study investigated 46 patients undergoing gastrectomy for gastric adenocarcinoma and analyzed 36 patients (58.1±10.8 years, 24 men and 12 women) who had dual energy X-ray absorptiometry (DXA) performed before and 1 year after gastrectomy. Systemic adjuvant chemotherapy was administered to 14 patients. Blood was sampled from all patients to determine serum calcium, phosphorous, and bone turnover marker levels before gastrectomy and at 1, 3, 6 and 12 months after surgery and for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D levels before and 12 months after surgery. The mean bone loss in the lumbar spine, total hip, femoral neck, and trochanter, which was calculated as the percentage change from the baseline to the level measured at 12 months, was 5.7% (P <0.01), 5.4% (P <0.01), 6.6% (P <0.01) and 8.7% (P <0.01), respectively. Bone loss was generally greater in the group receiving chemotherapy. The serum calcium and phosphorous levels were not changed significantly and remained within the normal range throughout the observation period. After gastrectomy, the level of ICTP increased and reached a peak at 1 and 3 months, and progressively declined to baseline by 12 months. The osteocalcin levels were not coupled to an increase before 6 months. The level of 25-hydroxyvitamin D at 12 months postgastrectomy was not significantly changed compared to the baseline, however, the PTH levels increased by a mean of 63.6% at 12 months compared to the baseline (P <0.01). Significant correlations were found between the percent change in the BMD at the lumbar spine and total hip and the percentage change for the PTH level from their baselines to 12 months. The changes in the BMD at total hip, femoral neck, and trochanter also correlated to the change in body weight at 12 months. The data obtained by this study provides evidence that profound bone loss occurs in the setting of a bone remodeling imbalance during the early postgastrectomy period and allows the speculation that the gastrectomy related bone loss may be partially due to an overproduction of PTH. [Copyright &y& Elsevier]

Abstract: This study prospectively investigated the changes of the serum levels of the sex steroids, IL-7, soluble receptor activator of nuclear factor κB ligand (sRANKL) and osteoprotegerin (OPG) in bone marrow transplantation (BMT) recipients. This study also examined whether the changes of these cytokine levels and sex steroids actually influence bone turnover and post-BMT bone loss by correlation analysis. Data were analyzed from 39 patients (33.6±6.4 years, 19 men and 20 women) who had DXA performed before BMT and at 1 year after BMT. The bone turnover markers, sex steroids and the cytokine levels were measured before BMT and serially after BMT. The mean bone loss in the lumbar spine and the total proximal femur was 5.9% (P <0.01) and 11.3% (P <0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas the bone resorption increased. For the female recipients, the estradiol levels declined at 1 week after BMT, and they did not recover to the basal levels. For the male recipients, the testosterone levels decreased at 1 week and then it increased to its baseline level. The IL-7 levels reached their maximum at 1 week and then declined to baseline level by 3 months. The serum sRANKL, OPG levels and the sRANKL/OPG ratio showed their peak at post-BMT 3 weeks. The mean daily dose of steroid was associated with suppressed bone formation, enhanced bone resorption and increased sRANKL levels. The IL-7 levels were also noted to be either positively correlated with the levels of ICTP or they were negatively correlated with the levels of osteocalcin at 1 and 3 weeks after BMT. Bone loss at the lumbar spine and the proximal femur was influenced by the decreased sex steroids and increased IL-7 levels. During the observation period, the IL-7 levels showed positive correlations with the sRANKL levels and the sRANKL/OPG ratio. For the female patients, the serum IL-7 levels were negatively associated with the estradiol levels at 1 and 3 weeks after BMT. All these findings suggest that IL-7 plays an important role for post-BMT bone loss, and this possibly happens via the RANKL pathway. These data also suggest that the up-regulation of IL-7 during the early post-BMT period may result from a deficiency of estrogen. [Copyright &y& Elsevier]

Abstract: Autosomal dominant familial neurohypophyseal diabetes insipidus is an inherited deficiency of arginine vasopressin (AVP), and this is caused by mutations in the AVP–neurophysin II (AVP–NP II) gene. Most of these mutations have been located in the signal peptide or in the NP II moiety. In the present study, we have analyzed the AVP–NP II gene in a Korean family. Clinical and genetic studies were performed on three members of the family, and on a normal healthy unrelated individual. The diagnosis of neurohypophyseal diabetes insipidus was done by performing a fluid deprivation test and a vasopressin challenge. For genetic analysis, the genomic DNA was extracted and the AVP–NP II gene was amplified by polymerase chain reaction (PCR). Clinical assessment of the affected individuals confirmed the diagnosis of neurohypophyseal diabetes insipidus. Genetic analysis of the AVP–NP II gene revealed a novel deletion mutation of a single nucleotide (guanine) within the splice acceptor site of intron 2 (IVS2 +1 delG). The affected individuals were heterozygous for this mutation. We also demonstrated through RT-PCR analysis of the mutant gene that this mutation resulted in the retention of intron 2 during pre-mRNA splicing. We concluded that a novel splicing mutation in the AVP–NP II gene causes neurohypophyseal diabetes insipidus in this family. [Copyright &y& Elsevier]

Aims: To evaluate the effects of initiating sodium‐glucose cotransporter‐2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase‐4 (DPP‐4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI). Materials and Methods: We used an active‐comparator, new‐user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP‐4 inhibitor users for analysis using propensity‐score matching. Results: During 13 708.59 person‐years of follow‐up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP‐4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all‐cause death and end‐stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all‐cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36–0.915), all‐cause death (HR 0.731, 95% CI 0.567–0.942), and ESRD (HR 0.076, 95% CI 0.018–0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI. Conclusions: The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI. [ABSTRACT FROM AUTHOR]

Purpose: Despite improvements in multiple myeloma (MM) survival rates, data on cardiovascular outcomes in long-term survivors remain lacking. Methods: This retrospective case–control study utilized the Korean National Health Insurance Service database (2009–2020) to compare the incidence of cardiovascular disease (CVD) between patients with MM and a matched control group, focusing on long-term (> 5 years) survivors. A preliminary case cohort (n = 15,402 patients with MM) and a matched control cohort (n = 123,216 patients without MM) were established based on birth year and sex. Following 1:1 propensity score matching, the final matched cohorts each comprised 15,402 participants. Results: The case and control cohorts were comparable in mean age (66.2 ± 11.5 years vs. 66.1 ± 11.3 years), sex, age distribution, and comorbidities. By the 8-year follow-up, the cumulative incidence of CV events (12.5% vs. 22.1%) and CVD risk were significantly lower in the case cohort. The 5-year landmark analysis revealed significant differences in CVD incidence between the cohorts (7.8% [case cohort] vs. 9.8% [control cohort]), with variations across age groups and sex, highlighting a significantly higher CVD risk among patients aged < 50 years in the case cohort (P < 0.001). Conclusions: These findings underscore the need for vigilant CVD monitoring in MM long-term survivors, particularly those aged < 50 years at first diagnosis. Implication for Cancer Survivors: This study highlights the importance of integrating cardiovascular monitoring and risk management into long-term care for MM survivors, with a focus on younger patients and personalized interventions. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate weight change in patients with new‐onset type 2 diabetes mellitus and the association of weight loss on diabetes remission in Korean adults. Materials and Methods: We used the health examination database of the Korean National Health Insurance Service. Patients diagnosed with type 2 diabetes mellitus from 2009 to 2012 were enrolled and followed to 2017. The baseline body weight was measured at the health examination closest to the time the patient was enrolled, and the change was calculated by examining the weight measured at the subsequent examination within 2 years. Remission was defined as fasting blood glucose less than 126 mg/dl at two or more consecutive health examinations after stopping medication. Results: In total, 114, 874 patients with new‐onset type 2 diabetes mellitus were analysed. Of these, 23 156 (20.2%) lost more than 5% of their body weight, and 2429 (2.1%) achieved remission. The adjusted odds ratio for remission in the weight loss group was 2.56 (95% confidence interval 2.35‐2.79) compared with the group with stable body weight. Sensitivity analysis according to the degree of weight change showed that the greater weight loss, the higher the likelihood of remission. In the subgroup analysis, the effects of weight loss on remission were significantly greater in subgroups of age <65 years, male sex and body mass index >25. Conclusion: Weight loss within the first 2 years of treating type 2 diabetes mellitus was associated with diabetes remission. Physicians should pay more attention to weight management in new‐onset type 2 diabetes mellitus, particularly for young and obese individuals. [ABSTRACT FROM AUTHOR]

