Diabetes & Metabolism Journal

Volume 46(2); March 2022

Reviews

Metabolic Risk/Epidemiology
Not Control but Conquest: Strategies for the Remission of Type 2 Diabetes Mellitus: Jinyoung Kim, Hyuk-Sang Kwon; Diabetes Metab J. 2022;46(2):165-180. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0377

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A durable normoglycemic state was observed in several studies that treated type 2 diabetes mellitus (T2DM) patients through metabolic surgery, intensive therapeutic intervention, or significant lifestyle modification, and it was confirmed that the functional β-cell mass was also restored to a normal level. Therefore, expert consensus introduced the concept of remission as a common term to express this phenomenon in 2009. Throughout this article, we introduce the recently updated consensus statement on the remission of T2DM in 2021 and share our perspective on the remission of diabetes. There is a need for more research on remission in Korea as well as in Western countries. Remission appears to be prompted by proactive treatment for hyperglycemia and significant weight loss prior to irreversible β-cell changes. T2DM is not a diagnosis for vulnerable individuals to helplessly accept. We attempt to explain how remission of T2DM can be achieved through a personalized approach. It may be necessary to change the concept of T2DM towards that of an urgent condition that requires rapid intervention rather than a chronic, progressive disease. We must grasp this paradigm shift in our understanding of T2DM for the benefit of our patients as endocrine experts.

Citations

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Weight change in patients with new‐onset type 2 diabetes mellitus and its association with remission: Comprehensive real‐world data
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Diabetes, Obesity and Metabolism.2024; 26(2): 567. CrossRef
The Diabetes Remission in India (DiRemI) study: Protocol for a prospective matched-control trial
Pramod Tripathi, Nidhi Kadam, Diptika Tiwari, Thejas Kathrikolly, Anagha Vyawahare, Baby Sharma, Malhar Ganla, Banshi Saboo, Patricia Khashayar
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Why Are Doctors Not Interested in Type 2 Diabetes Mellitus Remission?
Heung Yong Jin, Tae Sun Park
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Longitudinal associations of dietary fiber and its source with 48-week weight loss maintenance, cardiometabolic risk factors and glycemic status under metformin or acarbose treatment: a secondary analysis of the March randomized trial
Jia Liu, Yu An, Ning Yang, Yuan Xu, Guang Wang
Nutrition & Diabetes.2024;[Epub] CrossRef
Mechanisms and the strategy for remission of type 2 diabetes mellitus
Tien‐Jyun Chang
Journal of Diabetes Investigation.2023; 14(3): 351. CrossRef
Remission of type 2 diabetes: A critical appraisal
Michele Ricci, Juan José Mancebo-Sevilla, Lidia Cobos Palacios, Jaime Sanz-Cánovas, Almudena López-Sampalo, Halbert Hernández-Negrin, Miguel Angel Pérez-Velasco, Luis M. Pérez-Belmonte, Maria Rosa Bernal-López, Ricardo Gómez-Huelgas
Frontiers in Endocrinology.2023;[Epub] CrossRef
Incidence and predictors of remission and relapse of type 2 diabetes mellitus in Japan: Analysis of a nationwide patient registry (JDDM73)
Kazuya Fujihara, Laymon Khin, Koshiro Murai, Yurie Yamazaki, Kahori Tsuruoka, Noriko Yagyuda, Katsuya Yamazaki, Hiroshi Maegawa, Shiro Tanaka, Satoru Kodama, Hirohito Sone
Diabetes, Obesity and Metabolism.2023; 25(8): 2227. CrossRef
Use of SGLT2 inhibitors after bariatric/metabolic surgery: Risk/benefit balance
André J. Scheen
Diabetes & Metabolism.2023; 49(4): 101453. CrossRef
Cardiovascular Risk Reduction in Type 2 Diabetes: Further Insights into the Power of Weight Loss and Exercise
Seung-Hwan Lee
Endocrinology and Metabolism.2023; 38(3): 302. CrossRef
Unlocking the Potential of Type 2 Diabetes Mellitus Remission
Prakriti Sharma, Swarupa Chakole
Cureus.2023;[Epub] CrossRef
Global research trends of diabetes remission: a bibliometric study
Xue Yang, Zhiwei He, Qilin Chen, Yu Chen, Guofang Chen, Chao Liu
Frontiers in Endocrinology.2023;[Epub] CrossRef
Gastrointestinal adverse events of tirzepatide in the treatment of type 2 diabetes mellitus: A meta-analysis and trials sequential analysis
Keke Tong, Shuang Yin, Yunfeng Yu, Xinyu Yang, Gang Hu, Fei Zhang, Zhenjie Liu
Medicine.2023; 102(43): e35488. CrossRef
Optimal dose of tirzepatide for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis
Yunfeng Yu, Gang Hu, Shuang Yin, Xinyu Yang, Manli Zhou, Weixiong Jian
Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef

