Diabetes & Metabolism Journal

Original Article

Complications
Influence of Glucose Fluctuation on Peripheral Nerve Damage in Streptozotocin-Induced Diabetic Rats: Yu Ji Kim, Na Young Lee, Kyung Ae Lee, Tae Sun Park, Heung Yong Jin; Diabetes Metab J. 2022;46(1):117-128. Published online September 9, 2021; DOI: https://doi.org/10.4093/dmj.2020.0275

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Background
It is unclear whether glycemic variability (GV) is a risk factor for diabetic peripheral neuropathy (DPN), and whether control of GV is beneficial for DPN. The purpose of this study was to investigate the effect of GV on peripheral nerve damage by inducing glucose fluctuation in streptozotocin-induced diabetic rats.
Methods
Rats were divided into four groups: normal (normal glucose group [NOR]), diabetes without treatment (sustained severe hyperglycemia group; diabetes mellitus [DM]), diabetes+once daily insulin glargine (stable hyperglycemia group; DM+LAN), and diabetes+once daily insulin glargine with twice daily insulin glulisine (unstable glucose fluctuation group; DM+Lantus [LAN]+Apidra [API]). We measured anti-oxidant enzyme levels and behavioral responses against tactile, thermal, and pressure stimuli in the plasma of rats. We also performed a quantitative comparison of cutaneous and sciatic nerves according to glucose fluctuation.
Results
At week 24, intraepidermal nerve fiber density was less reduced in the insulin-administered groups compared to the DM group (P<0.05); however, a significant difference was not observed between the DM+LAN and DM+LAN+API groups irrespective of glucose fluctuation (P>0.05; 16.2±1.6, 12.4±2.0, 14.3±0.9, and 13.9±0.6 for NOR, DM, DM+LAN, and DM+LAN+API, respectively). The DM group exhibited significantly decreased glutathione levels compared to the insulin-administered groups (2.64±0.10 μmol/mL, DM+LAN; 1.93±0.0 μmol/mL, DM+LAN+API vs. 1.25±0.04 μmol/mL, DM; P<0.05).
Conclusion
Our study suggests that glucose control itself is more important than glucose fluctuation in the prevention of peripheral nerve damage, and intra-day glucose fluctuation has a limited effect on the progression of peripheral neuropathy in rats with diabetes.

Citations

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Glucose Fluctuation Inhibits Nrf2 Signaling Pathway in Hippocampal Tissues and Exacerbates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats
Haiyan Chi, Yujing Sun, Peng Lin, Junyu Zhou, Jinbiao Zhang, Yachao Yang, Yun Qiao, Deshan Liu, Eusebio Chiefari
Journal of Diabetes Research.2024; 2024: 1. CrossRef
Artesunate Inhibits Apoptosis and Promotes Survival in Schwann Cells via the PI3K/AKT/mTOR Axis in Diabetic Peripheral Neuropathy
Xin Zhang, Zhifang Liang, Ying Zhou, Fang Wang, Shan Wei, Bing Tan, Yujie Guo
Biological and Pharmaceutical Bulletin.2023; 46(6): 764. CrossRef
The Potential of Glucose Treatment to Reduce Reactive Oxygen Species Production and Apoptosis of Inflamed Neural Cells In Vitro
Juin-Hong Cherng, Shu-Jen Chang, Hsin-Da Tsai, Chung-Fang Chun, Gang-Yi Fan, Kenneth Dean Reeves, King Hei Stanley Lam, Yung-Tsan Wu
Biomedicines.2023; 11(7): 1837. CrossRef
Relationship between acute glucose variability and cognitive decline in type 2 diabetes: A systematic review and meta-analysis
Haiyan Chi, Min Song, Jinbiao Zhang, Junyu Zhou, Deshan Liu, Victor Manuel Mendoza-Nuñez
PLOS ONE.2023; 18(9): e0289782. CrossRef

Responses

Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015) (Diabetes Metab J 2021;45:115-9): Seong-Su Moon, Chong Hwa Kim, Seon Mee Kang, Eun Sook Kim, Tae Jung Oh, Jae-Seung Yun, Ho Chan Cho, Dae Jung Kim, Tae Sun Park; Diabetes Metab J. 2021;45(3):459-460. Published online May 25, 2021; DOI: https://doi.org/10.4093/dmj.2021.0084

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Citations

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Comorbidity Patterns and Management in Inpatients with Endocrine Diseases by Age Groups in South Korea: Nationwide Data
Sung-Soo Kim, Hun-Sung Kim
Journal of Personalized Medicine.2023; 14(1): 42. CrossRef

Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats (Diabetes Metab J 2020;44:842-53): Sun Hee Kim, Tae Sun Park, Heung Yong Jin; Diabetes Metab J. 2021;45(1):127-128. Published online January 22, 2021; DOI: https://doi.org/10.4093/dmj.2020.0289

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Brief Report

Complications
Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015): Seong-Su Moon, Chong Hwa Kim, Seon Mee Kang, Eun Sook Kim, Tae Jung Oh, Jae-Seung Yun, Ho Chan Cho, Dae Jung Kim, Tae Sun Park; Diabetes Metab J. 2021;45(1):115-119. Published online December 18, 2020; DOI: https://doi.org/10.4093/dmj.2020.0120

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This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance ServiceNational Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients.