Background: Insurance reimbursement provisions in South Korea limit osteoporosis medication availability for patients with T-scores exceeding − 2.5. This study aimed to evaluate the financial impact and fracture prevention of continuous denosumab therapy until a T-score>-2.0 (Dmab-C strategy), versus discontinuation of denosumab after reaching T-score>-2.5 (Dmab-D strategy) in osteoporosis patients. Methods: A cost-consequence analysis from a Korean healthcare system perspective was performed using a newly developed Markov model. The incidence of vertebral and non-vertebral fracture, fracture-related deaths, drug costs, and fracture-treatment costs were estimated and compared between Dmab-C and Dmab-D strategy over a lifetime in eligible patients aged 55 years. Results: Base-case analysis revealed that Dmab-C prevented 32.21 vertebral fracture (VF) and 12.43 non-VF events per 100 patients over a lifetime, while reducing 1.29 fracture-related deaths. Lifetime direct healthcare cost saving per patient was KRW 1,354,655 if Dmab-C replaces Dmab-D. When productivity losses were considered, Dmab-C saved KRW 29,025,949 per patient compared to Dmab-D. The additional treatment costs of Dmab-C could be offset by the higher subsequent treatment costs and fracture treatment costs of Dmab-D. The sensitivity analysis showed consistent patterns with results of the base-case analysis. Conclusion: Continuous treatment using denosumab until osteoporosis patients achieve and maintain a T-score of -2.0 would provide greater clinical and economic benefits in terms of fracture prevention and reduced mortality risks compared to outcomes from discontinuing treatment at a T-score of -2.5 or above. This new treatment strategy would effectively lower the risk of fractures and fracture-related mortality, ultimately leading to lower medical expenses. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the effects of repeated detection of non‐alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults. Materials and Methods: In this nationwide population‐based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20‐39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0‐4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points. Results: The multivariable‐adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57‐2.921), 3.45 (3.221‐3.694), 4.588 (4.303‐4.892) and 6.126 (5.77‐6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores. Conclusions: Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults. [ABSTRACT FROM AUTHOR]

The side effects and safety issues tied to calcium supplementation raise questions about its necessity in osteoporosis treatment. We retrospectively evaluated 189 postmenopausal osteoporosis patients treated with denosumab for 12 months. Patients exhibited neither renal dysfunction nor compromised general dietary intake. Patients were divided into three groups as follows: group A, weekly vitamin D 7000 IU; group B, daily vitamin D 1000 IU with elemental calcium 100 mg; and group C, daily vitamin D 1000 IU with elemental calcium 500 mg. All groups showed significant increases in bone density: +6.4 ± 4.7% for the lumbar spine, +2.2 ± 3.5% for the femoral neck, and +2.4 ± 3.8% for the total hip in group A; +7.0 ± 10.9% for the lumbar spine, +2.3 ± 5.2% for the femoral neck, and +2.4 ± 3.8% for the total hip in group B; and + 6.7 ± 8.7% for the lumbar spine, +2.5 ± 8.4% for the femoral neck, and +2.3 ± 4.0% for the total hip in group C. Serum calcium levels increased over time in all three groups with no significant difference. Changes in CTX and P1NP levels did not differ between the groups (all p > 0.05). With regular dietary intake, calcium supplementation levels showed no significant effect on bone density, bone marker changes, or hypocalcemia incidence during denosumab treatment. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome is associated with type 2 diabetes and its prevalence is increasing worldwide in young adults. We aimed to determine whether cumulative exposure to metabolic syndrome is associated with type 2 diabetes risk in young adults. Methods: Data of 1,376,540 participants aged 20–39 years without a history of type 2 diabetes and who underwent four annual health check-ups were collected. In this large-scale prospective cohort study, we evaluated the incidence rates and hazard ratios (HRs) of diabetes according to cumulative frequencies of metabolic syndrome over 4 years of consecutive annual health check-ups (burden score 0–4). Subgroup analyses were performed by sex and age. Results: During 5.18 years of follow-up, 18,155 young adults developed type 2 diabetes. The incidence of type 2 diabetes increased with burden score (P < 0.0001). The multivariable-adjusted HRs for type 2 diabetes were 4.757, 10.511, 18.288, and 31.749 in participants with a burden score of 1 to 4, respectively, compared to those with 0. In subgroup analyses, the risk of incident diabetes was greater in women than men and in the 20–29 years age group than the 30–39 years age group. The HRs were 47.473 in women and 27.852 in men with four burden scores. Conclusion: The risk of type 2 diabetes significantly increased with an increase in the cumulative burden of metabolic syndrome in young adults. Additionally, the association between cumulative burden and diabetes risk was stronger in women and the 20s age group. [ABSTRACT FROM AUTHOR]

Summary: It has been hypothesized that lipid profiles are associated with bone mineral density (BMD), but previous results have been controversial. In this study, serum triglycerides showed a significant inverse association with BMD, and the relationship is thought to correlate with vitamin D status among older adults. Introduction: The purpose of this study was to investigate the relationship between lipid profiles and bone mineral density (BMD) in older adults using data from the Korean National Health and Nutrition Examination Survey (KNHANES). Methods: We enrolled men older than 50 years and postmenopausal women who participated in the KNHANES 2008–2011. Subjects with liver cirrhosis, thyroid disease, or renal dysfunction and those receiving treatment for hyperlipidemia or osteoporosis were excluded. Results: A total of 4323 subjects (2286 men and 2037 women) was analyzed. The prevalence of osteoporosis was 8.7% in men older than 50 years and 38.4% in postmenopausal women. Osteopenia and osteoporosis groups were generally older and tended to have a lower body mass index compared to the normal group (p for trend < 0.001). The correlation between each lipid profile and BMD was analyzed in the linear model adjusted for age and body mass index. Total cholesterol and high-density lipoprotein cholesterol showed a negative correlation with BMD in the total population, but there was no significant correlation when analyzed separately for men and women. Triglycerides had a negative association with whole-body BMD in both men and women (p < 0.05). The adjusted odds ratio of logarithmic triglyceride level for osteoporosis was 2.50 (95% confidence interval 1.13–5.51) in women older than 65 years. Conclusion: Serum triglycerides showed a significant inverse association with BMD, and the relationship is thought to correlate with vitamin D status among older adults. [ABSTRACT FROM AUTHOR]

Differential diagnosis of thyrotoxicosis is essential because therapeutic approaches differ based on disease etiology. We aimed to perform differential diagnosis of thyrotoxicosis using machine learning algorithms with initial laboratory findings. This is a retrospective study through medical records. Patients who visited a single hospital for thyrotoxicosis from June 2016 to December 2021 were enrolled. In total, 230 subjects were analyzed: 124 (52.6%) patients had Graves' disease, 65 (28.3%) suffered from painless thyroiditis, and 41 (17.8%) were diagnosed with subacute thyroiditis. In consideration that results for the thyroid autoantibody test cannot be immediately confirmed, two different models were devised: Model 1 included triiodothyronine (T3), free thyroxine (FT4), T3 to FT4 ratio, erythrocyte sediment rate, and C-reactive protein (CRP); and Model 2 included all Model 1 variables as well as thyroid autoantibody test results, including thyrotropin binding inhibitory immunoglobulin (TBII), thyroid-stimulating immunoglobulin, anti-thyroid peroxidase antibody, and anti-thyroglobulin antibody (TgAb). Differential diagnosis accuracy was calculated using seven machine learning algorithms. In the initial blood test, Graves' disease was characterized by increased thyroid hormone levels and subacute thyroiditis showing elevated inflammatory markers. The diagnostic accuracy of Model 1 was 65–70%, and Model 2 accuracy was 78–90%. The random forest model had the highest classification accuracy. The significant variables were CRP and T3 in Model 1 and TBII, CRP, and TgAb in Model 2. We suggest monitoring the initial T3 and CRP levels with subsequent confirmation of TBII and TgAb in the differential diagnosis of thyrotoxicosis. [ABSTRACT FROM AUTHOR]

