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Diabetic Ketoacidosis as an Effect of Sodium-Glucose Cotransporter 2 Inhibitor: Real World Insights
Han-Sang Baek, Chaiho Jeong, Yeoree Yang, Joonyub Lee, Jeongmin Lee, Seung-Hwan Lee, Jae Hyoung Cho, Tae-Seo Sohn, Hyun-Shik Son, Kun-Ho Yoon, Eun Young Lee
Received January 22, 2024  Accepted May 13, 2024  Published online June 10, 2024  
DOI: https://doi.org/10.4093/dmj.2024.0036    [Epub ahead of print]
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AbstractAbstract PDFPubReader   ePub   
One of the notable adverse effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor is diabetic ketoacidosis (DKA) often characterized by euglycemia. In this retrospective review of patients with DKA from 2015 to 2023, 21 cases of SGLT2 inhibitorassociated DKA were identified. Twelve (57.1%) exhibited euglycemic DKA (euDKA) while nine (42.9%) had hyperglycemic DKA (hyDKA). More than 90% of these cases were patients with type 2 diabetes mellitus. Despite similar age, sex, body mass index, and diabetes duration, individuals with hyDKA showed poorer glycemic control and lower C-peptide levels compared with euDKA. Renal impairment and acidosis were worse in the hyDKA group, requiring hemodialysis in two patients. Approximately one-half of hyDKA patients had concurrent hyperosmolar hyperglycemic state. Common symptoms included nausea, vomiting, general weakness, and dyspnea. Seizure was the initial manifestation of DKA in two cases. Infection and volume depletion were major contributors, while carbohydrate restriction and inadequate insulin treatment also contributed to SGLT2 inhibitor-associated DKA. Despite their beneficial effects, clinicians should be vigilant for SGLT2 inhibitor risk associated with DKA.
Original Articles
Drug/Regimen
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Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun Lee, Seung Hee Yu, Sung Rae Kim, Kyu Jeung Ahn, Kee-Ho Song, In-Kyu Lee, Ho-Sang Shon, In Joo Kim, Soo Lim, Doo-Man Kim, Choon Hee Chung, Won-Young Lee, Soon Hee Lee, Dong Joon Kim, Sung-Rae Cho, Chang Hee Jung, Hyun Jeong Jeon, Seung-Hwan Lee, Keun-Young Park, Sang Youl Rhee, Sin Gon Kim, Seok O Park, Dae Jung Kim, Byung Joon Kim, Sang Ah Lee, Yong-Hyun Kim, Kyung-Soo Kim, Ji A Seo, Il Seong Nam-Goong, Chang Won Lee, Duk Kyu Kim, Sang Wook Kim, Chung Gu Cho, Jung Han Kim, Yeo-Joo Kim, Jae-Myung Yoo, Kyung Wan Min, Moon-Kyu Lee
Received March 8, 2023  Accepted June 28, 2023  Published online May 20, 2024  
DOI: https://doi.org/10.4093/dmj.2023.0077    [Epub ahead of print]
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Background
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
Cardiovascular Risk/Epidemiology
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Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study
Ye Seul Yang, Nam Hoon Kim, Jong Ha Baek, Seung-Hyun Ko, Jang Won Son, Seung-Hwan Lee, Sang Youl Rhee, Soo-Kyung Kim, Tae Seo Sohn, Ji Eun Jun, In-Kyung Jeong, Chong Hwa Kim, Keeho Song, Eun-Jung Rhee, Junghyun Noh, Kyu Yeon Hur, Committee of Clinical Practice Guidelines, Korean Diabetes Association
Diabetes Metab J. 2024;48(2):279-289.   Published online January 26, 2024
DOI: https://doi.org/10.4093/dmj.2023.0225
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  • 244 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD.
Methods
We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study.
Results
Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users.
Conclusion
The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.