Complications
Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease: Chan-Young Jung, Tae-Hyun Yoo; Diabetes Metab J. 2022;46(2):181-197. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0329

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Although diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease eventually requiring chronic kidney replacement therapy, the prevalence of DKD has failed to decline over the past 30 years. In order to reduce disease prevalence, extensive research has been ongoing to improve prediction of DKD onset and progression. Although the most commonly used markers of DKD are albuminuria and estimated glomerular filtration rate, their limitations have encouraged researchers to search for novel biomarkers that could improve risk stratification. Considering that DKD is a complex disease process that involves several pathophysiologic mechanisms such as hyperglycemia induced inflammation, oxidative stress, tubular damage, eventually leading to kidney damage and fibrosis, many novel biomarkers that capture one specific mechanism of the disease have been developed. Moreover, the increasing use of high-throughput omic approaches to analyze biological samples that include proteomics, metabolomics, and transcriptomics has emerged as a strong tool in biomarker discovery. This review will first describe recent advances in the understanding of the pathophysiology of DKD, and second, describe the current clinical biomarkers for DKD, as well as the current status of multiple potential novel biomarkers with respect to protein biomarkers, proteomics, metabolomics, and transcriptomics.

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Identification and validation of immune and cuproptosis - related genes for diabetic nephropathy by WGCNA and machine learning
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Specific Alternation of Gut Microbiota and the Role of Ruminococcus gnavus in the Development of Diabetic Nephropathy
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Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial
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Alexandra-Mihaela Visinescu, Emilia Rusu, Andrada Cosoreanu, Gabriela Radulian
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Omics and Artificial Intelligence in Kidney Diseases
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Pediatric Diabetic Nephropathy: Novel Insights from microRNAs
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Jinni Hong, Tingting Fu, Weizhen Liu, Yu Du, Junmin Bu, Guojian Wei, Miao Yu, Yanshan Lin, Cunyun Min, Datao Lin
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Nam Hoon Kim, Nan Hee Kim
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Complications
Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions: Md Jakir Hossain, Michael D. Kendig, Meg E. Letton, Margaret J. Morris, Ria Arnold; Diabetes Metab J. 2022;46(2):198-221. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0347

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Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.

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Long-term sensorimotor changes after a sciatic nerve block with bupivacaine and liposomal bupivacaine in a high-fat diet/low-dose streptozotocin rodent model of diabetes
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Compound Qiying Granules alleviates diabetic peripheral neuropathy by inhibiting endoplasmic reticulum stress and apoptosis
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Molecular Medicine.2023;[Epub] CrossRef
HCV affects KATP channels through GnT-IVa-mediated N-glycosylation of GLUT2 on the surface of pancreatic β-cells leading to impaired insulin secretion
Ben Niu, Lijing Ma, Lixuan Yao, Yating Zhang, Heng Su
Endocrine.2023; 84(2): 427. CrossRef
Multimodal Comparison of Diabetic Neuropathy in Aged Streptozotocin-Treated Sprague–Dawley and Zucker Diabetic Fatty Rats
Annalisa Canta, Valentina A. Carozzi, Alessia Chiorazzi, Cristina Meregalli, Norberto Oggioni, Virginia Rodriguez-Menendez, Barbara Sala, Roberto Cosimo Melcangi, Silvia Giatti, Raffaella Lombardi, Roberto Bianchi, Paola Marmiroli, Guido Cavaletti
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Pathophysiology
Glial and Vascular Cell Regulation of the Blood-Brain Barrier in Diabetes: Xiaolong Li, Yan Cai, Zuo Zhang, Jiyin Zhou; Diabetes Metab J. 2022;46(2):222-238. Published online March 18, 2022; DOI: https://doi.org/10.4093/dmj.2021.0146