Background: The co-occurrence of diabetes and osteoporosis is common in postmenopausal women. For the treatment of postmenopausal osteoporosis, current guidelines recommend initial treatment with bisphosphonates, but it is unclear whether bisphosphonates provide a similar degree of therapeutic efficacy in patients with diabetes. This study sought to compare the efficacy of monthly oral ibandronate for retaining bone mineral density (BMD) in diabetic and non-diabetic postmenopausal women with osteoporosis. Methods: Postmenopausal osteoporotic women with or without diabetes were enrolled in this study from three hospitals in an open-label approach from 2018 to 2020. Each group of patients received oral ibandronate 150 mg once monthly for 1 year. BMD, trabecular bone score (TBS), serum C-terminal telopeptide of type I collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP) were evaluated prospectively. Treatment-emergent adverse events and changes in glucose metabolism during drug use were also monitored. Results: Among the 120 study participants, 104 (86.7%) completed the study. Following 1 year of treatment, BMD increased by 3.41% vs. 3.71% in the lumbar spine, 1.30% vs. 1.18% in the femur neck, and 1.51% vs. 1.58% in the total hip in the non-diabetes and diabetes groups, respectively. There were no significant differences in BMD changes between the groups, and the differences in CTx or P1NP changes between groups were not significant. We did not observe any significant differences in baseline TBS values or the degree of change between before and after 1 year of ibandronate treatment in either group in this study. A total of 11 adverse events (9.2%) that recovered without sequelae occurred among the 120 included patients, and there was no significant difference in the frequency of adverse events between the groups (p = 0.862). The changes in fasting glucose and glycated hemoglobin levels between before and after treatment were not significant in the diabetic group. Conclusions: Bisphosphonate therapy showed similar increases in BMD and decreases in CTx and P1NP of postmenopausal women with and without diabetes. Monthly oral ibandronate can be a safe and effective therapeutic option in postmenopausal osteoporosis patients with type 2 diabetes. Trial registration: NCT number: NCT05266261, Date of registration: 04 March 2022. [ABSTRACT FROM AUTHOR]

Background Transfusional iron overload primarily results in reticuloendothelial iron accumulation, which is considered to be less harmful than parenchymal iron accumulation. However, systematic and comprehensive data on endocrine function in transfusion-associated haemochromatosis are limited. Methods We examined 25 aplastic anaemia patients (11 men and 14 women) diagnosed with transfusion-associated haemochromatosis at a single institution. Pituitary function was determined with a combined pituitary function test. On a different day, a 75-g oral glucose tolerance test was performed. The bone mineral density ( BMD) of the lumbar spine and total hip was assessed with dual-energy X-ray absorptiometry. Results Twenty-two (88%) of these 25 patients had at least one endocrine abnormality, and 12 had more than one abnormality. The most common pituitary hormonal deficiency involved the pituitary-gonadal axis; 54% of the total subjects had hypogonadotropic hypogonadism. Two patients had an insufficient cortisol response to corticotrophin-releasing hormone stimulation. No patient had a deficiency of growth hormone or thyroid-stimulating hormone. Twelve (48%) had diabetes mellitus, and these patients tended to have higher concentrations of ferritin, alanine aminotransferase and γ-glutamyl transferase. Osteoporosis ( T-score <−2·5 SD) was observed in 48% of patients. The reduction in BMD was more pronounced in the lumbar spine than in the total hip. The patients with osteoporosis were accompanied by hypogonadism, which predominantly affected the trabecular bone. Conclusions Our observations suggest that endocrinopathies are common in transfusion-associated haemochromatosis. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and retinal vein occlusion (RVO) using data from the National Health Insurance Service in South Korea.Research Design and Methods: We used an active comparator, new user design, and nationwide data from 2014 to 2017. Based on a 1:1 propensity score match, we included 47,369 new users of SGLT2 inhibitors and 47,369 users of other glucose-lowering drugs (oGLDs). In the matched sample, we used the Cox proportional hazards model to estimate hazard ratios (HRs) with 95% CIs for developing RVO. Based on the main outcome, exploratory subgroup analyses were undertaken.Results: During a follow-up of 2.57 years, the incidence rate of RVO was 2.19 and 1.79 per 1,000 person-years in patients treated with SGLT2 inhibitors and oGLDs, respectively. The new use of SGLT2 inhibitors was associated with an increased risk of RVO compared with oGLD use (HR 1.264 [95% CI 1.056, 1.513]). In the subgroup analyses, a significant interaction with SGLT2 inhibitors was observed for age and estimated glomerular filtration rate (eGFR); the HR for RVO was higher in patients aged ≥60 years and those with eGFR <60 mL/min/1.73 m2 than in others.Conclusions: In a matched cohort study, we found that SGLT2 inhibitors were associated with a significantly increased risk of RVO. Older patients and those with chronic kidney disease were at higher risk for RVO. [ABSTRACT FROM AUTHOR]

OBJECTIVE-- We aimed to determine the effects of thyroid hormone on A1C and glycated albumin (GA) in nondiabetic patients with overt hypothyroidism. RESEARCH DESIGNANDMETHODS-- A1C levels were measured in 45 nondiabetic patients with overt hypothyroidism and 180 euthyroid control subjects. A1C, GA, fasting blood glucose (FBG), 1,5-anhydroglucitol, and erythrocyte indexes were determined in 30 nondiabetic patients with overt hypothyroidism before and after thyroid hormone replacement. RESULTS-- A1C levels were higher in patients with hypothyroidism compared with control subjects. A1C levels were decreased by thyroid hormone replacement. Thyroid hormone replacement increased serum erythropoietin, reticulocyte count, and mean corpuscular hemoglobin (MCH). The change in A1C level was significantly correlated with the change in reticulocyte count or MCH. Thyroid hormone replacement decreased serum levels of albumin and GA. However, FBG and 1,5-anhydroglucitol levels were not altered. CONCLUSIONS-- Levels of A1C and GA are spuriously high in nondiabetic patients with overt hypothyroidism. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We aimed to investigate whether there are differences in the risk factors or markers for the progression of diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetes mellitus. Materials and Methods: We carried out a 3‐year retrospective cohort study of 604 patients with type 2 diabetes mellitus. The outcomes were the progression of DR (worsening of the DR stage) and DN (an estimated glomerular filtration rate decline >12%) at the 3‐year follow up. The mean hemoglobin A1c (HbA1c) level and HbA1c variability (HbA1c‐VAR) were calculated. Results: The mean HbA1c and HbA1c‐VAR levels were higher in the DR progressors (n = 67) than in the DR non‐progressors (n = 537). The mean HbA1c was a significant predictor for DR progression independent of the duration of diabetes and HbA1c‐VAR levels. The urine albumin‐to‐creatinine ratio at baseline and HbA1c‐VAR levels were higher in the DN progressors (n = 34) than in the DN non‐progressors (n = 570). The triglyceride to high‐density lipoprotein cholesterol ratio at baseline tended to be higher in the DN progressors than in the DN non‐progressors. HbA1c‐VAR levels and the triglyceride‐to‐high‐density lipoprotein cholesterol ratio were significant predictors for DN progression independent of estimated glomerular filtration rate and the urine albumin‐to‐creatinine ratio. Conclusions: Average glycemia was significantly associated with progression of DR, whereas glycemic variability and dyslipidemia were significantly associated with progression of DN in type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background and Aims: Previous studies have suggested that the hemoglobin glycation index (HGI) can be used as a predictor of diabetes-related complications. We examined the prognostic significance of a high HGI for cardiovascular disease (CVD) in an ongoing hospital-based cohort.Methods: From March 2003 to December 2004, 1302 consecutive patients with type 2 diabetes and without a prior history of CVD were enrolled. CVD was defined as the occurrence of coronary artery disease or ischemic stroke. The HGI was calculated as the measured glycated hemoglobin (HbA1c) minus predicted HbA1c. Predicted HbA1c were calculated for 1302 participants by inserting fasting blood glucose (FBG) into the equation, Predicted HbA1c level = 0.02106 × FBG [mg/dL] + 4.973. Cox proportional hazards models were used to identify the associations between the HGI and CVD after adjusting for confounding variables.Results: During 11.1 years of follow-up, 225 participants (17.2%) were newly diagnosed with CVD. The baseline HGI was significantly higher in subjects with incident CVD than in those without CVD, although the baseline FBG levels did not differ according to the occurrence of CVD. Compared with patients without CVD, those with CVD were older, had a longer duration of diabetes and hypertension, and used more insulin at baseline. A Cox hazard regression analysis revealed that the development of CVD was significantly associated with baseline HGI (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.31-2.87; p < 0.001, comparing the highest and lowest quartiles of HGI). This relationship was unchanged after additional adjustment for baseline HbA1c level (HR, 1.74; 95% CI, 1.08-2.81). The HRs of HbA1c in relation to outcomes were similar to or lower than those seen for HGI. After adjustment for HGI, the effect of the highest HbA1c on incident CVD disappeared.Conclusions: High HGI was independently associated with incident CVD in patients with type 2 diabetes. Patients with high HGI at baseline had a higher inherent risk for CVD. [ABSTRACT FROM AUTHOR]

