Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial: Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon, the Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) study investigators; Received August 7, 2023 Accepted November 30, 2023 Published online April 23, 2024; DOI: https://doi.org/10.4093/dmj.2023.0259 [Epub ahead of print]

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Abstract PDF: Background
Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy.
Methods
The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety.
Results
After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy.
Conclusion
Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Drug/Regimen
Two-Year Therapeutic Efficacy and Safety of Initial Triple Combination of Metformin, Sitagliptin, and Empagliflozin in Drug-Naïve Type 2 Diabetes Mellitus Patients: Young-Hwan Park, Minji Sohn, So Yeon Lee, Soo Lim; Diabetes Metab J. 2024;48(2):253-264. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0128

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We investigated the long-term efficacy and safety of initial triple therapy using metformin, a dipeptidyl peptidase-4 inhibitor, and a sodium-glucose cotransporter-2 inhibitor, in patients with type 2 diabetes mellitus.
Methods
We enrolled 170 drug-naïve patients with glycosylated hemoglobin (HbA1c) level >7.5% who had started triple therapy (metformin, sitagliptin, and empagliflozin). Glycemic, metabolic, and urinary parameters were measured for 24 months.
Results
After 24 months, HbA1c level decreased significantly from 11.0%±1.8% to 7.0%±1.7%. At 12 and 24 months, the rates of achievement of the glycemic target goal (HbA1c <7.0%) were 72.5% and 61.7%, respectively, and homeostasis model assessment of β-cell function and insulin resistance indices improved. Whole-body fat percentage decreased by 1.08%, and whole-body muscle percentage increased by 0.97% after 24 months. Fatty liver indices and albuminuria improved significantly. The concentration of ketone bodies was elevated at the baseline but decreased after 24 months. There were no serious adverse events, including ketoacidosis.
Conclusion
Initial triple combination therapy with metformin, sitagliptin, and empagliflozin led to achievement of the glycemic target goal, which was maintained for 24 months without severe hypoglycemia but with improved metabolic function and albuminuria. This combination therapy may be a good strategy for drug-naïve patients with type 2 diabetes mellitus.

Others
Glucose Regulation after Partial Pancreatectomy: A Comparison of Pancreaticoduodenectomy and Distal Pancreatectomy in the Short and Long Term: Jun Suh Lee, Minji Sohn, Kyuho Kim, Yoo-Seok Yoon, Soo Lim; Diabetes Metab J. 2023;47(5):703-714. Published online June 22, 2023; DOI: https://doi.org/10.4093/dmj.2022.0205

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Abstract PDF Supplementary Material PubReader ePub: Background
Long term quality of life is becoming increasingly crucial as survival following partial pancreatectomy rises. The purpose of this study was to investigate the difference in glucose dysregulation after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP).
Methods
In this prospective observational study from 2015 to 2018, 224 patients who underwent partial pancreatectomy were selected: 152 (67.9%) received PD and 72 (32.1%) received DP. Comprehensive assessment for glucose regulation, including a 75 g oral glucose tolerance test was conducted preoperatively, and 1, 12, and 52 weeks after surgery. Patients were further monitored up to 3 years to investigate development of new-onset diabetes mellitus (NODM) in patients without diabetes mellitus (DM) at baseline or worsening of glucose regulation (≥1% increase in glycosylated hemoglobin [HbA1c]) in those with preexisting DM.
Results
The disposition index, an integrated measure of β-cell function, decreased 1 week after surgery in both groups, but it increased more than baseline level in the PD group while its decreased level was maintained in the DP group, resulting in a between-group difference at the 1-year examination (P<0.001). During follow-up, the DP group showed higher incidence of NODM and worsening of glucose regulation than the PD group with hazard ratio (HR) 4.29 (95% confidence interval [CI], 1.49 to 12.3) and HR 2.15 (95% CI, 1.09 to 4.24), respectively, in the multivariate analysis including dynamic glycemic excursion profile. In the DP procedure, distal DP and spleen preservation were associated with better glucose regulation. DP had a stronger association with glucose dysregulation than PD.
Conclusion
Proactive surveillance of glucose dysregulation is advised, particularly for patients who receive DP.

Drug/Regimen
Effect of Lactobacillus plantarum LMT1-48 on Body Fat in Overweight Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial: Minji Sohn, Hyeyoung Jung, Woo Shun Lee, Tai Hoon Kim, Soo Lim; Diabetes Metab J. 2023;47(1):92-103. Published online April 29, 2022; DOI: https://doi.org/10.4093/dmj.2021.0370

