Diabetes & Metabolism Journal

Brief Report

Type 1 Diabetes
In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors: Seung-Ah Lee, Subin Kim, Seog-Young Kim, Jong Yoen Park, Hye Seung Jung, Sung Soo Chung, Kyong Soo Park; Diabetes Metab J. 2025;49(1):150-159. Published online October 24, 2024; DOI: https://doi.org/10.4093/dmj.2024.0174

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Abstract PDF Supplementary Material PubReader ePub: Four soluble factors—putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102—were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45–55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.

Original Articles

Drug/Regimen
Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial: Ji Hye Heo, Kyung Ah Han, Jun Hwa Hong, Hyun-Ae Seo, Eun-Gyoung Hong, Jae Myung Yu, Hye Seung Jung, Bong-Soo Cha; Diabetes Metab J. 2024;48(5):937-948. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0314

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Background
This study assessed the efficacy and safety of triple therapy with pioglitazone 15 mg add-on versus placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, patients with T2DM with an inadequate response to treatment with metformin (≥1,000 mg/day) plus dapagliflozin (10 mg/day) were randomized to receive additional pioglitazone 15 mg/day (n=125) or placebo (n=125) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) levels from baseline to week 24 (ClinicalTrials.gov identifier: NCT05101135).
Results
At week 24, the adjusted mean change from baseline in HbA1c level compared with placebo was significantly greater with pioglitazone treatment (–0.47%; 95% confidence interval, –0.61 to –0.33; P<0.0001). A greater proportion of patients achieved HbA1c <7% or <6.5% at week 24 with pioglitazone compared to placebo as add-on to 10 mg dapagliflozin and metformin (56.8% vs. 28% for HbA1c <7%, and 23.2% vs. 9.6% for HbA1c <6.5%; P<0.0001 for all). The addition of pioglitazone also significantly improved triglyceride, highdensity lipoprotein cholesterol levels, and homeostatic model assessment of insulin resistance levels, while placebo did not. The incidence of treatment-emergent adverse events was similar between the groups, and the incidence of fluid retention-related side effects by pioglitazone was low (1.5%).
Conclusion
Triple therapy with the addition of 15 mg/day of pioglitazone to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with T2DM inadequately controlled with dapagliflozin plus metformin.

Citations

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Ideal Combination of Oral Hypoglycemic Agents for Patients with Type 2 Diabetes Mellitus
Hye Soon Kim
Diabetes & Metabolism Journal.2024; 48(5): 882. CrossRef

Basic Research
Glucolipotoxicity Suppressed Autophagy and Insulin Contents in Human Islets, and Attenuation of PERK Activity Enhanced Them in an ATG7-Dependent Manner: Seoil Moon, Ji Yoon Lim, Mirang Lee, Youngmin Han, Hongbeom Kim, Wooil Kwon, Jin-Young Jang, Mi Na Kim, Kyong Soo Park, Hye Seung Jung; Diabetes Metab J. 2024;48(2):231-241. Published online September 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0366

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Background
Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it.
Methods
Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy.
Results
PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced ATG7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion.
Conclusion
This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi.

Citations

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Genetic knock-in of EIF2AK3 variants reveals differences in PERK activity in mouse liver and pancreas under endoplasmic reticulum stress
Shivesh Ghura, Noah R. Beratan, Xinglong Shi, Elena Alvarez-Periel, Sarah E. Bond Newton, Cagla Akay-Espinoza, Kelly L. Jordan-Sciutto
Scientific Reports.2024;[Epub] CrossRef
Pancreatic β-Cells, Diabetes and Autophagy
Yang Ou, Yan-Li Zhao, Heng Su
Endocrine Research.2024; : 1. CrossRef

Review

Pathophysiology
Endoplasmic Reticulum Stress and Dysregulated Autophagy in Human Pancreatic Beta Cells: Seoil Moon, Hye Seung Jung; Diabetes Metab J. 2022;46(4):533-542. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0070

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Abstract PDF PubReader ePub

Pancreatic beta cell homeostasis is crucial for the synthesis and secretion of insulin; disruption of homeostasis causes diabetes, and is a treatment target. Adaptation to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR) and adequate regulation of autophagy, which are closely linked, play essential roles in this homeostasis. In diabetes, the UPR and autophagy are dysregulated, which leads to beta cell failure and death. Various studies have explored methods to preserve pancreatic beta cell function and mass by relieving ER stress and regulating autophagic activity. To promote clinical translation of these research results to potential therapeutics for diabetes, we summarize the current knowledge on ER stress and autophagy in human insulin-secreting cells.

