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Background: It is unclear whether glycemic variability (GV) is a risk factor for diabetic peripheral neuropathy (DPN), and whether control of GV is beneficial for DPN. The purpose of this study was to investigate the effect of GV on peripheral nerve damage by inducing glucose fluctuation in streptozotocin-induced diabetic rats.Methods: Rats were divided into four groups: normal (normal glucose group [NOR]), diabetes without treatment (sustained severe hyperglycemia group; diabetes mellitus [DM]), diabetes+once daily insulin glargine (stable hyperglycemia group; DM+LAN), and diabetes+once daily insulin glargine with twice daily insulin glulisine (unstable glucose fluctuation group; DM+Lantus [LAN]+Apidra [API]). We measured anti-oxidant enzyme levels and behavioral responses against tactile, thermal, and pressure stimuli in the plasma of rats. We also performed a quantitative comparison of cutaneous and sciatic nerves according to glucose fluctuation.Results: At week 24, intraepidermal nerve fiber density was less reduced in the insulin-administered groups compared to the DM group (P0.05; 16.2±1.6, 12.4±2.0, 14.3±0.9, and 13.9±0.6 for NOR, DM, DM+LAN, and DM+LAN+API, respectively). The DM group exhibited significantly decreased glutathione levels compared to the insulin-administered groups (2.64±0.10 μmol/mL, DM+LAN; 1.93±0.0 μmol/mL, DM+LAN+API vs. 1.25±0.04 μmol/mL, DM; P

Background Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P

Primary aldosteronism is now recognized as the most common cause of secondary hypertension. Increasing evidence has demonstrated increased cardiovascular events in primary aldosteronism patients. Heart failure and atrial fibrillation are the most common cardiovascular complications occurring in these patients, and a few cases of coronary artery disease have been reported. Herein, we report a rare case of primary aldosteronism in a patient who presented with myocardial infarction associated with coronary embolism.A 52-year-old woman was admitted to our hospital because of chest pain. ST-segment elevation was observed on an electrocardiogram. Although no significant stenosis was observed, embolization of the far distal left anterior descending artery was noticed on angiography. Blood test results revealed hypokalemia and increased aldosterone-renin ratio. Abdominal computed tomography revealed an adenoma in the left adrenal gland. After adrenalectomy, the serum potassium level normalized, and blood pressure was well controlled.Primary aldosteronism must be considered in patients who have had various cardiovascular diseases, including embolisms and situations in which the discrimination of secondary hypertension is necessary.

Background Real-world data analysis is useful for identifying treatment patterns. Understanding drug prescription patterns of type 2 diabetes mellitus may facilitate diabetes management. We aimed to analyze treatment patterns of type 2 diabetes mellitus using Observational Medical Outcomes Partnership Common Data Model based on electronic health records. Methods This retrospective, observational study employed electronic health records of patients who visited Jeonbuk National University Hospital in Korea during January 2000–December 2019. Data were transformed into the Observational Medical Outcomes Partnership Common Data Model and analyzed using R version 4.0.3 and ATLAS ver. 2.7.6. Prescription frequency for each anti-diabetic drug, combination therapy pattern, and prescription pattern according to age, renal function, and glycated hemoglobin were analyzed. Results The number of adults treated for type 2 diabetes mellitus increased from 1,867 (2.0%) in 2000 to 9,972 (5.9%) in 2019. In the early 2000s, sulfonylurea was most commonly prescribed (73%), and in the recent years, metformin has been most commonly prescribed (64%). Prescription rates for DPP4 and SGLT2 inhibitors have increased gradually over the past few years. Monotherapy prescription rates decreased, whereas triple and quadruple combination prescription rates increased steadily. Different drug prescription patterns according to age, renal function, and glycated hemoglobin were observed. The proportion of patients with HbA1c ≤ 7% increased from 31.1% in 2000 to 45.6% in 2019, but that of patients visiting the emergency room for severe hypoglycemia did not change over time. Conclusion Medication utilization patterns have changed significantly over the past 20 years with an increase in the use of newer drugs and a shift to combination therapies. In addition, various prescription patterns were demonstrated according to the patient characteristics in actual practice. Although glycemic control has improved, the proportion within the target is still low, underscoring the need to improve diabetes management., Graphical Abstract