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Background
We investigated whether Lactobacillus plantarum strain LMT1-48, isolated from Korean fermented foods and newborn feces, is a suitable probiotic supplement to treat overweight subjects.
Methods
In this randomized, double-blind, placebo-controlled clinical trial, 100 volunteers with a body mass index of 25 to 30 kg/m² were assigned randomly (1:1) to receive 2×10¹⁰ colony forming units of LMT1-48 or to a placebo treatment group. Body composition was measured by dual-energy X-ray absorptiometry, and abdominal visceral fat area (VFA) and subcutaneous fat area were measured by computed tomography scanning. Changes in body fat, VFA, anthropometric parameters, and biomarkers were compared between the two treatment groups (ClinicalTrials.gov number: NCT03759743).
Results
After 12 weeks of treatment, the body weight decreased significantly from 76.6±9.4 to 75.7±9.2 kg in the LMT1-48 group but did not change in the placebo group (P=0.022 between groups). A similar pattern was found in abdominal VFA between the two groups (P=0.041). Serum insulin levels, the corresponding homeostasis model assessment of insulin resistance, and leptin levels decreased in the LMT1-48 group but increased in the placebo group (all P<0.05). Decrease in body weight and body mass index by treatment with LMT1-48 was correlated with increase in Lactobacillus levels significantly. LMT1-48 also increased Oscillibacter levels significantly, which were negatively correlated with triglyceride and alanine transaminase levels.
Conclusion
Administration of LMT1-48 decreased body weight, abdominal VFA, insulin resistance, and leptin levels in these subjects with overweight, suggesting its anti-obesogenic therapeutic potential.

Citations

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Beneficial effects of the probiotics and synbiotics supplementation on anthropometric indices and body composition in adults: A systematic review and meta‐analysis
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Obesity Reviews.2024;[Epub] CrossRef
The Effect of Lactobacillus plantarum on the Fecal Microbiota, Short Chain Fatty Acids, Odorous Substances, and Blood Biochemical Indices of Cats
Bing Han, Shukun Liang, Jintao Sun, Hui Tao, Zhenlong Wang, Baosheng Liu, Xiumin Wang, Jie Liu, Jinquan Wang
Microorganisms.2024; 12(1): 91. CrossRef
Natto alleviates hyperlipidemia in high-fat diet-fed mice by modulating the composition and metabolic function of gut microbiota
Le-Yuan Shang, Shuo Zhang, Min Zhang, Xiao-Dong Sun, Qi Wang, Yu-Jie Liu, Yan-Ni Zhao, Mei Zhao, Peng-Jiao Wang, Xiu-Li Gao
Journal of Functional Foods.2024; 112: 105968. CrossRef
Microbial-Based Bioactive Compounds to Alleviate Inflammation in Obesity
Oladayo Emmanuel Apalowo, Grace Adeola Adegoye, Tolulope Mobolaji Obuotor
Current Issues in Molecular Biology.2024; 46(3): 1810. CrossRef
Anti-obesogenic effects of plant natural products: A focus on Korean traditional foods
Gitishree Das, Luis Alfonso Jiménez Ortega, Sandra Gonçalves, J. Basilio Heredia, Maria de Lourdes Gomes Pereira, Anabela Romano, Han-Seung Shin, Jayanta Kumar Patra
Trends in Food Science & Technology.2024; : 104470. CrossRef
A 12-Week, Single-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Design Clinical Trial for the Evaluation of the Efficacy and Safety of Lactiplantibacillus plantarum SKO-001 in Reducing Body Fat
Seon Mi Shin, Jeong-Su Park, Sang Back Kim, Young Hee Cho, Hee Seo, Hak Sung Lee
Nutrients.2024; 16(8): 1137. CrossRef
3D printing of microencapsulated Lactobacillus rhamnosus for oral delivery
Pablo Rosas-Val, Masoud Adhami, Ana Brotons-Canto, Carlos Gamazo, Juan M. Irache, Eneko Larrañeta
International Journal of Pharmaceutics.2023; 641: 123058. CrossRef
Gut commensal Kineothrix alysoides mitigates liver dysfunction by restoring lipid metabolism and gut microbial balance
Kyoung Jin Choi, Mi Young Yoon, Ji-Eun Kim, Sang Sun Yoon
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Ameliorating Effects of Bifidobacterium longum subsp. infantis FB3-14 against High-Fat-Diet-Induced Obesity and Gut Microbiota Disorder
Ruixin Kou, Jin Wang, Ang Li, Yuanyifei Wang, Bowei Zhang, Jingmin Liu, Yi Sun, Shuo Wang
Nutrients.2023; 15(19): 4104. CrossRef
Effect of Continuous Ingestion of Bifidobacteria and Inulin on Reducing Body Fat: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Study
Yuhei Baba, Yasuo Saito, Mei Kadowaki, Naoki Azuma, Daisuke Tsuge
Nutrients.2023; 15(24): 5025. CrossRef
A Review of the Potential of Probiotic Bacteria in Managing the Body Weight of Obese Individuals
A Didban, L Manafi, R Mahmoudi
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Nutrients.2022; 14(21): 4492. CrossRef

Drug/Regimen
A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus: Bo-Yeon Kim, Hyuk-Sang Kwon, Suk Kyeong Kim, Jung-Hyun Noh, Cheol-Young Park, Hyeong-Kyu Park, Kee-Ho Song, Jong Chul Won, Jae Myung Yu, Mi Young Lee, Jae Hyuk Lee, Soo Lim, Sung Wan Chun, In-Kyung Jeong, Choon Hee Chung, Seung Jin Han, Hee-Seok Kim, Ju-Young Min, Sungrae Kim; Diabetes Metab J. 2022;46(6):855-865. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0264

