Diabetes & Metabolism Journal

Original Articles

Clinical Diabetes & Therapeutics
Effectiveness and Safety of Adding Basal Insulin Glargine in Patients with Type 2 Diabetes Mellitus Exhibiting Inadequate Response to Metformin and DPP-4 Inhibitors with or without Sulfonylurea: Yu Mi Kang, Chang Hee Jung, Seung-Hwan Lee, Sang-Wook Kim, Kee-Ho Song, Sin Gon Kim, Jae Hyeon Kim, Young Min Cho, Tae Sun Park, Bon Jeong Ku, Gwanpyo Koh, Dol Mi Kim, Byung-Wan Lee, Joong-Yeol Park; Diabetes Metab J. 2019;43(4):432-446. Published online June 19, 2019; DOI: https://doi.org/10.4093/dmj.2018.0092

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Background

We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM).

Methods

This was a single-arm, multicenter, 24-week, open-label, phase 4 study in patients with inadequately controlled (HbA1c ≥7.5%) T2DM despite the use of DPP-4 inhibitor and metformin. A total of 108 patients received insulin glargine while continuing oral antidiabetic drugs (OADs). The primary efficacy endpoint was the percentage of subjects achieving HbA1c ≤7.0%. Other glycemic profiles were also evaluated, and the safety endpoints were adverse events (AEs) and hypoglycemia.

Results

The median HbA1c at baseline (8.9%; range, 7.5% to 11.1%) decreased to 7.6% (5.5% to 11.7%) at 24 weeks. Overall, 31.7% subjects (n=33) achieved the target HbA1c level of ≤7.0%. The mean differences in body weight and fasting plasma glucose were 1.2±3.4 kg and 56.0±49.8 mg/dL, respectively. Hypoglycemia was reported in 36 subjects (33.3%, 112 episodes), all of which were fully recovered. There was no serious AE attributed to insulin glargine. Body weight change was significantly different between SU users and nonusers (1.5±2.5 kg vs. −0.9±6.0 kg, P=0.011).

Conclusion

The combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs.

Citations

Citations to this article as recorded by

Glycaemic control with add‐on thiazolidinedione or a sodium‐glucose co‐transporter‐2 inhibitor in patients with type 2 diabetes after the failure of an oral triple antidiabetic regimen: A 24‐week, randomized controlled trial
Jaehyun Bae, Ji Hye Huh, Minyoung Lee, Yong‐Ho Lee, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2021; 23(2): 609. CrossRef
Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease
Kyung-Soo Kim, Byung-Wan Lee
Clinical and Molecular Hepatology.2020; 26(4): 430. CrossRef

Complication
Soluble Dipeptidyl Peptidase-4 Levels Are Associated with Decreased Renal Function in Patients with Type 2 Diabetes Mellitus: Eun-Hee Cho, Sang-Wook Kim; Diabetes Metab J. 2019;43(1):97-104. Published online October 8, 2018; DOI: https://doi.org/10.4093/dmj.2018.0030

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Background

Dipeptidyl peptidase-4 (DPP-4) is strongly expressed in the kidney, and soluble levels of this protein are used as a marker in various chronic inflammatory diseases, including diabetes, coronary artery disease, and cancer. This study examined the association between the serum soluble DPP-4 levels and renal function or cardiovascular risk in patients with type 2 diabetes mellitus.

Methods

In this retrospective analysis, soluble DPP-4 levels were measured in preserved sera from 140 patients with type 2 diabetes mellitus who had participated in our previous coronary artery calcium (CAC) score study.

Results

The mean±standard deviation soluble DPP-4 levels in our study sample were 645±152 ng/mL. Univariate analyses revealed significant correlations of soluble DPP-4 levels with the total cholesterol (r=0.214, P=0.019) and serum creatinine levels (r=−0.315, P<0.001) and the estimated glomerular filtration rate (eGFR; estimated using the modification of diet in renal disease equation) (r=0.303, P=0.001). The associations of soluble DPP-4 levels with serum creatinine and GFR remained significant after adjusting for age, body mass index, and duration of diabetes. However, no associations were observed between soluble DPP-4 levels and the body mass index, waist circumference, or CAC score.

Conclusion

These data suggest the potential use of serum soluble DPP-4 levels as a future biomarker of deteriorated renal function in patients with type 2 diabetes mellitus.