Background: The hemoglobin glycation index (HGI) is an index of differences in the glycation of hemoglobin according to blood glucose level. The glycation gap (G-gap) is an empiric measure of the extent of disagreement between hemoglobin A1C (HbA1C) and glycated albumin (GA). The aim of this study was to investigate the extent of agreement between the HGI and G-gap with respect to GA level, and to elucidate factors related to a high HGI.Method: Data were obtained from 105 patients with type 2 diabetes, and fasting blood glucose (FBG), HbA1c, and GA values were measured simultaneously. The G-gap was calculated as the difference between the measured and GA-based predicted HbA1c levels. HGI was calculated as the difference between measured and FBG-based predicted HbA1c levels.Results: The HGI and G-gap were highly correlated according GA (r=0.722, P<0.001). In general, the two indices were similar in terms of both direction and magnitude. The classification of patients as high, moderate, or low glycators based on HGI versus G-gap was consistent for the majority of the population and only 5% of patients were reclassified from high to low or low to high. Fasting C-peptide levels decreased linearly, and the percentage of patients using insulin increased linearly, between the lowest and highest HGI tertile (both P<0.05).Conclusions: There was 95% agreement between the HGI and G-gap using GA among type 2 diabetes patients. Furthermore, a high HGI was associated with a higher prevalence of insulin use among type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Although sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are major regulators in bone metabolism, their associations with osteoporotic fracture (OF) in Asians are inconclusive. Furthermore, there have been no clinical studies separately considering non-vertebral and vertebral fractures in terms of the blood levels of SOST and DKK1. Among 513 consecutive postmenopausal Korean women, we identified 103 cases defined as subjects with OF (i.e., non-vertebral and/or vertebral fractures). The controls were randomly selected from the remaining 410 subjects and matched 1:1 to cases according to both age and body mass index. Non-vertebral and morphological vertebral fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma levels of SOST and DKK1 were measured. Plasma SOST levels were lower in subjects with OF than in the control group. Each standard deviation decrement of plasma SOST concentration was associated with a multivariable-adjusted odds ratio of 1.77 for any prevalent OF type. The odds for OF was 2.97-fold higher in subjects in the lowest SOST tertile compared with subjects in the highest SOST tertile. These associations remained significant when the non-vertebral and vertebral fractures were analyzed separately. However, prevalent OF was not associated with plasma DKK1 levels, regardless of the type of fracture and the adjustment model employed. Consistently, plasma SOST levels were positively related with BMD values at all measured skeletal sites, although this was not observed for DKK1. Circulating SOST but not DKK1 may be a potential biomarker for predicting bone health in Asians. [ABSTRACT FROM AUTHOR]

Aims: This study was to determine the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes.Methods: We used data from the Korean National Health Insurance Service from 2014 to 2017. New drug users were screened, dipeptidyl peptidase 4 inhibitors (DPP4i) were set as the active comparator, and the differences between the two groups were corrected through propensity score matching. NAFLD was evaluated by the fatty liver index (FLI), which was calculated using body mass index, waist circumference, triglycerides, and gamma glutamyl peptidase.Results: After 1:1 matching, 25,371 patients in each group who received medication for an average of 299 days were analyzed. Despite similar baseline FLI of each group, the FLI of the SGLT2i users was 44.4 ± 26.7 and the FLI of the DPP4i users was 48.9 ± 27.3 (P value < 0.001) after treatment. SGLT2i showed more significant decrements than DPP4i in all components of FLI. The more the adherence to the SGLT2i increased, the greater the decrease in FLI.Conclusions: SGLT2i showed a significant reduction in FLI and its components. We suggest that SGLT2i may have beneficial effects in reducing the prevalence of NAFLD in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Several factors increase the risk of fragility fracture, including low bone mineral density, falls, and poor physical performance. The associations among these factors have been investigated; however, most of the subjects of previous studies were either elderly men or elderly women, and the associations were controversial. The aim of this study was to evaluate the associations between physical performance and bone mineral density, and the history of falls and fractures, stratified by gender and age group. We analyzed 5368 subjects who were aged 50 years or older, including 1288 younger men (younger than 70 years), 1615 younger women (younger than 70 years), 1087 older men (70 years or older), and 1378 older women (70 years or older). We used the one-leg standing time (OLST) for assessing static balance and the timed up-and-go test (TUGT) for assessing dynamic balance. The subjects in the worst performance quartile for the OLST were more likely to have osteoporosis than those in the best performance quartile. Additionally, women who had experienced a fracture during the past 2 years were 1.68 times more likely to be in the worst performance quartile for the OLST than women without a previous fracture. Although the TUGT time was not associated with either the incidence of osteoporosis or the fracture history, the odds ratios for falling were 1.51 and 1.28 as the TUGT time increased by one standard deviation in younger men and younger women, respectively. The findings of the present study show that the OLST was associated with the incidence of osteoporosis and previous fracture and that the TUGT time was associated with the incidence of falling. [ABSTRACT FROM AUTHOR]