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As a structural barrier, the blood-brain barrier (BBB) is located at the interface between the brain parenchyma and blood, and modulates communication between the brain and blood microenvironment to maintain homeostasis. The BBB is composed of endothelial cells, basement membrane, pericytes, and astrocytic end feet. BBB impairment is a distinguishing and pathogenic factor in diabetic encephalopathy. Diabetes causes leakage of the BBB through downregulation of tight junction proteins, resulting in impaired functioning of endothelial cells, pericytes, astrocytes, microglia, nerve/glial antigen 2-glia, and oligodendrocytes. However, the temporal regulation, mechanisms of molecular and signaling pathways, and consequences of BBB impairment in diabetes are not well understood. Consequently, the efficacy of therapies diabetes targeting BBB leakage still lags behind the requirements. This review summarizes the recent research on the effects of diabetes on BBB composition and the potential roles of glial and vascular cells as therapeutic targets for BBB disruption in diabetic encephalopathy.

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Others
Links between Thyroid Disorders and Glucose Homeostasis: Young Sil Eom, Jessica R. Wilson, Victor J. Bernet; Diabetes Metab J. 2022;46(2):239-256. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2022.0013

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Thyroid disorders and diabetes mellitus often coexist and are closely related. Several studies have shown a higher prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. Thyroid hormone affects glucose homeostasis by impacting pancreatic β-cell development and glucose metabolism through several organs such as the liver, gastrointestinal tract, pancreas, adipose tissue, skeletal muscles, and the central nervous system. The present review discusses the effect of thyroid hormone on glucose homeostasis. We also review the relationship between thyroid disease and diabetes mellitus: type 1, type 2, and gestational diabetes, as well as guidelines for screening thyroid function with each disorder. Finally, we provide an overview of the effects of antidiabetic drugs on thyroid hormone and thyroid disorders.

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Editorial

Variability of Metabolic Risk Factors: Causative Factor or Epiphenomenon?: Hye Jin Yoo; Diabetes Metab J. 2022;46(2):257-259. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2022.0060

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Original Articles

COVID-19
Impact of COVID-19 Lockdown on the Metabolic Control Parameters in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis: Ifan Ali Wafa, Nando Reza Pratama, Nurizzah Farahiyah Sofia, Elsha Stephanie Anastasia, Tiffany Konstantin, Maharani Ayuputeri Wijaya, M. Rifqi Wiyono, Lilik Djuari, Hermina Novida; Diabetes Metab J. 2022;46(2):260-272. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0125

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Background
Abrupt implementation of lockdowns during the coronavirus disease 2019 (COVID-19) pandemic affected the management of diabetes mellitus in patients worldwide. Limited access to health facilities and lifestyle changes potentially affected metabolic parameters in patients at risk. We conducted a meta-analysis to determine any differences in the control of metabolic parameters in patients with diabetes, before and during lockdown.
Methods
We performed searches of five databases. Meta-analyses were carried out using random- or fixed-effect approaches to glycaemic control parameters as the primary outcome: glycosylated hemoglobin (HbA1c), random blood glucose (RBG), fasting blood glucose (FBG), time-in-range (TIR), time-above-range (TAR), time-below-range (TBR). Mean difference (MD), confidence interval (CI), and P value were calculated. Lipid profile was a secondary outcome and is presented as a descriptive analysis.
Results
Twenty-one studies enrolling a total of 3,992 patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM) were included in the study. Patients with T1DM showed a significant improvement of TIR and TAR (MD=3.52% [95% CI, 0.29 to 6.74], I²=76%, P=0.03; MD=–3.36% [95% CI, –6.48 to –0.25], I²=75%, P=0.03), while FBG among patients with T2DM significantly worsened (MD=3.47 mg/dL [95% CI, 1.22 to 5.73], I²=0%, P<0.01). No significant difference was found in HbA1c, RBG, and TBR. Use of continuous glucose monitoring in T1DM facilitated good glycaemic control. Significant deterioration of lipid parameters during lockdown, particularly triglyceride, was observed.
Conclusion
Implementation of lockdowns during the COVID-19 pandemic did not worsen glycaemic control in patients with diabetes. Other metabolic parameters improved during lockdown, though lipid parameters, particularly triglyceride, worsened.