Citations

Citations to this article as recorded by

Factors Involved in the Development of Diabetic Kidney Disease in Patients With Slowly Progressive Type 1 Diabetes Mellitus: A Retrospective Cohort Study
Hideyuki Okuma, Takahiro Tsutsumi, Masashi Ichijo, Tetsuro Kobayashi, Kyoichiro Tsuchiya
Cureus.2024;[Epub] CrossRef
SIGNIFICANCE OF URINARY AMINOPEPTIDASE N AND DIPEPTIDYL PEPTIDASE IV IN EARLY DIAGNOSIS OF KIDNEY DAMAGE IN CHILDREN WITH TYPE 1 DIABETES MELLITUS IN NORTH-EASTERN REGION OF UKRAINE
Iryna Vikhrova, Andrii Loboda, Igor Zmyslia
Eastern Ukrainian Medical Journal.2024; 12(4): 808. CrossRef
Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway
Sarah M. AL-Qabbaa, Samaher I. Qaboli, Tahani K. Alshammari, Maha A. Alamin, Haya M. Alrajeh, Lama A. Almuthnabi, Rana R. Alotaibi, Asma S. Alonazi, Anfal F. Bin Dayel, Nawal M. Alrasheed, Nouf M. Alrasheed
International Journal of Molecular Sciences.2023; 24(7): 6532. CrossRef
Evaluation of the efficacy of dipeptidyl peptidase-4 enzyme and selenium element in people with kidney failure in Kirkuk governorate
Ibrahim Abdullah Ali Al-Jubouri, Nadia Ahmed Saleh Al-Jubouri
Materials Today: Proceedings.2022; 60: 795. CrossRef
Cardiovascular Effects of Incretin-Based Therapies: Integrating Mechanisms With Cardiovascular Outcome Trials
John R. Ussher, Amanda A. Greenwell, My-Anh Nguyen, Erin E. Mulvihill
Diabetes.2022; 71(2): 173. CrossRef
Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches
Harshit Sajal, Shashank M. Patil, Ranjith Raj, Abdullah M. Shbeer, Mohammed Ageel, Ramith Ramu
Molecules.2022; 27(16): 5133. CrossRef
Association Between DPP4 Inhibitor Use and the Incidence of Cirrhosis, ESRD, and Some Cancers in Patients With Diabetes
Yewon Na, Soo Wan Kim, Ie Byung Park, Soo Jung Choi, Seungyoon Nam, Jaehun Jung, Dae Ho Lee
The Journal of Clinical Endocrinology & Metabolism.2022; 107(11): 3022. CrossRef
An update on the interaction between COVID-19, vaccines, and diabetic kidney disease
Yang Yang, Shubiao Zou, Gaosi Xu
Frontiers in Immunology.2022;[Epub] CrossRef
Comparative Efficacy of Lobeglitazone Versus Pioglitazone on Albuminuria in Patients with Type 2 Diabetes Mellitus
Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
Diabetes Therapy.2021; 12(1): 171. CrossRef
Renoprotective Effects of DPP-4 Inhibitors
Daiji Kawanami, Yuichi Takashi, Hiroyuki Takahashi, Ryoko Motonaga, Makito Tanabe
Antioxidants.2021; 10(2): 246. CrossRef
Serum levels of soluble dipeptidyl peptidase-4 in type 2 diabetes are associated with severity of liver fibrosis evaluated by transient elastography (FibroScan) and the FAST (FibroScan-AST) score, a novel index of non-alcoholic steatohepatitis with signif
Masaaki Sagara, Toshie Iijima, Masato Kase, Kanako Kato, Shintaro Sakurai, Takuya Tomaru, Teruo Jojima, Isao Usui, Yoshimasa Aso
Journal of Diabetes and its Complications.2021; 35(5): 107885. CrossRef
Distinctive CD26 Expression on CD4 T-Cell Subsets
Oscar J. Cordero, Carlos Rafael-Vidal, Rubén Varela-Calviño, Cristina Calviño-Sampedro, Beatriz Malvar-Fernández, Samuel García, Juan E. Viñuela, José M. Pego-Reigosa
Biomolecules.2021; 11(10): 1446. CrossRef
The Long-Term Study of Urinary Biomarkers of Renal Injury in Spontaneously Hypertensive Rats
Sebastián Montoro-Molina, Andrés Quesada, Francisco O’Valle, Natividad Martín Morales, María del Carmen de Gracia, Isabel Rodríguez-Gómez, Antonio Osuna, Rosemary Wangensteen, Félix Vargas
Kidney and Blood Pressure Research.2021; 46(4): 502. CrossRef
Assessment of retinol-binding protein-4, fibroblast growth factor-21, and dipeptidyl peptidase-4 in relation to obesity and insulin resistance of type 2 diabetes mellitus among Egyptian patients
Ayat I. Ghanem, Atef A. Bassyouni, Ghada A. Omar
Journal of The Arab Society for Medical Research.2021; 16(1): 32. CrossRef
Serum Dipeptidyl peptidase-4 level is related to adiposity in type 1 diabetic adolescents
Amany Ibrahim, Shaimaa Salah, Mona Attia, Hanan Madani, Samah Ahmad, Noha Arafa, Hend Soliman
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2020; 14(4): 609. CrossRef
Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma
Masayuki Takeda, Yuichiro Ohe, Hidehito Horinouchi, Toyoaki Hida, Junichi Shimizu, Takashi Seto, Kaname Nosaki, Takumi Kishimoto, Itaru Miyashita, Masayuki Yamada, Yutaro Kaneko, Chikao Morimoto, Kazuhiko Nakagawa
Lung Cancer.2019; 137: 64. CrossRef