Observational Health Data Sciences and Informatics is an international collaboration created an international data network of researchers (Observational Medical Outcomes Partnership Common Data Model, OMOP-CDM). This retrospective, observational study was aim to analyze treatment patterns of type 2 diabetes mellitus (T2DM) using HIRA national patient sample (NPS) from 2012 to 2017 transformed into OMOP-CDM. ATLAS ver. 2.7.6, an OHDSI’s open-source software is publicly available, was used for analysis. HIRA-NPS contain about 1.4 million patients. The proportion of adult patients treated for T2DM increased from 78,581 (5.5%) in 2012 to 101,710 (7.0%) in 2017. Ages 50-69 were the most common (47.7% in 2017), and T2DM was most noticeably increased from 28.7% to 44.9% among those aged 70 and over for 5 years. Metformin was the most prescribed drug (82.8%) followed by sulfornylurea (SU) (62.4%), DPP-4 inhibitor (29.5%) in 2012. In 2017, metformin was still the most prescribed (87.0%), and DPP-4 inhibitor prescription increased rapidly up to 62.7%, while the SU prescription rate decreased to 46.5%. Prescription of the most recently approved SGLT2 inhibitors also continued to increase, reaching 7.2% in 2017. The rate of insulin prescription decreased from 20.2% to 17.5%. Over time, mono and dual therapy decreased while triple and quadruple combinations steadily increased. Dual combination was the most common with metformin and DPP-4 inhibitor, triple combination was the most with metformin, SU, and DPP-4 inhibitor in 2017. Drug prescriptions for hypertension remained unchanged from 71.2% in 2012 to 70.0% in 2017, while prescriptions for dyslipidemia increased from 50.7% in 2012 to 68.4% in 2017. Antiplatelet drugs prescriptions decreased slightly from 47.3% to 42.6%. T2DM is constantly increasing, and medication utilization patterns have changed significantly over the past 5 years with a shift towards newer drugs. Disclosure K. Lee: None. H. Jin: None. Y. Kim: None. T. Park: None.

Herein, we report a case of rupture of nonfunctional adrenal adenoma treated by nonsurgical supportive management due to high risk for operation. A patient with end stage renal disease (ESRD) who was on hemodialysis visited our emergency room and complained of a sudden abdominal pain after a fall. A retroperitoneal hemorrhage with hematoma formation around the adrenal adenoma, which was caused by rupture of the adrenal adenoma, was detected by abdominal computed tomography (CT). Supportive management was performed, with serial CT follow-up instead of surgical adrenalectomy treatment because of high operative risk, due to hemodialysis. After 1 week, the patient’s vital signs stabilized and the patient did not further complain about abdominal symptoms. However, supportive embolization was performed and the size of hematoma was more decreased. We report a case of a patient on hemodialysis who experienced a rupture of a nonfunctioning adrenal adenoma, which was caused by low-energy trauma. The patient’s conditions improved with nonsurgical supportive management including embolization. Physicians should consider both surgical and nonsurgical management for the rupture of adrenal adenomas, depending on the patient situation. Therefore, nonsurgical supportive management such as embolization can be one therapeutic option for treating nonfunctioning adrenal adenoma rupture caused by low-energy trauma in a patient who has risks for operation due to combined comorbidities.

The worldwide diabetes epidemic is estimated to currently afflict almost 500 million persons. Long-term diabetes damages multi ple organ systems with the blood vessels, eyes, kidneys and nervous systems being particularly vulnerable. These complications of diabetes reduce lifespan, impede quality of life and impose a huge social and economic burden on both the individual and society. Peripheral neuropathy is a debilitating complication that will impact over half of all persons with diabetes. There is no treatment for diabetic neuropathy and a disturbingly long history of therapeutic approaches showing promise in preclinical studies but fail ing to translate to the clinic. These failures have prompted re-examination of both the animal models and clinical trial design. This review focuses on the functional and structural parameters used as indices of peripheral neuropathy in preclinical and clinical studies and the extent to which they share a common pathogenesis and presentation. Nerve conduction studies in large myelinat ed fibers have long been the mainstay of preclinical efficacy screening programs and clinical trials, supplemented by quantitative sensory tests. However, a more refined approach is emerging that incorporates measures of small fiber density in the skin and cornea alongside these traditional assays at both preclinical and clinical phases.

