Diabetes & Metabolism Journal

Volume 45(3); May 2021

Reviews

Pathophysiology
Hyperinsulinemia in Obesity, Inflammation, and Cancer: Anni M.Y. Zhang, Elizabeth A. Wellberg, Janel L. Kopp, James D. Johnson; Diabetes Metab J. 2021;45(3):285-311. Published online March 29, 2021; DOI: https://doi.org/10.4093/dmj.2020.0250; Correction in: Diabetes Metab J 2021;45(4):622

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The relative insufficiency of insulin secretion and/or insulin action causes diabetes. However, obesity and type 2 diabetes mellitus can be associated with an absolute increase in circulating insulin, a state known as hyperinsulinemia. Studies are beginning to elucidate the cause-effect relationships between hyperinsulinemia and numerous consequences of metabolic dysfunctions. Here, we review recent evidence demonstrating that hyperinsulinemia may play a role in inflammation, aging and development of cancers. In this review, we will focus on the consequences and mechanisms of excess insulin production and action, placing recent findings that have challenged dogma in the context of the existing body of literature. Where relevant, we elaborate on the role of specific signal transduction components in the actions of insulin and consequences of chronic hyperinsulinemia. By discussing the involvement of hyperinsulinemia in various metabolic and other chronic diseases, we may identify more effective therapeutics or lifestyle interventions for preventing or treating obesity, diabetes and cancer. We also seek to identify pertinent questions that are ripe for future investigation.

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Type 1 Diabetes
Non-Insulin Antidiabetes Treatment in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis: Xiaoling Cai, Chu Lin, Wenjia Yang, Lin Nie, Linong Ji; Diabetes Metab J. 2021;45(3):312-325. Published online March 15, 2021; DOI: https://doi.org/10.4093/dmj.2020.0171

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In order to evaluate the efficacy and side effects of the non-insulin antidiabetes medications as an adjunct treatment in type 1 diabetes mellitus (T1DM), we conducted systematic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between the date of inception and March 2020 to produce a systematic review and meta-analysis. Overall, 57 studies were included. Compared with placebo, antidiabetes agents in adjunct to insulin treatment resulted in significant reduction in glycosylated hemoglobin (weighted mean difference [WMD], –0.30%; 95% confidence interval [CI], –0.34 to –0.25%; P<0.01) and body weight (WMD, –2.15 kg; 95% CI, –2.77 to –1.53 kg; P<0.01), and required a significantly lower dosage of insulin (WMD, –5.17 unit/day; 95% CI, –6.77 to –3.57 unit/day; P<0.01). Compared with placebo, antidiabetes agents in adjunct to insulin treatment increased the risk of hypoglycemia (relative risk [RR], 1.04; 95% CI, 1.01 to 1.08; P=0.02) and gastrointestinal side effects (RR, 1.99; 95% CI, 1.61 to 2.46; P<0.01) in patients with T1DM. Compared with placebo, the use of non-insulin antidiabetes agents in addition to insulin could lead to glycemic improvement, weight control and lower insulin dosage, while they might be associated with increased risks of hypoglycemia and gastrointestinal side effects in patients with T1DM.

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Drug/Regimen
Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus: Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha; Diabetes Metab J. 2021;45(3):326-336. Published online April 19, 2021; DOI: https://doi.org/10.4093/dmj.2020.0272

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Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction. Among available oral antidiabetic agents, only the thiazolidinediones (TZDs) primarily target insulin resistance. TZDs improve insulin sensitivity by activating peroxisome proliferator-activated receptor γ. Rosiglitazone and pioglitazone have been used widely for T2DM treatment due to their potent glycemic efficacy and low risk of hypoglycemia. However, their use has decreased because of side effects and safety issues, such as cardiovascular concerns and bladder cancer. Lobeglitazone (Chong Kun Dang Pharmaceutical Corporation), a novel TZD, was developed to meet the demands for an effective and safe TZD. Lobeglitazone shows similar glycemic efficacy to pioglitazone, with a lower effective dose, and favorable safety results. It also showed pleiotropic effects in preclinical and clinical studies. In this article, we summarize the pharmacologic, pharmacokinetic, and clinical characteristics of lobeglitazone.

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Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
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Editorial

Early Glycosylated Hemoglobin Target Achievement Predicts Clinical Outcomes in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: Joonyub Lee, Jae Hyoung Cho; Diabetes Metab J. 2021;45(3):337-338. Published online May 25, 2021; DOI: https://doi.org/10.4093/dmj.2021.0078; Correction in: Diabetes Metab J 2021;45(4):621

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Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study (Diabetes Metab J 2021;45:368-78)
Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim
Diabetes & Metabolism Journal.2021; 45(4): 617. CrossRef

Original Articles

Drug/Regimen
Effect of Dapagliflozin as an Add-on Therapy to Insulin on the Glycemic Variability in Subjects with Type 2 Diabetes Mellitus (DIVE): A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study: Seung-Hwan Lee, Kyung-Wan Min, Byung-Wan Lee, In-Kyung Jeong, Soon-Jib Yoo, Hyuk-Sang Kwon, Yoon-Hee Choi, Kun-Ho Yoon; Diabetes Metab J. 2021;45(3):339-348. Published online May 28, 2020; DOI: https://doi.org/10.4093/dmj.2019.0203

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Background

Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.

