Diabetes & Metabolism Journal

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

Citations to this article as recorded by

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

Complications
Deterioration of Sleep Quality According to Glycemic Status: Myung Haeng Hur, Mi-Kyoung Lee, Kayeon Seong, Jun Hwa Hong; Diabetes Metab J. 2020;44(5):679-686. Published online April 17, 2020; DOI: https://doi.org/10.4093/dmj.2019.0125

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Background

Type 2 diabetes mellitus (T2DM) is a progressive disease with multiple complications. The present study aimed to determine the effects of glycemic status on sleep quality in individuals with T2DM, prediabetes, and normal glucose tolerance (NGT).

Methods

A total of 90 participants were categorized into three groups, T2DM (n=30), prediabetes (n=30), and NGT (n=30). Objective sleep quality was measured with the actigraph wrist-worn device over 3 nights and subjective sleep quality was evaluated with a questionnaire.

Results

The duration of diabetes in the T2DM group was 2.23 years and the glycosylated hemoglobin (HbA1c) levels in the T2DM, prediabetes, and NGT groups were 7.83%, 5.80%, and 5.31%, respectively. Sleep efficiency decreased across the T2DM, prediabetes, and NGT groups (86.25%, 87.99%, and 90.22%, respectively; P=0.047). Additionally, HbA1c levels revealed a significant negative correlation with sleep efficiency (r=−0.348, P=0.001). The sleep quality questionnaire results were similar among the three groups.

Conclusion

Although the participants in the present study were not necessarily conscious of their sleep disturbances, deterioration in sleep quality progressed according to glycemic status.

Citations

Citations to this article as recorded by

Risk factors of non communicable diseases among recently diagnosed diabetic patients in a tertiary care Hospital
Yusra Amin, Sonia Mushtaq, Rukhsana Farooq
Indian Journal of Clinical Anatomy and Physiology.2024; 10(4): 205. CrossRef
Metabolic health tracking using Ultrahuman M1 continuous glucose monitoring platform in non- and pre-diabetic Indians: a multi-armed observational study
Monik Chaudhry, Mohit Kumar, Vatsal Singhal, Bhuvan Srinivasan
Scientific Reports.2024;[Epub] CrossRef
Influence of sleep quality and other associated factors on glycemic control among diabetic patients: A hospital-based study
Yusra Amin, Sonia Mushtaq, Rukhsana Taj, Umara Giyas, Sunil Sachadev
Indian Journal of Clinical Anatomy and Physiology.2024; 11(1): 32. CrossRef
Interventional effects of Pueraria oral liquid on T2DM rats and metabolomics analysis
Hong-Bo Yang, Jie-Yu Song, Chan Xu, Jin Li, Chan Zhang, Sun Xie, Chun-li Teng
Biomedicine & Pharmacotherapy.2024; 175: 116780. CrossRef
Replacing sedentary time with sleep and physical activity: associations with physical function and wellbeing in Type 2 diabetes
Alix Covenant, Thomas Yates, Alex V. Rowlands, Paddy C. Dempsey, Charlotte L. Edwardson, Andrew P. Hall, Melanie J. Davies, Joseph Henson
Diabetes Research and Clinical Practice.2024; 217: 111886. CrossRef
Relation between sleep quality and glycemic control among type 2 diabetic patients
Asmaa Ali Elsayed Ali
Frontiers of Nursing.2023; 10(1): 115. CrossRef
Heart rate variability in different sleep stages is associated with metabolic function and glycemic control in type 2 diabetes mellitus
Wenquan Cheng, Hongsen Chen, Leirong Tian, Zhimin Ma, Xingran Cui
Frontiers in Physiology.2023;[Epub] CrossRef
Association Between Diabetic Retinopathy and Insomnia Risk: A Nationwide Population-Based Study
Yoo Hyun Um, Tae-Won Kim, Jong-Hyun Jeong, Seung-Chul Hong, Ho-Jun Seo, Kyung-Do Han
Frontiers in Endocrinology.2022;[Epub] CrossRef
Nutritional Biomarkers and Factors Correlated with Poor Sleep Status among Young Females: A Case-Control Study
Sara AL-Musharaf, Lama AlAjllan, Ghadeer Aljuraiban, Munirah AlSuhaibani, Noura Alafif, Syed Danish Hussain
Nutrients.2022; 14(14): 2898. CrossRef
The impact of sleep disorders on microvascular complications in patients with type 2 diabetes (SLEEP T2D): the protocol of a cohort study and feasibility randomised control trial
Christina Antza, Ryan Ottridge, Smitaa Patel, Gemma Slinn, Sarah Tearne, Matthew Nicholls, Brendan Cooper, Asad Ali, Abd A. Tahrani
Pilot and Feasibility Studies.2021;[Epub] CrossRef
Early Development of Bidirectional Associations between Sleep Disturbance and Diabetes
Yongin Cho
Diabetes & Metabolism Journal.2020; 44(5): 668. CrossRef