Background Human common salivary protein 1 (CSP1) is one of a variety of molecules in saliva but its function remains to be determined. The gold standard method for diagnosis of diabetes mellitus (DM) is to check levels of glucose or HbA1C in plasma or serum. The purpose of this study was to examine whether Salivary CSP1 concentration would be useful alternative for DM diagnosis. Methods The qualities of monoclonal antibodies (mAbs) to recombinant human CSP1 (rhCSP1) were tested by western blotting (WB) and immunohistochemistry. A sandwich ELISA was fabricated with the qualified capture and detector mAbs for measurement of CSP1 level in saliva. CSP1 levels of healthy adults and DM patients were measured by the sandwich ELISA and their results were statistically analyzed by Student's t-test. The receiver operating characteristic (ROC) curve was constructed and the area under the curve (AUC) was calculated. Results The tested mAbs recognized a 27-kDa CSP1 of saliva in WB and stained only a salivary gland in immunohistochemistry. Pearson's correlation coefficient with standard curve between OD450nm value vs. CSP level showed good linearity (r2 = 0.995). The median values (25th to 75th percentiles) of saliva CSP1 in 10 healthy adults and 18 DM patients using the sandwich ELISA were 3.92 µg/mL (3.15 - 4.02) and 4.35 µg/mL (3.94 - 5.11), respectively. Statistically, there was a significant difference of CSP1 level in two groups (p = 0.026). The sensitivity value of CSP1 was 64.71 while the specificity value was 88.89 with 0.784 of AUC (p = 0.003). These results suggested that the fabricated sandwich ELISA was a good diagnostic test tool for discriminating DM patients from healthy individuals. Conclusions The present data showed a significant increase of CSP1 levels for DM patients compared with control group, indicating that CSP1 level in saliva could be used as a potential biomarker of detection or screening of DM patients. However, further studies are necessary to provide scientific and clinical validation.

The comparative effectiveness of oral hypoglycemic agents on glycemic control and chronic complications in clinical practice is unknown in Korea. This study aimed to compare glycemic control and the incidence of hypoglycemia and chronic complications among adult patients with type 2 diabetes prescribed metformin, dipeptidyl peptidase-4 inhibitors (DPP4I), and sulfonylurea (SU) as monotherapy or dual combination therapy.We retrospectively analyzed propensity-matched cohort data from 3 national university hospitals in Korea. All electronic health records were transformed into a unified Observational Medical Outcomes Partnership Common Data Model and analyzed using ATLAS, an open-source analytical tool, and R software. Glycemic control was assessed as the first observation of a reduction in glycosylated hemoglobin (HbA1c) level below 7% after prescription of the drug. Differences in the incidence of chronic complications were compared based on the first observation of each complication. Glycemic control and chronic complications were evaluated in patients who maintained the same prescription for at least 3 and 12 months, respectively.Patients who received metformin had lower hazard of reaching HbA1c levels below 7% as compared with those who received SU, and had higher hazard compared with those who received DPP4I (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.98; and HR, 1.68; 95% CI, 1.42-1.99, respectively). The incidence of hypoglycemia was significantly higher in the SU group than in the metformin and DPP4I groups (metformin vs SU; HR, 0.30; 95% CI, 0.21-0.43; SU vs DPP4I; HR, 4.42; 95% CI, 2.35-8.31). Metformin + DPP4I had similar hazard of reaching HbA1c levels below 7% compared with metformin + SU (HR, 1.19; 95% CI, 0.99-1.43) and the incidence of hypoglycemia was significantly lower in the metformin + DPP4I group (HR 0.13; 95% CI 0.05-0.30). There was no significant difference in the analysis of the occurrence of chronic complications.SU followed by metformin was effective, and both drugs showed an increased hazard of reaching HbA1c levels below 7% compared with DPP4I. Metformin + DPP4I is comparatively effective for HbA1c level reduction below 7% compared with metformin + SU. Hypoglycemia was high in the SU-containing therapy.

Aim: Cardiac autonomic neuropathy (CAN) is a common and important chronic complication in diabetic patients. Heart failure resulting from cardiomyopathy is also a lethal complication in diabetic pa...

In this review, we consider the diverse risk factors in diabetes patients beyond hyperglycemia that are being recognized as contributors to diabetic peripheral neuropathy (DPN). Interest in such alternative mechanisms has been encouraged by the recognition that neuropathy occurs in subjects with metabolic syndrome and pre-diabetes and by the reporting of several large clinical studies that failed to show reduced prevalence of neuropathy after intensive glucose control in patients with type 2 diabetes. Animal models of obesity, dyslipidemia, hypertension, and other disorders common to both pre-diabetes and diabetes have been used to highlight a number of plausible pathogenic mechanisms that may either damage the nerve independent of hyperglycemia or augment the toxic potential of hyperglycemia. While pathogenic mechanisms stemming from hyperglycemia are likely to be significant contributors to DPN, future therapeutic strategies will require a more nuanced approach that considers a range of concurrent insults derived from the complex pathophysiology of diabetes beyond direct hyperglycemia.