Citations

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Glucolipotoxicity Suppressed Autophagy and Insulin Contents in Human Islets, and Attenuation of PERK Activity Enhanced Them in an ATG7-Dependent Manner
Seoil Moon, Ji Yoon Lim, Mirang Lee, Youngmin Han, Hongbeom Kim, Wooil Kwon, Jin-Young Jang, Mi Na Kim, Kyong Soo Park, Hye Seung Jung
Diabetes & Metabolism Journal.2024; 48(2): 231. CrossRef
Endoplasmic reticulum stress: A possible connection between intestinal inflammation and neurodegenerative disorders
Giorgio Vivacqua, Romina Mancinelli, Stefano Leone, Rosa Vaccaro, Ludovica Garro, Simone Carotti, Ludovica Ceci, Paolo Onori, Luigi Pannarale, Antonio Franchitto, Eugenio Gaudio, Arianna Casini
Neurogastroenterology & Motility.2024;[Epub] CrossRef
Docosahexanoic Acid Attenuates Palmitate-Induced Apoptosis by Autophagy Upregulation via GPR120/mTOR Axis in Insulin-Secreting Cells
Seok-Woo Hong, Jinmi Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Endocrinology and Metabolism.2024; 39(2): 353. CrossRef
HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy
Uma Maheswari Deshetty, Nivedita Chatterjee, Shilpa Buch, Palsamy Periyasamy
Viruses.2024; 16(6): 903. CrossRef
Gallic acid suppresses the progression of clear cell renal cell carcinoma through inducing autophagy via the PI3K/Akt/Atg16L1 signaling pathway
Tianxiang Zhang, Xi Zhang, Yang Fei, Jinsen Lu, Dairan Zhou, Li Zhang, Song Fan, Jun Zhou, Chaozhao Liang, Yang Su
International Journal of Oncology.2024;[Epub] CrossRef
Dysregulation of pancreatic β-cell autophagy and the risk of type 2 diabetes
Hayder M. Al-kuraishy, Majid S. Jabir, Ali I. Al-Gareeb, Daniel J. Klionsky, Ali K. Albuhadily
Autophagy.2024; 20(11): 2361. CrossRef
Endoplasmic reticulum stress mechanisms and exercise intervention in type 2 diabetes mellitus
Qianyu Chen, Xiaoqin Zhao, Zujie Xu, Yiyao Liu
Biomedicine & Pharmacotherapy.2024; 177: 117122. CrossRef
Tangningtongluo Tablet ameliorates pancreatic damage in diabetic mice by inducing autophagy and inhibiting the PI3K/Akt/mTOR signaling pathway
Ying Ren, Xiangka Hu, Mushuang Qi, Wanjun Zhu, Jin Li, Shuyu Yang, Chunmei Dai
International Immunopharmacology.2024; 142: 113032. CrossRef
Ambient air fine particulate matter (PM10 and PM2.5) and risk of type 2 diabetes mellitus and mechanisms of effects: a global systematic review and meta-analysis
Salah Azizi, Mohammad Hadi Dehghani, Ramin Nabizadeh
International Journal of Environmental Health Research.2024; : 1. CrossRef
Pancreatic islet remodeling in cotadutide-treated obese mice
Renata Spezani, Thatiany Souza Marinho, Luiz E. Macedo Cardoso, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Life Sciences.2023; 327: 121858. CrossRef
Modulation of Unfolded Protein Response Restores Survival and Function of β-Cells Exposed to the Endocrine Disruptor Bisphenol A
Laura Maria Daian, Gabriela Tanko, Andrei Mircea Vacaru, Luiza Ghila, Simona Chera, Ana-Maria Vacaru
International Journal of Molecular Sciences.2023; 24(3): 2023. CrossRef
Interplay of skeletal muscle and adipose tissue: sarcopenic obesity
Min Jeong Park, Kyung Mook Choi
Metabolism.2023; 144: 155577. CrossRef
Identification and analysis of type 2 diabetes-mellitus-associated autophagy-related genes
Kun Cui, Zhizheng Li
Frontiers in Endocrinology.2023;[Epub] CrossRef
Sestrin2 in diabetes and diabetic complications
Xiaodan Zhang, Zirui Luo, Jiahong Li, Yaxuan Lin, Yu Li, Wangen Li
Frontiers in Endocrinology.2023;[Epub] CrossRef
Crosstalk between autophagy and insulin resistance: evidence from different tissues
Asie Sadeghi, Maryam Niknam, Mohammad Amin Momeni-Moghaddam, Maryam Shabani, Hamid Aria, Alireza Bastin, Maryam Teimouri, Reza Meshkani, Hamed Akbari
European Journal of Medical Research.2023;[Epub] CrossRef
Beta cell lipotoxicity in the development of type 2 diabetes: the need for species-specific understanding
Patricia Thomas, Meurig T. Gallagher, Gabriela Da Silva Xavier
Frontiers in Endocrinology.2023;[Epub] CrossRef