Methods

In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).

Results

At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, P<0.001), glycated albumin (−3.94%±2.55% vs. −0.67%±2.48%, P<0.001), and CGM-derived mean glucose (−41.6±39.2 mg/dL vs. 1.1±46.2 mg/dL, P<0.001) levels were observed in the dapagliflozin group compared with the placebo group. SD and MAGE were significantly decreased in the dapagliflozin group, but not in the placebo group. However, the difference in ΔSD and ΔMAGE failed to reach statistical significance between two groups. No significant differences in the incidence of safety endpoints were observed between the two groups.

Conclusion

Dapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.

Citations

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Selective sodium-glucose cotransporter-2 inhibitors in the improvement of hemoglobin and hematocrit in patients with type 2 diabetes mellitus: a network meta-analysis
Yuanyuan Luo, Ruojing Bai, Wei Zhang, Guijun Qin
Frontiers in Endocrinology.2024;[Epub] CrossRef
Continuous Glucose Monitoring Profiles and Health Outcomes After Dapagliflozin Plus Saxagliptin vs Insulin Glargine
Donald C Simonson, Marcia A Testa, Ella Ekholm, Maxwell Su, Tina Vilsbøll, Serge A Jabbour, Marcus Lind
The Journal of Clinical Endocrinology & Metabolism.2024;[Epub] CrossRef
Impact of empagliflozin on insulin needs in patients with heart failure and diabetes: An EMPEROR‐Pooled analysis
Khawaja M. Talha, Jennifer Green, Gerasimos Filippatos, Stuart Pocock, Faiez Zannad, Martina Brueckmann, Elke Schueler, Anne Pernille Ofstad, João Pedro Ferreira, Stefan D. Anker, Javed Butler, Julio Rosenstock, Milton Packer
Diabetes, Obesity and Metabolism.2024;[Epub] CrossRef
Risk of Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Treated with Dapagliflozin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Zhigui Zheng, Dongyuan He, Jianguo Chen, Xiaohui Xie, Yunan Lu, Binbin Wu, Xinxin Jiang
Clinical Drug Investigation.2023; 43(4): 209. CrossRef
Effect of SGLT2 Inhibitors and Metformin on Inflammatory and Prognostic Biomarkers in Type 2 Diabetes Patients
Yang Cao, Ning Liang, Ting Liu, Jingai Fang, Xiaodong Zhang
Endocrine, Metabolic & Immune Disorders - Drug Targets.2023; 23(4): 530. CrossRef
What is Glycaemic Variability and which Pharmacological Treatment Options are Effective? A Narrative Review
Juan Miguel Huertas Cañas, Maria Alejandra Gomez Gutierrez, Andres Bedoya Ossa
European Endocrinology.2023; 19(2): 4. CrossRef
La variabilité glycémique : un facteur de risque singulier à conjuguer au pluriel
Louis Monnier, Claude Colette, Fabrice Bonnet, David Owens
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Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes
Min Jeong Park, Kyung Mook Choi
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Effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on serum urate levels in patients with and without diabetes: a systematic review and meta-regression of 43 randomized controlled trials
Alicia Swee Yan Yip, Shariel Leong, Yao Hao Teo, Yao Neng Teo, Nicholas L. X. Syn, Ray Meng See, Caitlin Fern Wee, Elliot Yeung Chong, Chi-Hang Lee, Mark Y. Chan, Tiong-Cheng Yeo, Raymond C. C. Wong, Ping Chai, Ching-Hui Sia
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Hypoglycemic agents and glycemic variability in individuals with type 2 diabetes: A systematic review and network meta-analysis
SuA Oh, Sujata Purja, Hocheol Shin, Minji Kim, Eunyoung Kim
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The Clinical Effect of Dapagliflozin in Patients with Angiographically Confirmed Coronary Artery Disease and Concomitant Type 2 Diabetes Mellitus
Yana Yu. Dzhun, Yevhen Yu. Marushko, Yanina A. Saienko, Nadiya M. Rudenko, Borys M. Mankovsky
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Alessandro Bellis, Ciro Mauro, Emanuele Barbato, Antonio Ceriello, Antonio Cittadini, Carmine Morisco
International Journal of Molecular Sciences.2021; 22(2): 775. CrossRef
Glycemic Variability Impacted by SGLT2 Inhibitors and GLP 1 Agonists in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis
Heeyoung Lee, Se-eun Park, Eun-Young Kim
Journal of Clinical Medicine.2021; 10(18): 4078. CrossRef
Effect of Dapagliflozin on Glycemic Variability in Patients with Type 2 Diabetes under Insulin Glargine Combined with Other Oral Hypoglycemic Drugs
Menghui Luo, Xiaocen Kong, Huiying Wang, Xiaofang Zhai, Tingting Cai, Bo Ding, Yun Hu, Ting Jing, Xiaofei Su, Huiqin Li, Jianhua Ma, Yoshifumi Saisho
Journal of Diabetes Research.2020; 2020: 1. CrossRef
Time in Range from Continuous Glucose Monitoring: A Novel Metric for Glycemic Control
Jee Hee Yoo, Jae Hyeon Kim
Diabetes & Metabolism Journal.2020; 44(6): 828. CrossRef