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Cardiovascular Risk/Epidemiology
Performance of Diabetes and Kidney Disease Screening Scores in Contemporary United States and Korean Populations: Liela Meng, Keun-Sang Kwon, Dae Jung Kim, Yong-ho Lee, Jeehyoung Kim, Abhijit V. Kshirsagar, Heejung Bang; Diabetes Metab J. 2022;46(2):273-285. Published online September 9, 2021; DOI: https://doi.org/10.4093/dmj.2021.0054

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Background
Risk assessment tools have been actively studied, and they summarize key predictors with relative weights/importance for a disease. Currently, standardized screening scores for type 2 diabetes mellitus (DM) and chronic kidney disease (CKD)—two key global health problems—are available in United States and Korea. We aimed to compare and evaluate screening scores for DM (or combined with prediabetes) and CKD, and assess the risk in contemporary United States and Korean populations.
Methods
Four (2×2) models were evaluated in the United States-National Health and Nutrition Examination Survey (NHANES 2015–2018) and Korea-NHANES (2016–2018)—8,928 and 16,209 adults. Weighted statistics were used to describe population characteristics. We used logistic regression for predictors in the models to assess associations with study outcomes (undiagnosed DM and CKD) and diagnostic measures for temporal and cross-validation.
Results
Korean adult population (mean age 47.5 years) appeared to be healthier than United States counterpart, in terms of DM and CKD risks and associated factors, with exceptions of undiagnosed DM, prediabetes and prehypertension. Models performed well in own country and external populations regarding predictor-outcome association and discrimination. Risk tests (high vs. low) showed area under the curve >0.75, sensitivity >84%, specificity >45%, positive predictive value >8%, and negative predictive value >99%. Discrimination was better for DM, compared to the combined outcome of DM and prediabetes, and excellent for CKD due to age.
Conclusion
Four easy-to-use screening scores for DM and CKD are well-validated in contemporary United States and Korean populations. Prevention of DM and CKD may serve as first-step in public health, with these self-assessment tools as basic tools to help health education and disparity.

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Cardiovascular Risk/Epidemiology
Mean and Variability of Lipid Measurements and Risk for Development of Subclinical Left Ventricular Diastolic Dysfunction: Jiyun Park, Mira Kang, Jiyeon Ahn, Min Young Kim, Min Sun Choi, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Jeong Hoon Yang, Sang-Man Jin; Diabetes Metab J. 2022;46(2):286-296. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0080

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Background
Subclinical left ventricular diastolic dysfunction (LVDD) is an emerging consequence of increased insulin resistance, and dyslipidemia is one of the few correctable risk factors of LVDD. This study evaluated the role of mean and visit-to-visit variability of lipid measurements in risk of LVDD in a healthy population.
Methods
This was a 3.7-year (interquartile range, 2.1 to 4.9) longitudinal cohort study including 2,817 adults (median age 55 years) with left ventricular ejection fraction >50% who underwent an annual or biannual health screening between January 2008 and July 2016. The mean, standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), non-HDL-C, and triglycerides were obtained from three to six measurements during the 5 years preceding the first echocardiogram.
Results
Among the 2,817 patients, 560 (19.9%) developed LVDD. The mean of no component of lipid measurements was associated with risk of LVDD. CV (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.10 to 1.67), SD (HR, 1.27; 95% CI, 1.03 to 1.57), and VIM (HR, 1.26; 95% CI, 1.03 to 1.55) of LDL-C and all the variability parameters of apoB were significantly associated with development of LVDD. The association between CV-LDL and risk of LVDD did not have significant interaction with sex, increasing/decreasing trend at baseline, or use of stain and/or lipid-modifying agents.
Conclusion
The variability of LDL-C and apoB, rather than their mean, was associated with risk for LVDD.