Aims We investigated the specificity of the 75 g oral glucose tolerance test (OGTT) and the clinical usefulness of the 2 h post loading glucose (2 h PLG) value in the clinical care of diabetes patients. Methods The 75 g OGTT data of 1755 subjects were analyzed. The relationships and degrees of consistency among 2 h PLG, fasting plasma glucose (FPG), and HbA1c values were assessed. We also investigated the degree of contribution of 2 h PLG in the prescription of glucose-lowering agents and in the pitfall group for use of 75 g OGTT. Results Among 595 subjects with normal FPG, only 329 (55.3%) showed normal 2 h PLG level, and 66 (11.1%) patients could be considered as having diabetes. Among 454 diabetes patients (based on FPG and HbA1c), 409(90.1%) showed 2 h PLG values in the range of diabetes, 45 (9.9%) subjects did not exhibit diabetes. Pitfall group who used 75 g OGTT for diagnosis diabetes (lower 2 h PLG value compared to fasting and upper 2 h PLG value compared to fasting) showed differences in body weight and height. Conclusions Based on OGTT results, around 10% patients cannot be diagnosed with diabetes based solely on the 2 h PLG value. Further studies on differences in glucose loading according to body weight, individual life pattern, and calorie requirement are needed for improvement of the specificity of the OGTT in the clinical management of diabetes.

Analyzing the treatment patterns of type 2 diabetes (T2DM) in real practice helps to understand the flow of diabetes management and establish further management plans. Observational Health Data Sciences and Informatics (OHDSI) is an international collaboration created an international data network (Observational Medical Outcomes Partnership Common Data Model, OMOP-CDM). This study was aim to analyze treatment patterns of T2DM using the OMOP-CDM based on electronic health record (EHR) data and to assess whether CDM analysis was feasible to diabetes research. This is a retrospective, observational study using the EHR data of Jeonbuk National University Hospital (JNUH) transformed into OMOP-CDM. The data consisted of medical records of patients visits from January 2000 to December 2019. ATLAS ver. 2.7.6, an OHDSI’s open-source software is publicly available, was used for analysis. The 20 year old EHR data of a JNUH contain about 1.5 million patients. The proportion of adult patients treated for T2DM increased from 1,867 (1.6%) in 2000 to 9,972 (5.1%) in 2019. Sulfonylurea (SU) was the most prescribed drug (73%) followed by metformin (55%) in 2000. On the other hand, in 2019, metformin was the most prescribed (64%), and DPP-4 inhibitor prescription increased rapidly up to 55%, while the SU prescription rate decreased to 36%. The rate of insulin treatment ranged from 16% to 24%, which is higher than national surveyed based on health insurance data. Over time, monotherapy decreased while dual, triple, and quadruple combinations steadily increased. Dual combination was the most common with metformin and DPP-4 inhibitor, triple combination was the most with metformin, SU, and DPP-4 inhibitor in 2019. In analysis of annual HbA1c trends, the proportion of patients with HbA1c of 7% or lower increased (from 32.8% 2000 to 50.2% in 2019). Proportion of patients with HbA1c of 9% or more decreased from 30% to 12%. However, it was found that about half of T2DM patients still had HbA1c values above the target range. In addition, the number of patients who visited our emergency room for severe hypoglycemia did not decrease. Present study revealed that CDM analysis was feasible for diabetes research. Medication utilization patterns have changed significantly over the past 20 years with a shift towards newer drugs. Despite these changes and clinical efforts, improvement in glycemic control is still a challenge and hypoglycemic is still a problem to overcome.

Background: Nonfunctioning pituitary adenomas (NFPAs) are most common pituitary tumors, and primary pituitary gland malignancies are extremely rare. Most malignant pituitary gland lesions metastasize from other sites. Primary malignant lesions, such as sarcomas, usually develop after radiotherapy or chemotherapy for other diseases. We report a rare case of primary sellar leiomyosarcoma (LMS) without prior therapy that arose concurrently with a pituitary adenoma. Clinical Case: A 56-year-old woman with ptosis of the right eye, headache, and progressive visual deficits visited our neurosurgery department. She had no medical history besides hypertension. Twelve months ago, she was referred to us because of decreased visual acuity and a 3.5×3.6-cm-sized pituitary mass detected on brain MRI. Normal pituitary functions with mild hyperprolactinemia suggested a nonfunctioning pituitary mass with stalk compression. After transsphenoidal surgery, histopathology revealed a pituitary adenoma; MRI immediately post-surgery revealed no grossly remnant lesion. However, during the current visit, sellar MRI revealed a re-growing mass in the pituitary fossa extending to the sphenoid sinus and compressing the optic chiasm with a suprasellar extension. Functional endoscopic sinus surgery was performed, and histopathology revealed a composite tumor, i.e., a mesenchymal tumor with a pituitary adenoma. On immunohistochemical staining, smooth muscle actin, synaptophysin, and chromagranin were positive; tumor cell mitosis was observed at 7/10 high-power fields. Finally, a composite tumor of myxoid leiomyosarcoma and pituitary adenoma was diagnosed. Hence, systemic chemotherapy with radiotherapy was planned for the remnant lesion. Hormonal replacement therapy with hydrocortisone and thyroxine was also started for subsequent hypopituitarism. Conclusion: NFPA is benign and has good prognosis if it is not grow in size or is completely resected. Conversely, primary sarcomas, such as LMS, show rapid extension and aggressive local invasion. Although their incidence is extremely rare, few primary pituitary sarcoma cases with or without pituitary adenoma have been reported. In the former case, initial diagnosis of pituitary adenoma may lead to delayed diagnosis of combined malignant lesions. Thus, clinicians should consider this possibility and high index of suspicion is required when diagnosing a pituitary mass.