Complications
Association of Urinary N-Acetyl-β-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy: Min Sun Choi, Ji Eun Jun, Sung Woon Park, Jee Hee Yoo, Jiyeon Ahn, Gyuri Kim, Sang-Man Jin, Kyu Yeon Hur, Moon-Kyu Lee, Jae Hyeon Kim; Diabetes Metab J. 2021;45(3):349-357. Published online February 2, 2021; DOI: https://doi.org/10.4093/dmj.2019.0211

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Background
Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy.
Methods
This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimatethe severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed.
Results
The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV.
Conclusion
This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.

Citations

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Determination of Diabetes-associated Cardiovascular Autonomic Neuropathy Risk Factors among Insulin and Non-insulin Dependent Diabetics
Ibrahim Abdulsada, Zain Alabdeen Obaid, Farah Almerza, Mays Alwaeli, Anmar Al-Elayawi, Taha Al-Dayyeni, Harir Al-Tuhafy
The Journal of Medical Research.2023; 9(6): 141. CrossRef
Association between carotid atherosclerosis and presence of intracranial atherosclerosis using three-dimensional high-resolution vessel wall magnetic resonance imaging in asymptomatic patients with type 2 diabetes
Ji Eun Jun, You-Cheol Hwang, Kyu Jeong Ahn, Ho Yeon Chung, Geon-Ho Jahng, Soonchan Park, In-Kyung Jeong, Chang-Woo Ryu
Diabetes Research and Clinical Practice.2022; 191: 110067. CrossRef

Complications
Association between Sleep Quality and Painless Diabetic Peripheral Neuropathy Assessed by Current Perception Threshold in Type 2 Diabetes Mellitus: Dughyun Choi, Bo-Yeon Kim, Chan-Hee Jung, Chul-Hee Kim, Ji-Oh Mok; Diabetes Metab J. 2021;45(3):358-367. Published online August 6, 2020; DOI: https://doi.org/10.4093/dmj.2019.0219

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Background

It is known that the painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes mellitus (T2DM). However, it is not known that the painless DPN also is associated with poor sleep quality in T2DM. The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2DM.

Methods

A total of 146 patients of T2DM who do not have any painful symptoms of DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire.

Results

The percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, P<0.001). In the subscale results, stimulus values at 2,000 Hz, hypoesthesia and hyperesthesia were more common in the poor sleep quality group than in the good sleep quality group (45.7% vs. 25.0%, P=0.009; 34.3% vs. 18.4%, P=0.029; 40.0% vs. 19.7%, P=0.007, respectively). The association of painless DPN and poor sleep quality remained significant after adjustment for significant covariates (odds ratio, 3.825; 95% confidence interval, 1.674 to 8.742; P<0.001).

Conclusion

The current study showed that painless DPN was associated with poor sleep quality. Future studies are required to clarify the pathophysiologic causal relationship between painless DPN and sleep quality.

Citations

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Deteriorated sleep quality and associate factors in patients with type 2 diabetes mellitus complicated with diabetic peripheral neuropathy
Lin Fu, Liping Zhong, Xin Liao, Lingrui Wang, Youyi Wang, Xiuquan Shi, Yanna Zhou
PeerJ.2024; 12: e16789. CrossRef
Sleep impairment: Is it an overlooked burden in painful diabetic peripheral neuropathy? A single-centre, cross-sectional study from south India
Adlin Lawrence, Himsikhar Khataniar, Sinimol Joseph, Thenmozhi Nagarajan, Soumya Umesh, John Michael Raj A
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2022; 16(8): 102568. CrossRef
Sleep: an emerging therapeutic target in diabetes care
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Complications
Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study: Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2021;45(3):368-378. Published online October 20, 2020; DOI: https://doi.org/10.4093/dmj.2020.0046