Citations

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  • Enhancing Patient Outcomes: Prioritizing SGLT2is and GLP-1RAs in Diabetes with CVD
    Gwanpyo Koh
    Diabetes & Metabolism Journal.2024; 48(2): 208.     CrossRef
Editorial
The Growing Challenge of Diabetes Management in an Aging Society
Seung-Hwan Lee
Diabetes Metab J. 2023;47(5):630-631.   Published online September 26, 2023
DOI: https://doi.org/10.4093/dmj.2023.0279
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  • 110 Download
  • 2 Web of Science
  • 2 Crossref
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Citations

Citations to this article as recorded by  
  • Balancing act: The dilemma of rapid hyperglycemia correction in diabetes management
    Ke-Xin Zhang, Cheng-Xia Kan, Xiao-Dong Sun
    World Journal of Diabetes.2024; 15(2): 129.     CrossRef
  • Interactive virtual assistance for mental health promotion and self-care management in elderly with type 2 diabetes (IVAM-ED): study protocol and statistical analysis plan for a randomized controlled trial
    Frederico Ludwig da Costa, Lucas Strassburger Matzenbacher, Vicenzo Gheno, Maria Antônia Bertuzzo Brum, Laura Gomes Boabaid de Barros, Isabela Semmelmann Maia, Luiza Machado Blank, Lucas Friedrich Fontoura, Janine Alessi, Gabriela Heiden Telo
    Trials.2024;[Epub]     CrossRef
Reviews
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Current Trends of Big Data Research Using the Korean National Health Information Database
Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee
Diabetes Metab J. 2022;46(4):552-563.   Published online July 27, 2022
DOI: https://doi.org/10.4093/dmj.2022.0193
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  • 295 Download
  • 37 Web of Science
  • 38 Crossref
AbstractAbstract PDFPubReader   ePub   
Recently, medical research using big data has become very popular, and its value has become increasingly recognized. The Korean National Health Information Database (NHID) is representative of big data that combines information obtained from the National Health Insurance Service collected for claims and reimbursement of health care services and results obtained from general health examinations provided to all Korean adults. This database has several strengths and limitations. Given the large size, various laboratory data, and questionnaires obtained from medical check-ups, their longitudinal nature, and long-term accumulation of data since 2002, carefully designed studies may provide valuable information that is difficult to obtain from other forms of research. However, consideration of possible bias and careful interpretation when defining causal relationships is also important because the data were not collected for research purposes. After the NHID became publicly available, research and publications based on this database have increased explosively, especially in the field of diabetes and metabolism. This article reviews the history, structure, and characteristics of the Korean NHID. Recent trends in big data research using this database, commonly used operational diagnosis, and representative studies have been introduced. We expect further progress and expansion of big data research using the Korean NHID.

Citations

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    Journal of Affective Disorders.2024; 351: 694.     CrossRef
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    The Journal of Clinical Endocrinology & Metabolism.2024;[Epub]     CrossRef
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    Diabetes Research and Clinical Practice.2024; 210: 111639.     CrossRef
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    Endocrinology and Metabolism.2023; 38(5): 525.     CrossRef
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    npj Parkinson's Disease.2023;[Epub]     CrossRef
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    Endocrinology and Metabolism.2023; 38(1): 129.     CrossRef
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    JMIR Public Health and Surveillance.2023; 9: e41203.     CrossRef
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Drug/Regimen
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A Century of Progress in Diabetes Care with Insulin: A History of Innovations and Foundation for the Future
Seung-Hwan Lee, Kun-Ho Yoon
Diabetes Metab J. 2021;45(5):629-640.   Published online September 30, 2021
DOI: https://doi.org/10.4093/dmj.2021.0163
  • 9,457 View
  • 493 Download
  • 15 Web of Science
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The year 2021 marks the 100th anniversary of the discovery of insulin, which has greatly changed the lives of people with diabetes and become a cornerstone of advances in medical science. A rapid bench-to-bedside application of the lifesaving pancreatic extract and its immediate commercialization was the result of a promising idea, positive drive, perseverance, and collaboration of Banting and colleagues. As one of the very few proteins isolated in a pure form at that time, insulin also played a key role in the development of important methodologies and in the beginning of various fields of modern science. Since its discovery, insulin has evolved continuously to optimize the care of people with diabetes. Since the 1980s, recombinant DNA technology has been employed to engineer insulin analogs by modifying their amino acid sequence, which has resulted in the production of insulins with various profiles that are currently used. However, unmet needs in insulin treatment still exist, and several forms of future insulins are under development. In this review, we discuss the past, present, and future of insulin, including a history of ceaseless innovations and collective intelligence. We believe that this story will be a solid foundation and an unerring guide for the future.