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Risk of cardiovascular events according to the tricyclic antidepressant dosage in patients with chronic pain: a retrospective cohort study
Hyunji Koo, Seung Hun You, Sewon Park, Kyeong Hye Jeong, Nakyung Jeon, Sun-Young Jung
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How does diabetic peripheral neuropathy impact patients' burden of illness and the economy? A retrospective study in Beijing, China
Qi Pan, Sijia Fei, Lina Zhang, Huan Chen, Jingyi Luo, Weihao Wang, Fei Xiao, Lixin Guo
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Chronic disease management program applied to type 2 diabetes patients and prevention of diabetic complications: a retrospective cohort study using nationwide data
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Pharmacological and Nonpharmacological Treatments for Painful Diabetic Peripheral Neuropathy
Han Na Jang, Tae Jung Oh
Diabetes & Metabolism Journal.2023; 47(6): 743. CrossRef
Are herbal medicines alone or in combination for diabetic peripheral neuropathy more effective than methylcobalamin alone? A systematic review and meta-analysis
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Pathogenesis and Treatment of Diabetic Peripheral Neuropathy
Seon Mee Kang
The Journal of Korean Diabetes.2022; 23(4): 222. CrossRef
Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015) (Diabetes Metab J 2021;45:115-9)
Seong-Su Moon, Chong Hwa Kim, Seon Mee Kang, Eun Sook Kim, Tae Jung Oh, Jae-Seung Yun, Ho Chan Cho, Dae Jung Kim, Tae Sun Park
Diabetes & Metabolism Journal.2021; 45(3): 459. CrossRef
Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015) (Diabetes Metab J 2021;45:115-9)
Tímea Csákvári, Diána Elmer, Lilla Horváth, Imre Boncz
Diabetes & Metabolism Journal.2021; 45(3): 454. CrossRef
Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study (Diabetes Metab J 2021;45:368-78)
Ja Young Jeon
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Original Articles

Drug/Regimen
Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study: Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Kim, Hye Soon Kim, Il Seong Nam-Goong, Eun Sook Kim, Jin Ook Chung, Dong-Hyeok Cho, Chang Won Lee, Young Il Kim, Dong Jin Chung, Kyu Chang Won, In Joo Kim, Tae Sun Park, Duk Kyu Kim, Hosang Shon; Diabetes Metab J. 2021;45(5):675-683. Published online August 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0107

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Background

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Methods

From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.

Results

In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy.

Conclusion

This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Citations

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Estimating Type 2 Diabetes Prevalence: A Model of Drug Consumption Data
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Efficacy and safety of enavogliflozin versus dapagliflozin added to metformin plus gemigliptin treatment in patients with type 2 diabetes: A double-blind, randomized, comparator-active study: ENHANCE-D study
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Effectiveness and safety of teneligliptin added to patients with type 2 diabetes inadequately controlled by oral triple combination therapy: A multicentre, randomized, double‐blind, and placebo‐controlled study
Minyoung Lee, Woo‐je Lee, Jae Hyeon Kim, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2022; 24(6): 1105. CrossRef
A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
Diabetes, Obesity and Metabolism.2022; 24(9): 1800. CrossRef
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

Drug/Regimen
Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats: Sun Hee Kim, Tae Sun Park, Heung Yong Jin; Diabetes Metab J. 2020;44(6):842-853. Published online May 28, 2020; DOI: https://doi.org/10.4093/dmj.2019.0190

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Background

Metformin is widely marketed medication for the treatment of diabetes, but its pharmacological effect on diabetic peripheral neuropathy remains unclear. In this study, the effect of metformin on peripheral nerves in diabetic rats was investigated using diverse neuronal parameters of nerve fibers.

Methods

Rats were assigned to one of four groups (n=7 to 10 per group): normal, diabetes mellitus (DM), DM+metformin (100 mg/kg), and DM+alpha lipoic acid (ALA, 100 mg/kg). DM was induced by streptozotocin/high-fat diet (STZ/HFD). After 12 weeks, the sensory thresholds to mechanical and heat stimuli were assessed. Repeated sensory tests, immunofluorescence microscopic comparison of peripheral nerves, and biochemical blood analysis were performed after 24 weeks.