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Background
To evaluate the association of time to reach the target glycosylated hemoglobin (HbA1c) level with long-term durable glycemic control and risk of diabetic complications in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
Methods
In a longitudinal observational cohort, 194 patients with T2DM newly diagnosed between January 2011 and March 2013 were followed up over 6 years. Patients were classified according to the time needed to reach the target HbA1c (<7.0%): <3, 3 to 6 (early achievement group), and ≥6 months (late achievement group). Risks of microvascular complications including diabetic retinopathy, nephropathy, and neuropathy as well as macrovascular events including ischemic heart disease, ischemic stroke, and peripheral arterial disease were assessed by multivariable Cox proportional hazards analysis.
Results
During a median follow-up of 6.53 years, 66 microvascular and 14 macrovascular events occurred. Maintenance of durable glycemic control over 6 years was more likely in the early achievement groups than in the late achievement group (34.5%, 30.0%, and 16.1% in <3, 3 to 6, and ≥6 months, respectively, P=0.039). Early target HbA1c achievement was associated with lower risk of composite diabetic complications (adjusted hazard ratio [HR, 0.47; 95% confidence interval [CI], 0.26 to 0.86 in <3 months group) (adjusted HR, 0.50; 95% CI, 0.23 to 1.10 in 3 to 6 months group, in reference to ≥6 months group). Similar trends were maintained for risks of microvascular and macrovascular complications, although statistical significance was not reached for macrovascular complications.
Conclusion
Early target HbA1c achievement was associated with long-term durable glycemic control and reduced risk of diabetic complications in newly diagnosed T2DM.

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Glycemic control and cardiovascular complications of type 2 diabetes mellitus
I. V. Druk, S. S. Safronova
Meditsinskiy sovet = Medical Council.2023; (13): 130. CrossRef
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Kun Lu, Tingqing Yu, Xinyi Cao, Hui Xia, Shaokang Wang, Guiju Sun, Liang Chen, Wang Liao
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Cuijie Qin, Chuang Li, Yunpeng Luo, Zhen Li, Hui Cao
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Evaluation of Left Ventricular Function in Diabetes Patients with Microvascular Disease by Three-Dimensional Speckle Tracking Imaging
青周
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Validity of the diagnosis of diabetic microvascular complications in Korean national health insurance claim data
Hyung Jun Kim, Moo-Seok Park, Jee-Eun Kim, Tae-Jin Song
Annals of Clinical Neurophysiology.2022; 24(1): 7. CrossRef
Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials
Wei-Tse Hung, Yuan-Jung Chen, Chun-Yu Cheng, Bruce Ovbiagele, Meng Lee, Chia-Yu Hsu
Diabetes Research and Clinical Practice.2022; 189: 109937. CrossRef
Peripheral arterial disease progression and ankle brachial index: a cohort study with newly diagnosed patients with type 2 diabetes
João Soares Felício, Franciane Trindade Cunha de Melo, Giovana Miranda Vieira, Vitória Teixeira de Aquino, Fernanda de Souza Parente, Wanderson Maia da Silva, Nivin Mazen Said, Emanuele Rocha da Silva, Ana Carolina Contente Braga de Souza, Maria Clara Ner
BMC Cardiovascular Disorders.2022;[Epub] CrossRef
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Chen Long, Yaling Tang, Jiangsheng Huang, Suo Liu, Zhenhua Xing
Frontiers in Endocrinology.2022;[Epub] CrossRef
The Degree of Glycemic Control for the First Three Months Determines the Next Seven Years
Nami Lee, Dae Jung Kim
Journal of Korean Medical Science.2022;[Epub] CrossRef
Inhibition of advanced glycation end products and protein oxidation by leaf extracts and phenolics from Chilean bean landraces
Felipe Ávila, Nadia Cruz, Jazmin Alarcon-Espósito, Nélida Nina, Hernán Paillan, Katherine Márquez, Denis Fuentealba, Alberto Burgos-Edwards, Cristina Theoduloz, Carmina Vejar-Vivar, Guillermo Schmeda-Hirschmann
Journal of Functional Foods.2022; 98: 105270. CrossRef
Mediation Effect of Self-Efficacy Between Health Beliefs and Glycated Haemoglobin Levels in Elderly Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study
Anqi Zhang, Jinsong Wang, Xiaojuan Wan, Jing Zhang, Zihe Guo, Yamin Miao, Shuhan Zhao, Shuo Bai, Ziyi Zhang, Weiwei Yang
Patient Preference and Adherence.2022; Volume 16: 3015. CrossRef
Early Glycosylated Hemoglobin Target Achievement Predicts Clinical Outcomes in Patients with Newly Diagnosed Type 2 Diabetes Mellitus
Joonyub Lee, Jae Hyoung Cho
Diabetes & Metabolism Journal.2021; 45(3): 337. CrossRef
Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study (Diabetes Metab J 2021;45:368-78)
Ja Young Jeon
Diabetes & Metabolism Journal.2021; 45(4): 613. CrossRef
Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study (Diabetes Metab J 2021;45:368-78)
Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim
Diabetes & Metabolism Journal.2021; 45(4): 617. CrossRef
Plasma Nesfatin-1: Potential Predictor and Diagnostic Biomarker for Cognitive Dysfunction in T2DM Patient
Dandan Xu, Yue Yu, Yayun Xu, Jinfang Ge
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2021; Volume 14: 3555. CrossRef

Cardiovascular risk/Epidemiology
Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Yang-Hyun Kim, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2021;45(3):379-389. Published online December 11, 2020; DOI: https://doi.org/10.4093/dmj.2020.0008