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Guideline/Fact Sheet
Article image
2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim, Sang Youl Rhee, You-Bin Lee, Sang-Man Jin, Jae Hyeon Kim, Chong Hwa Kim, Dae Jung Kim, SungWan Chun, Eun-Jung Rhee, Hyun Min Kim, Hyun Jung Kim, Donghyun Jee, Jae Hyun Kim, Won Seok Choi, Eun-Young Lee, Kun-Ho Yoon, Seung-Hyun Ko, Committee of Clinical Practice Guidelines, Korean Diabetes Association
Diabetes Metab J. 2021;45(4):461-481.   Published online July 30, 2021
DOI: https://doi.org/10.4093/dmj.2021.0156
  • 26,022 View
  • 1,675 Download
  • 131 Web of Science
  • 148 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

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Original Articles
Drug/Regimen
Article image
Effect of Dapagliflozin as an Add-on Therapy to Insulin on the Glycemic Variability in Subjects with Type 2 Diabetes Mellitus (DIVE): A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study
Seung-Hwan Lee, Kyung-Wan Min, Byung-Wan Lee, In-Kyung Jeong, Soon-Jib Yoo, Hyuk-Sang Kwon, Yoon-Hee Choi, Kun-Ho Yoon
Diabetes Metab J. 2021;45(3):339-348.   Published online May 28, 2020
DOI: https://doi.org/10.4093/dmj.2019.0203
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.

Methods

In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).

Results

At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, P<0.001), glycated albumin (−3.94%±2.55% vs. −0.67%±2.48%, P<0.001), and CGM-derived mean glucose (−41.6±39.2 mg/dL vs. 1.1±46.2 mg/dL, P<0.001) levels were observed in the dapagliflozin group compared with the placebo group. SD and MAGE were significantly decreased in the dapagliflozin group, but not in the placebo group. However, the difference in ΔSD and ΔMAGE failed to reach statistical significance between two groups. No significant differences in the incidence of safety endpoints were observed between the two groups.

Conclusion

Dapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.

Citations

Citations to this article as recorded by  
  • Selective sodium-glucose cotransporter-2 inhibitors in the improvement of hemoglobin and hematocrit in patients with type 2 diabetes mellitus: a network meta-analysis
    Yuanyuan Luo, Ruojing Bai, Wei Zhang, Guijun Qin
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Continuous Glucose Monitoring Profiles and Health Outcomes After Dapagliflozin Plus Saxagliptin vs Insulin Glargine
    Donald C Simonson, Marcia A Testa, Ella Ekholm, Maxwell Su, Tina Vilsbøll, Serge A Jabbour, Marcus Lind
    The Journal of Clinical Endocrinology & Metabolism.2024;[Epub]     CrossRef
  • Impact of empagliflozin on insulin needs in patients with heart failure and diabetes: An EMPEROR‐Pooled analysis
    Khawaja M. Talha, Jennifer Green, Gerasimos Filippatos, Stuart Pocock, Faiez Zannad, Martina Brueckmann, Elke Schueler, Anne Pernille Ofstad, João Pedro Ferreira, Stefan D. Anker, Javed Butler, Julio Rosenstock, Milton Packer
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  • Dapagliflozin in heart failure and type 2 diabetes: Efficacy, cardiac and renal effects, safety
    Pei-Ling Yu, You Yu, Shuang Li, Bai-Chen Mu, Ming-Hua Nan, Min Pang
    World Journal of Diabetes.2024; 15(7): 1518.     CrossRef
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Complications
Article image
Differences in Clinical Outcomes between Patients with and without Hypoglycemia during Hospitalization: A Retrospective Study Using Real-World Evidence
Jeongmin Lee, Tong Min Kim, Hyunah Kim, Seung-Hwan Lee, Jae Hyoung Cho, Hyunyong Lee, Hyeon Woo Yim, Kun-Ho Yoon, Hun-Sung Kim
Diabetes Metab J. 2020;44(4):555-565.   Published online May 8, 2020
DOI: https://doi.org/10.4093/dmj.2019.0064
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  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Some patients admitted to hospitals for glycemic control experience hypoglycemia despite regular meals and despite adhering to standard blood glucose control protocols. Different factors can have a negative impact on blood glucose control and prognosis after discharge. This study investigated risk factors for hypoglycemia and its effects on glycemic control during the hospitalization of patients in the general ward.