Original Articles

Drug/Regimen
Comparison of Prevailing Insulin Regimens at Different Time Periods in Hospitalized Patients: A Real-World Experience from a Tertiary Hospital: Sun Joon Moon, Hun Jee Choe, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Diabetes Metab J. 2022;46(3):439-450. Published online October 20, 2021; DOI: https://doi.org/10.4093/dmj.2021.0065

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Abstract PDF Supplementary Material PubReader ePub: Background
Prevailing insulin regimens for glycemic control in hospitalized patients have changed over time. We aimed to determine whether the current basal-bolus insulin (BBI) regimen is superior to the previous insulin regimen, mainly comprising split-mixed insulin therapy.
Methods
This was a single tertiary center, retrospective observational study that included non-critically ill patients with type 2 diabetes mellitus who were treated with split-mixed insulin regimens from 2004 to 2007 (period 1) and with BBI from 2008 to 2018 (period 2). Patients from each period were analyzed after propensity score matching. The mean difference in glucose levels and the achievement of fasting and preprandial glycemic targets by day 6 of admission were assessed. The total daily insulin dose, incidence of hypoglycemia, and length of hospital stay were also evaluated.
Results
Among 244 patients from each period, both fasting glucose (estimated mean±standard error, 147.4±3.1 mg/dL vs. 129.4±3.2 mg/dL, P<0.001, day 6) and preprandial glucose (177.7±2.8 mg/dL vs. 152.8±2.8 mg/dL, P<0.001, day 6) were lower in period 2 than in period 1. By day 6 of hospital admission, 42.6% and 67.2% of patients achieved a preprandial glycemic target of <140 mg/dL in periods 1 and 2, respectively (relative risk, 2.00; 95% confidence interval, 1.54 to 2.59), without an increased incidence of hypoglycemia. Length of stay was shorter in period 2 (10.23±0.26 days vs. 8.70±0.26 days, P<0.001).
Conclusion
BBI improved glycemic control in a more efficacious manner than a split-mixed insulin regimen without increasing the risk of hypoglycemia in a hospital setting.

Drug/Regimen
Efficacy and Safety of Self-Titration Algorithms of Insulin Glargine 300 units/mL in Individuals with Uncontrolled Type 2 Diabetes Mellitus (The Korean TITRATION Study): A Randomized Controlled Trial: Jae Hyun Bae, Chang Ho Ahn, Ye Seul Yang, Sun Joon Moon, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Diabetes Metab J. 2022;46(1):71-80. Published online June 16, 2021; DOI: https://doi.org/10.4093/dmj.2020.0274

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub

Background
To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM).
Methods
In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting self-monitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without noct urnal hypoglycemia at week 12.
Results
Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014).
Conclusion
The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663).