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Background
Previous studies have suggested that depression in patients with diabetes is associated with worse health outcomes. The aim of this study was to evaluate the risk of cardiovascular disease (CVD) and mortality in patients with diabetes with comorbid depression.
Methods
We examined the general health check-up data and claim database of the Korean National Health Insurance Service (NHIS) of 2,668,615 participants with type 2 diabetes mellitus who had examinations between 2009 and 2012. As NHIS database has been established since 2002, those who had been diagnosed with depression or CVD since 2002 were excluded. The 2,228,443 participants were classified into three groups according to the claim history of depression; normal group (n=2,166,979), transient depression group (one episode of depression, n=42,124) and persistent depression group (at least two episodes of depression, n=19,340). The development of CVD and mortality were analyzed from 2009 to 2017.
Results
Those with depression showed a significantly increased risk for stroke (transient depression group: hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.15 to 1.26) (persistent depression group: HR, 1.54; 95% CI, 1.46 to 1.63). Those with depression had an increased risk for myocardial infarction (transient depression group: HR, 1.25; 95% CI, 1.18 to 1.31) (persistent depression group: HR, 1.38; 95% CI, 1.29 to 1.49). The persistent depression group had an increased risk for all-cause mortality (HR, 1.66; 95% CI, 1.60 to 1.72).
Conclusion
Coexisting depression in patients with diabetes has a deleterious effect on the development of CVD and mortality. We suggest that more attention should be given to patients with diabetes who present with depressive symptoms.

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The mediating effect of depression on new-onset stroke in diabetic population: Evidence from the China health and retirement longitudinal study
Gege Jiang, Yaoling Wang, Liping Wang, Minfang Chen, Wei Li
Journal of Affective Disorders.2023; 321: 208. CrossRef
Frailty and outcomes in lacunar stroke
Sima Vazquez, Zehavya Stadlan, Justin M Lapow, Eric Feldstein, Smit Shah, Ankita Das, Alexandria F Naftchi, Eris Spirollari, Akash Thaker, Syed Faraz Kazim, Jose F Dominguez, Neisha Patel, Christeena Kurian, Ji Chong, Stephan A Mayer, Gurmeen Kaur, Chirag
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Comparison of Operational Definition of Type 2 Diabetes Mellitus Based on Data from Korean National Health Insurance Service and Korea National Health and Nutrition Examination Survey
Jong Ha Baek, Yong-Moon Park, Kyung Do Han, Min Kyong Moon, Jong Han Choi, Seung-Hyun Ko
Diabetes & Metabolism Journal.2023; 47(2): 201. CrossRef
The Association between Dietary Carotenoid Intake and Risk of Depression among Patients with Cardiometabolic Disease
Jie Liang, Yuhao Wang, Min Chen
International Heart Journal.2023; 64(2): 223. CrossRef
Associations of concomitant retinopathy and depression with mortality in a nationally representative population
Zheng Lyu, Yilin Chen, Zhuoting Zhu, Xiaoyang Luo, Ying Cui, Jie Xie, Zhifan Chen, Junbin Liu, Xiyu Wu, Gabrella Bulloch, Qianli Meng
Journal of Affective Disorders.2023; 336: 15. CrossRef
Clinical insights into the cross-link between mood disorders and type 2 diabetes: A review of longitudinal studies and Mendelian randomisation analyses
Chiara Possidente, Giuseppe Fanelli, Alessandro Serretti, Chiara Fabbri
Neuroscience & Biobehavioral Reviews.2023; 152: 105298. CrossRef
Prevalence of depression and association with all-cause and cardiovascular mortality among individuals with type 2 diabetes: a cohort study based on NHANES 2005–2018 data
Zhen Feng, Wai Kei Tong, Xinyue Zhang, Zhijia Tang
BMC Psychiatry.2023;[Epub] CrossRef
Cholecystectomy Increases the Risk of Type 2 Diabetes in the Korean Population
Ji Hye Huh, Kyong Joo Lee, Yun Kyung Cho, Shinje Moon, Yoon Jung Kim, Eun Roh, Kyung-do Han, Dong Hee Koh, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm
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Shinje Moon, Sangmo Hong, Kyungdo Han, Cheol-Young Park
European Journal of Endocrinology.2023; 189(3): 363. CrossRef
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Lijun Zhang, Yanping Bao, Shuhui Tao, Yimiao Zhao, Meiyan Liu
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Teng Hu, Fangkun Yang, Kewan He, Jiajun Ying, Hanbin Cui
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Comorbidity of Type 2 Diabetes Mellitus and Depression: Clinical Evidence and Rationale for the Exacerbation of Cardiovascular Disease
Mengmeng Zhu, Yiwen Li, Binyu Luo, Jing Cui, Yanfei Liu, Yue Liu
Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef
Understanding and Utilizing Claim Data from the Korean National Health Insurance Service (NHIS) and Health Insurance Review & Assessment (HIRA) Database for Research
Dae-Sung Kyoung, Hun-Sung Kim
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Kyung-Soo Kim, Sangmo Hong, You-Cheol Hwang, Hong-Yup Ahn, Cheol-Young Park
Journal of General Internal Medicine.2022; 37(16): 4153. CrossRef
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Himanshu Verma, Anindita Bhattacharjee, Naveen Shivavedi, Prasanta Kumar Nayak
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Lipid cutoffs for increased cardiovascular disease risk in non-diabetic young people
Mee Kyoung Kim, Kyungdo Han, Hun-Sung Kim, Kun-Ho Yoon, Seung-Hwan Lee
European Journal of Preventive Cardiology.2022; 29(14): 1866. CrossRef
Risk factors associated with mortality among individuals with type 2 diabetes and depression across two cohorts
Christopher Rohde, Jens Steen Nielsen, Jakob Schöllhammer Knudsen, Reimar Wernich Thomsen, Søren Dinesen Østergaard
European Journal of Endocrinology.2022; 187(4): 567. CrossRef
Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2021;45:379-89)
Jin Hwa Kim
Diabetes & Metabolism Journal.2021; 45(5): 789. CrossRef
Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2021;45:379-89)
Inha Jung, Eun-Jung Rhee, Won-Young Lee
Diabetes & Metabolism Journal.2021; 45(5): 793. CrossRef
Affective Temperament and Glycemic Control – The Psychological Aspect of Obesity and Diabetes Mellitus
Natalia Lesiewska, Anna Kamińska, Roman Junik, Magdalena Michalewicz, Bartłomiej Myszkowski, Alina Borkowska, Maciej Bieliński
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2021; Volume 14: 4981. CrossRef