Letter

Letter: The Necessity of the Simple Tests for Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus Patients without Neuropathic Symptoms in Clinical Practice (Diabetes Metab J 2018;42:442-6): Jun Hwa Hong; Diabetes Metab J. 2018;42(6):544-545. Published online December 17, 2018; DOI: https://doi.org/10.4093/dmj.2018.0238

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Original Article

Clinical Care/Education
Patient Understanding of Hypoglycemia in Tertiary Referral Centers: Nan Hee Cho, Nam Kyung Kim, Eugene Han, Jun Hwa Hong, Eon Ju Jeon, Jun Sung Moon, Mi Hae Seo, Ji Eun Lee, Hyun-Ae Seo, Mi-Kyung Kim, Hye Soon Kim; Diabetes Metab J. 2018;42(1):43-52. Published online February 23, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.1.43

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Background

Hypoglycemia is an important complication in the treatment of patients with diabetes. We surveyed the insight by patients with diabetes into hypoglycemia, their hypoglycemia avoidance behavior, and their level of worry regarding hypoglycemia.

Methods

A survey of patients with diabetes, who had visited seven tertiary referral centers in Daegu or Gyeongsangbuk-do, Korea, between June 2014 and June 2015, was conducted. The survey contained questions about personal history, symptoms, educational experience, self-management, and attitudes about hypoglycemia.

Results

Of 758 participants, 471 (62.1%) had experienced hypoglycemia, and 250 (32.9%) had experienced hypoglycemia at least once in the month immediately preceding the study. Two hundred and forty-two (31.8%) of the participants had received hypoglycemia education at least once, but only 148 (19.4%) knew the exact definition of hypoglycemia. Hypoglycemic symptoms identified by the participants were dizziness (55.0%), sweating (53.8%), and tremor (40.8%). They mostly chose candy (62.1%), chocolate (37.7%), or juice (36.8%) as food for recovering hypoglycemia. Participants who had experienced hypoglycemia had longer duration of diabetes and a higher proportion of insulin usage. The mean scores for hypoglycemia avoidance behavior and worry about hypoglycemia were 21.2±10.71 and 23.38±13.19, respectively. These scores tended to be higher for participants with higher than 8% of glycosylated hemoglobin, insulin use, and experience of emergency room visits.

Conclusion

Many patients had experienced hypoglycemia and worried about it. We recommend identifying patients that are anxious about hypoglycemia and educating them about what to do when they develop hypoglycemic symptoms, especially those who have a high risk of hypoglycemia.

Citations

Citations to this article as recorded by

Severe Hypoglycemia Increases Dementia Risk and Related Mortality: A Nationwide, Population-based Cohort Study
Eugene Han, Kyung-do Han, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Seung-Hyun Ko, Yong-ho Lee
The Journal of Clinical Endocrinology & Metabolism.2022; 107(5): e1976. CrossRef
Severe hypoglycemia as a preventable risk factor for cardiovascular disease in patients with type 2 diabetes mellitus
Soo-Yeon Choi, Seung-Hyun Ko
The Korean Journal of Internal Medicine.2021; 36(2): 263. CrossRef
Severe hypoglycemia and the risk of end stage renal disease in type 2 diabetes
Jae-Seung Yun, Yong-Moon Park, Kyungdo Han, Hyung-Wook Kim, Seon-Ah Cha, Yu-Bae Ahn, Seung-Hyun Ko
Scientific Reports.2021;[Epub] CrossRef
Response: Patient Understanding of Hypoglycemia in Tertiary Referral Centers (Diabetes Metab J 2018;42:43-52)
Nan Hee Cho, Hye Soon Kim
Diabetes & Metabolism Journal.2018; 42(2): 175. CrossRef
Letter: Patient Understanding of Hypoglycemia in Tertiary Referral Centers (Diabetes Metab J 2018;42:43-52)
Jae-Han Jeon
Diabetes & Metabolism Journal.2018; 42(2): 173. CrossRef

Response

Response: GDF15 Is a Novel Biomarker for Impaired Fasting Glucose (Diabetes Metab J 2014;38:472-9): Jun Hwa Hong, Bon Jeong Ku, Minho Shong; Diabetes Metab J. 2015;39(1):84-86. Published online February 16, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.1.84

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Original Article

GDF15 Is a Novel Biomarker for Impaired Fasting Glucose: Jun Hwa Hong, Hyo Kyun Chung, Hye Yoon Park, Kyong-Hye Joung, Ju Hee Lee, Jin Gyu Jung, Koon Soon Kim, Hyun Jin Kim, Bon Jeong Ku, Minho Shong; Diabetes Metab J. 2014;38(6):472-479. Published online December 15, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.6.472

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Background

Growth differentiation factor-15 (GDF15) is a protein that belongs to the transforming growth factor β superfamily. An elevated serum level of GDF15 was found to be associated with type 2 diabetes mellitus (T2DM). T2DM is an inflammatory disease that progresses from normal glucose tolerance (NGT) to impaired fasting glucose (IFG). Hence, we aimed to validate the relationship between GDF15 and IFG.

