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대한당뇨병학회> Diabetes and Metabolism Journal (DMJ)> Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals

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Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals

Heung Yong Jin , Seong-su Moon , Nigel A. Calcutt
  • : 대한당뇨병학회
  • : Diabetes and Metabolism Journal (DMJ) 45권1호
  • : 연속간행물
  • : 2021년 01월
  • : 27-42(16pages)

DOI


목차

DIABETIC NEUROPATHY
CLINICAL ASSESSMENT OF DIABETIC NEUROPATHY
MODELS OF DIABETIC NEUROPATHY
CONCLUSIONS AND SPECULATION
CONFLICTS OF INTEREST
ORCID
FUNDING
ACKNOWLEDGMENTS
REFERENCES

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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.

UCI(KEPA)

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  • : 의약학분야  > 내과학
  • : KCI등재
  • : SCI,SCOPUS
  • : 격월
  • : 2233-6079
  • :
  • : 학술지
  • : 연속간행물
  • : 1972-2021
  • : 2808


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1Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status

저자 : Chan-hee Jung , Jang Won Son , Shinae Kang , Won Jun Kim , Hun-sung Kim , Hae Soon Kim , Mihae Seo , Hye-jung Shin , Seong-su Lee , Su Jin Jeong , Yongin Cho , Seung Jin Han , Hyang Mi Jang , Mira Rho

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 1-13 (13 pages)

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Background: This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data.
Methods: This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated.
Results: In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes.
Conclusion: The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

2Treatment of Diabetic Kidney Disease: Current and Future

저자 : Tomotaka Yamazaki , Imari Mimura , Tetsuhiro Tanaka , Masaomi Nangaku

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 11-26 (16 pages)

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Diabetic kidney disease (DKD) is the major cause of end-stage kidney disease. However, only renin-angiotensin system inhibitor with multidisciplinary treatments is effective for DKD. In 2019, sodium-glucose cotransporter 2 (SGLT2) inhibitor showed efficacy against DKD in Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, adding a new treatment option. However, the progression of DKD has not been completely controlled. The patients with transient exposure to hyperglycemia develop diabetic complications, including DKD, even after normalization of their blood glucose. Temporary hyperglycemia causes advanced glycation end product (AGE) accumulations and epigenetic changes as metabolic memory. The drugs that improve metabolic memory are awaited, and AGE inhibitors and histone modification inhibitors are the focus of clinical and basic research. In addition, incretin-related drugs showed a renoprotective ability in many clinical trials, and these trials with renal outcome as their primary endpoint are currently ongoing. Hypoxia-inducible factor prolyl hydroxylase inhibitors recently approved for renal anemia may be renoprotective since they improve tubulointerstitial hypoxia. Furthermore, NF-E2-related factor 2 activators improved the glomerular filtration rate of DKD patients in Bardoxolone Methyl Treatment: Renal Function in chronic kidney disease/Type 2 Diabetes (BEAM) trial and Phase II Study of Bardoxolone Methyl in Patients with Chronic Kidney Disease and Type 2 Diabetes (TSUBAKI) trial. Thus, following SGLT2 inhibitor, numerous novel drugs could be utilized in treating DKD. Future studies are expected to provide new insights.

3Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals

저자 : Heung Yong Jin , Seong-su Moon , Nigel A. Calcutt

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 27-42 (16 pages)

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(기관인증 필요)

초록보기

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.

4The Role of Adipose Tissue Lipolysis in Diet-Induced Obesity: Focus on Vimentin

저자 : Eun Roh , Hye Jin Yoo

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 43-45 (3 pages)

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5Importance of Awareness and Treatment for Diabetes in Influenza Vaccination Coverage of Diabetic Patients under 65 Years: A Population-Based Study

저자 : Yu Mi Ko , Seung Hyun Ko , Kyoungdo Han , Yong-moon Park , Joon Young Choi , Shin Young Kim , So Hyang Song , Chi Hong Kim , Sung Kyoung Kim

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 45-56 (12 pages)

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Background: Influenza is a global public health problem causing considerable morbidity and mortality. Although vaccination is the most effective way to prevent infection, vaccination coverage is insufficient in people with chronic disease under 65 years, especially diabetes. The purpose of this study was to evaluate influenza vaccination coverage and identify factors associated with influenza vaccination in Korean diabetic adults under 65 years.
Methods: Data were obtained from 24,821 subjects in the Korea National Health and Nutrition Examination Survey (2014 to 2017). Socioeconomic, health-related, and diabetic factors were investigated for their relations with influenza vaccination in diabetic patients under 65 years using univariate and multivariate analyses.
Results: Among 24,821 subjects, 1,185 were diabetic patients under 65 years and their influenza vaccination rate was 36.5%. Socioeconomic (older age, female gender, non-smoker, light alcohol drinker, lower educational level, and employed status), health-related factors (lower fasting glucose and glycosylated hemoglobin level, good self-perceived health status, more comorbidities, recent health screening, more outpatient visits, and diet therapy), and diabetic factors (more awareness and getting treated) were associated with influenza vaccination. In multivariate analysis, more awareness and getting treated for diabetes were associated with influenza vaccination in diabetic patients under 65 years (odds ratio, 1.496 and 1.413; 95% confidence interval, 1.022 to 2.188 and 1.018 to 2.054, respectively).
Conclusion: Influenza vaccination rate was low in diabetic patients under 65 years, especially in those with unawareness and not getting treated for diabetes. Active screening and treatment for diabetes may be helpful to improve the influenza vaccination rate in these patients.