Background: Metformin is widely marketed medication for the treatment of diabetes, but its pharmacological effect on diabetic peripheral neuropathy remains unclear. In this study, the effect of metformin on peripheral nerves in diabetic rats was investigat ed using diverse neuronal parameters of nerve fibers. Methods: Rats were assigned to one of four groups (n=7 to 10 per group): normal, diabetes mellitus (DM), DM+metformin (100 mg/kg), and DM+alpha lipoic acid (ALA, 100 mg/kg). DM was induced by streptozotocin/high-fat diet (STZ/HFD). After 12 weeks, the sensory thresholds to mechanical and heat stimuli were assessed. Repeated sensory tests, immunofluorescence micro scopic comparison of peripheral nerves, and biochemical blood analysis were performed after 24 weeks. Results: Both DM+metformin and DM+ALA groups showed similar trends to diverse sensory tests at 24 weeks compared to DM group although the degree of change were different according to the stimulated senses. There was no significant difference in the comparison of the intraepidermal nerve fiber density (IENFD) of peripheral nerves between the DM+metformin and DM+ALA groups (11.83±0.07 fibers/mm vs. 12.37±1.82 fibers/mm, respectively). Both groups showed preserved IENFD significantly compared with DM group (8.46±1.98 fibers/mm, P

Objective: The aim was to investigate the glucose profiles and compare the degree of glycemic variability between kidney and liver transplantation patients during the early postoperative period. Methods: The continuous glucose monitoring (CGM) data of 31 patients including 24 with kidney transplantation (KT) and seven with liver transplantation (LT) were analyzed. Results: Post-transplantation diabetes mellitus (PTDM) occurred in 42.1% (8/19) and 16.7% (1/6) of KT and LT patients, respectively, during this early period after transplantation, except for patients with preexisting diabetes (5 KT, 1 LT). Glycemic variability after LT was better than that in KT patients. The average mean amplitude of glycemic excursion (MAGE) and mean absolute glucose (MAG) levels were 91.18±26.51 vs. 65.66±22.55 (P Conclusion: The transplanted organ is also an important factor affecting glucose control and the occurrence of PTDM in patients who receive transplantation. Further studies involving CGM follow-up at regular intervals in PTDM or preexisting diabetic patients after KT or LT may clarify the role of transplanted organs in glucose control in recipients of organ transplants. Disclosure H. Jin: None. Y. Kim: None. K. Lee: None. T. Park: None.

Background: The most common cause of hypopituitarism is pituitary adenoma. In recent years there is increased reporting of rare causes of hypopituitarism acquired in adulthood, such as other sellar and parasellar masses, brain damage, vascular lesions, infiltrative/immunological/inflammatory diseases and infectious diseases. We report an unusual case of hypopituitarism associated with simultaneously occurring suprasellar tumor and meningitis. Clinical case: A 45-year-old man was brought to the Emergency Department after being found collapsed at his home with a reduced level of consciousness. About 1 week ago, the patient was complaint headache, nausea and vomiting. He had no significant medical history. His initial assessment showed a blood pressure of 130/70 mmHg, heart rate 133/min, and body temperature 38.5 ºC. Initial laboratory finding revealed serum sodium level of 149 mmol/L (135-150), potassium level of 4.3 mmol/L (3.5-5.5), serum osmolality 292 mOsm/Kg (275-295) and urine osmolality 504 mOsm/Kg (400-800). His random cortisol level was 31.8 ug/dl, TSH 0.568 uIu/ml (0.55-4.78), and free T4 10.75 pmol/L (11.5-22.7). From clinical examination and initial investigations, he was diagnosed as having meningitis or encephalitis and was promptly commenced on empirical i.v. antibiotics. The magnetic resonance imaging (MRI) of the brain revealed diffuse leptomeningeal enhancement in both cerebral hemisphere and 1.8*1.5*1.1cm sized, oval-shaped mass in suprasellar portion, which combined peripheral edema. Examination of the cerebrospinal fluid (CSF) following lumbar puncture confirmed meningitis, antibiotics and antiviral agent were continued. After 2 weeks, he suddenly underwent hypotension and polyuria, despite inflammatory markers of blood were improved. Laboratory finding showed serum osmolality 337 mOsm/Kg, urine osmolality 271 mOsm/Kg, serum sodium 153 mmol/L, random cortisol 1.3 ug/dl, and free T4 5.19 uIu/ml. When coupled with the initial results of the brain imaging, this result helped to confirm a hypopituitarism associated with suprasellar tumor and meningitis. The patient's clinical status promptly improved with intravenous hydrocortisone and desmopressin. After that, levothyroxine supplement was started. He had good response to hormone replacement. Conclusion: Hypopituitarism may develop rapidly or slowly depending on the underlying etiology and may involve one, multiple, or all of the pituitary hormones. The clinical presentations of hypopituitarism are usually nonspecific and the recognition of these patients remains the challenge. We emphasize the importance of careful clinical assessment and focused investigations, including cranial imaging and pituitary hormone profiling to establish the underlying diagnosis.

