Diabetes & Metabolism Journal

Review

Pathophysiology
Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice: Yun Kyung Cho, Chang Hee Jung; Diabetes Metab J. 2023;47(6):757-766. Published online July 24, 2023; DOI: https://doi.org/10.4093/dmj.2023.0072

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With the increasing use of immune-checkpoint inhibitors (ICIs), such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death-1 (PD-1), for the treatment of malignancies, cases of ICI-induced type 1 diabetes mellitus (ICI-T1DM) have been reported globally. This review focuses on the features and pathogenesis of this disease. T1DM is an immune-related adverse event that occurs following the administration of anti-PD-1 or anti-programmed death ligand-1 (PDL1) alone or in combination with anti-CTLA-4. More than half of the reported cases presented as abrupt-onset diabetic ketoacidosis. The primary mechanism of ICI-T1DM is T-cell stimulation, which results from the loss of interaction between PD-1 and PD-L1 in pancreatic islet. The similarities and differences between ICI-T1DM and classical T1DM may provide insights into this disease entity. ICI-T1DM is a rare but often life-threatening medical emergency that healthcare professionals and patients need to be aware of. Early detection of and screening for this disease is imperative. At present, the only known treatment for ICI-T1DM is insulin injection. Further research into the mechanisms and risk factors associated with ICI-T1DM development may contribute to a better understanding of this disease entity and the identification of possible preventive strategies.

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Letter

Waist Circumference and Body Mass Index Variability and Incident Diabetic Microvascular Complications: A Post Hoc Analysis of ACCORD Trial (Diabetes Metab J 2022;46:767-80): Yun Kyung Cho; Diabetes Metab J. 2023;47(1):147-149. Published online January 26, 2023; DOI: https://doi.org/10.4093/dmj.2023.0002

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Original Articles

Clinical Diabetes & Therapeutics
Asian Subpopulations May Exhibit Greater Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Meta-Analysis of Cardiovascular Outcome Trials: Yu Mi Kang, Yun Kyung Cho, Jiwoo Lee, Seung Eun Lee, Woo Je Lee, Joong-Yeol Park, Ye-Jee Kim, Chang Hee Jung, Michael A. Nauck; Diabetes Metab J. 2019;43(4):410-421. Published online December 27, 2018; DOI: https://doi.org/10.4093/dmj.2018.0070

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Abstract PDF Supplementary Material PubReader

Background

Based on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit.

Methods

Three CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed.

Results

Overall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction <0.001), and more substantial risk reductions were observed in subjects of African origin (relative risk [RR], 0.78; 95% CI, 0.60 to 0.99) and in Asians (RR, 0.35; 95% CI, 0.09 to 1.32). However, post hoc analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (P<0.0001).

Conclusion

Long-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus. Our findings of a particularly effective reduction in CV events with GLP-1 RA in Asian populations merits further exploration and dedicated trials in specific populations.