Citations

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Time for Using Machine Learning for Dose Guidance in Titration of People With Type 2 Diabetes? A Systematic Review of Basal Insulin Dose Guidance
Camilla Heisel Nyholm Thomsen, Stine Hangaard, Thomas Kronborg, Peter Vestergaard, Ole Hejlesen, Morten Hasselstrøm Jensen
Journal of Diabetes Science and Technology.2024; 18(5): 1185. CrossRef
Comparative efficacy and safety of weekly tirzepatide versus weekly insulin in type 2 diabetes: A network meta‐analysis of randomized clinical trials
Hazem Ayesh, Sajida Suhail, Suhail Ayesh, Kevin Niswender
Diabetes, Obesity and Metabolism.2024; 26(9): 3801. CrossRef
Basal insulin titration algorithms in patients with type 2 diabetes: the simplest is the best (?)
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INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2023; 19(3): 240. CrossRef

Letter

Letter: Early Assessment of the Risk for Gestational Diabetes Mellitus: Can Fasting Parameters of Glucose Metabolism Contribute to Risk Prediction? (Diabetes Metab J 2019;43:785–93): Ye Seul Yang, Hye Seung Jung; Diabetes Metab J. 2020;44(1):199-200. Published online February 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0023

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Comparison of the Effect of Face-to-face and Social Media-based Training on the Self-care of Women with Gestational Diabetes Mellitus (GDM) in Birjand
Mohaddeseh Hosseinzadeh, Gholamreza Sharifzadeh, Mostafa Hosseinzadeh, Marzieh Torshizi
Modern Care Journal.2022;[Epub] CrossRef

Brief Report

Genetics
Identification of Two Cases of Ciliopathy-Associated Diabetes and Their Mutation Analysis Using Whole Exome Sequencing: Min Kyeong Kim, Soo Heon Kwak, Shinae Kang, Hye Seung Jung, Young Min Cho, Seong Yeon Kim, Kyong Soo Park; Diabetes Metab J. 2015;39(5):439-443. Published online October 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.5.439

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Background

Alström syndrome and Bardet-Biedl syndrome are autosomal recessively inherited ciliopathies with common characteristics of obesity, diabetes, and blindness. Alström syndrome is caused by a mutation in the ALMS1 gene, and Bardet-Biedl syndrome is caused by mutations in BBS1-16 genes. Herein we report genetically confirmed cases of Alström syndrome and Bardet-Biedl syndrome in Korea using whole exome sequencing.

Methods

Exome capture was done using SureSelect Human All Exon Kit V4+UTRs (Agilent Technologies). HiSeq2000 system (Illumina) was used for massive parallel sequencing. Sanger sequencing was used for genotype confirmation and familial cosegregation analysis.

Results

A 21-year old Korean woman was clinically diagnosed with Alström syndrome. She had diabetes, blindness, obesity, severe insulin resistance, and hearing loss. Whole exome sequencing revealed a nonsense mutation in exon 10 of ALMS1 (c.8776C>T, p.R2926X) and a seven base-pair deletion resulting in frameshift mutation in exon 8 (c.6410_6416del, p.2137_2139del). A 24-year-old Korean man had Bardet-Biedl syndrome with diabetes, blindness, obesity, and a history of polydactyly. Whole exome sequencing revealed a nonsynonymous mutation in exon 11 of the BBS1 gene (c.1061A>G, p.E354G) and mutation at the normal splicing recognition site of exon 7 of the BBS1 gene (c.519-1G>T).

Conclusion

We found novel compound heterozygous mutations of Alström syndrome and Bardet-Biedl syndrome using whole exome sequencing. The whole exome sequencing successfully identified novel genetic variants of ciliopathy-associated diabetes.