ENPP1 K121Q Genotype Not Associated with Coronary Artery Calcification in Korean Patients with Type 2 Diabetes Mellitus: Dae Joon Jeong, Dong Gyu Lee, Hee-Jung Kim, Eun Hee Cho, Sang-Wook Kim; Korean Diabetes J. 2010;34(5):320-326. Published online October 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.5.320

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Abstract PDF PubReader

Background

Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) generates inorganic pyrophosphate, a solute that serves as an essential physiological inhibitor of calcification. Inactivating mutations of ENPP1 are associated with generalized calcification in infancy and an increased risk of developing type 2 diabetes mellitus (T2DM). We hypothesized that the ENPP1 K121Q variant may be associated with increased coronary artery calcification in T2DM patients.

Methods

The study subjects were aged 34 to 85 years and showed no evidence of clinical cardiovascular disease prior to recruitment. A total of 140 patients with T2DM were assessed for their coronary artery calcium (CAC) scores and ENPP1 K121Q polymorphisms were identified.

Results

The prevalence of subjects carrying the KQ genotype was 12.9% (n = 18). There were no 121QQ homozygotes. Patients with the KQ genotype did not show a significantly higher CAC score (122 vs. 18; P = 0.858). We matched each patient with the KQ genotype to a respective control with the KK genotype by gender, age, and duration of diabetes. When compared to matched controls, we observed no significant difference in CAC score (P = 0.959).

Conclusions

The ENPP1 K121Q polymorphism does not appear to be associated with coronary artery calcification in patients with T2DM.

Citations

Citations to this article as recorded by

Evaluation of NPP1 as a Novel Biomarker of Coronary Artery Disease: A Pilot Study in Human Beings
Amir Hooshang Mohammadpour, Saeed Nazemi, Fatemeh Mashhadi, Atefeh Rezapour, Mohammad Afshar, Sepideh Afzalnia, Afsaneh Mohammadi, Hamid Reza Mashreghi Moghadam, Maryam Moradian, Seyed Mohammad Hasan Moallem, Saeed Falahaty, Azadeh Zayerzadeh, Sepideh Ely
Advanced Pharmaceutical Bulletin.2018; 8(3): 489. CrossRef
ENPP1 121Q functional variant enhances susceptibility to coronary artery disease in South Indian patients with type 2 diabetes mellitus
S. Sumi, Surya Ramachandran, V RamanKutty, Maulin M. Patel, T. N. Anand, Ajit S Mullasari, C. C. Kartha
Molecular and Cellular Biochemistry.2017; 435(1-2): 67. CrossRef
Genetics in Arterial Calcification
Frank Rutsch, Yvonne Nitschke, Robert Terkeltaub, Dwight A. Towler
Circulation Research.2011; 109(5): 578. CrossRef
Distribution of allelic variants of genes inhibitors and activators ectopic calcification in patients with acute coronary syndrome
V. Yu. Harbuzova, O. A. Obukhova, I. O. Rozumenko, Ye. I. Dubovyk, T. M. Oleshko, Ye. A. Harbuzova, D. V. Shvachko, O. V. Ataman
Faktori eksperimental'noi evolucii organizmiv.1970; 21: 306. CrossRef

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