Methods

The participants were divided into the following three groups: NGT (n=137), IFG (n=29), and T2DM (n=75). The controls and T2DM outpatients visited the hospital for routine health check-ups. We used fasting blood glucose to detect IFG in nondiabetic patients. We checked the body mass index (BMI), C-reactive protein level, metabolic parameters, and fasting serum GDF15 level.

Results

Age, BMI, triglyceride, insulin, glucose, homeostatic model assessment-insulin resistance (HOMA-IR), and GDF15 levels were elevated in the IFG and T2DM groups compared to the NGT group. In the correlation analysis between metabolic parameters and GDF15, age and HOMA-IR had a significant positive correlation with GDF15 levels. GDF15 significantly discriminated between IFG and NGT, independent of age, BMI, and HOMA-IR. The serum levels of GDF15 were more elevated in men than in women. As a biomarker for IFG based on the receiver operating characteristic curve analysis, the cutoff value of GDF15 was 510 pg/mL in males and 400 pg/mL in females.

Conclusion

GDF15 had a positive correlation with IR independent of age and BMI, and the serum level of GDF15 was increased in the IFG and T2DM groups. GDF15 may be a novel biomarker for detecting IFG in nondiabetic patients.

Citations

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Case Reports

Maintenance of Insulin Therapy by Desensitization in Insulin Allergy Patient.: Jun Hwa Hong, Ji Hye Lee, Jong Ho Shin, Dong Pil Kim, Bong Suk Ko, Byung Joon Kim, Hyun Jin Kim, Kang Seo Park; Korean Diabetes J. 2008;32(6):529-531. Published online December 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.6.529

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Abstract PDF

Allergic reaction to human insulin is uncommon. But they can cause mild to severe symptoms such as dyspnea, hypotensive shock, etc. Here we report the case of a patient with type 2 diabetes and insulin allergy successfully managed with desensitization. A 60-year-old man with insulin allergy was transferred. He had poorly controlled type 2 diabetes (fasting blood glucose 230 mg/dL). He developed itching sense and erythema at the injection sites of human insulin in a few minutes. And serum IgE level was elevated to 1618.0 IU/mL. The insulin was changed to other preparations, including short and long-acting insulin analogues, with similar responses. He was commenced on twice a day injection protocol in addition to his oral hypoglycemic agents, and achieved fair control (fasting blood glucose 100 mg/dL) on 24 units of Novomix Flex Pen per day, with little or no skin or systemic reaction. This is the case report of insulin allergy in type 2 diabetes being successfully managed by desensitization.

Citations

Citations to this article as recorded by

Allergic reaction to recombinant human insulin
Seong Jin Choi, Min Kwan Kwon, Moon Park, Soo Ya Bae, Hyun Ho Oh, Jong Ho Lee, Ji In Moon, Chan Sun Park, Jong Chul Won, Kyung Soo Ko, Byoung Doo Rhee, Jung Min Kim
Allergy, Asthma & Respiratory Disease.2015; 3(4): 302. CrossRef
Two Cases of Allergy to Insulin in Gestational Diabetes
Gi Jun Kim, Shin Bum Kim, Seong Il Jo, Jin Kyeong Shin, Hee Sun Kwon, Heekyung Jeong, Jang Won Son, Seong Su Lee, Sung Rae Kim, Byung Kee Kim, Soon Jib Yoo
Endocrinology and Metabolism.2015; 30(3): 402. CrossRef
Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature
Joselyn Rojas, Marjorie Villalobos, María Sofía Martínez, Mervin Chávez-Castillo, Wheeler Torres, José Carlos Mejías, Edgar Miquilena, Valmore Bermúdez
Case Reports in Immunology.2014; 2014: 1. CrossRef
Clinical applications of drug desensitization in the Asia-Pacific region
Bernard Yu-Hor Thong
Asia Pacific Allergy.2011; 1(1): 2. CrossRef

A case of Rhino-Orbital Mucormycosis in Newly Diagnosed type 1 Diabetic patient.: Jae Min Lee, Kyu Yuop Hwang, Gi Young Choi, Hyo Jung Nam, Dong Hyun Seo, Sun Hyun Park, Jun hwa Hong, Hyun Jin Kim, Kang Seo Park; Korean Diabetes J. 2005;29(5):495-499. Published online September 1, 2005

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Abstract PDF: Rhino-orbital mucormycosis was a rare, but mostly fatal fungal infection, usually found in poorly controlled diabetics or other immunocompromised hosts. This fungal infection begins from the nose, and rapidly spreads to the paranasal sinus (PNS), orbits and central nervous system(CNS), and finally extends to the entire organ. Early diagnosis and treatment is the only way to increase the survival rate. Herein Is reported We experienced a case of rhino-orbital mucormycosis, with type 1 diabetes mellitus, which was confirmed by a maxillary sinus biopsy. A 38-year-old male had been frequently treated for tonsillitis, but with no history of diabetes mellitus. He was admitted with mental change, accompanied by a fever, facial tenderness and swelling, with progressive visual acuity loss. During admission, CT and MRI of the in orbital area were performed. A biopsy in of the nasal cavity was also performed, and the mucormycosis was diagnosed through the pathological finding. The patient was treated with intravenous amphotericn B and an endoscopic antrostomy.

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