Background: We sought to identify the distribution and cut-off value of the ‘homeostasis model assessment of insulin resistance’ (HOMA-IR) according to gender and menopausal status for metabolic syndrome in Koreans. Methods: Data were from the Korean National Health and Nutrition Examination Survey in 2008–2010. The subjects included adults aged 20 years or older. We excluded participants who had diabetes or fasting serum glucose ≥ 7 mmol/L. Finally, 11,121 subjects (4,911 men, 3,597 premenopausal women, 2,613 postmenopausal women) were enrolled. The modified Adult Treatment Panel III criteria were used to define metabolic syndrome. Results: The mean HOMA-IR was 2.11 (2.07–2.15) for men, 2.0 (1.97–2.04) for premenopausal women, and 2.14 (2.2–2.19) for postmenopausal women. The first cut-off values in men, premenopausal women, and postmenopausal women were 2.23 (sensitivity 70.6%, specificity 66.9%), 2.39 (sensitivity 72.3%, specificity 76.4%), and 2.48 (sensitivity 51.9%, specificity 80.2%), respectively. Based on the first HOMA-IR cut-off value, the prevalence of metabolic syndrome was 22.9% in men, 13.7% in premenopausal women, and 51.6% in postmenopausal women. The second cut-off value was around 3.2 in all three groups. Based on the second HOMA-IR cut-off value, the prevalence of metabolic syndrome was 50.8% in men, 42.5% in premenopausal women, and 71.6% in postmenopausal women. Conclusion: In conclusion, the first cut-off values for HOMA-IR were 2.2–2.5 and the second cut-off value was 3.2 in Korea. The distribution of HOMA-IR showed differences according to gender and menopausal status. When we apply HOMA-IR, we should consider gender, menopausal status, and the prevalence of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objective: The glycation gap (G-gap) is an empirical measure of the extent of the difference between HbA1C and fructosamine levels. Several studies have shown that the presence of a G-gap is linked to diabetic nephropathy, but possible artifacts caused by dependence of the fructosamine level on the extent of serum protein metabolism require careful consideration. We investigated the consistency of G-gaps measured by assaying glycated albumin (GA) levels to identify factors associated with G-gap variations.Method: A total of 457 pairs of observations, like an HbA1c and GA measurement at the same clinic visit, were obtained from 170 Korean patients with type 2 diabetes. HbA1c and GA levels were measured simultaneously in two or three separate occasions. Each G-gap was calculated as the difference between the measured HbA1c level and that predicted by the GA level. All patients underwent abdominal computed tomography, and the areas of subcutaneous and visceral fat were measured.Results: The G-gaps were all significantly inter-correlated over time (γ=0.755, P<0.001).The direction of each G-gap was consistent. The body mass index (BMI), visceral fat area, and the estimated glomerular filtration rate (eGFR) increased linearly from the lowest to the highest G-gap quartile (all P values <0.05). Upon multivariate analysis, both visceral fat area and the eGFR were significantly associated with a G-gap.Conclusions: A G-gap determined using GA measurements is consistent within an individual over time. The G-gap is associated with visceral fat and kidney function in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background Periostin is preferentially expressed by the periosteum, which mainly covers the long bones. Therefore, the role of periostin in osteoporotic fracture (OF) may differ depending on bone type. We performed a case–control study to investigate whether periostin can serve as a predictor of OF risk, particularly after dividing OFs into non-vertebral and vertebral fractures. Methods Among 532 consecutive postmenopausal women not taking any drug or without any disease that could affect bone metabolism, 133 cases with OF ( i.e. , non-vertebral and/or vertebral fractures) and 133 age- and body mass index-matched controls were enrolled. Non-vertebral ( i.e. , forearm, humerus, hip, and pelvis; n = 81) and morphological vertebral (n = 62) fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma periostin levels were also measured. Results Plasma periostin was markedly higher in subjects with non-vertebral fracture than their controls even after adjustment for BMD and potential confounders ( P = 0.006). Each standard deviation increment of plasma periostin was associated with a multivariable-adjusted odds ratio of 1.59 for non-vertebral fracture. The odds for non-vertebral fracture were 2.48-fold higher in subjects in the highest periostin tertile compared with those in the lowest periostin tertile (95% confidence interval = 1.10–5.61). However, associations between plasma periostin and vertebral fracture were not observed, regardless of the adjustment model used. Consistently, plasma periostin levels were inversely associated with proximal femur BMD ( P = 0.007 to 0.030) but not lumbar spine BMD. In subgroup analyses, plasma periostin had no correlation with the levels of classical bone turnover markers. Conclusions Plasma periostin may be a potential biomarker of the risk of OF, especially in non-spinal skeletal sites, such as the limbs, rather than spine. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that acute myocardial infarction (AMI) might accelerate development of new onset diabetes in patients with coronary artery disease independent of known risk factors. Methods: We conducted a retrospective cohort study within COACT (CathOlic medical center percutAneous Coronary inTervention) registry. From a total of 9,127 subjects, 2,036 subjects were diabetes naïve and followed up for at least one year with both index and follow-up laboratory data about diabetes. Cox proportional hazard model was used to derive hazard ratios (HRs) and 95% confidence interval (CI) for new onset diabetes associated with AMI in univariate and multivariate analysis after adjusting several covariates. Results: The overall hazard for diabetes was higher in AMI compared to non-AMI patients (p by log rank <0.01) with HR of 1.78 and 95% CI of 1.37–2.32 in univariate analysis. This association remained significant after adjusting covariates (HR, 1.54; 95% CI, 1.14–2.07; p<0.01). AMI was an independent predictor for higher quartile of WBC count in multivariate ordinal logistic regression analysis (OR, 6.75; 95% CI, 5.53–8.22, p<0.01). In subgroup analysis, the diabetogenic effect of AMI was more prominent in the subgroup without MetS compared to MetS patients (p for interaction<0.05). Compared to the reference group of non-AMI+nonMetS, the group of AMI+non-MetS (HR, 2.44; 95% CI, 1.58–3.76), non-AMI+MetS (HR, 3.42; 95% CI, 2.34–4.98) and AMI+MetS (HR, 4.12; 95% CI, 2.67–6.36) showed higher HR after adjusting covariates. However, the hazard was not different between the non-AMI+MetS and AMI+non-MetS groups. Conclusions: AMI patients have a greater risk of new-onset diabetes when compared to non AMI patients, especially those with mild metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Objective This study aimed to assess insulin resistance according to maternal age at childbirth. Patients and methods The data used in this study were obtained from the 2010 Korean National Health and Nutrition Examination Survey. This study included a total of 2233 nondiabetic female subjects ≥30 years of age that were subdivided into groups according to their obesity and abdominal obesity ( AOB) statuses. The homoeostasis model assessment of insulin resistance ( HOMA- IR) was used to quantify the insulin resistance according to age at first childbirth and last childbirth. Results Age at first childbirth showed a negative relationship with HOMA- IR in both the nonobese and non- AOB groups, while age at last childbirth showed a positive relationship with HOMA- IR in both the nonobese and non- AOB groups. A multivariate logistic regression analysis revealed that ages at first and last childbirth were significantly associated with the highest HOMA- IR quartile. The odds ratio was 0·9 (95% confidence interval: 0·82-0·98) for age at first childbirth, and 1·07 (95% confidence interval: 1·01-1·14) for age at last childbirth in the nonobese and non- AOB groups. Conclusion In conclusion, this study suggests that insulin resistance is increased in females who experienced their first childbirth at a younger age or their last childbirth at a later age, particularly in nonobese individuals. Because these data suggest that childbearing age could be an independent risk factor for diabetes, a high-quality prospective study assessing the relationship between childbearing age and insulin resistance should be performed. [ABSTRACT FROM AUTHOR]

Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis. We examined 93 patients with DTC over 12 months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1 year. The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12 months, were − 0.88, − 1.3 and − 0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine − 2.1%, femoral neck − 2.2%, and hip − 2.1%; all P < 0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine ( P = 0.041) and femoral neck ( P = 0.010). TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period. [ABSTRACT FROM AUTHOR]

Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients. Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis. Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%. Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures. [ABSTRACT FROM AUTHOR]

Aims Evidence that pancreatic fat accumulation has a role in obesity, metabolic syndrome and type 2 diabetes mellitus (DM) is emerging. However, data on the influence of pancreatic steatosis on subclinical atherosclerosis are lacking. Methods We examined 198 patients with type 2 DM. Pancreatic computed tomography (CT) attenuations were assessed using CT imaging. Obesity was defined as BMI ≥ 25 kg/m 2 according to the Asian-specific BMI cut-offs. We defined pancreatic steatosis as pancreatic attenuations below median levels. Results The pancreatic attenuations was significantly correlated with age ( r = −0.302, p < 0.001), visceral fat area ( r = −0.194, p = 0.006) and vascular stiffness ( r = −0.242, p = 0.001). In the non-obese group (BMI < 25 kg/m 2 ), pancreatic steatosis was associated with a higher prevalence of carotid artery plaque and vascular stiffness. In the non-obese group, patients with pancreatic steatosis, compared with those without, had an odds ratio (OR) of 3.1 (95% CI 1.2–8.1) for carotid atherosclerosis, after adjusting for age, gender and BMI. However, significant associations between pancreatic steatosis and atherosclerosis were not found in the obese group. Conclusion Ectopic fat in the pancreas is strongly associated with carotid atherosclerosis in non-obese subjects with type 2 DM. This finding highlights the importance of pancreatic fat deposits related to a higher risk of cardiovascular disease, especially in non-obese subjects. [ABSTRACT FROM AUTHOR]