Lifestyle
Reducing Carbohydrate from Individual Sources Has Differential Effects on Glycosylated Hemoglobin in Type 2 Diabetes Mellitus Patients on Moderate Low-Carbohydrate Diets: Hajime Haimoto, Shiho Watanabe, Keiko Maeda, Takashi Murase, Kenji Wakai; Diabetes Metab J. 2021;45(3):390-403. Published online July 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0033

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Background

We evaluated decreases in glycosylated hemoglobin (HbA1c) achieved by reducing carbohydrate from various sources in type 2 diabetes mellitus patients.

Methods

We followed up 138 male and 107 female outpatients on a moderate low-carbohydrate diet without diabetic medication for 6 months. Changes in carbohydrate sources (Δcarbohydrate) were assessed from 3-day dietary records at baseline and 6 months, and associations with changes in HbA1c (ΔHbA1c) were examined with Spearman's correlation coefficients (r_s) and multiple regression analysis.

Results

ΔHbA1c was −1.5%±1.6% in men and −0.9%±1.3% in women, while Δtotal carbohydrate was −115.3±103.7 g/day in men and −63.6±71.1 g/day in women. Positive associations with ΔHbA1c were found for Δtotal carbohydrate (r_s=0.584), Δcarbohydrate from soft drinks (0.368), confectionery (0.361), rice (0.325), bread (0.221), Chinese soup noodles (0.199) in men, and Δtotal carbohydrate (0.547) and Δcarbohydrate from rice (0.376) and confectionery (0.195) in women. Reducing carbohydrate sources by 50 g achieved decreases in HbA1c of 0.43% for total carbohydrate, 1.33% for soft drinks, 0.88% for confectionery, 0.63% for bread, 0.82% for Chinese soup noodles and 0.34% for rice in men and 0.45% for total carbohydrate, 0.67% for confectionery and 0.34% for rice in women, although mean reductions in carbohydrate from these sources were much smaller than that from rice.

Conclusion

Decreases in HbA1c achieved by reducing carbohydrate from soft drinks, confectionery, bread and Chinese soup noodles were 2- to 4-fold greater than that for rice. Our results will enable patients to decrease HbA1c efficiently (UMIN000009866).

Citations

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Exploring diet associations with Covid-19 and other diseases: a Network Analysis–based approach
Rashmeet Toor, Inderveer Chana
Medical & Biological Engineering & Computing.2022; 60(4): 991. CrossRef
Comprehensive Understanding for Application in Korean Patients with Type 2 Diabetes Mellitus of the Consensus Statement on Carbohydrate-Restricted Diets by Korean Diabetes Association, Korean Society for the Study of Obesity, and Korean Society of Hyperte
Jong Han Choi, Jee-Hyun Kang, Suk Chon
Diabetes & Metabolism Journal.2022; 46(3): 377. CrossRef
Associations of Dietary Salt and Its Sources with Hemoglobin A1c in Patients with Type 2 Diabetes Not Taking Anti-Diabetic Medications: Analysis Based on 6-Month Intervention with a Moderate Low-Carbohydrate Diet
Hajime Haimoto, Takashi Murase, Shiho Watanabe, Keiko Maeda, Kenji Wakai
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2021; Volume 14: 4569. CrossRef

Pathophysiology
Relationships between Islet-Specific Autoantibody Titers and the Clinical Characteristics of Patients with Diabetes Mellitus: Yiqian Zhang, Tong Yin, Xinlei Wang, Rongping Zhang, Jie Yuan, Yi Sun, Jing Zong, Shiwei Cui, Yunjuan Gu; Diabetes Metab J. 2021;45(3):404-416. Published online July 21, 2020; DOI: https://doi.org/10.4093/dmj.2019.0239

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Background

Dysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.