Objective. This study used a continuous glucose monitoring system (CGMS) to investigate the glucose profiles and assess the degree of hyperglycemic excursion after kidney or liver transplantation during the early period after operation. Methods. Patients to whom a CGMS was attached during a postoperative period of approximately one month after transplantation were included. The CGM data of 31 patients including 24 with kidney transplantation (KT) and seven with liver transplantation (LT) were analyzed. Results. Hyperglycemia over 126 mg/dL (fasting) or 200 g/dL (postprandial) occurred in 42.1% (8/19) and 16.7% (1/6) of KT and LT patients, respectively, during this early period after transplantation, except for patients with preexisting diabetes (5 KT, 1 LT). The average mean amplitude of glycemic excursion (MAGE) and mean absolute glucose (MAG) levels were 91.18±26.51 vs. 65.66±22.55 (P<0.05) and 24.62±7.78 vs. 18.18±7.07 (P<0.05) in KT vs. LT patients, respectively, in patients without preexisting DM or PTDM patients who showed normal glucose levels. Average increase from the lowest level to the peak glucose value was higher in KT patients than LT patients (P<0.05). Conclusions. The transplanted organ also needs to be considered as an important factor affecting glucose control and the occurrence of more severe glucose excursions in patients who receive transplantation although immunosuppression agents are well-known important factors; however, our study was limited to the early posttransplantation period. Further studies involving CGM follow-up at regular intervals based on the time since transplantation are needed.

Although diabetic peripheral neuropathy (DPN) and chemotherapy-induced peripheral neuropathy (CIPN) are different disease entities, they share similar neuropathic symptoms that impede quality of life for these patients. Despite having very similar downstream effects, there have been no direct comparisons between DPN and CIPN with respect to symptom severity and therapeutic responses. We compared peripheral nerve damage due to hyperglycemia with that caused by paclitaxel (PAC) treatment as represented by biochemical parameters, diverse sensory tests, and immunohistochemistry of cutaneous and sciatic nerves. The therapeutic effects of alpha-lipoic acid and DA-9801 were also compared in the two models. Animals were divided into seven groups (n = 7-10) as follows: normal, diabetes (DM), DM + alpha-lipoic acid 100 mg/kg (ALA), DM + DA-9801 (100 mg/kg), paclitaxel-treated rat (PAC), PAC + ALA (100 mg/kg), and PAC + DA-9801 (100 mg/kg). The sensory thresholds of animals to mechanical, heat, and pressure stimuli were altered by both hyperglycemia and PAC when compared with controls, and the responses to sensory tests were different between both groups. There were no significant differences in the biochemical markers of blood glutathione between DM and PAC groups (p .05). Quantitative comparisons of peripheral nerves by intraepidermal nerve fiber density (IENFD) analysis indicated that the DM and PAC groups were similar (6.18 ± 1.03 vs. 5.01 ± 2.57). IENFD was significantly improved after ALA and DA-9801 treatment in diabetic animals (7.6 ± 1.28, 7.7 ± 1.28, respectively, p .05) but did not reach significance in the PAC-treated groups (6.05 ± 1.76, 5.66 ± 1.26, respectively, p .05). Sciatic nerves were less damaged in the PAC-treated groups compared with the DM groups with respect to axonal diameter and area (8.60 ± 1.14 μm vs. 6.66 ± 1.07 μm, and 59.04 ± 15.16 μm

