Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals

The worldwide diabetes epidemic is estimated to currently afflict almost 500 million persons. Long-term diabetes damages multiple 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 failing 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 myelinated 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.

Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015)

This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance ServiceNational Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients.

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

Comparison of Serum PCSK9 Levels in Subjects with Normoglycemia, Impaired Fasting Glucose, and Impaired Glucose Tolerance

We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations in individuals with normoglycemia, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). This was a pilot, cross-sectional study including 92 individuals who had not been diagnosed with or treated for diabetes. We measured PCSK9 levels in three groups of subjects; namely, normoglycemia (n=57), IFG (n=21), and IGT (n=14). Individuals with IFG and IGT showed higher PCSK9 concentrations than those in the normoglycemic group, with the highest serum PCSK9 concentrations found in individuals with IGT (55.25±15.29 ng/mL for normoglycemia, 63.47±17.78 ng/mL for IFG, 72.22±15.46 ng/mL for IGT, analysis of variance P=0.001). There were no significant differences in high- or low-density lipoprotein cholesterol among groups. Serum PCSK9 levels are increased in patients with prediabetes compared to subjects with normoglycemia.

γ-Linolenic Acid versus α-Lipoic Acid for Treating Painful Diabetic Neuropathy in Adults: A 12-Week, Double-Placebo, Randomized, Noninferiority Trial

Background@#This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). @*Methods@#This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS). @*Results@#Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was −0.65 (−1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ1 =0.51). For the TSS, the treatment difference was −0.05 (−1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ2 =0.054). There were no serious adverse events associated with the treatments. @*Conclusion@#GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.

Clinical Characteristics and Mortality Predictors of COVID-19 Patients Hospitalized at Nationally-Designated Treatment Hospitals

Background@#Coronavirus disease 2019 (COVID-19) was first reported in December 2019 in China, and then it has disseminated worldwide. In Korea, a religious group-related super-spreading event triggered a sudden outbreak in Daegu city and Gyeongsangbuk-do in southeast Korea. This study was undertaken to document the clinical characteristics of patients hospitalized in Gyeongsangbuk-do. @*Methods@#Three hundred and fifty-two patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection hospitalized at Dongguk University Gyeongju Hospital or at the Andong Medical Center between February 18th and June 30th were enrolled in this study. Medical records were reviewed and demographic and clinical features, including comorbidities, symptoms, radiological and laboratory findings on admission were analyzed. In addition, we sought to identify risk factors of mortality. @*Results@#Mean age of the 352 study subjects was 56 years (range, 14–95). The mortality rate was 6.8% and mean age at death was 81 years (range, 57–91). The most common symptom was cough (31.8%) followed by a febrile sensation (28.4%), sputum (17.0%), sore throat (15.6%), and myalgia (13.1%). Eighty-one (23.0%) patients were asymptomatic, but a half of these patients exhibited pneumonic infiltration at presentation. Chest radiology showed no active lesion in 41.8% of the study subjects, bilateral pneumonia in 46.9%, and unilateral pneumonic infiltration in 11.4%. Among 24 patients that died, 18 subjects were transferred from a care facility. An age of ≥ 70 years, previous history of malignancy or diabetes, and fever (≥ 37.5°C) on admission were found to be significant risk factors of mortality. @*Conclusion@#Patients aged ≥ 70 years, those with fever on admission, and patients with an underlying malignancy or diabetes were found to be more likely to succumb to COVID-19.Elderly in care facilities or hospitalized patients with an underlying disease should receive more attention and be considered for preventive quarantine.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement

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.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement / 대한내과학회지

Acromegaly is a chronic disorder caused by excessive growth hormone (GH) secretion. In most cases, the excess GH originates from GH-producing pituitary adenomas. Surgery is the preferred first-line treatment for patients with acromegaly, but medical management is considered when the disease persists after surgery or in cases where patients refuse surgery or are poor candidates for surgery. Somatostatin analogues are commonly used to treat acromegaly. The Korean Endocrine Society and the Korean Neuroendocrine Study Group have developed a position statement for the use of somatostatin analogues in the medical treatment of acromegaly. This position statement is based on evidence from the current literature and expert opinions. In the case of discrepancies among expert opinions, the experts voted to determine the recommended approach.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement / 대한내과학회지

Acromegaly is a chronic disorder caused by excessive growth hormone (GH) secretion. In most cases, the excess GH originates from GH-producing pituitary adenomas. Surgery is the preferred first-line treatment for patients with acromegaly, but medical management is considered when the disease persists after surgery or in cases where patients refuse surgery or are poor candidates for surgery. Somatostatin analogues are commonly used to treat acromegaly. The Korean Endocrine Society and the Korean Neuroendocrine Study Group have developed a position statement for the use of somatostatin analogues in the medical treatment of acromegaly. This position statement is based on evidence from the current literature and expert opinions. In the case of discrepancies among expert opinions, the experts voted to determine the recommended approach.