Methods

A total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.

Results

Compared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUC_CP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUC_CP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.

Conclusion

Diabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.

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Relationship between β-Cell Autoantibodies and Their Combination with Anthropometric and Metabolic Components and Microvascular Complications in Latent Autoimmune Diabetes in Adults
Tomislav Bulum, Marijana Vučić Lovrenčić, Jadranka Knežević Ćuća, Martina Tomić, Sandra Vučković-Rebrina, Lea Duvnjak
Biomedicines.2023; 11(9): 2561. CrossRef
RETRACTED ARTICLE: MiRNA-27a mediates insulin resistance in 3T3-L1 cells through the PPARγ
Yangming Zhuang, Ming Li
Molecular and Cellular Biochemistry.2022; 477(4): 1107. CrossRef
Correlation between Insulin Resistance and Microalbuminuria Creatinine Ratio in Postmenopausal Women
Han Na, Rong Wang, Hai-Long Zheng, Xiao-Pan Chen, Lin-Yang Zheng, Faustino R. Perez-Lopez
International Journal of Endocrinology.2022; 2022: 1. CrossRef
The longitudinal loss of islet autoantibody responses from diagnosis of type 1 diabetes occurs progressively over follow-up and is determined by low autoantibody titres, early-onset, and genetic variants
C L Williams, R Fareed, G L M Mortimer, R J Aitken, I V Wilson, G George, K M Gillespie, A J K Williams, Chitrabhanu Ballav, Atanu Dutta, Michelle Russell-Taylor, Rachel Besser, James Bursell, Shanthi Chandran, Sejal Patel, Anne Smith, Manohara Kenchaiah,
Clinical and Experimental Immunology.2022; 210(2): 151. CrossRef

Pathophysiology
Distinct Dose-Dependent Association of Free Fatty Acids with Diabetes Development in Nonalcoholic Fatty Liver Disease Patients: Fuxi Li, Junzhao Ye, Yanhong Sun, Yansong Lin, Tingfeng Wu, Congxiang Shao, Qianqian Ma, Xianhua Liao, Shiting Feng, Bihui Zhong; Diabetes Metab J. 2021;45(3):417-429. Published online March 15, 2021; DOI: https://doi.org/10.4093/dmj.2020.0039

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Background
Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear.
Methods
Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.
Results
There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals.
Conclusion
A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.

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Mortality in metabolic dysfunction-associated steatotic liver disease: A nationwide population-based cohort study
Eugene Han, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Sang Hoon Ahn, Yong-ho Lee, Seung Up Kim
Metabolism.2024; 152: 155789. CrossRef
Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis
Limin Cao, Yu An, Huiyuan Liu, Jinguo Jiang, Wenqi Liu, Yuhan Zhou, Mengyuan Shi, Wei Dai, Yanling Lv, Yuhong Zhao, Yanhui Lu, Liangkai Chen, Yang Xia
BMC Medicine.2024;[Epub] CrossRef
Metabolic Dysfunction-Associated Fatty Liver Disease and Mortality: A Population-Based Cohort Study
Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
Diabetes & Metabolism Journal.2023; 47(2): 220. CrossRef
Experimental model and novel therapeutic targets for non-alcoholic fatty liver disease development
Yujin Jin, Kyung-Sun Heo
The Korean Journal of Physiology & Pharmacology.2023; 27(4): 299. CrossRef
Triglyceride and glucose index is a simple and easy‐to‐calculate marker associated with nonalcoholic fatty liver disease
Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
Obesity.2022; 30(6): 1279. CrossRef
Mongolian medicine in treating type 2 diabetes mellitus combined with nonalcoholic fatty liver disease via FXR/LXR-mediated P2X7R/NLRP3/NF-κB pathway activation
Shuyin Bao, Xiuzhi Wang, Qianqian Ma, Chengxi Wei, Jixing Nan, Wuliji Ao
Chinese Herbal Medicines.2022; 14(3): 367. CrossRef
Triglyceride Glucose-Waist Circumference Is Superior to the Homeostasis Model Assessment of Insulin Resistance in Identifying Nonalcoholic Fatty Liver Disease in Healthy Subjects
Hwi Seung Kim, Yun Kyung Cho, Eun Hee Kim, Min Jung Lee, Chang Hee Jung, Joong-Yeol Park, Hong-Kyu Kim, Woo Je Lee
Journal of Clinical Medicine.2021; 11(1): 41. CrossRef