Citations

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Journal of Clinical Lipidology.2024;[Epub] CrossRef
Coronary Artery Disease in South Asian Patients: Cardiovascular Risk Factors, Pathogenesis and Treatments
Vincenzo Sucato, Giuseppe Coppola, Girolamo Manno, Giuseppe Vadalà, Giuseppina Novo, Egle Corrado, Alfredo Ruggero Galassi
Current Problems in Cardiology.2023; 48(8): 101228. CrossRef
Retrospective Analysis of the Effectiveness of Oral Semaglutide in Type 2 Diabetes Mellitus and Its Effect on Cardiometabolic Parameters in Japanese Clinical Settings
Hodaka Yamada, Masashi Yoshida, Shunsuke Funazaki, Jun Morimoto, Shiori Tonezawa, Asuka Takahashi, Shuichi Nagashima, Kimura Masahiko, Otsuka Kiyoshi, Kazuo Hara
Journal of Cardiovascular Development and Disease.2023; 10(4): 176. CrossRef
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L. Yu. Khamnueva, L. S. Andreeva
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Role of diabetes in stroke: Recent advances in pathophysiology and clinical management
Sian A. Bradley, Kevin J. Spring, Roy G. Beran, Dimitrios Chatzis, Murray C. Killingsworth, Sonu M. M. Bhaskar
Diabetes/Metabolism Research and Reviews.2022;[Epub] CrossRef
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Harold Edward Bays, Jennifer Ng, Jeffrey Sicat, Michelle Look
Obesity Pillars.2022; 2: 100011. CrossRef
Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations
Calvin Ke, K. M. Venkat Narayan, Juliana C. N. Chan, Prabhat Jha, Baiju R. Shah
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Effect of race on cardiometabolic responses to once-weekly exenatide: insights from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)
Timothy M. E. Davis, Anna Giczewska, Yuliya Lokhnygina, Robert J. Mentz, Naveed Sattar, Rury R. Holman
Cardiovascular Diabetology.2022;[Epub] CrossRef
Generalizability of the Results of Cardiovascular Outcome Trials of Glucagon-Like Peptide 1 Receptor Agonists in Chinese Patients with Type 2 Diabetes Mellitus
Xiaoling Cai, Linong Ji
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Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes
Jae-Seung Yun, Seung-Hyun Ko
Metabolism.2021; 123: 154838. CrossRef
Sex and ethnic differences in the cardiovascular complications of type 2 diabetes
Jian L. Yeo, Emer M. Brady, Gerry P. McCann, Gaurav S. Gulsin
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Efficacy and Safety of GLP-1 Receptor Agonists in Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Yuan Zhu, Jiao Xu, Dong Zhang, Xingyu Mu, Yi Shi, Shangtao Chen, Zengxiang Wu, Shuangqing Li
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Subpopulation Differences in the Cardiovascular Efficacy of Long-Acting Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis
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Can the Oral Glucose Tolerance Test (OGTT) done at Postpartum (PPT) 1 Wddk Substitute OGTT at PPT 6 Week OGTT at PPT 6 Week in Diagnosing Rersistent PPT Glucose Intolerance in the Patients with Gastrational Diagetes Melltus (GDM)?.: Yoo Lee Kim, Yong Wook Cho, Seok Won Park, Yun Kyung Cho, Hwa Young Lee, In Hyun Kim, Jong Gun Won, Hye Sun Jun, Ho Taek Lee, Seog Ki Lee, Sang Jong Lee; Korean Diabetes J. 2000;24(2):267-280. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although 75 g-OGTT at PPT 6 week is necessary to diagnose persistent PPT glucose intolerance (PPGI) in GDM patients, it 1s difficult to perform this test because many patients drop-out during the follow-up period. Thus we tested whether OGTT done at PPT 1 week can substitute OGTT at PPT 6 week in diagnosing PPGI in GDM patients. METHOD: In 370 GDM patients, 75 g-OGTT was performed at PPT 1 week and repeat OGTT was done in 196 patients at PPT 6 week. Results of OGTT were classified as normal glucose tolerance(NGT), impaired glucose tolerance(IGT), and diabetes mellitus (DM) according to National Diabetes Data Group(NDDG) criteria. Changes in glucose tolerance state between PPT 1 and 6 week were assessed, and the predictability of clinical characteristics for these changes were investigated by logistic regression analysis. RESULTS: Among 370 GDM patients who performed OGTT at PPT 1 week, 79.4% had NGT, 12.2% had IGT, and 8.4% had DM. 53% (196/370) of subjects repeated OGTT at PPT 6 week. In OGTT at PPT 6 week, 77.6% (152/196, 140/149 in NGT, 4/26 in IGT and 8/21 in DM) were in the same glucose tolerance state as at PPT 1 week. The glucose tolerance improved in 14.8% (29/196, 16/26 in IGT and 13/21 in DM) and deteriorated in 7,6% (15/196, 9/149 in NGT and 6/26 in IGT). 94%(140/149) of patients who had NGT at PPT 1 week had NGT at PPT b week and 48.9/o (23/47) of patients who had abnormal glucose tolerance at PPT 1 week had abnormal glucose tolerance at PPT 6 week. Mean fasting plasma glucose level on OGTT became lower at PPT 1 week than during pregnancy (4.6+/-0,8 vs 5.1+/-1.2mmol/L, p<0.05) and became higher at PPT 6 week than at PPT 1 week (5.4+/-1.1 vs 4.6+/-0.8 mmol/L, p<0.05). Mean plasma glucose level at 2 hour after glucose load was significantly lower at PPT 6 week than at PPT 1 week (7.2+/-2.7 vs 8.3+/-2.5 mmol/L). When the subjects were grouped into NGT, IGT, and DM according to glucose tolerance state at PPT 6 week, the NGT group already showed normal glucose tolerance at PPT 1 week. The IGT and DM group showed slightly lower glucose levels at PPT 1 week than during pregnancy but became high to the level during pregnancy at PPT 6 week. In the patients group showing deterioration in glucose tolerance state between PPT 1 and 6 week, prevalence of insulin treatment was higher (63.4% vs 9.4, 20.7%), the gestational age at diagnosis of GDM were lower (25.0+/-6.2 week vs 29.8+/-3.3, 29.9+/-4,8 waek), and prepregnant weight was higher (113.4+/-21.2% vs 102.5+/-12.4, 102.4+/-14.6%) than those in the patients groups showing no change and improvement in glucose tolerance state, Weight gain until diagnosis of GDM during pregnancy(5.7+/-4.4kg vs 9.4+/-3.4kg) and weight change between prepregnancy and PPT 5 week(-1,3+/-3.5kg vs 1.5+/-29kg) was smaller in the deterioration group than those in the no change group. Logistic regression analysis performed using improvement and deterioration of glucose tolerance state between PPT 1 and 6 week as an outcome of interest revealed that an earlier diagnosis of GDM and a smaller weight at PPT 6 week than prepregnant weight were independent predictors for deterioration of glucose tolerance between PPT 1 and 6 week. In conclusion, OGTT done at PPT 1 week can substitute OGTT at PPT 6 week in a large subgroup of GDM patients who has NGT at PPT 1 week without any risk factors for deterioration in glucose tolerance.

