Diabetes & Metabolism Journal

2021

Original Articles

Drug/Regimen
Glucagon-Like Peptide-1 Receptor Agonist Differentially Affects Brain Activation in Response to Visual Food Cues in Lean and Obese Individuals with Type 2 Diabetes Mellitus: Jae Hyun Bae, Hyung Jin Choi, Kang Ik Kevin Cho, Lee Kyung Kim, Jun Soo Kwon, Young Min Cho; Diabetes Metab J. 2020;44(2):248-259. Published online November 4, 2019; DOI: https://doi.org/10.4093/dmj.2019.0018

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Background

To investigate the effects of a glucagon-like peptide-1 receptor agonist on functional brain activation in lean and obese individuals with type 2 diabetes mellitus (T2DM) in response to visual food cues.

Methods

In a randomized, single-blinded, crossover study, 15 lean and 14 obese individuals with T2DM were administered lixisenatide or normal saline subcutaneously with a 1-week washout period. We evaluated brain activation in response to pictures of high-calorie food, low-calorie food, and nonfood using functional magnetic resonance imaging and measured appetite and caloric intake in participants who were given access to an ad libitum buffet.

Results

Obese individuals with T2DM showed significantly greater activation of the hypothalamus, pineal gland, parietal cortex (high-calorie food vs. low-calorie food, P<0.05), orbitofrontal cortex (high-calorie food vs. nonfood, P<0.05), and visual cortex (food vs. nonfood, P<0.05) than lean individuals with T2DM. Lixisenatide injection significantly reduced the functional activation of the fusiform gyrus and lateral ventricle in obese individuals with T2DM compared with that in lean individuals with T2DM (nonfood vs. high-calorie food, P<0.05). In addition, in individuals who decreased their caloric intake after lixisenatide injection, there were significant interaction effects between group and treatment in the posterior cingulate, medial frontal cortex (high-calorie food vs. low-calorie food, P<0.05), hypothalamus, orbitofrontal cortex, and temporal lobe (food vs. nonfood, P<0.05).

Conclusion

Brain responses to visual food cues were different in lean and obese individuals with T2DM. In addition, acute administration of lixisenatide differentially affected functional brain activation in these individuals, especially in those who decreased their caloric intake after lixisenatide injection.

Citations

Citations to this article as recorded by

Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)
Jae Hyun Bae
Diabetes & Metabolism Journal.2024; 48(1): 157. CrossRef
Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial
Natalia McInnes, Stephanie Hall, Heather A. Lochnan, Stewart B. Harris, Zubin Punthakee, Ronald J. Sigal, Irene Hramiak, Mohammed Azharuddin, Joanne F. Liutkus, Jean‐François Yale, Farah Sultan, Ada Smith, Rose E. Otto, Diana Sherifali, Yan Yun Liu, Hertz
Diabetes, Obesity and Metabolism.2023; 25(11): 3347. CrossRef
Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy
Hussein Zaitoon, Ronit Lubetzky, Achiya Z. Amir, Hadar Moran-Lev, Liora Sagi, Michal Yacobi-Bach, Ophir Borger, Efrat Chorna, Yael Lebenthal, Avivit Brener
Acta Diabetologica.2023; 60(8): 1099. CrossRef
What can functional brain imaging teach us about remission of type 2 diabetes?
Dhruti Hirani, Shahd Alabdulkader, Alexander. D. Miras, Victoria Salem
Diabetic Medicine.2023;[Epub] CrossRef
Fasting oxyntomodulin, glicentin, and gastric inhibitory polypeptide levels are associated with activation of reward‐ and attention‐related brain centres in response to visual food cues in adults with obesity: A cross‐sectional functional MRI study
Nikolaos Perakakis, Olivia M. Farr, Christos S. Mantzoros
Diabetes, Obesity and Metabolism.2021; 23(5): 1202. CrossRef
Aberrant Brain Functional Connectivity Strength and Effective Connectivity in Patients with Type 2 Diabetes Mellitus
Xi Guo, Su Wang, Yu-Chen Chen, Heng-Le Wei, Gang-Ping Zhou, Yu-Sheng Yu, Xindao Yin, Kun Wang, Hong Zhang, Eusebio Chiefari
Journal of Diabetes Research.2021; 2021: 1. CrossRef