Mean glucose values alone cannot explain the patterns of morbidity and mortality due to dysglycemia in diabetes. Development of continuous glucose monitoring systems has improved the analysis and interpretation of glycemic variability. The roles of glycemic components other than constant hyperglycemia in diabetic complications must be investigated because large clinical studies have indicated that risk factors besides the average glucose value of HbA1c are involved in chronic macrocomplications/microcomplications of diabetes. Among these complications, the pathogenesis of diabetic peripheral neuropathy is particularly complex, and several factors related to glucose and nonglucose pathways have been suggested as risk factors. There is little information regarding the effect of glycemic variability on diabetic peripheral neuropathy, unlike other microvascular complications of retinopathy and nephropathy, and whether glycemic variability causes harmful effects is still a matter of debate. In this review, we discuss the relationships between glycemic variability and diabetic peripheral neuropathy, focusing on somatosensory peripheral neuropathies rather than autonomic neuropathies.

Background Recently, the human common salivary protein 1 (CSP1) was identified as an ortholog of the Demilune cell and parotid protein of mouse. However, its function remains to be determined. Here, we show that the serum CSP1 concentration of diabetes mellitus (DM) patients is much higher than that of healthy controls. Methods Recombinant human CSP1 was expressed as a Glutathione-S-transferase (GST)-tagged protein, and the purified fusion protein was used as an immunogen to generate monoclonal antibody (mAb) to CSP1. The produced mAb was tested as a probe in Western blotting of human saliva and in immunohistochemistry of various human tissues. The serum CSP1 levels of 31 DM patients and 38 normal adults were quantified by a house-fabricated CSP1 sandwich enzyme-linked immunosorbent assay (ELISA) system. Results Immunoblot analysis by mAb-hCSP1#4 showed that CSP1 in human saliva exists in a 27 kDa glycosylated form. Among the various human tissues tested, the salivary gland was the only tissue stained with mAb-hCSP1#4 by immunohistochemistry. Quantification of serum CSP1 concentration by CSP1 ELISA showed that the median values (25th–75th percentile) of DM patients and healthy adults were 22.2 (15.8–28.2) and 3.2 (0–11.4), respectively. Student's t-test results indicated that there was a statistically significant difference between the two groups (P

Objective Although bariatric surgery including gastrectomy has recently emerged as a useful treatment for type 2 DM with obesity, it is not clear whether gastrectomy itself can have beneficial effects on glucose metabolism. Therefore, in this study, we investigated changes in blood glucose in patients with and without diabetes who underwent gastrectomy. Methods From Jan 2010 to May 2014, 77 patients with diabetes and 77 patients without diabetes who underwent gastrectomy at Chonbuk National University Hospital, South Korea, were included. We compared fasting plasma glucose levels and HbA1c value before and after gastric surgery. Results After gastrectomy, 59 patients (38.3%) showed reduced fasting plasma glucose levels at the 1 year point, and 80 patients (51.9%) exhibited reduced fasting plasma glucose at 3 years, irrespective of their diabetes status. Among 77 patients with diabetes, decreased fasting plasma glucose was observed in 22 (28.6%) and 46 patients (59.7%) 1 and 3 years after gastrectomy, respectively. In patients who exhibited reduced fasting plasma glucose after gastrectomy, the degree of reduced glucose was as follows: 56.4±48.5 vs 23.2±16.1 mg/dL after 1 year, 58.3±52.3 vs 18.4±13.7 mg/dL after 3 years, in DM and non-DM patient respectively. Conclusions Although there was a significant drop in mean fasting glucose after gastrectomy, not all patients experienced a drop in fasting glucose. Gastrectomy did not show a consistent association with glucose reduction in patients with and without diabetes, and in about half of the patients, fasting plasma glucose levels increased after gastrectomy. Therefore, bariatric surgery including gastrectomy needs to be performed with care in diabetes, and glucose monitoring including oral glucose tolerance tests should be done for assessing or prediction of the glucose state after gastric surgery in non-DM patients.

Disorders of the endocrine system including hormone hyperfunction and hypofunction have multiple effects on cardiovascular system. However, in clinical practice, there are many cases of delayed or overlooked diagnosis of underlying endocrine dysfunction in patients presenting chest pain or other cardiac symptoms. Herein, we report three cases of endocrine hyperfunction presenting as coronary spasm; Graves’ hyperthyroidism, pheochromocytoma, and primary hyperparathyroidism. Chest pains disappear after treatment for these endocrine diseases. Endocrine hyperfunctions such as the three cases described above should be considered as possible diagnosis in patients with complaint of chest pain. High index of suspicion are needed.