COVID-19
Use of Renin-Angiotensin-Aldosterone System Inhibitors and Severe COVID-19 Outcomes in Patients with Hypertension: A Nationwide Cohort Study: Jae Hyun Bae, Sun Kyu Choi, Nam Hoon Kim, Juneyoung Lee, Sin Gon Kim; Diabetes Metab J. 2021;45(3):430-438. Published online February 22, 2021; DOI: https://doi.org/10.4093/dmj.2020.0279

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Background
Angiotensin-converting enzyme 2 facilitates the entry of severe acute respiratory syndrome coronavirus 2 into the human body. We investigated the association of renin-angiotensin-aldosterone system (RAAS) inhibitor use with severe coronavirus disease 2019 (COVID-19) outcomes in hypertensive patients.
Methods
We identified hypertensive patients with confirmed COVID-19 from the Korean Health Insurance Review and Assessment Service from inception to May 15, 2020. The primary outcome was the composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), continuous renal replacement therapy (CRRT), extracorporeal membrane oxygenation (ECMO), and death from COVID-19. The individual components were evaluated as secondary outcomes.
Results
Of 1,374 hypertensive patients with COVID-19, 1,076 (78.3%) and 298 (21.7%) were users and never-users of RAAS inhibitors, respectively. The RAAS inhibitor users were not associated with the risk of the primary outcome (adjusted odds ratio [aOR], 0.72; 95% confidence interval [CI], 0.46 to 1.10). The risk of ICU admission was significantly lower in the users than the never-users (aOR, 0.44; 95% CI, 0.24 to 0.84). The RAAS inhibitors were beneficial only in ICU admissions that did not require IMV (aOR, 0.28; 95% CI, 0.14 to 0.58). The risk of death from COVID-19 was comparable between the groups (aOR, 1.09; 95% CI, 0.64 to 1.85). We could not evaluate the risks of CRRT and ECMO owing to the small number of events.
Conclusion
RAAS inhibitor use was not associated with the composite of severe outcomes in the hypertensive patients with COVID-19 but significantly lowered the risk of ICU admission, particularly in patients who did not require IMV.

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Systematic review and meta-analysis of the clinical outcomes of ACEI/ARB in East-Asian patients with COVID-19
Nancy Xurui Huang, Qi Yuan, Fang Fang, Bryan P. Yan, John E. Sanderson, Masaki Mogi
PLOS ONE.2023; 18(1): e0280280. CrossRef
Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research
Jordan Loader, Frances C. Taylor, Erik Lampa, Johan Sundström
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Rumen Filev, Lionel Rostaing, Mila Lyubomirova, Boris Bogov, Krassimir Kalinov, Dobrin Svinarov
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Basic Research
MondoA Is Required for Normal Myogenesis and Regulation of the Skeletal Muscle Glycogen Content in Mice: Hui Ran, Yao Lu, Qi Zhang, Qiuyue Hu, Junmei Zhao, Kai Wang, Xuemei Tong, Qing Su; Diabetes Metab J. 2021;45(3):439-451. Published online May 18, 2020; DOI: https://doi.org/10.4093/dmj.2019.0212; Correction in: Diabetes Metab J 2021;45(5):797

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Background

Skeletal muscle is the largest tissue in the human body, and it plays a major role in exerting force and maintaining metabolism homeostasis. The role of muscle transcription factors in the regulation of metabolism is not fully understood. MondoA is a glucose-sensing transcription factor that is highly expressed in skeletal muscle. Previous studies suggest that MondoA can influence systemic metabolism homeostasis. However, the function of MondoA in the skeletal muscle remains unclear.

Methods

We generated muscle-specific MondoA knockout (MAKO) mice and analyzed the skeletal muscle morphology and glycogen content. Along with skeletal muscle from MAKO mice, C2C12 myocytes transfected with small interfering RNA against MondoA were also used to investigate the role and potential mechanism of MondoA in the development and glycogen metabolism of skeletal muscle.

Results

MAKO caused muscle fiber atrophy, reduced the proportion of type II fibers compared to type I fibers, and increased the muscle glycogen level. MondoA knockdown inhibited myoblast proliferation, migration, and differentiation by inhibiting the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Further mechanistic experiments revealed that the increased muscle glycogen in MAKO mice was caused by thioredoxin-interacting protein (TXNIP) downregulation, which led to upregulation of glucose transporter 4 (GLUT4), potentially increasing glucose uptake.

Conclusion

MondoA appears to mediate mouse myofiber development, and MondoA decreases the muscle glycogen level. The findings indicate the potential function of MondoA in skeletal muscle, linking the glucose-related transcription factor to myogenesis and skeletal myofiber glycogen metabolism.

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Byungyong Ahn
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Huiyi Ke, Yu Luan, Siming Wu, Yemin Zhu, Xuemei Tong
Frontiers in Endocrinology.2021;[Epub] CrossRef

Letter

Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals (Diabetes Metab J 2021;45:27-42): Otto Jesus Hernandez Fustes; Diabetes Metab J. 2021;45(3):452-453. Published online May 25, 2021; DOI: https://doi.org/10.4093/dmj.2021.0020

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