Relationship Among Urinary Glycosaminoglycan (GAG) Excretion Rates, Urinary Albumin Excretion and Macrovascular Disease in Patients with Type 2 Diabetes Mellitus.: Yoon Sang Choi, Sang Hoon Kim, Hyang Kim, Yun Kyung Cho, Hyun Ju Um, Si Yong Kim, Byong Ik Kim, Yoo Lee Kim, Hwa Young Lee, Sang Jong Lee; Korean Diabetes J. 2000;24(2):245-255. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Increased loss of proteoglycan (PG) from glomerular basement membrane (GBM) has been postulated to alter glomerular charge selectivity which contributes to urinary loss of albumin. The glycosaminoglycan (GAG) is the degradation products of PG. Recently, one of the hypothesis suggested that urinary albumin execretion(UAE) reflects not only merely a glomerular manifes-tation but also a macrovascular disease (by Deckert et al), Wasty et al. reported a significant decrease in total GAG concentration and marked changes in their distribution in atherosclarotic plaques in human. Thus, the alterations in the metabolism of GAG might play a role in the pathogenesis of diabetic macroangiopathy. Therefore, we investigated the relationship among urinary GAG execretion rates, UAE and macrovascular disease in patients with type 2 diabetes mellitus. METHODS: We measured urinary excretion rates of GAS in type 2 diabetic patients with and without macrovascular disease ( cerebrovascular disease, ischemic heart disease and other peripheral vascular disease ) and investigated the relationships among urinary execretion of GAG, UAE and macrovascular disease in 103 patients with type 2 diabetes mellitus. RESULTS: 1) Among total 103 patients, 66 patients (64.0%) showed normoal-buminuria, 18 patients (17.5%) showed microabluminuria and 19 paitents (18.4%) showed macro albuminuria respectively. The duration of diabetes mellitus and the prevalence of hypertension, diabetic retinopathy and macrovascular disease were increased according to the degree of UAE. 2) The urinary excretion rates of GAG in type 2 diabetes mellitus with normo-, microand macro-albuminuria were 6.72+/-4.05, 9.17+/-3.26 and 14.20+/-6.13 microgram glucuronic acid/min respectively (p<0.05). The urinary GAG levels were significantly correlated with UAE (r=0.43, p<0.05). 3) The urinary excretion rates of GAG in type 2 diabetes mellitus with (n=26) and without (n=77) macrovascular disease were 6.21+/-2.75 and 9,31+/-5.59 ug glucuronic acid/min, respectively (p<0.05). CONCLUSION: 1) The urinary excretion rates of GAG were decreased in patients with macro vascular complications of type 2 diabetes mellitus. 2) The urinary excretion rates of GAG may be a possible marker of macrovascular disease in type 2 diabetes mellitus. Yet, further large prospective studies are necessary to confirm our findings.