Methods

This retrospective study included patients who were admitted between 2009 and 2018. Patients were provided regular meals at fixed times according to ideal body weights during hospitalization. We categorized the patients into two groups: those with and those without hypoglycemia during hospitalization.

Results

Of the 3,031 patients, 379 experienced at least one episode of hypoglycemia during hospitalization (HYPO group). Hypoglycemia occurred more frequently particularly in cases of premixed insulin therapy. Compared with the control group, the HYPO group was older (61.0±16.8 years vs. 59.1±16.5 years, P=0.035), with more females (60.4% vs. 49.6%, P<0.001), lower body mass index (BMI) (23.5±4.2 kg/m2 vs. 25.1±4.4 kg/m2, P<0.001), and higher prevalence of type 1 diabetes mellitus (6.1% vs. 2.6%, P<0.001), They had longer hospital stay (11.1±13.5 days vs. 7.6±4.6 days, P<0.001). After discharge the HYPO group had lower glycosylated hemoglobin reduction rate (−2.0%±0.2% vs. −2.5%±0.1%, P=0.003) and tended to have more frequent cases of cardiovascular disease.

Conclusion

Hypoglycemia occurred more frequently in older female patients with lower BMI and was associated with longer hospital stay and poorer glycemic control after discharge. Therefore, clinicians must carefully ensure that patients do not experience hypoglycemia during hospitalization.

Citations

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    Ana Carreira, Pedro Castro, Filipe Mira, Miguel Melo, Pedro Ribeiro, Lèlita Santos
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    Sung-Woo Kim
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Editorial
Obesity and Metabolic Syndrome
Changes in Metabolic Profile Over Time: Impact on the Risk of Diabetes
Yunjung Cho, Seung-Hwan Lee
Diabetes Metab J. 2019;43(4):407-409.   Published online August 20, 2019
DOI: https://doi.org/10.4093/dmj.2019.0141
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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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AbstractAbstract PDFSupplementary MaterialPubReader   
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

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  • 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
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Clinical Diabetes & Therapeutics
Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
Hae Kyung Yang, Seung-Hwan Lee, Juyoung Shin, Yoon-Hee Choi, Yu-Bae Ahn, Byung-Wan Lee, Eun Jung Rhee, Kyung Wan Min, Kun-Ho Yoon
Diabetes Metab J. 2019;43(3):287-301.   Published online December 20, 2018
DOI: https://doi.org/10.4093/dmj.2018.0054
  • 6,434 View
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  • 14 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin.

Methods

A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24.

Results

The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups.

Conclusion

In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.

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  • The effect of acarbose on inflammatory cytokines and adipokines in adults: a systematic review and meta-analysis of randomized clinical trials
    Ali Mohammadian, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Niloufar Rasaei, Hossein Bahari, Samira Rastgoo, Reza Bagheri, Farideh Shiraseb, Omid Asbaghi
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    Sachithanantham Annapoorani Sivaraman, Varatharajan Sabareesh
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    Elnaz Golalipour, Dorsa Hosseininasab, Mahlagha Nikbaf-Shandiz, Niloufar Rasaei, Hossein Bahari, Mahya Mehri Hajmir, Samira Rastgoo, Farideh Shiraseb, Omid Asbaghi
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    Sina Raissi Dehkordi, Naseh Pahlavani, Mahlagha Nikbaf-Shandiz, Reza Bagheri, Niloufar Rasaei, Melika Darzi, Samira Rastgoo, Hossein Bahari, Farideh Shiraseb, Omid Asbaghi
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    Heliyon.2022; 8(5): e09501.     CrossRef
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    Nahal Shayegan, Aida Iraji, Nasim Bakhshi, Ali Moazzam, Mohammad Ali Faramarzi, Somayeh Mojtabavi, Seyyed Mehrdad Mostafavi Pour, Maliheh Barazandeh Tehrani, Bagher Larijani, Zahra Rezaei, Pardis Yousefi, Mehdi Khoshneviszadeh, Mohammad Mahdavi
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    Lawrence Blonde, Guillermo E. Umpierrez, S. Sethu Reddy, Janet B. McGill, Sarah L. Berga, Michael Bush, Suchitra Chandrasekaran, Ralph A. DeFronzo, Daniel Einhorn, Rodolfo J. Galindo, Thomas W. Gardner, Rajesh Garg, W. Timothy Garvey, Irl B. Hirsch, Danie
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Complications
Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus
Yeoree Yang, Eun-Young Lee, Jae-Hyoung Cho, Yong-Moon Park, Seung-Hyun Ko, Kun-Ho Yoon, Moo-Il Kang, Bong-Yun Cha, Seung-Hwan Lee
Diabetes Metab J. 2018;42(6):496-512.   Published online September 28, 2018
DOI: https://doi.org/10.4093/dmj.2018.0026
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus.