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Background
Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice.
Methods
In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled.
Results
Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42.
Conclusion
Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

Citations

Citations to this article as recorded by

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697. CrossRef
Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703. CrossRef
Will lobeglitazone rival pioglitazone? A systematic review and critical appraisal
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Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(4): 102747. CrossRef
Lobeglitazone

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Oldies but Goodies: Thiazolidinedione as an Insulin Sensitizer with Cardioprotection
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Clinical Diabetes & Therapeutics
Progression to Gestational Diabetes Mellitus in Pregnant Women with One Abnormal Value in Repeated Oral Glucose Tolerance Tests: Sunyoung Kang, Min Hyoung Kim, Moon Young Kim, Joon-Seok Hong, Soo Heon Kwak, Sung Hee Choi, Soo Lim, Kyong Soo Park, Hak C. Jang; Diabetes Metab J. 2019;43(5):607-614. Published online February 28, 2019; DOI: https://doi.org/10.4093/dmj.2018.0159

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Background

Women with one abnormal value (OAV) in a 100 g oral glucose tolerance test (OGTT) during pregnancy are reported to have an increased risk of adverse pregnancy outcomes. However, there is limited data about whether women with OAV will progress to gestational diabetes mellitus (GDM) when the OGTT is repeated.

Methods

To identify clinical and metabolic predictors for GDM in women with OAV, we conducted a retrospective study and identified women with OAV in the OGTT done at 24 to 30 weeks gestational age (GA) and repeated the second OGTT between 32 and 34 weeks of GA.

Results

Among 137 women with OAV in the initial OGTT, 58 (42.3%) had normal, 40 (29.2%) had OAV and 39 (28.5%) had GDM in the second OGTT. Maternal age, prepregnancy body mass index, weight gain from prepregnancy to the second OGTT, GA at the time of the OGTT, and parity were similar among normal, OAV, and GDM groups. Plasma glucose levels in screening tests were different (151.8±15.7, 155.8±14.6, 162.5±20.3 mg/dL, P<0.05), but fasting, 1-, 2-, and 3-hour glucose levels in the initial OGTT were not. Compared to women with screen negative, women with untreated OAV had a higher frequency of macrosomia.

Conclusion

We demonstrated that women with OAV in the initial OGTT significantly progressed to GDM in the second OGTT. Clinical parameters predicting progression to GDM were not found. Repeating the OGTT in women with OAV in the initial test may be helpful to detect GDM progression.

Citations

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Maternal and fetal outcomes of pregnancies associated with single versus double abnormal values in 100 gr glucose tolerance test
Mohammadali Shahriari, Ali Shahriari, Maryam Khooshideh, Anahita Dehghaninezhad, Arezoo Maleki-Hajiagha, Rana Karimi
Journal of Diabetes & Metabolic Disorders.2023; 22(2): 1347. CrossRef
One abnormal value or vomiting after oral glucose tolerance test in pregnancy: incidence and impact on maternal-fetal outcomes
Humberto Navarro-Martinez, Juana-Antonia Flores-Le Roux, Gemma Llauradó, Lucia Gortazar, Antonio Payà, Laura Mañé, Juan Pedro-Botet, David Benaiges
Gynecological Endocrinology.2023;[Epub] CrossRef
Analysis of the gut microflora in women with gestational diabetes mellitus
Xuping Wang, Bingfeng Bian, Fuman Du, Chaofeng Xiang, Yu Liu, Na Li, Binhong Duan
International Journal of Diabetes in Developing Countries.2023;[Epub] CrossRef
The association between gestational impaired glucose tolerance and hyperglycemic markers: A prospective study
Ohad Gluck, Hadas Ganer Herman, Nataly Fainstein, Neri Katz, Jacob Bar, Michal Kovo
International Journal of Gynecology & Obstetrics.2022; 156(1): 82. CrossRef
Association of abnormal-glucose tolerance during pregnancy with exposure to PM2.5 components and sources
Dejian Mai, Chengfang Xu, Weiwei Lin, Dingli Yue, Shaojie Fu, Jianqing Lin, Luan Yuan, Yan Zhao, Yuhong Zhai, Huiying Mai, Xiaoling Zeng, Tingwu Jiang, Xuejiao Li, Jiajia Dai, Boning You, Qin Xiao, Qing Wei, Qiansheng Hu
Environmental Pollution.2022; 292: 118468. CrossRef
Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus
So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim
Diabetes & Metabolism Journal.2022; 46(1): 140. CrossRef
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2021; 36(3): 628. CrossRef
Gestational Diabetes Mellitus: Diagnosis and Glycemic Control
Tae Jung Oh, Hak Chul Jang
The Journal of Korean Diabetes.2020; 21(2): 69. CrossRef
Health literacy and diabetes control in pregnant women
Azar Pirdehghan, Mohammad Eslahchi, Farzaneh Esna-Ashari, Shiva Borzouei
Journal of Family Medicine and Primary Care.2020; 9(2): 1048. CrossRef