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Metabolic Risk/Epidemiology
Prevalence of Type 2 Diabetes Mellitus among Korean Children, Adolescents, and Adults Younger than 30 Years: Changes from 2002 to 2016: Yong Hee Hong, In-Hyuk Chung, Kyungdo Han, Sochung Chung, on Behalf of the Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity; Diabetes Metab J. 2022;46(2):297-306. Published online October 26, 2021; DOI: https://doi.org/10.4093/dmj.2021.0038

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Background
Despite the importance of and social concern regarding prevention of diabetes at younger ages, limited data are available. This study sought to analyze changes in the prevalence of type 2 diabetes mellitus (T2DM) in Koreans younger than 30 years according to sex, age, and level of income.
Methods
The dataset analyzed in this study was derived from health insurance claims recorded in the National Health Insurance Service (NHIS) database. Participants’ level of income was categorized as low (quintile 1, <20% of insurance premium) or others (quintile 2–5).
Results
In males and females, the prevalence of T2DM per 10,000 people steadily increased from 2.57 in 2002 to 11.41 in 2016, and from 1.96 in 2002 to 8.63 in 2016. The prevalence of T2DM in girls was higher in the age group of 5 to 14 years. Even though the prevalence was higher among those older than 20 years, the increase had started earlier, in the early 2000s, in younger age group. Adolescents aged 10 to 19 years in low-income families showed a remarkable increase in prevalence of T2DM, especially in boys.
Conclusion
The prevalence of T2DM in young Koreans increased more than 4.4-fold from 2002 to 2016, and the increase started in the early 2000s in younger age groups and in low-income families. This is the first study to examine the trend in prevalence of T2DM in children, adolescents, and young adults in Korea. Future studies and collaborations with social support systems to prevent T2DM at an early age group should be performed.

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Metabolic Risk/Epidemiology
Iron Overload and the Risk of Diabetes in the General Population: Results of the Chinese Health and Nutrition Survey Cohort Study: He Gao, Jinying Yang, Wenfei Pan, Min Yang; Diabetes Metab J. 2022;46(2):307-318. Published online March 7, 2022; DOI: https://doi.org/10.4093/dmj.2020.0287

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Background
Recent studies have found that there are significant associations between body iron status and the development of diabetes. In the present study, we aimed to analyze the association among iron overload (IO), insulin resistance (IR), and diabetes in Chinese adults, and to explore the sex difference.
Methods
Men and women (age >19 years) who participated in the Chinese Health and Nutrition Survey and did not have diabetes at baseline were followed between 2009 and 2015 (n=5,779). Over a mean of 6 years, 75 participants were diagnosed with incident diabetes. Logistic regression was used to assess the risk factors associated with IO. Cox proportional hazard regression was used to estimate the risk of incident diabetes and to determine whether the risk differed among subgroups. Causal mediation analysis (CMA) was used to explore the mechanism linking IO and diabetes.
Results
According to sex-stratified multivariable-adjusted Cox proportional hazards regression, IO increased the risk of incident diabetes. Women with IO had a higher risk of diabetes than men. Subgroup analysis with respect to age showed that the association between IO and diabetes was stronger in older women and younger men (P<0.001). CMA showed that liver injury (alanine transaminase) and lipid metabolism abnormalities (triglyceride, apolipoprotein B) contributed to the association between IO and diabetes.
Conclusion
IO is associated with diabetes and this association is sex-specific. IO may indirectly induce IR via liver injury and lipid metabolism abnormalities, resulting in diabetes.