6Persistent Anxiety Is Associated with Higher Glycemia Post-Transition to Adult Services in Asian Young Adults with Diabetes

저자 : Ling Zhu , Suresh Rama Chandran , Wee Boon Tan , Xiaohui Xin , Su-yen Goh , Daphne Su-lyn Gardner

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 45-56 (12 pages)

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Background: There is little longitudinal information on psychological burden and metabolic outcomes in young adults with diabetes (YAD) in Asia. We aimed to evaluate the association between psychological status and glycemia at baseline and 2 years following transition in a cohort of YAD in Singapore.
Methods: Subjects with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), aged 17 to 25 years, were recruited from the YAD clinic in Singapore General Hospital. The Hospital Anxiety and Depression and Problem Areas for Diabetes scales were administered at transition (baseline) and at 18 to 24 months. Glycosylated hemoglobin (HbA1c) assessed during routine visits was tracked longitudinally.
Results: A total of 98 T1DM (74.8%) and 33 T2DM (25.2%) subjects were recruited between January 2011 and November 2017. At baseline, mean HbA1c was 8.6%±1.7%. Only 26.0% achieved HbA1c of ≤7.5% and 16.8% achieved HbA1c of <7%. At baseline, prevalence of anxiety was 29.8%. At 24 months, 14.1% had persistent anxiety. Those with persistent anxiety had the highest mean HbA1c, particularly at 6 months (persistently anxious vs. persistently non-anxious: 9.9%±1.2% vs. 8.2%±1.9%, P=0.009). At baseline, 9.2% of subjects had depression. This group also had poorer glycemia at baseline (HbA1c of depressed vs non-depressed: 9.6%±2.1% vs. 8.5%±1.6%, P=0.04), which persisted up to 24 months.
Conclusion: The majority of YAD in Singapore have suboptimal glycemia. Psychological distress is a critical harbinger of poorer metabolic outcomes.

7Age at Diagnosis and the Risk of Diabetic Nephropathy in Young Patients with Type 1 Diabetes Mellitus

저자 : Jong Ha Baek , Woo Je Lee , Byung-wan Lee , Soo Kyoung Kim , Gyuri Kim , Sang-man Jin , Jae Hyeon Kim

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 46-54 (9 pages)

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Background: The aim of this study was to evaluate characteristics and risk of diabetic complications according to age at diagnosis among young adults with type 1 diabetes mellitus (T1DM).
Methods: A total of 255 T1DM patients aged less than 40 years were included. Patients were categorized into three groups (<20, 20 to 29, and 30 to 40 years) according to age at diagnosis. Diabetic nephropathy (DN) was defined when spot urine-albumin creatinine ratio was 300 mg/g or more and/or estimated glomerular filtration ratio (eGFR) level was 60 mL/min/1.73 m2 or less.
Results: Median age at diagnosis was 25 years and disease duration was 14 years. Individuals diagnosed with T1DM at childhood/adolescent (age <20 years) had lower stimulated C-peptide levels. They received more intensive insulin treatment with higher total daily insulin doses compared to older onset groups. The prevalence of DN was higher in the childhood/adolescent-onset group than in older onset groups (25.3% vs. 15.3% vs. 9.6%, P=0.022). The eGFR was inversely associated with disease duration whilst the degree of decrease was more prominent in the childhood/adolescent-onset group than in the later onset group (aged 30 to 40 years; P<0.001). Childhood/adolescent-onset group was independently associated with the risk of DN compared to the older onset group (aged 30 to 40 years; odds ratio, 3.47; 95% confidence interval, 1.45 to 8.33; P=0.005).
Conclusion: In individuals with childhood/adolescent-onset T1DM, the reduction in renal function is more prominent with disease duration. Early age-onset T1DM is an independent risk of DN.