Epidemiology
Oral Glucose Tolerance Testing Allows Better Prediction of Diabetes in Women with a History of Gestational Diabetes Mellitus: Tae Jung Oh, Yeong Gi Kim, Sunyoung Kang, Joon Ho Moon, Soo Heon Kwak, Sung Hee Choi, Soo Lim, Kyong Soo Park, Hak C. Jang, Joon-Seok Hong, Nam H. Cho; Diabetes Metab J. 2019;43(3):342-349. Published online December 7, 2018; DOI: https://doi.org/10.4093/dmj.2018.0086

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Background

We aimed to identify the postpartum metabolic factors that were associated with the development of diabetes in women with a history of gestational diabetes mellitus (GDM). In addition, we examined the role of the oral glucose tolerance test (OGTT) in the prediction of future diabetes.

Methods

We conducted a prospective study of 179 subjects who previously had GDM but did not have diabetes at 2 months postpartum. The initial postpartum examination including a 75-g OGTT and the frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed 12 months after delivery, and annual follow-up visits were made thereafter.

Results

The insulinogenic index (IGI30) obtained from the OGTT was significantly correlated with the acute insulin response to glucose (AIRg) obtained from the FSIVGTT. The disposition indices obtained from the OGTT and FSIVGTT were also significantly correlated. Women who progressed to diabetes had a lower insulin secretory capacity including IGI30, AIRg, and disposition indices obtained from the FSIVGTT and OGTT compared with those who did not. However, the insulin sensitivity indices obtained from the OGTT and FSIVGTT did not differ between the two groups. Multivariate logistic regression analysis showed that the 2-hour glucose and disposition index obtained from the FSIVGTT were significant postpartum metabolic risk factors for the development of diabetes.

Conclusion

We identified a crucial role of β-cell dysfunction in the development of diabetes in Korean women with previous GDM. The 2-hour glucose result from the OGTT is an independent predictor of future diabetes. Therefore, the OGTT is crucial for better prediction of future diabetes in Korean women with previous GDM.

Citations

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Diagnosis and management of gestational diabetes mellitus
Tae Jung Oh
Journal of the Korean Medical Association.2023; 66(7): 414. CrossRef
Risk factors for women with gestational diabetes mellitus developing type 2 diabetes and the impact on children's health
Yi‐Ling Chiou, Chich‐Hsiu Hung, Ching‐Yun Yu, Te‐Fu Chan, Ming‐Gwo Liu
Journal of Clinical Nursing.2022; 31(7-8): 1005. CrossRef
Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus
So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim
Diabetes & Metabolism Journal.2022; 46(1): 140. CrossRef
Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications
Joon Ho Moon, Hak Chul Jang
Diabetes & Metabolism Journal.2022; 46(1): 3. CrossRef
Higher Muscle Mass Protects Women with Gestational Diabetes Mellitus from Progression to Type 2 Diabetes Mellitus
Yujin Shin, Joon Ho Moon, Tae Jung Oh, Chang Ho Ahn, Jae Hoon Moon, Sung Hee Choi, Hak Chul Jang
Diabetes & Metabolism Journal.2022; 46(6): 890. CrossRef
Pancreatic fat accumulation is associated with decreased β‐cell function and deterioration in glucose tolerance in Korean adults
Sang Ouk Chin, You‐Cheol Hwang, In‐Jin Cho, In‐Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung
Diabetes/Metabolism Research and Reviews.2021;[Epub] CrossRef
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2021; 36(3): 628. CrossRef
Bihormonal dysregulation of insulin and glucagon contributes to glucose intolerance development at one year post-delivery in women with gestational diabetes: a prospective cohort study using an early postpartum 75-g glucose tolerance test
Riyoko Shigeno, Ichiro Horie, Masaki Miwa, Ayako Ito, Ai Haraguchi, Shoko Natsuda, Satoru Akazawa, Ai Nagata, Yuri Hasegawa, Shoko Miura, Kiyonori Miura, Atsushi Kawakami, Norio Abiru
Endocrine Journal.2021; 68(8): 919. CrossRef
Risk factors during the early postpartum period for type 2 diabetes mellitus in women with gestational diabetes
Maki Kawasaki, Naoko Arata, Naoko Sakamoto, Anna Osamura, Siori Sato, Yoshihiro Ogawa, Ichiro Yasuhi, Masako Waguri, Yuji Hiramatsu
Endocrine Journal.2020; 67(4): 427. CrossRef
Cod-Liver Oil Improves Metabolic Indices and hs-CRP Levels in Gestational Diabetes Mellitus Patients: A Double-Blind Randomized Controlled Trial
Shuli Yang, Ruixin Lin, Lihui Si, Zhuo Li, Wenwen Jian, Qing Yu, Yan Jia
Journal of Diabetes Research.2019; 2019: 1. CrossRef

Clinical Diabetes & Therapeutics
Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks: Soo Lim, Kyoung Min Kim, Sin Gon Kim, Doo Man Kim, Jeong-Taek Woo, Choon Hee Chung, Kyung Soo Ko, Jeong Hyun Park, Yongsoo Park, Sang Jin Kim, Hak Chul Jang, Dong Seop Choi; Diabetes Metab J. 2017;41(5):377-385. Published online October 24, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.5.377

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Background

The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus.