Aims/Introduction Little is known about the long-term effects of Roux-en-Y gastric bypass ( RYGB) in severely obese Asian individuals. Methods and Materials A total of 33 severely obese patients with type 2 diabetes underwent RYGB. All patients were followed up for 2 years. Visceral and abdominal subcutaneous fat areas were assessed using computed tomography ( CT) before, and 12 and 24 months after RYGB. The muscle attenuation ( MA) of paraspinous muscles observed by CT were used as indices of intramuscular fat. Results The mean percentage weight loss was 22.2 ± 5.3% at 12 months, and 21.3 ± 5.1% at 24 months after surgery. Compared with the baseline values, the visceral fat area was 53.6 ± 17.1% lower 24 months after surgery, and the abdominal subcutaneous fat area was 32.7 ± 16.1% lower 24 months after surgery. The MA increased from 48.7 ± 10.0 at baseline to 52.2 ± 8.9 ( P = 0.009) 12 months after surgery. The MA after the first 12 months maintained changes until 24 months. Triglycerides and free fatty acids were reduced after surgery, whereas the high-density lipoprotein cholesterol levels were increased significantly after surgery. At the last follow-up visit, 18 patients (55%) had diabetes remission. The percentage of iron and vitamin D deficiency was 30% and 52%, respectively. Conclusions We found that patients subjected to RYGB had significant sustained reductions in visceral and intramuscular fat. There were durable improvements in the cardiometabolic abnormalities without any significant comorbidities. However, there were mild nutritional deficiencies in these patients despite daily supplementation with multivitamins and minerals. [ABSTRACT FROM AUTHOR]

Background: FDG (2-[18F]Fluoro-2-D-deoxyglucose-positron emission tomography (PET)/computed tomography (CT), which can detect a change in glucose metabolism in cancer cells, has been introduced as a diagnostic and prognostic tool in papillary thyroid carcinoma (PTC). However, differences in the clinicopathological and biological characteristics between primary PTCs with FDG uptake and those without FDG uptake are not well established. Methods: A total of 188 patients with PTC who had preoperative PET/CT scans were enrolled to compare the differences of clinicopathological parameters between FDG-avid (F-PTC; n=150) and non-FDG-avid tumors (FN-PTC; n=38). Immunohistochemical staining for glucose transporter (GLUT)-1 and hypoxia-inducible factor-1 alpha (HIF-1α) was performed. Results: FN-PTCs were smaller; had a lower incidence of lymphatic invasion, vascular invasion, multifocality, and central lymph node metastasis; and had a lower maximum standardized uptake value than F-PTCs. After exclusion of high-risk patients for recurrence, FN-PTCs remained smaller ( p<0.001) and had less lymphatic invasion ( p=0.061). Among tumors larger than the spatial resolution of the PET/CT scan, macrocalcification was more frequent in FN-PTC than in F-PTC ( p=0.043). While FN-PTC and F-PTC showed no difference in GLUT-1 expression (50% vs. 75%, p=0.363), FN-PTC showed lower HIF-1α immunoreactivity than F-PTC (25.0% vs. 75.0%, p=0.032). Conclusion: Tumor size and macrocalcification are clinicopathological differences between FN-PTC and F-PTC. Biologically, HIF-1α may be responsible for increased FDG uptake in PTC. [ABSTRACT FROM AUTHOR]

Background: Galectin-3 (G3) immunostaining of fine-needle aspiration (FNA) samples from thyroid nodules is very useful for the diagnosis of malignancy. The objective of the present study was to determine whether the absence of G3 immunostaining in preoperative FNA samples is associated with favorable clinicopathological parameters, including lymph node (LN) metastasis, in papillary thyroid carcinoma (PTC). Methods: The records of 868 patients with PTC who had prethyroidectomy ultrasonography-guided FNA with G3 immunostaining between January 2006 and December 2009 were retrospectively reviewed. G3 immunostaining was considered positive if the percentage of tumor cells showing definite cytoplasmic immunostaining exceeded 5%. Patients who had negative G3 immunostaining of FNA samples were assigned to the G3-negative (G3N) group; whereas those who had positive G3 immunostaining were assigned to the G3-positive (G3P) group. Results: There were 92 patients who were assigned to the G3N group (10.6%) because of the negative staining for G3 in the preoperative FNA samples from their thyroid nodules. The proportion of PTC subtypes in the G3N and G3P groups was similar ( p=0.376). There was less frequent thyroid capsular invasion (46.7% vs. 66.5%, p<0.001), extrathyroidal extension (28.3% vs. 48.5%, p<0.001), and LN metastasis (22.2% vs. 48.7%, p<0.001) in the G3N group than the G3P group. In multivariate regression analysis, G3N expression predicted a lower risk of LN metastasis (odds ratio=0.37, 95% confidence interval 0.18-0.78) after adjustment for other clinicopathological parameters. Over a median follow-up of 33 months, no association was observed between G3N and disease-free survival. Conclusion: The absence of G3 expression in FNA samples from PTC is associated with pathological parameters considered less aggressive than is the case for PTCs with G3 expression, including being a negative predictor of negative LN involvement. Long-term follow-up studies, however, are needed to verify whether G3N patients have lower recurrence and mortality rates. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the independent predictors of coronary artery stenosis in patients with type 2 diabetes mellitus (DM) and subclinical atherosclerosis. A total of 232 patients with type 2 DM and subclinical atherosclerosis underwent multislice computed tomography coronary angiography. Subclinical atherosclerosis was determined by the carotid intima-media thickness (IMT) or carotid plaque. Multislice computed tomography coronary angiography revealed significant coronary stenosis (>50% in diameter) in 71 subjects (31%). The subjects who had significant coronary stenosis were much older and had had a longer duration of DM. In particular, the log-transformed albumin/creatinine ratio (ACR) was greater in the subjects with significant coronary stenosis compared to the subjects without significant coronary stenosis. The age- and gender-adjusted odds ratio for significant coronary stenosis increased in proportion to albuminuria with a given estimated glomerular filtration rate. The ACR as a continuous variable (odds ratio 4.167, 95% confidence interval 1.497 to 11.599) or categorical variable (ACR >30 μg/mg, odds ratio 4.619, 95% confidence interval 1.562 to 13.659) was associated with an increased risk of significant coronary stenosis, independent of conventional cardiovascular risk factors. In receiver operating characteristic analysis, the ACR had an additive effect with carotid IMT for predicting significant coronary stenosis (area under the curve 0.625 with carotid IMT; area under the curve 0.710 with carotid IMT plus ACR, p = 0.0144). In conclusion, the presence of albuminuria is an independent predictor for significant coronary stenosis in patients with type 2 DM and subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