Diagnosis and Management of Diabetic Peripheral Neuropathy / 임상당뇨병

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and is diagnosed as the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes. The prevalence of DPN was reported at 33.5% of type 2 diabetes patients by the Korean diabetes neuropathy study group. Early diagnosis is recommended to prevent diabetic foot ulcers, amputation, or disability. A questionnaire asking about symptoms and neurologic examination of feet is commonly used as a screening tool. However, complete diagnostic tests for DPN are not well established because of incomplete understanding of the pathogenetic mechanisms leading to the nerve injury, the various clinical manifestations, and the unclear natural history. Therefore, DPN has not been paid sufficient attention by clinicians. The roles of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are well known. Pathogenetically oriented or symptomatic agents are other options, though such treatments do not always produce a satisfactory outcome. Therefore, DPN remains a challenge for physicians to screen, diagnose, and treat. There have been recent advances in understanding the mechanisms underlying DPN and in the development of new diagnostic modalities and treatments. In this review, diagnosis and management of DPN will be discussed.

Association between Blood Mercury Level and Visceral Adiposity in Adults

No abstract available.

A Pregnant Woman with Type 2 Diabetes Unintentionally Exposed to Metformin and Voglibose until the Second Trimester of Pregnancy: A Case Report / 임상당뇨병

Use of oral hypoglycemic agents during pregnant women with type 2 diabetes is controversial due to safety issues. Recently, randomized controlled trials support short-term safety of glyburide and metformin for the treatment of gestational diabetes mellitus. However, long-term safety data are not available. Moreover, use of oral hypoglycemic agents, except for metformin and glyburide, during pregnancy were limited to a few case reports. We report the case of a pregnant woman with type 2 diabetes unintentionally exposed to metformin and voglibose in addition to lercanidipine and bisoprolol during fetal organogenesis. The patient was continuously exposed to oral agents because we were not aware of her pregnancy until 22 weeks of gestation. After pregnancy was confirmed, we replaced oral hypoglycemic agents with insulin and discontinue betablockers. Delivery occurred without maternal or fetal complications.

A Case of Sheehan's Syndrome that Manifested as Bilateral Ptosis

Hypothyroidism can cause a variety of signs and symptoms of the neuromuscular system. However, ptosis in a patient with hypothyroidism is very rare. We report here on a case of central hypothyroidism that was due to Sheehan's syndrome and it manifested as bilateral ptosis in a 51-yr-old woman. She complained of exertional dyspnea and weakness. About 25-yr ago, she had a history of severe postpartum vaginal bleeding. The laboratory studies demonstrated hypopituitarism with secondary hypothyroidism. The ptosis was improved by replacement of thyroid hormone. Hypothyroidism should be considered in the differential diagnosis of patients who manifest with ptosis and that prompt replacement of hormone can lead to a complete recovery.

The Use of HbA1c for Diagnosis of Type 2 Diabetes in Korea / 대한내과학회지

BACKGROUND/AIMS: An HbA1c test result > or = 6.5% has recently been recommended as the defining criterion for diabetes by the American Diabetes Association. We compared the detection of diabetes using oral glucose tolerance test (OGTT)-based and HbA1c-based diagnostic criteria. Additionally, we identified the optimal HbA1c threshold for diabetes in Korea. METHODS: This study was a cross-sectional retrospective design using data from 405 subjects without known diabetes who underwent OGTT and HbA1c tests for the diagnosis of diabetes between January, 2005, and June, 2010, at Dongguk University Gyeongju Hospital, Korea. The OGTT is considered to be the gold standard for diagnosing diabetes. Based on a receiver operating characteristics (ROC) curve, optimal sensitivity and specificity were derived for identifying the HbA1c threshold. RESULTS: For diabetes, HbA1c at 6.5% gave a sensitivity of 52.9%, specificity of 95.1%, positive predictive value of 92.9%, and a negative predictive value of 62.7%. A total of 47.1% of subjects with newly diagnosed diabetes had HbA1c levels <6.5%. Results were similar in sex- and age-stratified analyses. To identify diabetes based on OGTT, the HbA1c threshold of 6.1% had an area under the curve (AUC) of 0.849 with 77.8% sensitivity and 71.7% specificity. CONCLUSIONS: In a Korean population, diabetes prevalence was lower using the HbA1c-based diagnostic criteria. An HbA1c threshold of 6.1% optimally identified diabetes by OGTT-based diagnostic criteria in Korea. Further large-scale, population-based studies are needed to evaluate the HbA1c threshold for diagnosing diabetes in Korea.