Methods

A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52).

Results

During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone.

Conclusion

Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.

Citations

Citations to this article as recorded by

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697. CrossRef
Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703. CrossRef
The benefits of adipocyte metabolism in bone health and regeneration
Lisa-Marie Burkhardt, Christian H. Bucher, Julia Löffler, Charlotte Rinne, Georg N. Duda, Sven Geissler, Tim J. Schulz, Katharina Schmidt-Bleek
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Will lobeglitazone rival pioglitazone? A systematic review and critical appraisal
Kalyan Kumar Gangopadhyay, Awadhesh Kumar Singh
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(4): 102747. CrossRef
Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study
Jun Hwa Hong, Jun Sung Moon, Kayeon Seong, Soo Lim
Diabetes Research and Clinical Practice.2023; 203: 110872. CrossRef
Bone Mineral Density Evaluation Among Type 2 Diabetic Patients in Rural Haryana, India: An Analytical Cross-Sectional Study
Nitish Khandelwal, Surbhi Rajauria, Siddhesh Pandurang Kanjalkar, Omkar Shivaji Chavanke, Sanjay Rai
Cureus.2023;[Epub] CrossRef
Lobeglitazone and Its Therapeutic Benefits: A Review
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Obesity and Metabolic Syndrome
Relationship between Regional Body Fat Distribution and Diabetes Mellitus: 2008 to 2010 Korean National Health and Nutrition Examination Surveys: Soo In Choi, Dawn Chung, Jung Soo Lim, Mi Young Lee, Jang Yel Shin, Choon Hee Chung, Ji Hye Huh; Diabetes Metab J. 2017;41(1):51-59. Published online December 21, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.51

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Background

The aim of this study was to investigate the association between regional body fat distribution, especially leg fat mass, and the prevalence of diabetes mellitus (DM) in adult populations.

Methods

A total of 3,181 men and 3,827 postmenopausal women aged 50 years or older were analyzed based on Korea National Health and Nutrition Examination Surveys (2008 to 2010). Body compositions including muscle mass and regional fat mass were measured using dual-energy X-ray absorptiometry.

Results

The odds ratios (ORs) for DM was higher with increasing truncal fat mass and arm fat mass, while it was lower with increasing leg fat mass. In a partial correlation analysis adjusted for age, leg fat mass was negatively associated with glycosylated hemoglobin in both sexes and fasting glucose in women. Leg fat mass was positively correlated with appendicular skeletal muscle mass and homeostasis model assessment of β cell. In addition, after adjusting for confounding factors, the OR for DM decreased gradually with increasing leg fat mass quartiles in both genders. When we subdivided the participants into four groups based on the median values of leg fat mass and leg muscle mass, higher leg fat mass significantly lowered the risk of DM even though they have smaller leg muscle mass in both genders (P<0.001).

Conclusion

The relationship between fat mass and the prevalence of DM is different according to regional body fat distribution. Higher leg fat mass was associated with a lower risk of DM in Korean populations. Maintaining leg fat mass may be important in preventing impaired glucose tolerance.

Citations

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Epidemiology
Application of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline to the Korean National Health and Nutrition Examination Surveys from 1998 to 2012: Young Shin Song, Tae Jung Oh, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Hak Chul Jang, Kyong Soo Park, Soo Lim; Diabetes Metab J. 2017;41(1):38-50. Published online December 16, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.38

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Abstract PDF Supplementary Material PubReader

Background

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline for the treatment of blood cholesterol recommends statin therapy for individuals at high risk of atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate serial trends in the percentages of Korean adults considered eligible for statin therapy according to the new ACC/AHA cholesterol guideline.

Methods

Data from the Korean National Health and Nutrition Examination Survey (KNHANES) I (1998, n=7,698), II (2001, n=5,654), III (2005, n=5,269), IV (2007 to 2009, n=15,727), and V (2010 to 2012, n=16,304), which used a stratified, multistage, probability sampling design, were used as representative of the entire Korean population.

Results

The percentage of adults eligible for statin therapy according to the ACC/AHA cholesterol guideline increased with time: 17.0%, 19.0%, 20.8%, 20.2%, and 22.0% in KNHANES I, II, III, IV, and V, respectively (P=0.022). The prevalence of ASCVD was 1.4% in KNHANES I and increased to 3.3% in KNHANES V. The percentage of diabetic patients aged 40 to 75 years with a low density lipoprotein cholesterol levels of 70 to 189 mg/dL increased from 4.8% in KNHANES I to 6.1% in KNHANES V. People with an estimated 10-year ASCVD risk ≥7.5% and aged 40 to 75 years accounted for the largest percentage among the four statin benefit groups: 9.1% in KNHANES I and 11.0% in KNHANES V.