Citations

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Genotype–phenotype associations in Alström syndrome: a systematic review and meta-analysis
Brais Bea-Mascato, Diana Valverde
Journal of Medical Genetics.2024; 61(1): 18. CrossRef
Differentiating monogenic and syndromic obesities from polygenic obesity: Assessment, diagnosis, and management
Angela K. Fitch, Sonali Malhotra, Rushika Conroy
Obesity Pillars.2024; 11: 100110. CrossRef
Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients
Naglaa M. Kamal, Ahmed N. Sahly, Babajan Banaganapalli, Omran M. Rashidi, Preetha J. Shetty, Jumana Y. Al-Aama, Noor A. Shaik, Ramu Elango, Omar I. Saadah
Saudi Journal of Biological Sciences.2020; 27(1): 271. CrossRef
Established and emerging strategies to crack the genetic code of obesity
V. Tam, M. Turcotte, D. Meyre
Obesity Reviews.2019; 20(2): 212. CrossRef
Identifying Pathogenic Variants of Monogenic Diabetes Using Targeted Panel Sequencing in an East Asian Population
Seung Shin Park, Se Song Jang, Chang Ho Ahn, Jung Hee Kim, Hye Seung Jung, Young Min Cho, Young Ah Lee, Choong Ho Shin, Jong Hee Chae, Jae Hyun Kim, Sung Hee Choi, Hak C Jang, Jee Cheol Bae, Jong Cheol Won, Sung-Hoon Kim, Jong-Il Kim, Soo Heon Kwak, Kyong
The Journal of Clinical Endocrinology & Metabolism.2019; 104(9): 4188. CrossRef
Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes
Sheila Castro-Sánchez, María Álvarez-Satta, Mohamed A. Tohamy, Sergi Beltran, Sophia Derdak, Diana Valverde, Anand Swaroop
PLOS ONE.2017; 12(8): e0183081. CrossRef

Response

Response: Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased β-Cell Function Similar to Impaired Glucose Tolerance (Diabetes Metab J 2015;39:147-53): Tae Jung Oh, Se Hee Min, Chang Ho Ahn, Eun Ky Kim, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Diabetes Metab J. 2015;39(3):270-271. Published online June 15, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.3.270

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Citations

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Prevalence of Impaired Glucose Tolerance/Prediabetes in Local Adult Obese Population Presenting to A Tertiary Care Hospital
Niktash Khan Hadi, Muhammad Salman Aamir, Tahir Ghaffar, Sulaiman Khan, Siraj ul Islam, Shafiullah Khan, Nizamuddin ., Muhammad Ali
Pakistan Journal of Health Sciences.2023; : 84. CrossRef

Original Articles

Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased β-Cell Function Similar to Impaired Glucose Tolerance: Tae Jung Oh, Se Hee Min, Chang Ho Ahn, Eun Ky Kim, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Diabetes Metab J. 2015;39(2):147-153. Published online March 9, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.2.147

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Abstract PDF PubReader

Background

Subjects with normal glucose tolerance (NGT) who have a high 1-hour postload plasma glucose level (≥155 mg/dL; NGT 1 hour-high) have been shown to be at higher risk for type 2 diabetes than subjects with NGT 1 hour-low postload plasma glucose level (<155 mg/dL). We compared β-cell function in subjects with NGT 1 hour-high, NGT 1 hour-low, and impaired glucose tolerance (IGT).

Methods

We classified subjects into NGT 1 hour-low (n=149), NGT 1 hour-high (n=43), and IGT (n=52). The β-cell function was assessed based on insulinogenic index (IGI), oral disposition index (DI), and insulin secretion-sensitivity index-2 (ISSI-2).

Results

Insulin sensitivity was comparable between the subjects with NGT 1 hour-high and NGT 1 hour-low. The β-cell function with/without adjusting insulin sensitivity was significantly different among the three groups. The IGI (pmol/mmol) was 116.8±107.3 vs. 64.8±47.8 vs. 65.8±80.6 (P=0.141), oral DI was 3.5±4.2 vs. 1.8±1.4 vs. 1.8±3.1 (P<0.001), and ISSI-2 was 301.2±113.7 vs. 213.2±67.3 vs. 172.5±87.5 (P<0.001) in NGT 1 hour-low, NGT 1 hour-high, and IGT, respectively. Post hoc analyses revealed that oral DI and ISSI-2 were significantly different between NGT 1 hour-low and NGT 1 hour-high but comparable between NGT 1 hour-high and IGT.