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Quantitative susceptibility mapping for iron monitoring of multiple subcortical nuclei in type 2 diabetes mellitus: a systematic review and meta-analysis
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Complications
SUDOSCAN in Combination with the Michigan Neuropathy Screening Instrument Is an Effective Tool for Screening Diabetic Peripheral Neuropathy: Tae Jung Oh, Yoojung Song, Hak Chul Jang, Sung Hee Choi; Diabetes Metab J. 2022;46(2):319-326. Published online September 16, 2021; DOI: https://doi.org/10.4093/dmj.2021.0014

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Background
Screening for diabetic peripheral neuropathy (DPN) is important to prevent severe foot complication, but the detection rate of DPN is unsatisfactory. We investigated whether SUDOSCAN combined with Michigan Neuropathy Screening Instrument (MNSI) could be an effective tool for screening for DPN in people with type 2 diabetes mellitus (T2DM) in clinical practice.
Methods
We analysed the data for 144 people with T2DM without other cause of neuropathy. The presence of DPN was confirmed according to the Toronto Consensus criteria. Electrochemical skin conductance (ESC) of the feet was assessed using SUDOSCAN. We compared the discrimination power of following methods, MNSI only vs. SUDOSCAN only vs. MNSI plus SUDOSCAN vs. MNSI plus 10-g monofilament test.
Results
Confirmed DPN was detected in 27.8% of the participants. The optimal cut-off value of feet ESC to distinguish DPN was 56 μS. We made the DPN screening scores using the corresponding odds ratios for MNSI-Questionnaire, MNSI-Physical Examination, SUDOSCAN, and 10-g monofilament test. For distinguishing the presence of DPN, the MNSI plus SUDOSCAN model showed higher areas under the receiver operating characteristic curve (AUC) than MNSI only model (0.717 vs. 0.638, P=0.011), and SUDOSCAN only model or MNSI plus 10-g monofilament test showed comparable AUC with MNSI only model.
Conclusion
The screening model for DPN that includes both MNSI and SUDOSCAN can detect DPN with acceptable discrimination power and it may be useful in Korean patients with T2DM.

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Association of sudomotor dysfunction with risk of diabetic retinopathy in patients with type 2 diabetes
Ming Wang, Niuniu Chen, Yaxin Wang, Jiaying Ni, Jingyi Lu, Weijing Zhao, Yating Cui, Ronghui Du, Wei Zhu, Jian Zhou
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Whether coagulation dysfunction influences the onset and progression of diabetic peripheral neuropathy: A multicenter study in middle‐aged and aged patients with type 2 diabetes
Jiali Xie, Xinyue Yu, Luowei Chen, Yifan Cheng, Kezheng Li, Mengwan Song, Yinuo Chen, Fei Feng, Yunlei Cai, Shuting Tong, Yuqin Qian, Yiting Xu, Haiqin Zhang, Junjie Yang, Zirui Xu, Can Cui, Huan Yu, Binbin Deng
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Peripheral Neuropathy in Diabetes Mellitus: Pathogenetic Mechanisms and Diagnostic Options
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Ken Munene Nkonge, Dennis Karani Nkonge, Teresa Njeri Nkonge
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Jean-Pierre Riveline, Roberto Mallone, Clarisse Tiercelin, Fetta Yaker, Laure Alexandre-Heymann, Lysa Khelifaoui, Florence Travert, Claire Fertichon, Jean-Baptiste Julla, Tiphaine Vidal-Trecan, Louis Potier, Jean-Francois Gautier, Etienne Larger, Jean-Pas
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Ana Cristina García-Ulloa, Paloma Almeda-Valdes, Teresa Enedina Cuatecontzi-Xochitiotzi, Jorge Alberto Ramírez-García, Michelle Díaz-Pineda, Fernanda Garnica-Carrillo, Alejandra González-Duarte, K M Venkat Narayan, Carlos Alberto Aguilar-Salinas, Sergio H
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Lifestyle
Changes in Patterns of Physical Activity and Risk of Heart Failure in Newly Diagnosed Diabetes Mellitus Patients: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2022;46(2):327-336. Published online November 24, 2021; DOI: https://doi.org/10.4093/dmj.2021.0046