Conclusion

Application of the 2013 ACC/AHA guideline has found that the percentage of Korean adults in the statin benefit groups has increased over the past 15 years.

Citations

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Sex differences in risk factors for subclinical hypothyroidism
Jeonghoon Ha, Jeongmin Lee, Kwanhoon Jo, Dong-Jun Lim, Moo Il Kang, Bong Yun Cha, Min-Hee Kim
Endocrine Connections.2018; 7(4): 511. CrossRef

Others
Rg3 Improves Mitochondrial Function and the Expression of Key Genes Involved in Mitochondrial Biogenesis in C2C12 Myotubes: Min Joo Kim, Young Do Koo, Min Kim, Soo Lim, Young Joo Park, Sung Soo Chung, Hak C. Jang, Kyong Soo Park; Diabetes Metab J. 2016;40(5):406-413. Published online August 12, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.5.406

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Background

Panax ginseng has glucose-lowering effects, some of which are associated with the improvement in insulin resistance in skeletal muscle. Because mitochondria play a pivotal role in the insulin resistance of skeletal muscle, we investigated the effects of the ginsenoside Rg3, one of the active components of P. ginseng, on mitochondrial function and biogenesis in C2C12 myotubes.

Methods

C2C12 myotubes were treated with Rg3 for 24 hours. Insulin signaling pathway proteins were examined by Western blot. Cellular adenosine triphosphate (ATP) levels and the oxygen consumption rate were measured. The protein or mRNA levels of mitochondrial complexes were evaluated by Western blot and quantitative reverse transcription polymerase chain reaction analysis.

Results

Rg3 treatment to C2C12 cells activated the insulin signaling pathway proteins, insulin receptor substrate-1 and Akt. Rg3 increased ATP production and the oxygen consumption rate, suggesting improved mitochondrial function. Rg3 increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor, which are transcription factors related to mitochondrial biogenesis. Subsequent increased expression of mitochondrial complex IV and V was also observed.

Conclusion

Our results suggest that Rg3 improves mitochondrial function and the expression of key genes involved in mitochondrial biogenesis, leading to an improvement in insulin resistance in skeletal muscle. Rg3 may have the potential to be developed as an anti-hyperglycemic agent.