AIMS This descriptive, exploratory, correlational analysis investigated patients with type 2 diabetes and their diabetes knowledge, depression, diabetes-management self-efficacy, and social support and sought to determine the effects of these factors on psychological insulin resistance among type 2 diabetes patients in South Korea. METHODS This descriptive cross-sectional study included 136 patients with type 2 diabetes who visited an endocrinology clinic. A structured questionnaire and electronic medical records were used to collect data regarding demographic and disease-related characteristics as well as scores on the Diabetes Knowledge Tests, Center for Epidemiologic Studies Depression Scale, Diabetes Management Self-efficacy Scale, Social Support Scale, and Psychological Insulin Resistance Scale, between September and December 2017. Data were analysed using descriptive statistics, independent t-tests, a one-way ANOVA, Pearson's correlation coefficient, and stepwise multiple regression. RESULTS The total score for psychological insulin resistance was 60.92 ± 14.75 of a maximum of 90. Stepwise multiple regression showed that diabetes knowledge, diabetes-management self-efficacy, social support, absence of diabetes complications, and depression explained 38.6% of the variance in psychological insulin resistance. CONCLUSION Diabetes knowledge was found to have the largest influence on psychological insulin resistance, followed by social support, absence of complications, depression, and diabetes-management self-efficacy. Development of interventions that consider all these factors is required, and the effects of such interventions should be tested through further research.

Strict glucose control is a well-proven therapeutic approach for peripheral neuropathies in patients with diabetes. Alpha lipoic acid (ALA) has also been accepted as a therapeutic agent for diabetic peripheral neuropathy (DPN) in the respect of pathogenesis. However, the potential of ALA as a treatment for DPN in comparison to that of glucose control is unclear. In this study, we compared the neuroprotective potential of glucose control and ALA. Animals were divided into 6 groups based on the intervention used, as follows: normal, diabetes (DM), DM+racemic form of ALA, DM+R form of ALA, DM+once daily insulin glargine, and DM+once daily insulin glargine with twice daily insulin glulisine. Various sensory tests were performed after 12 weeks of treatment, and immunohistochemistry of nerve fibers obtained from the sciatic and cutaneous nerves was performed after 24 weeks of treatment. There were no significant differences between the ALA-treated and insulin-treated DM groups in the sensory tests or in antioxidant activity. The axonal diameters and myelin sheath area of the sciatic nerves and the cutaneous small nerves, as assessed based on intraepidermal nerve fiber density, were similar in the ALA-treated and insulin-treated animals, although there was a non-significant trend for a mild increase in the both basal and rapid-acting insulin group compared with non-treated DM group. In conclusion, our results suggest that the neuroprotective benefits of ALA and insulin-based glucose control may be similar, although glucose control may have had slightly more beneficial effects in this animal model of diabetes. Of note, glucose levels should be strictly controlled, including corrections for fluctuations in the glucose level, to obtain therapeutic benefits in DPN.

Inflammatory pathway from hyperglycemia to diabetic peripheral neuropathy is very important in diagnosis and management. Inflammatory cytokine can be used for prediction and progression of diabetic peripheral neuropathy.

Background: The Survey of Autonomic Symptom (SAS) scale was reported as an easy instrument to assess the autonomic symp toms in patients with early diabetic neuropathy. In this study, we investigated the relationship between the SAS scale and the parameters of cardiac autonomic neuropathy (CAN) in Korean patients with diabetic peripheral neuropathy (DPN). Methods: The SAS scale was tested in 30 healthy controls and 73 patients with DPN at Chonbuk National University Hospital, in Korea. The SAS score was compared to the parameters of the CAN test and the total symptom score (TSS) for DPN in patients with DPN. Results: The SAS symptom score and total impact score were increased in patients with DPN compared to the control group (P=0.01), particularly in sudomotor dysfunction (P=0.01), and vasomotor dysfunction (P=0.01). The SAS score was increased in patients with CAN compared to patients without CAN (P

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

Present study investigated the morphologic changes of autonomic nerves in the adipose tissue in diabetic animal model. Male obese type 2 diabetic db/db mice and age matched non-diabetic db/m control mice were used. Epididymal adipose tissue from diabetic db/db mice with that from control heterozygous db/m mice was compared using confocal microscopy-based method to visualize intact whole adipose tissue. Immunohistochemistry with tyrosine hydroxylase for sympathetic (SP), choline acetyltransferase for parasympathetic (PSP), and protein gene product 9.5 (PGP 9.5) for whole autonomic nerves was performed. The quantity of immunostained portion of SP, PSP, and PGP 9.5 stained nerve fibers showed decreased trend in diabetic group; however, the ratio of SP/PSP of adipose tissue was higher in diabetic group compared with control group as follows (0.70±0.30 vs. 0.95±0.25, P