We prospectively examined the association between type 2 diabetes mellitus (T2DM) progression and common T2DM-risk gene variants in 870 non-diabetic participants in a Chungju Metabolic Disease Cohort Study in Korea. We genotyped the following six single nucleotide polymorphisms (SNPs): KCNQ1 (potassium voltage-gated channel, KQT-like subfamily member 1) rs2237892, CDKAL1 (regulatory subunit-associated protein 1-like 1) rs7554840, CDKN2A/B (cyclin-dependent kinase inhibitor 2A/B) rs1081161, SCL30A8 (solute carrier family 30 member 8 gene) rs13266634, TCF7L2 (transcription factor 7-like 2) rs7903146, and PPARG (peroxisome proliferator activated receptor gamma) rs1801282. Anthropometric data and metabolic parameters were obtained at baseline and year 4. Pancreatic β cell function was assessed by the homeostasis model assessment index of β cells (HOMA-β). After 4 years, 137 subjects developed T2DM (15.7%). A significant association was found in the variant of KCNQ1 rs2237892, whereas the SNPs of CDKAL1, CDKN2A/B, SCL30A8, TCF7L2 and PPARG were not associated. The C-allele carriers of KCNQ1 conferred a significantly increased risk for T2DM compared with the T/T genotype, independently of clinical risk factors (odds ratio=2.61, 95% confidence intervals=1.02-6.69, P=0.04). Although no differences were observed at baseline among the KCNQ1 variants, HOMA-β levels by year 4 were significantly lower in the C-allele carriers after controlling for metabolic parameters. The genetic variations in KCNQ1 are associated with future development of T2DM in Koreans, which might be mediated by differences in insulin secretory function. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography/computed tomography (PET/CT) scan has a role in the surveillance of patients with a history of thyroid carcinoma. Its efficacy after remnant ablation as far as detecting persistent or recurrent thyroid carcinoma before other surveillance methods is not known, however. In intermediate-to-high risk thyroid carcinoma patients we studied whether PET/CT scan, performed 6-12 months after the first remnant ablation, could provide more information than ultrasonography (US) and thyrotropin-stimulated serum thyroglobulin (Tg) determination with diagnostic whole-body scan (DxWBS). Methods: We studied 71 subjects with differentiated thyroid cancer (DTC) who were intermediate-to-high risk for persistent/recurrent disease and who had received PET/CT scan, US, and DxWBS simultaneously with stimulated Tg levels 6-12 months after remnant ablation. To evaluate the diagnostic efficacy of PET/CT scan, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. Results: Ten subjects (14%) had persistent/recurrent disease detected 6-12 months after remnant ablation. Persistence/recurrence was detected in nine (12.7%) of these patients by conventional methods, including US and DxWBS, along with stimulated Tg levels. The remaining case was detected solely by a PET/CT scan, which showed a mediastinal prevascular lesion; this was confirmed by a therapeutic WBS after additional radioiodine therapy. Among the six patients whose PET/CT scan showed positive results, five had persistent/recurrent disease. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET/CT scan for detecting persistent/recurrent thyroid carcinoma were 50%, 98.4%, 83.3%, 92.3%, and 91.5%, respectively. Conclusion: In intermediate-to-high risk patients with DTC seen 6-12 months after their first remnant ablation, there is almost no complementary role for adding a PET/CT scan to conventional follow-up methods, an US and a DxWBS simultaneously with stimulated Tg levels. [ABSTRACT FROM AUTHOR]

Aims: Basal insulin requirement in patients with type 2 diabetes is difficult to determine because of individual variability in insulin sensitivity and secretion. We aimed to identify factors that influence basal insulin requirement in insulin-naïve patients with type 2 diabetes.Methods: We studied 50 insulin-naïve patients with type 2 diabetes. Their basal insulin requirement was calculated by 8h overnight intravenous insulin infusion. Patients underwent abdominal computed tomography; subcutaneous and visceral fat areas were measured.Results: The basal insulin requirement was 31.3 ± 16.9 units/day, and it varied widely from 0.2 to 1.4 units/kg. It was positively correlated with visceral fat area (γ=0.485, P<0.001), body mass index (BMI, γ=0.339, P=0.008), glycated hemoglobin (HbA1C, γ=0.327, P=0.019), alanine aminotransferase (ALT, γ=0.310, P=0.027), and triglyceride (γ=0.305, P=0.032). However, body weight, waist circumference and total fat mass were not related to basal insulin requirement. Multiple linear regression analysis showed that visceral fat area, HbA1C, and ALT are independent predictors of basal insulin requirement.Conclusions: Visceral obesity was a better predictor than generalized obesity for basal insulin requirement at the initiation of insulin therapy in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Aims: We aimed to evaluate the association between diabetic microangiopathy and subclinical atherosclerosis as a marker of cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes. Methods: A total of 142 newly diagnosed type 2 diabetics who were free from CVD underwent evaluation of diabetic microangiopathy. Subclinical atherosclerosis was assessed by measuring carotid intima-media thickness (IMT), and the 10-year absolute risk of CVD was estimated using the UK Prospective Diabetes Study (UKPDS) Risk Engine. Results: Subclinical atherosclerosis was found in 27 subjects (19.0%). The rates of hypertension and diabetic retinopathy were significantly higher among patients with subclinical atherosclerosis. The UKPDS 10-year risk for CVD was significantly increased in subjects with subclinical atherosclerosis. Old age, hypertension and the presence of diabetic retinopathy showed a significant association to subclinical atherosclerosis after further adjustments for gender, body mass index, smoking status, HbA1c, HDL cholesterol, LDL cholesterol and the presence of diabetic nephropathy. Conclusions: This study shows that diabetic retinopathy is an independent risk marker for subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. We suggest that a diagnosis of diabetic retinopathy may warrant a more careful cardiovascular assessment even in the early stages of diabetes. [Copyright &y& Elsevier]

Abstract: Objective: To clarify the association of serum calcium level with metabolic syndrome (MetS) and diabetes in middle-aged and elderly Korean subjects. Design and patients: We conducted a population-based, cross-sectional survey of 1329 participants aged over 40 years (median age 65.8) in a rural area of Chungju, Korea, in 2007. Measurements: Serum level of albumin, calcium, 25-hydroxy-vitamin D and intact parathyroid hormone were measured in a central laboratory. Results: The prevalence of MetS increased progressively with elevated serum albumin-corrected calcium levels (P <0.001 for trend). After adjusting for various covariates, subjects in the highest quintile group (2.45–2.99mmol/L) compared with the lowest quintile group (2.05–2.24mmol/L) of serum calcium levels had an odds ratio (OR) for having MetS of 3.11 (95% confidence intervals, CI, 1.95–4.97; P for trend <0.001). Excluding the subjects with hypocalcemia and hypercalcemia (n =1064) did not alter this significant association. After multiple adjustment, subjects with serum calcium levels in the fourth to fifth quintiles had a 2.0- to 3.0-fold increased OR of having diabetes (first quintile reference, fourth quintiles OR 2.38; 95% CI 1.32–4.28, fifth quintiles OR 3.32; 95% CI 1.87–5.88; P for trend <0.001).The associations of serum calcium levels with the incidences of MetS or diabetes were unchanged after adjustment for 25(OH)D and PTH levels. Conclusions: Altered calcium homeostasis was associated with an increased risk of having MetS and diabetes in this demographic group. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis associated with thyroid dysfunction has been traditionally viewed as a secondary consequence of altered thyroid function, but there was recently a report about the direct effects of thyroid-stimulating hormone (TSH) on bone remodeling, which was mediated via the TSH receptor found on osteoblast and osteoclast precursor cells. Endogenous subclinical thyroid dysfunction seems to be an appropriate model to examine the direct effect of TSH on bone metabolism while ruling out the direct effect of thyroid hormone on bone metabolism. Thus, we aimed to investigate the relationship between subclinical thyroid dysfunction and bone mineral metabolism in women. Methods: We enrolled 413 women (mean age: 52.2 ± 6.6 years) in our study. Serum levels of TSH, free T4 and the biochemical markers of bone turnover were measured by the standard methods. BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Results: Femoral neck BMD was significantly reduced both in the subclinical hyperthyroid group and in the subclinical hypothyroid group as compared with the euthyroid group (one-way ANOVA, p <0.001; post-hoc analysis, p = 0.041, p = 0.033). In contrast to the femoral neck BMD, the lumbar spine BMD showed no difference between the two groups. Additionally, serum calcium and alkaline phosphatase levels, urine deoxypyridinoline levels, and urine calcium to creatinine ratio showed no differences between the two groups. Conclusions: Women having subclinical hyperthyroidism and women with subclinical hypothyroidsm have reduced femoral neck BMD. Additional studies are required to elucidate the mechanism for this finding. [Copyright &y& Elsevier]