Citations

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Young Jin Lee, Su Hyun Yu, Gwang Yeong Seok, Su Yeon Kim, Mi Jeong Kim, Inhye Jeong, Wan Heo, Bo Su Lee, Seon Gil Do, Bok Kyung Han, Young Jun Kim
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Ginsenosides for the treatment of insulin resistance and diabetes: Therapeutic perspectives and mechanistic insights
Tae Hyun Kim
Journal of Ginseng Research.2024; 48(3): 276. CrossRef
Preparation and bioactivity of the rare ginsenosides Rg3 and Rh2: An updated review
Wenqi Xu, Wei Lyu, Cuicui Duan, Fumin Ma, Xiaolei Li, Dan Li
Fitoterapia.2023; 167: 105514. CrossRef
Ginsenoside Rc, an Active Component of Panax ginseng, Alleviates Oxidative Stress-Induced Muscle Atrophy via Improvement of Mitochondrial Biogenesis
Aeyung Kim, Sang-Min Park, No Soo Kim, Haeseung Lee
Antioxidants.2023; 12(8): 1576. CrossRef
Ginsenoside Rg3 protects glucocorticoid‑induced muscle atrophy in vitro through improving mitochondrial biogenesis and myotube growth
Ryuni Kim, Jee Kim, Sang-Jin Lee, Gyu-Un Bae
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Rui Fan, Yuntao Hao, Qian Du, Jiawei Kang, Meihong Xu, Yong Li
Nutrients.2022; 14(10): 2051. CrossRef
Ginseng and ginsenosides: Therapeutic potential for sarcopenia
Weiwei Zha, Yuanhai Sun, Wenwen Gong, Linghuan Li, Wonnam Kim, Hanbing Li
Biomedicine & Pharmacotherapy.2022; 156: 113876. CrossRef
Bioactive Oligopeptides from Ginseng (Panax ginseng Meyer) Suppress Oxidative Stress-Induced Senescence in Fibroblasts via NAD+/SIRT1/PGC-1α Signaling Pathway
Na Zhu, Mei-Hong Xu, Yong Li
Nutrients.2022; 14(24): 5289. CrossRef
Review of ginsenosides targeting mitochondrial function to treat multiple disorders: Current status and perspectives
Qingxia Huang, Song Gao, Daqing Zhao, Xiangyan Li
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The Effects of Korean Red Ginseng on Biological Aging and Antioxidant Capacity in Postmenopausal Women: A Double-Blind Randomized Controlled Study
Tae-Ha Chung, Ji-Hye Kim, So-Young Seol, Yon-Ji Kim, Yong-Jae Lee
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A comprehensive review on the phytochemistry, pharmacokinetics, and antidiabetic effect of Ginseng
Yage Liu, Hao Zhang, Xuan Dai, Ruyuan Zhu, Beibei Chen, Bingke Xia, Zimengwei Ye, Dandan Zhao, Sihua Gao, Alexander N. Orekhov, Dongwei Zhang, Lili Wang, Shuzhen Guo
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Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes
Federica Zatterale, Michele Longo, Jamal Naderi, Gregory Alexander Raciti, Antonella Desiderio, Claudia Miele, Francesco Beguinot
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Stereoisomer-specific ginsenoside 20(S)-Rg3 reverses replicative senescence of human diploid fibroblasts via Akt-mTOR-Sirtuin signaling
Kyeong-Eun Yang, Hyun-Jin Jang, In-Hu Hwang, Eun Mi Hong, Min-Goo Lee, Soon Lee, Ik-Soon Jang, Jong-Soon Choi
Journal of Ginseng Research.2020; 44(2): 341. CrossRef
Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms
Wenxiang Fan, Yongliang Huang, Hui Zheng, Shuiqin Li, Zhuohong Li, Li Yuan, Xi Cheng, Chengshi He, Jianfeng Sun
Biomedicine & Pharmacotherapy.2020; 132: 110915. CrossRef
Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells
Taeui Hong, Moon Young Kim, Dat Da Ly, Su Jung Park, Young Woo Eom, Kyu-Sang Park, Soon Koo Baik
Stem Cell Research & Therapy.2020;[Epub] CrossRef
Mitochondrial Dysfunction in Adipocytes as a Primary Cause of Adipose Tissue Inflammation
Chang-Yun Woo, Jung Eun Jang, Seung Eun Lee, Eun Hee Koh, Ki-Up Lee
Diabetes & Metabolism Journal.2019; 43(3): 247. CrossRef
Ginsenoside Rg3 upregulates myotube formation and mitochondrial function, thereby protecting myotube atrophy induced by tumor necrosis factor-alpha
Sang-Jin Lee, Ju Hyun Bae, Hani Lee, Hyunji Lee, Jongsun Park, Jong-Sun Kang, Gyu-Un Bae
Journal of Ethnopharmacology.2019; 242: 112054. CrossRef
Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes
Litao Bai, Jialiang Gao, Fan Wei, Jing Zhao, Danwei Wang, Junping Wei
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Ginseng and obesity
Zhipeng Li, Geun Eog Ji
Journal of Ginseng Research.2018; 42(1): 1. CrossRef
Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions
Padmanaban Mohanan, Sathiyamoorthy Subramaniyam, Ramya Mathiyalagan, Deok-Chun Yang
Journal of Ginseng Research.2018; 42(2): 123. CrossRef
Inactivation of glycogen synthase kinase-3β (GSK-3β) enhances skeletal muscle oxidative metabolism
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Anti-Fatigue Effects of Small Molecule Oligopeptides Isolated from Panax ginseng C. A. Meyer in Mice
Lei Bao, Xiaxia Cai, Junbo Wang, Yuan Zhang, Bin Sun, Yong Li
Nutrients.2016; 8(12): 807. CrossRef

Clinical Care/Education
Hyperglycemia Is Associated with Impaired Muscle Quality in Older Men with Diabetes: The Korean Longitudinal Study on Health and Aging: Ji Won Yoon, Yong-Chan Ha, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Soo Lim, Young Joo Park, Jae Young Lim, Ki Woong Kim, Kyong Soo Park, Hak Chul Jang; Diabetes Metab J. 2016;40(2):140-146. Published online March 31, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.2.140

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Background

The study aimed to investigate the influence of hyperglycemia on muscle quality in older men with type 2 diabetes.

Methods

This was a subsidiary study of the Korean Longitudinal Study of Health and Aging. Among 326 older men consenting to tests of body composition and muscle strength, 269 men were ultimately analyzed after the exclusion because of stroke (n=30) and uncertainty about the diagnosis of diabetes (n=27). Body composition was measured using dual-energy X-ray absorptiometry and computed tomography. Muscle strength for knee extension was measured using an isokinetic dynamometer. Muscle quality was assessed from the ratio of leg strength to the entire corresponding leg muscle mass.

Results

The muscle mass, strength, and quality in patients with type 2 diabetes did not differ significantly from controls. However, when patients with diabetes were subdivided according to their glycemic control status, patients with a glycosylated hemoglobin (HbA1c) level of ≥8.5% showed significantly decreased leg muscle quality by multivariate analysis (odds ratio, 4.510; P=0.045) after adjustment for age, body mass index, smoking amount, alcohol consumption, physical activity, and duration of diabetes. Physical performance status was also impaired in subjects with an HbA1c of ≥8.5%.

Conclusion

Poor glycemic control in these older patients with diabetes was associated with significant risk of decreased muscle quality and performance status. Glycemic control with an HbA1c of <8.5% might be needed to reduce the risk of adverse skeletal and functional outcomes in this population.