Covid-19
The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea: Mi Kyung Kim, Jae-Han Jeon, Sung-Woo Kim, Jun Sung Moon, Nan Hee Cho, Eugene Han, Ji Hong You, Ji Yeon Lee, Miri Hyun, Jae Seok Park, Yong Shik Kwon, Yeon-Kyung Choi, Ki Tae Kwon, Shin Yup Lee, Eon Ju Jeon, Jin-Woo Kim, Hyo-Lim Hong, Hyun Hee Kwon, Chi Young Jung, Yin Young Lee, Eunyeoung Ha, Seung Min Chung, Jian Hur, June Hong Ahn, Na-young Kim, Shin-Woo Kim, Hyun Ha Chang, Yong Hoon Lee, Jaehee Lee, Keun-Gyu Park, Hyun Ah Kim, Ji-Hyun Lee; Diabetes Metab J. 2020;44(4):602-613. Published online August 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0146

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Background

Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes.

Methods

We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group.

Results

Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease.

Conclusion

DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

Citations

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Liman Luo, Menglu Fu, Yuanyuan Li, Shuiqing Hu, Jinlan Luo, Zhihui Chen, Jing Yu, Wenhua Li, Ruolan Dong, Yan Yang, Ling Tu, Xizhen Xu
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Ji Hong You, Sang Ah Lee, Sung-Youn Chun, Sun Ok Song, Byung-Wan Lee, Dae Jung Kim, Edward J. Boyko
Endocrinology and Metabolism.2020; 35(4): 901. CrossRef

COVID-19
Independent Impact of Diabetes on the Severity of Coronavirus Disease 2019 in 5,307 Patients in South Korea: A Nationwide Cohort Study: Sun Joon Moon, Eun-Jung Rhee, Jin-Hyung Jung, Kyung-Do Han, Sung-Rae Kim, Won-Young Lee, Kun-Ho Yoon; Diabetes Metab J. 2020;44(5):737-746. Published online October 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0141

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Background
Inconsistent results have been observed regarding the independent effect of diabetes on the severity of coronavirus disease 2019 (COVID-19). We conducted a nationwide population-based cohort study to evaluate the relationship between diabetes and COVID-19 severity in South Korea.
Methods
Patients with laboratory-confirmed COVID-19 aged ≥30 years were enrolled and medical claims data were obtained from the Korean Health Insurance Review and Assessment Service. Hospitalization, oxygen treatment, ventilator application, and mortality were assessed as severity outcomes. Multivariate logistic regression analyses were performed after adjusting for age, sex, and comorbidities.
Results
Of 5,307 COVID-19 patients, the mean age was 56.0±14.4 years, 2,043 (38.5%) were male, and 770 (14.5%) had diabetes. The number of patients who were hospitalized, who received oxygen, who required ventilator support, and who died was 4,986 (94.0%), 884 (16.7%), 121 (2.3%), and 211 (4.0%), respectively. The proportion of patients with diabetes in the abovementioned outcome groups was 14.7%, 28.1%, 41.3%, 44.6%, showing an increasing trend according to outcome severity. In multivariate analyses, diabetes was associated with worse outcomes, with an adjusted odds ratio (aOR) of 1.349 (95% confidence interval [CI], 1.099 to 1.656; P=0.004) for oxygen treatment, an aOR of 1.930 (95% CI, 1.276 to 2.915; P<0.001) for ventilator use, and an aOR of 2.659 (95% CI, 1.896 to 3.729; P<0.001) for mortality.
Conclusion
Diabetes was associated with worse clinical outcomes in Korean patients with COVID-19, independent of other comorbidities. Therefore, patients with diabetes and COVID-19 should be treated with caution.

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Basic Research
Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy: Chang-Yun Woo, Ji Yeon Baek, Ah-Ram Kim, Chung Hwan Hong, Ji Eun Yoon, Hyoun Sik Kim, Hyun Ju Yoo, Tae-Sik Park, Ranjan Kc, Ki-Up Lee, Eun Hee Koh; Diabetes Metab J. 2020;44(4):581-591. Published online November 4, 2019; DOI: https://doi.org/10.4093/dmj.2019.0063

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Background

Ceramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes. Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy.

Methods

We used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes.

Results

OLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity.

Conclusion

We showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production. Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.

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Cardiovascular Risk/Epidemiology
Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults: Eun-Jung Rhee, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Yang-Hyun Kim, Won-Young Lee; Diabetes Metab J. 2020;44(4):592-601. Published online April 20, 2020; DOI: https://doi.org/10.4093/dmj.2019.0104; Correction in: Diabetes Metab J 2020;44(5):783

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Background

Recent studies suggest an association between diabetes and increased risk of heart failure (HF). However, the associations among obesity status, glycemic status, and risk of HF are not known. In this study, we analyzed whether the risk of HF increases in participants according to baseline glycemic status and whether this increased risk is associated with obesity status.