A Case of Thyroid Amyloidosis Misrecognized as Subacute Thyroiditis

Amyloid deposition in the thyroid is found in about 30-80% of the patients with primary or secondary amyloidosis. In a few patients with amyloidosis, the thyroid is enlarged and so called amyloid goiter occurs. The thyroid function usually remains normal, but occasionally hypothyroidism or thyrotoxicosis occurs in patients with thyroid amyloidosis. We have experienced one case of thyroid amyloidosis due to bronchiectasis and the patient developed painful goiter and transient thyrotoxicosis resembling subacute thyroiditis. Biopsies from the gastric antrum, duodenum, colon, kidney and thyroid were positive for deposition of amyloid. When patients have signs and symptoms of subacute thyroiditis, but they develop an unusual course, then the diagnosis of thyroid amyloidosis should be considered.

The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes / 당뇨병

BACKGROUND: The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.

Leptin is Negatively Associated with Femoral Bone Mineral Density in Postmenopausal Women with Type 2 Diabetes Mellitus / 당뇨병

BACKGROUND: Serum leptin level and bone mineral density (BMD) are widely assumed to be positively associated with body fat mass. Numerous attempts have been made to document the relationship between leptin and BMD, but the results are inconsistent, especially in diabetic patients. METHODS: A total of 60 Korean postmenopausal women with type 2 diabetes mellitus were included in the present study. The BMDs of lumbar spines (L1 to L4) and proximal femurs (trochanter, neck, and total) were measured by dual-energy X-ray absorptiometry (DXA), and biochemical markers including leptin, HbA1c, C-peptide and urine albumin-creatinine ratio (ACR) were measured for each patient. RESULTS: Negative associations between leptin and BMD of femoral neck, trochanter, and total femur in postmenopausal women with type 2 diabetes mellitus were documented in a model adjusted for age, body fat mass, and fasting insulin level (r = -0.308, P = 0.020 and r = - 0.303, P = 0.025 and r = - 0.290, P = 0.032 respectively). Multiple linear regression analysis was performed revealing negative associations between leptin and BMD of the femoral neck (beta = -0.369), trochanter (beta = -0.324), and total femur (beta = -0.317). CONCLUSION: The results of the present study suggest a negative relationship between leptin and femoral BMD. In addition, leptin may have a negative effect on BMD in postmenopausal women with type 2 diabetes mellitus.

The Association Between Urinary Albumin to Creatinine Ratio and Coronary Artery Calcification in Type 2 Diabetic Patients / 당뇨병

BACKGROUND: Atherosclerosis, the most common cause of death in type 2 diabetic patients, is closely associated with coronary artery calcium deposition. The coronary calcifications can be easily measured using coronary calcium scoring computed tomography (CT). And microalbuminuria is known as an independent risk factor of cardiovascular disease. So, we examined the association of urinary albumin to creatinine ratio (UACR) and coronary calcification score (CCS) in type 2 diabetic patients. METHODS: Among type 2 diabetic patients who underwent the multidetector CT scanning for the evaluation of CCS at Kyungpook National University Hospital between December 2007 and May 2008, 155 subjects were included. CCS, demographic and laboratory data were assessed. RESULTS: Coronary artery calcifications were identified in 90 patients (51%) and mean, median CCS was 205.8 +/- 476.9, 8.74 (0, 132.0). 60 subjects revealed UACR greater than 30 ug/mg. With the UACR increment, CCS revealed a significant increase (P < 0.001). Age, duration of diabetes, serum Apo A1 level, serum high sensitivity C-reactive protein (hs-CRP) level were also associated with CCS. However, after adjusting for age, UACR and CCS exhibited a significant positive relationship (P = 0.002). CONCLUSION: Increased UACR is associated with coronary artery calcification in type 2 diabetic patients and these results will be useful in early evaluating the presence of macrovascular complications in these patients.

The characteristics of non palpable thyroid nodule and relation to prediction of malignant nodule / 대한내과학회지

BACKGROUND: Thyroid nodules are commonly encountered in clinical practice and a p revalence of general population is 19~67% by ultrasonography. We made a study to investigate clinical characteristics, malignancy ratio of thyroid incidentalomas and predicting factors for diagnosis of malignancy, to provide recommendation for evaluation. METHODS: We retrospectively evaluated the medical records of 320 patients who visited Kyungpook National University Hospital from July 2001 to December 2003 with non palpable thyroid nodules. We reviewed physical examination, ultrasonographic findings, laboratory findings, histology of thyroid nodules and did statististic analysis to examine relationship to malignancy. RESULTS: 52 patients revealed papillary carcinomas and malignancy rate whin incidentalomas is 9.3%. Sonographic findings of solid structure, hypoechogenecity, punctate calcification, ill defined margin, irregular shape showed meaningful diagnostic value for malignancy. CONCLUSIONS: Combination of meaningful sonographic findings increased possibility of maliganancy and require active mangements including recurrent fine needle aspiration and surgery if needed.