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Clinical Care/Education
Clinical Characteristics and Metabolic Predictors of Rapid Responders to Dipeptidyl Peptidase-4 Inhibitor as an Add-on Therapy to Sulfonylurea and Metformin: Ye An Kim, Won Sang Yoo, Eun Shil Hong, Eu Jeong Ku, Kyeong Seon Park, Soo Lim, Young Min Cho, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi; Diabetes Metab J. 2015;39(6):489-497. Published online November 27, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.489

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Abstract PDF PubReader

Background

Dipeptidyl peptidase-4 (DPP-4) inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU). We evaluated the efficacy and safety of this triple therapy and the characteristics of rapid responders and hypoglycemia-prone patients.

Methods

We included 807 patients with type 2 diabetes who were prescribed a newly added DPP-4 inhibitor to ongoing metformin and SU in 2009 to 2011. Glycemia and other metabolic parameters at baseline, 12, 24, and 52 weeks, as well as episodes of hypoglycemia were analyzed. Rapid responders were defined as patients with ≥25% reduction in glycosylated hemoglobin (HbA1c) within 12 weeks.

Results

At baseline, while on the submaximal metformin and SU combination, the mean HbA1c level was 8.4%. Twelve weeks after initiation of DPP-4 inhibitor add-on, 269 patients (34.4%) achieved an HbA1c level ≤7%. Sixty-six patients (8.2%, 47 men) were rapid responders. The duration of diabetes was shorter in rapid responders, and their baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and homeostasis model assessment of insulin resistance were significantly higher. Patients who experienced hypoglycemia after taking DPP-4 inhibitor add-on were more likely to be female, to have a lower body weight and lower triglyceride and FPG levels, and to have higher homeostasis model assessment of β-cells.

Conclusion

An oral hypoglycemic triple agent combination including a DPP-4 inhibitor was effective in patients with uncontrolled diabetes. Proactive dose reduction of SU should be considered when a DPP-4 inhibitor is added for rapid responders and hypoglycemia-prone patients.

Citations

Citations to this article as recorded by

A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes
Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
Medicine.2016; 95(44): e5155. CrossRef

Optimal Waist Circumference Cutoff Value Based on Insulin Resistance and Visceral Obesity in Koreans with Type 2 Diabetes: Jung Soo Lim, Young Ju Choi, Soo-Kyung Kim, Byoung Wook Huh, Eun Jig Lee, Kap Bum Huh; Diabetes Metab J. 2015;39(3):253-263. Published online April 24, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.3.253

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Abstract PDF Supplementary Material PubReader

Background

Visceral obesity is the most powerful contributor to the development of metabolic syndrome (MetS) and cardiovascular diseases. In light of visceral obesity, however, there is a paucity of data on the appropriate cutoff point of waist circumference (WC) in subjects with type 2 diabetes. The aim of this study was to investigate the optimal cutoff value for WC that signals insulin resistance (IR) and visceral obesity in Koreans with type 2 diabetes.

Methods

We evaluated 4,252 patients with type 2 diabetes (male 2,220, female 2,032, mean age 57.24 years) who visited our clinic between January 2003 and June 2009. WC was measured at the midpoint between the lower rib and the iliac crest, and insulin sensitivity was assessed by the rate constant of plasma glucose disappearance (Kitt %/min) using an insulin tolerance test. Visceral fat thickness was measured using ultrasonography. Statistical analysis was performed using receiver operating characteristic curve.

Results

The optimal cutoff points for WC for identifying the presence of IR and visceral obesity, as well as two or more metabolic components, were 87 cm for men and 81 cm for women. Moreover, these cutoff points had the highest predictive powers for the presence of visceral obesity. The MetS defined by new criteria correlated with the increased carotid intima-media thickness in female subjects.

Conclusion

Our results suggest that the optimal cutoff values for WC in Koreans with type 2 diabetes should be reestablished based on IR and visceral obesity.

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Review

Therapeutic Approaches for Preserving or Restoring Pancreatic β-Cell Function and Mass: Kyong Yeun Jung, Kyoung Min Kim, Soo Lim; Diabetes Metab J. 2014;38(6):426-436. Published online December 15, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.6.426

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Abstract PDF PubReader

The goal for the treatment of patients with diabetes has today shifted from merely reducing glucose concentrations to preventing the natural decline in β-cell function and delay the progression of disease. Pancreatic β-cell dysfunction and decreased β-cell mass are crucial in the development of diabetes. The β-cell defects are the main pathogenesis in patients with type 1 diabetes and are associated with type 2 diabetes as the disease progresses. Recent studies suggest that human pancreatic β-cells have a capacity for increased proliferation according to increased demands for insulin. In humans, β-cell mass has been shown to increase in patients showing insulin-resistance states such as obesity or in pregnancy. This capacity might be useful for identifying new therapeutic strategies to reestablish a functional β-cell mass. In this context, therapeutic approaches designed to increase β-cell mass might prove a significant way to manage diabetes and prevent its progression. This review describes the various β-cell defects that appear in patients with diabetes and outline the mechanisms of β-cell failure. We also review common methods for assessing β-cell function and mass and methodological limitations in vivo. Finally, we discuss the current therapeutic approaches to improve β-cell function and increase β-cell mass.

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