Antepartum Characteristics Predicting Persistent Postpartum Glucose lntolerance in the Patients with Gestational Diabetes Mellitus (GDM).: Yoo Lee Kim, Yong Wook Cho, Seok Won Park, Seog Ki Lee, In Sup Ahn, Byung Wook Na, Jun Lee, Yun Kyung Cho, Hwa Young Lee, Sang Jong Lee; Korean Diabetes J. 2000;24(1):46-59. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The aim of this study is to investigate the prevalence of persistent postpartum glucose intolerance and to examine antepartum clinical characteri-stics for their predictability of persistent postpartum glucose intolerance in the patients with GDM. METHODS: In 211 GDM patients who showed more than two abnormal glucose values of O'Sullivan and Mahan's criteria on 100g-oral glucose tolerance test (OGTT), 75g-OGTT were performed at 6 weeks postpartum. The incidence of postpartum normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were investigated and antepartum ciinical parameters were compared among the three groups, Predictability of antepartum clinical characteristics for postpartum IGT and DM were also investigated by logistic regression analysis. RESULTS: When we grouped the patients into postpartum NGT, IGT, DM according to the results of 75g-OGTT performed 6 weeks postpartum, The incidence were 81,5% of subjects had NGT, 9.0% had IGT, and 9.5% had DM. Plasma glucose levels and GAUC on antepartum 100 g-OGTT(NGT: 1660+/-159, IGT: 1948+/-730, DM: 2538+/-629mmol/L ' min), and proportion of patients receiving insulin therapy increased progressively and significantly in association with worsening postpartum glucose tolerance. Frequency of positive family history of DM in qroups with IGT and DM (63,2% & 80.0%) were significantly higher than that in group with NGT(37,2%). Weight gain before diagnosis of GDM in groups with IGT and DM(6.7+/-3.9kg & 6.8+/-4.1 kg) were significantly smaller than that of group with NGT(9.5+/-3,5kg), Gestational age at diagnosis of GDM in group with DM(25.8+/-5.4 weeks) was significantly shorter than that in group with NGT(30.0+/-3,3 weeks), Proportion of subjects diagnosed earlier than 24 weeks of gestation were significantly higher in groups with IGT (15.8%) and DM (25.0%) than in group with NGT (1.2%). Proportions of subjects delivered heavier infants, > or =4 kg,were significantly higher in the DM group (40.0%) than in the NGT group (9.3%). In the patients having fasting plasma glucose levels hlgher than 5.8 mmol/L on antepartum 100g-OGTT, the prevalence of persistent glucose intolerance was significantly higher than in the patients FPG level lower than 5.8 mmol/L (61.9% vs 7.7%), Logistic regression analysis were performed using IGT and DM as the outcome of interest. The GAUC on antepartum 100g-OGTT, family history of DM, and the gestational age at diagnosis of GDM were independent predictors for both postpartum DM and postpartum IGT. CONCLUSION: The prevalence of persistent postpartum glucose intolerance in GDM patients were 18.5% and the most important independent predictor for persistent postpartum glucose intolerance was the degree of severity in glucose intolerance during pregnancy.

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