Conclusion

Among Korean subjects with NGT, those who have a higher 1-hour postload glucose level have a compromised insulin-sensitivity adjusted β-cell function to a similar degree as IGT subjects.

Citations

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Diabetes/Metabolism Research and Reviews.2021;[Epub] CrossRef
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Kyong Hye Joung, Sang Hyun Ju, Ji Min Kim, Sorim Choung, Jae Min Lee, Kang Seo Park, Hyun Jin Kim, Bon Jeong Ku
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The 1-h post-load plasma glucose as a novel biomarker for diagnosing dysglycemia
Ram Jagannathan, Martin Buysschaert, José Luis Medina, Karin Katz, Sarah Musleh, Brenda Dorcely, Michael Bergman
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Elevated 1‐hour post‐load plasma glucose identifies obese youth with abnormal glucose metabolism and an unfavourable inflammatory profile
Anastasios Serbis, Vasileios Giapros, Anna Challa, Nikolaos Chaliasos, Ekaterini Siomou
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One‐hour postload plasma glucose concentration in people with normal glucose homeostasis predicts future diabetes mellitus: a 12‐year community‐based cohort study
Tae Jung Oh, Soo Lim, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Young Min Cho, Kyong Soo Park, HakChul Jang, Nam H. Cho
Clinical Endocrinology.2017; 86(4): 513. CrossRef
An elevated 1-h post- load glucose level during the oral glucose tolerance test detects prediabetes
Martin Buysschaert, Michael Bergman, Donald Yanogo, Ram Jagannathan, Benoit Buysschaert, Vanessa Preumont
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Delayed insulin secretion response during an OGTT is associated with an increased risk for incidence of diabetes in NGT subjects
Yun Sun, Junfeng Han, Ziwei Lin, Lige Song, Chen Wang, Weiping Jia
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Letter: Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased β-Cell Function Similar to Impaired Glucose Tolerance (Diabetes Metab J2015;39:147-53)
Hee Kyung Kim
Diabetes & Metabolism Journal.2015; 39(3): 268. CrossRef

Increasing Trend in the Number of Severe Hypoglycemia Patients in Korea: Jin Taek Kim, Tae Jung Oh, Ye An Lee, Jun Ho Bae, Hyo Jeong Kim, Hye Seung Jung, Young Min Cho, Kyong Soo Park, Soo Lim, Hak Chul Jang, Hong Kyu Lee; Diabetes Metab J. 2011;35(2):166-172. Published online April 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.2.166

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Background

To investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects.

Methods

We analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009.

Results

A total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69±12 years, mean duration of diabetes was 13.8±9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users.

Conclusion

We identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia.

Citations

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A Survey on Ubiquitous Healthcare Service Demand among Diabetic Patients: Soo Lim, So-Youn Kim, Jung Im Kim, Min Kyung Kwon, Sei Jin Min, Soo Young Yoo, Seon Mee Kang, Hong Il Kim, Hye Seung Jung, Kyong Soo Park, Jun Oh Ryu, Hayley Shin, Hak Chul Jang; Diabetes Metab J. 2011;35(1):50-57. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.50

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Background

Advanced information technology can be used when developing diagnostic and treatment strategies to provide better care for diabetic patients. However, the levels of need and demand for the use of technological advances have not been investigated in diabetic patients. We proposed and developed an individualized, ubiquitous (U)-healthcare service using advanced information technology for more effective glucose control. Prior to our service initiation, we surveyed patient needs and other pertinent information.

Methods

During August 2009, we conducted a 34-item questionnaire survey among patients with diabetes who were older than 40 years in two certain hospitals in Korea.