Methods

In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements.

Results

A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%).

Conclusion

CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

Citations

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    Natsumi Matsuoka-Uchiyama, Haruhito A. Uchida, Shugo Okamoto, Yasuhiro Onishi, Katsuyoshi Katayama, Mariko Tsuchida-Nishiwaki, Hidemi Takeuchi, Rika Takemoto, Yoshiko Hada, Ryoko Umebayashi, Naoko Kurooka, Kenji Tsuji, Jun Eguchi, Hirofumi Nakajima, Kenic
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    Yun-Ru Lai, Chih-Cheng Huang, Wen-Chan Chiu, Rue-Tsuan Liu, Nai-Wen Tsai, Hung-Chen Wang, Wei-Che Lin, Ben-Chung Cheng, Yu-Jih Su, Chih-Min Su, Sheng-Yuan Hsiao, Pei-Wen Wang, Jung-Fu Chen, Cheng-Hsien Lu
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Editorial
Epidemiology
Hidden Risks behind Normal Fasting Glucose: Is It Significant?
Seung-Hwan Lee
Diabetes Metab J. 2018;42(3):196-197.   Published online June 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.0083
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Original Article
Epidemiology
Serum Betatrophin Concentrations and the Risk of Incident Diabetes: A Nested Case-Control Study from Chungju Metabolic Disease Cohort
Seung-Hwan Lee, Marie Rhee, Hyuk-Sang Kwon, Yong-Moon Park, Kun-Ho Yoon
Diabetes Metab J. 2018;42(1):53-62.   Published online November 3, 2017
DOI: https://doi.org/10.4093/dmj.2018.42.1.53
  • 3,839 View
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AbstractAbstract PDFPubReader   
Background

Betatrophin is a newly identified hormone derived from the liver and adipose tissue, which has been suggested to regulate glucose and lipid metabolism. Circulating levels of betatrophin are altered in various metabolic diseases, although the results are inconsistent. We aimed to examine whether betatrophin is a useful biomarker in predicting the development of diabetes.

Methods

A nested case-control study was performed using a prospective Chungju Metabolic disease Cohort Study. During a 4-year follow-up period, we analyzed 167 individuals who converted to diabetes and 167 non-converters, who were matched by age, sex, and body mass index. Serum betatrophin levels were measured by an ELISA (enzyme-linked immunosorbent assay).

Results

Baseline serum betatrophin levels were significantly higher in the converter group compared to the non-converter group (1,315±598 pg/mL vs. 1,072±446 pg/mL, P<0.001). After adjusting for age, sex, body mass index, fasting plasma glucose, systolic blood pressure, total cholesterol, and family history of diabetes, the risk of developing diabetes showed a stepwise increase across the betatrophin quartile groups. Subjects in the highest baseline quartile of betatrophin levels had more than a threefold higher risk of incident diabetes than the subjects in the lowest quartile (relative risk, 3.275; 95% confidence interval, 1.574 to 6.814; P=0.010). However, no significant relationships were observed between serum betatrophin levels and indices of insulin resistance or β-cell function.

Conclusion

Circulating levels of betatrophin could be a potential biomarker for predicting new-onset diabetes. Further studies are needed to understand the underlying mechanism of this association.

Citations

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