8Metagenomic Analysis of the Gut Microbiome Reveals Enrichment of Menaquinones (Vitamin K2) Pathway in Diabetes Mellitus

저자 : Nihar Ranjan Dash , Mohammad Tahseen Al Bataineh

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 77-90 (14 pages)

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Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with a high prevalence worldwide, especially among overweight and obese populations. T2DM is multifactorial with several genetic and acquired risk factors that lead to insulin resistance. Mounting evidence indicates that alteration of gut microbiome composition contribute to insulin resistance and inflammation. However, the precise link between T2DM and gut microbiome role and composition remains unknown.
Methods: We evaluated the metabolic capabilities of the gut microbiome of twelve T2DM and six healthy individuals through shotgun metagenomics using MiSeq platform.
Results: We identified no significant differences in the overall taxonomic composition between healthy and T2DM subjects when controlling for differences in diet. However, results showed that T2DM enriched in metabolic pathways involved in menaquinone (vitamin K2) superpathway biosynthesis (PWY-5838) as compared to healthy individuals. Covariance analysis between the bacterial genera and metabolic pathways displaying difference in abundance (analysis of variance P< 0.05) in T2DM as compared to healthy subjects revealed that genera belonging Firmicutes, Actinobacteria, and Bacteroidetes phyla contribute significantly to vitamin K2 biosynthesis. Further, the microbiome corresponding to T2DM with high glycosylated hemoglobin (HbA1c) ( >6.5%) exhibit high abundance of genes involved in lysine biosynthesis and low abundance of genes involved in creatinine degradation as compared to T2DM with lower HbA1c (<6.5%).
Conclusion: The identified differences in metabolic capabilities provide important information that may eventually lead to the development of novel biomarkers and more effective management strategies to treat T2DM.

9Notch1 Has an Important Role in β-Cell Mass Determination and Development of Diabetes

저자 : Young Sil Eom , A-ryeong Gwon , Kyung Min Kwak , Jin-young Youn , Heekyoung Park , Kwang-won Kim , Byung-joon Kim

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 86-97 (12 pages)

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Background: Notch signaling pathway plays an important role in regulating pancreatic endocrine and exocrine cell fate during pancreas development. Notch signaling is also expressed in adult pancreas. There are few studies on the effect of Notch on adult pancreas. Here, we investigated the role of Notch in islet mass and glucose homeostasis in adult pancreas using Notch1 antisense transgenic (NAS).
Methods: Western blot analysis was performed for the liver of 8-week-old male NAS mice. We also conducted an intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test in 8-week-old male NAS mice and male C57BL/6 mice (control). Morphologic observation of pancreatic islet and β-cell was conducted in two groups. Insulin secretion capacity in islets was measured by glucose-stimulated insulin secretion (GSIS) and perifusion.
Results: NAS mice showed higher glucose levels and lower insulin secretion in IPGTT than the control mice. There was no significant difference in insulin resistance. Total islet and β-cell masses were decreased in NAS mice. The number of large islets (≥250 μm) decreased while that of small islets (<250 μm) increased. Reduced insulin secretion was observed in GSIS and perifusion. Neurogenin3, neurogenic differentiation, and MAF bZIP transcription factor A levels increased in NAS mice.
Conclusion: Our study provides that Notch1 inhibition decreased insulin secretion and decreased islet and β-cell masses. It is thought that Notch1 inhibition suppresses islet proliferation and induces differentiation of small islets. In conclusion, Notch signaling pathway may play an important role in β-cell mass determination and diabetes.

10Vimentin Deficiency Prevents High-Fat Diet-Induced Obesity and Insulin Resistance in Mice

저자 : Seoyeon Kim , Inyeong Kim , Wonkyoung Cho , Goo Taeg Oh , Young Mi Park

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 45권 1호 발행 연도 : 2021 페이지 : pp. 97-109 (13 pages)

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Background: Obesity and type 2 diabetes mellitus are world-wide health problems, and lack of understanding of their linking mechanism is one reason for limited treatment options. We determined if genetic deletion of vimentin, a type 3 intermediate filament, affects obesity and type 2 diabetes mellitus.
Methods: We fed vimentin-null (Vim-/-) mice and wild-type mice a high-fat diet (HFD) for 10 weeks and measured weight change, adiposity, blood lipids, and glucose. We performed intraperitoneal glucose tolerance tests and measured CD36, a major fatty acid translocase, and glucose transporter type 4 (GLUT4) in adipocytes from both groups of mice.
Results: Vim-/- mice fed an HFD showed less weight gain, less adiposity, improved glucose tolerance, and lower serum level of fasting glucose. However, serum triglyceride and non-esterified fatty acid levels were higher in Vim-/- mice than in wild-type mice. Vimentin-null adipocytes showed 41.1% less CD36 on plasma membranes, 27% less uptake of fatty acids, and 50.3% less GLUT4, suggesting defects in intracellular trafficking of these molecules.
Conclusion: We concluded that vimentin deficiency prevents obesity and insulin resistance in mice fed an HFD and suggest vimentin as a central mediator linking obesity and type 2 diabetes mellitus.

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