Methods

We analyzed the risk of HF according to baseline glycemic status (normoglycemia, impaired fasting glucose [IFG], and diabetes) in 9,720,220 Koreans who underwent Korean National Health Screening in 2009 without HF at baseline with a median follow-up period of 6.3 years. The participants were divided into five and six groups according to baseline body mass index (BMI) and waist circumference, respectively.

Results

Participants with IFG and those with diabetes showed a 1.08- and 1.86-fold increased risk of HF, respectively, compared to normoglycemic participants. Compared to the normal weight group (BMI, 18.5 to 22.9 kg/m²), the underweight group (BMI <18.5 kg/m²) showed a 1.7-fold increased risk of HF, and those with BMI ≥30 kg/m² showed a 1.1-fold increased risk of HF, suggesting a J-shaped association with BMI. When similar analyses were performed for different glycemic statuses, the J-shaped association between BMI and HF risk was consistently observed in both groups with and without diabetes.

Conclusion

Participants with IFG and diabetes showed a significantly increased HF risk compared to normoglycemic participants. This increased risk of HF was mostly prominent in underweight and class II obese participants than in participants with normal weight.

Citations

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Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee
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O. V. Tsygankova, N. E. Evdokimova, V. V. Veretyuk, L. D. Latyntseva, A. S. Ametov
Diabetes mellitus.2022; 25(6): 535. CrossRef
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Tae-Eun Kim, Hyeongsu Kim, JiDong Sung, Duk-Kyung Kim, Myoung-Soon Lee, Seong Woo Han, Hyun-Joong Kim, Sung Hea Kim, Kyu-Hyung Ryu
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Diabetes and Heart Failure
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Eun-Jung Rhee
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Letter: Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults (Diabetes Metab J 2020;44:592-601)
Darae Kim
Diabetes & Metabolism Journal.2020; 44(5): 777. CrossRef
Response: Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults (Diabetes Metab J 2020;44:592-601)
Eun-Jung Rhee, Won-Young Lee
Diabetes & Metabolism Journal.2020; 44(5): 781. CrossRef

Drug/Regimen
An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment: Sung Woon Park, Seunghyun Lee, Won Chul Cha, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee, Sung-Min Park, Sang-Man Jin; Diabetes Metab J. 2020;44(1):56-66. Published online October 21, 2019; DOI: https://doi.org/10.4093/dmj.2018.0227

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Background

We aimed to describe the outcome of a computerized intravenous insulin infusion (CII) protocol integrated to the electronic health record (EHR) system and to improve the CII protocol in silico using the EHR-based predictors of the outcome.

Methods

Clinical outcomes of the patients who underwent the CII protocol between July 2016 and February 2017 and their matched controls were evaluated. In the CII protocol group (n=91), multivariable binary logistic regression analysis models were used to determine the independent associates with a delayed response (taking ≥6.0 hours for entering a glucose range of 70 to 180 mg/dL). The CII protocol was adjusted in silico according to the EHR-based parameters obtained in the first 3 hours of CII.

Results

Use of the CII protocol was associated with fewer subjects with hypoglycemia alert values (P=0.003), earlier (P=0.002), and more stable (P=0.017) achievement of a glucose range of 70 to 180 mg/dL. Initial glucose level (P=0.001), change in glucose during the first 2 hours (P=0.026), and change in insulin infusion rate during the first 3 hours (P=0.029) were independently associated with delayed responses. Increasing the insulin infusion rate temporarily according to these parameters in silico significantly reduced delayed responses (P<0.0001) without hypoglycemia, especially in refractory patients.

Conclusion

Our CII protocol enabled faster and more stable glycemic control than conventional care with minimized risk of hypoglycemia. An EHR-based adjustment was simulated to reduce delayed responses without increased incidence of hypoglycemia.

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Response: An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment (Diabetes Metab J 2020;44:56–66)
Sung Woon Park, Seunghyun Lee, Won Chul Cha, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee, Sung-Min Park, Sang-Man Jin
Diabetes & Metabolism Journal.2020; 44(2): 358. CrossRef
Letter: An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment (Diabetes Metab J 2020;44:56–66)
Dongwon Yi
Diabetes & Metabolism Journal.2020; 44(2): 354. CrossRef

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