Background: Peroxisome proliferator-activated receptor (PPAR)γ is involved mainly in adipocyte differentiation and has been suggested to play an important role in the pathogenesis of insulin resistance and atherosclerosis. We investigated the frequencies of two common polymorphisms of PPARγ gene, exon 6 C→T substitution and exon B Pro12Ala in healthy subjects and analyzed the correlations between the different genotypes and insulin resistance, metabolic syndrome and cardiovascular risk factors. Methods: Anthropometric measurements, fasting glucose, insulin and lipid profiles were measured in 253 Korean females. Homeostatic model assessments and quantitative insulin sensitivity check indices were calculated. Metabolic syndrome was diagnosed according to the NCEP-ATP III guidelines and the Western Pacific Region of WHO for obesity criteria for waist circumference. Polymerase chain reaction (PCR)–restriction fragment-length polymorphism and real-time PCR were performed for genotyping of the DNAs. Results: For C161T polymorphism, allele frequencies were 0.804 and 0.196 for T allele, and 0.947 for proline and 0.053 for alanine. There was no Ala12Ala homozygote in the population. No differences were seen in the mean values of age, body mass index (BMI), blood pressure, fasting blood glucose level, fasting insulin levels, HOMA and QUICKI among different genotypes when analyzed as a whole, except that subjects with Pro12Ala had significantly higher body weight than those with Pro12Pro genotype. However, mean BMI, percent body fat and weight showed significant differences between genotypes in younger age group (≤50 years). Although overall prevalence of metabolic syndrome had no association with the genotypes, the prevalence of decreased high-density lipoprotein cholesterol component was lower in those with the T allele than in those with the CC genotype. There was no association of the genotypes with glucose tolerance status. When the subjects were divided into four groups according to the combination of the genetic alleles of the two polymorphisms, subjects having Pro12Ala and T allele, simultaneously, showed significantly higher mean weight than those without Ala allele. Pro12Ala polymorphism seems to affect body weight, similar to the previous studies, and the effect was potentiated with the presence of T allele of C161T polymorphism. Conclusions: Although either polymorphism failed to show significant association with insulin resistance, the fact that the prevalence of decreased HDL-C was lower in those with the T allele of C161T polymorphism suggests that this polymorphism might have a protective effect on atherosclerotic lipid profiles, which needs further investigation. [Copyright &y& Elsevier]

Aims: The status of metabolic abnormalities including impaired fasting glucose (IFG) can change over time, yet little is known about how exposure duration to IFG is related to diabetes risk.Methods: Using nationally representative data from the Korean National Health Insurance system, 2,513,127 people who were free of diabetes and who received four consecutive annual health examinations commencing in 2006 or 2007 were followed up at the end of 2016. IFG was defined as fasting blood glucose levels of 100-125 mg/dL. Participants were classified numerically according to the cumulative number of IFG diagnoses.Results: Over 4 years, 53% of the population participants remained normoglycemic, while 3% had persistent IFG and 44% had intermittent IFG. The risk of type 2 diabetes mellitus (DM) increased gradually with increasing IFG exposure score. Subjects with an IFG exposure score of 2, 3, or 4 had a 3.75- to 9.77-fold increased hazard ratio (HR) for incident diabetes (IFG exposure score 0 reference; score 2, HR 3.75, 95% confidence interval [CI] 3.67-3.83; score 3, HR 6.21, 95% CI 6.08-6.36; score 4, HR 9.77, 95% CI 9.53-10.02).Conclusions: Cumulative IFG exposure was associated with a higher risk of type 2 DM in a dose-response fashion. [ABSTRACT FROM AUTHOR]

Bone mineral density (BMD) assessments alone might not be sufficient for assessing fracture risk in the whole population, and decreased balance is an important risk factor for fracture. The aim of this study was to evaluate the association between baseline physical performance and fracture risk. This community-based cohort study was conducted in rural areas. The follow-up examination was performed in 4015 subjects for approximately 4 years. We used the one-leg standing time (OLST) to assess static balance and the timed up-and-go test (TUGT) to assess dynamic balance. Fractures were assessed during the medical interview. The participants were divided into quartile groups according to their performance level, and the lowest baseline OLST performance was associated with a 2.1-fold increased risk of major osteoporotic fracture (MOF) independent of age, gender, hip BMD, fall incidence, and lifestyle factors. The participants in the low performance quartile of baseline OLST or TUGT performance had an increased incidence of osteoporosis and falling compared to that in the participants in the highest baseline performance quartile after adjusting for covariates. Among the participants with a femoral neck T-score above −2.5, the participants with an OLST below 14 s had a 1.7-fold higher risk of MOF than the participants with an OLST of 14 s or more. The measurement of static balance by the OLST predicted the risk of fracture in Korean adults independent of BMD and fall history. Our results suggest that the OLST may have clinical utility in identifying individuals at risk of fracture, especially those who might not be adequately identified by BMD measurements alone. • Low one-leg standing time (OLST) was associated with higher fracture risk. • Low OLST resulted in higher incidence of falls and osteoporosis. • An OLST under 14 s resulted in high fracture risk despite T-score above −2.5. [ABSTRACT FROM AUTHOR]

Bone loss is highly prevalent after gastrectomy in gastric cancer patients. Therefore, the efficacy of medical treatment should be evaluated in patients undergoing gastrectomy. We conducted an unblinded, randomized controlled trial of patients who underwent gastrectomy to treat gastric cancer. The intention-to-treat participants (n = 107) were randomly assigned to receive either alendronate at a weekly dose of 70 mg and daily elemental calcium (500 mg) with cholecalciferol (1000 IU) or daily elemental calcium (500 mg) with cholecalciferol (1000 IU) only. The primary endpoint was defined by the changes in bone mineral density of four measurement sites: the lumbar spine, femur neck, total hip, and trochanter. Changes in bone turnover markers, osteocalcin and collagen I carboxyterminal telopeptide were also observed. At baseline, there were no differences between the two groups in bone mineral density. In the lumbar spine and trochanter, there were no significant percentage changes compared with the baseline in the alendronate group, but a significant decrease was noted in the control group (p < 0.001 for both lumbar spine and trochanter). In the femur neck and total hip, a larger decrease was observed compared with the baseline in the control group (p < 0.001 for both femur neck and total hip). Significant percentage increases in serum osteocalcin compared with baseline were noted in the control group (p for trend <0.001), but there was no change in the alendronate group (p for trend = 0.713). Collagen I carboxyterminal telopeptide significantly declined in the alendronate group over 12 months (p for trend <0.001). Prevention and treatment with bisphosphonate effectively reduces bone loss by suppressing bone resorption in gastric cancer patients undergoing gastrectomy. • Bone loss is highly prevalent after gastrectomy in gastric cancer patients. • The efficacy and safety of bisphosphonate was evaluated in patients who underwent gastrectomy by an unblinded, randomized controlled trial. • In the alendronate group, bone mineral density decreased in femoral neck and total hip, but less compared to the control group. • Bisphosphonate effectively reduces bone loss in gastric cancer patients undergoing gastrectomy. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to identify a threshold for the cholesterol level at which the risk of cardiovascular disease (CVD) begins to increase in people with type 2 diabetes mellitus (DM). Methods: Using the Korean National Health Insurance Service database, 2,077,135 people aged ≥ 40 years with type 2 DM who underwent regular health checks between 2009 and 2012 were included. Subjects with previous CVD were excluded. Cox regression analyses were performed to estimate the risk of CVD for each low-density lipoprotein cholesterol (LDL-C) group using the < 70 mg/dL as the reference group. Results: There were 78,560 cases of stroke (3.91%), and 50,791 myocardial infarction (MI, 2.53%) during a median follow-up of 7.1 years. Among participants not taking statins, LDL-C levels of 130–159 mg/dL and ≥ 160 mg/dL were significantly associated with the risk of MI: the hazard ratios (HRs) (95% confidence interval) were 1.19 (1.14–1.25) and 1.53 (1.46–1.62), respectively. Among participants taking statins, all categories of LDL-C level ≥ 70 mg/dL were significantly associated with increased risk of stroke and MI. Conclusions: We identified an increased risk of CVD in people with an LDL-C level ≥ 130 mg/dL among individuals with type 2 DM not taking statins. The risk of CVD was significantly higher in those taking statins with an LDL-C level ≥ 70 mg/dL. [ABSTRACT FROM AUTHOR]

The article focuses on the effects of parathyroid hormone (PTH) on the bones by signaling interaction between PHT receptor 1 (PHTR1) and T cells. It states that the intermittent (iPTH) stimulates bone formation, which leads to increase bone mass. It says that the (iPTH) treatment was approved by the U.S. Food and Drug Administration for treating osteoporosis.