Results

The mean age of the 228 participants was 61.2±9 years, and males made up 49.1% of the sample. Seventy-one percent replied that they wanted individualized healthcare service, and they also wanted their health information to be delivered through mobile devices such as a cellular phone or a personal digital assistant (40.4%). Most patients had never heard of U-healthcare services (81.1%); however, after explaining the concept, 71.1% of participants responded that they would use the service if it was provided. Despite their willingness, participants were concerned about technical difficulty in using the service (26.3%) as well as the cost of the service (29.8%).

Conclusion

The current study suggests that more than 70% of diabetic patients are interested in using U-healthcare services. To encourage widespread use, the application program or device of U-healthcare services should be simple, easy to use and affordable while also including a policy for the protection of private information.

Citations

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Review

Autophagy in Diabetes.: Hye Seung Jung, Myung Shik Lee; Korean Diabetes J. 2009;33(6):453-457. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.453

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Abstract PDF: Diabetes mellitus is characterized by decreased insulin secretion and action. Decreased insulin secretion results from a reduction in mass and/or function of pancreatic beta-cells. Apoptosis, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress responses have been suggested as mechanisms for the changes in beta-cells in type 2 diabetes; however, the underlying causes have not been clearly elucidated. Autophagy is an intracellular process that maintains cellular homeostasis through degradation and recycling of organelles. Recently, we reported reduction of beta-cell mass in autophagy-deficient mice. Pancreatic insulin content was also decreased due to the decreased beta-cell mass and the reduced number of insulin granules. Morphological analysis of these beta-cells revealed an accumulation of ubiquitinated proteins, swollen mitochondria, and distended ER. Insulin secretory function ex vivo was also impaired. As a result, autophagy-deficient mice showed hypoinsulinemia and hyperglycemia. These results suggested that autophagy is necessary to maintain the structure, mass and function of beta-cells. In addition, as autophagy may play a protective role against ER stress and rejuvenate organelle function, impaired autophagy may lead to mitochondrial dysfunction and ER stress, which have been implicated as causes of insulin resistance. Therefore, in addition to beta-cell homeostasis, dysregulated autophagy may possibly be involved in insulin resistance.

Original Article

Effects of Islet Transplantation on Endogenous beta-cell Regeneration after Partial Pancreatectomy in Rodents.: Hye Seung Jung, You Ran Ahn, Seung Hoon Oh, Jung Hwa Jung, Tae Hyun Kim, You Cheol Hwang, Mira Kang, Yongsuk Bae, Young seok Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2007;31(2):113-122. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.113

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Abstract PDF: BACKGROUND
Islet transplantation is one of regimens supplying the deficient insulin in diabetes patients, but the effects of islet grafts on the changes of endogenous beta-cells are not clear. In the present study, we examined the changes of endogenous beta-cell mass after islet transplantation in partially pancreatectomized mice. METHODS: Balb/c mice were 70% pancreatectomized, transplanted with syngeneic islets (group IV), and were compared with pancreatectomized mice treated with insulin (group III) or no insulin (group II). Blood glucose levels and body weight were monitored. Remnant pancreas was obtained at 6 or 10 days after pancreatectomy, and immunohistochemical staining was done for the evaluation of beta-cell mass changes. RESULTS: Hyperglycemia and weight loss were induced after pancreatectomy. After islet transplantation or insulin treatment, blood glucose levels recovered to normal, and body weight started to increase. Plasma insulin levels were higher and beta-cell mass was larger in group IV than in group II (P < 0.05). Especially, the difference of beta-cell mass between them was more evident at 7 days as compared to at 3 day after transplantation. When compared to group III, group IV showed larger individual beta-cell area after 7 days and larger beta-cell mass after 3 days of islet transplantation (P < 0.05). CONCLUSION: These observations indicate that islet transplantation plays a role in enhancing remnant beta-cell regeneration after partial pancreatectomy in rodents.

Review

Adiponectin and Diabetes Mellitus.: Hye Seung Jung, Kyong Soo Park; Korean Diabetes J. 2004;28(4):239-249. Published online August 1, 2004

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21 Download

Abstract PDF: No abstract available.

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