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Background
Exercise is recommended for type 2 diabetes mellitus (T2DM) patients to prevent cardiovascular disease. However, the effects of physical activity (PA) for reducing the risk of heart failure (HF) has yet to be elucidated. We aimed to assess the effect of changes in patterns of PA on incident HF, especially in newly diagnosed diabetic patients.
Methods
We examined health examination data and claims records of 294,528 participants from the Korean National Health Insurance Service who underwent health examinations between 2009 and 2012 and were newly diagnosed with T2DM. Participants were classified into the four groups according to changes in PA between before and after the diagnosis of T2DM: continuously inactive, inactive to active, active to inactive, and continuously active. The development of HF was analyzed until 2017.
Results
As compared with those who were continuously inactive, those who became physically active after diagnosis showed a reduced risk for HF (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.66 to 0.93). Those who were continuously active had the lowest risk for HF (aHR, 0.77; 95% CI, 0.62 to 0.96). As compared with those who were inactive, those who exercised regularly, either performing vigorous or moderate PA, had a lower HF risk (aHR, 0.79; 95% CI, 0.69 to 0.91).
Conclusion
Among individuals with newly diagnosed T2DM, the risk of HF was reduced in those with higher levels of PA after diagnosis was made. Our results suggest either increasing or maintaining the frequency of PA after the diagnosis of T2DM may lower the risk of HF.

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Basic Research
DA-1241, a Novel GPR119 Agonist, Improves Hyperglycaemia by Inhibiting Hepatic Gluconeogenesis and Enhancing Insulin Secretion in Diabetic Mice: Youjin Kim, Si Woo Lee, Hyejin Wang, Ryeong-Hyeon Kim, Hyun Ki Park, Hangkyu Lee, Eun Seok Kang; Diabetes Metab J. 2022;46(2):337-348. Published online January 21, 2022; DOI: https://doi.org/10.4093/dmj.2021.0056

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Background
We investigated the antidiabetic effects of DA-1241, a novel G protein-coupled receptor (GPR) 119 agonist, in vitro and in vivo.
Methods
DA-1241 was administrated to high-fat diet (HFD)-fed C57BL/6J mice for 12 weeks after hyperglycaemia developed. Oral/intraperitoneal glucose tolerance test and insulin tolerance test were performed. Serum insulin and glucagon-like peptide-1 (GLP-1) levels were measured during oral glucose tolerance test. Insulinoma cell line (INS-1E) cells and mouse islets were used to find whether DA-1241 directly stimulate insulin secretion in beta cell. HepG2 cells were used to evaluate the gluconeogenesis and autophagic process. Autophagic flux was evaluated by transfecting microtubule-associated protein 1 light chain 3-fused to green fluorescent protein and monomeric red fluorescent (mRFP-GFP-LC3) expression vector to HepG2 cells.
Results
Although DA-1241 treatment did not affect body weight gain and amount of food intake, fasting blood glucose level decreased along with increase in GLP-1 level. DA-1241 improved only oral glucose tolerance test and showed no effect in intraperitoneal glucose tolerance test. No significant effect was observed in insulin tolerance test. DA-1241 did not increase insulin secretion in INS-1E cell and mouse islets. DA-1241 reduced triglyceride content in the liver thereby improved fatty liver. Additionally, DA-1241 reduced gluconeogenic enzyme expression in HepG2 cells and mouse liver. DA-1241 reduced autophagic flow in HepG2 cells.
Conclusion
These findings suggested that DA-1241 augmented glucose-dependent insulin release via stimulation of GLP-1 secretion, and reduced hepatic gluconeogenesis, which might be associated with autophagic blockage, leading to improved glycaemic control.

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Mohan Patil, Ilaria Casari, Leon N. Warne, Marco Falasca
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Deanne H Hryciw, Rhiannon K Patten, Raymond J Rodgers, Joseph Proietto, Dana S Hutchinson, Andrew J McAinch
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Letter

Trends and Risk Factors of Metabolic Syndrome among Korean Adolescents, 2007 to 2018 (Diabetes Metab J 2021;45:880-9): Dae Jung Kim; Diabetes Metab J. 2022;46(2):349-350. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0353

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