Results

Both DM+metformin and DM+ALA groups showed similar trends to diverse sensory tests at 24 weeks compared to DM group although the degree of change were different according to the stimulated senses. There was no significant difference in the comparison of the intraepidermal nerve fiber density (IENFD) of peripheral nerves between the DM+metformin and DM+ALA groups (11.83±0.07 fibers/mm vs. 12.37±1.82 fibers/mm, respectively). Both groups showed preserved IENFD significantly compared with DM group (8.46±1.98 fibers/mm, P<0.05). Sciatic nerve morphology of the experimental animals showed a similar trend to the IENFD, with respect to axonal diameter, myelin sheath thickness, and myelinated fiber diameter.

Conclusion

Metformin has beneficial pharmacological effects on the preservation of peripheral nerves in diabetic rats and its effects are comparable to those of ALA.

Citations

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Metformin improves diabetic neuropathy by reducing inflammation through up-regulating the expression of miR-146a and suppressing oxidative stress
Fengmin Liu, Fangqin You, Lihang Yang, Siyun Wang, Diya Xie
Journal of Diabetes and its Complications.2024; 38(6): 108737. CrossRef
Effect of Metformin on the Functional and Electrophysiological Recovery of Crush Injury-Induced Facial Nerve Paralysis in Diabetic Rats
Kyung Hoon Sun, Cheol Hee Choi, Gwang-Won Cho, Chul Ho Jang
Journal of Personalized Medicine.2023; 13(9): 1317. CrossRef
Is metformin neuroprotective against diabetes mellitus-induced neurodegeneration? An updated graphical review of molecular basis
Fatemeh Karami, Hamidreza Jamaati, Natalie Coleman-Fuller, Maryam Shokrian Zeini, A. Wallace Hayes, Mina Gholami, Mahsa Salehirad, Mohammad Darabi, Majid Motaghinejad
Pharmacological Reports.2023; 75(3): 511. CrossRef
Early Diagnosis through Estimation of Inflammatory Biomarkers and the Neuroprotective Role of Metformin in Diabetic Peripheral Neuropathy
Laxmi Sri, Prabhakar Orsu
International Journal of Pharmaceutical Sciences and Nanotechnology(IJPSN).2023; 16(2): 6427. CrossRef
Bidirectional association between diabetic peripheral neuropathy and vitamin B12 deficiency: Two longitudinal 9-year follow-up studies using a national sample cohort
Heung Yong Jin, Kyung Ae Lee, Yu Ji Kim, In Sun Gwak, Tae Sun Park, Sang Woo Yeom, Jong Seung Kim
Primary Care Diabetes.2023; 17(5): 436. CrossRef
An overview of painful diabetic peripheral neuropathy: Diagnosis and treatment advancements
Jonathan M. Hagedorn, Alyson M. Engle, Tony K. George, Jay Karri, Newaj Abdullah, Erik Ovrom, Jhon E. Bocanegra-Becerra, Ryan S. D'Souza
Diabetes Research and Clinical Practice.2022; 188: 109928. CrossRef
The role of MicroRNA networks in tissue-specific direct and indirect effects of metformin and its application
Qinzhi Yang, Gang Wang, Dan Fang, Xiaojun Gao, Yu Liang, Liqun Wang, Jianbo Wu, Min Zeng, Mao Luo
Biomedicine & Pharmacotherapy.2022; 151: 113130. CrossRef
Is metformin a possible treatment for diabetic neuropathy?
Juechun Wei, Yanling Wei, Meiyan Huang, Peng Wang, Shushan Jia
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Metformin as a potential therapeutic for neurological disease: mobilizing AMPK to repair the nervous system
Sarah Demaré, Asha Kothari, Nigel A. Calcutt, Paul Fernyhough
Expert Review of Neurotherapeutics.2021; 21(1): 45. CrossRef
Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats (Diabetes Metab J 2020;44:842-53)
Bo Kyung Koo
Diabetes & Metabolism Journal.2021; 45(1): 125. CrossRef
Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats (Diabetes Metab J 2020;44:842-53)
Sun Hee Kim, Tae Sun Park, Heung Yong Jin
Diabetes & Metabolism Journal.2021; 45(1): 127. CrossRef
Impacts of statin and metformin on neuropathy in patients with type 2 diabetes mellitus: Korean Health Insurance data
Hong Ki Min, Se Hee Kim, Jong Han Choi, Kyomin Choi, Hae-Rim Kim, Sang-Heon Lee
World Journal of Clinical Cases.2021; 9(33): 10198. CrossRef

Drug/Regimen
γ-Linolenic Acid versus α-Lipoic Acid for Treating Painful Diabetic Neuropathy in Adults: A 12-Week, Double-Placebo, Randomized, Noninferiority Trial: Jong Chul Won, Hyuk-Sang Kwon, Seong-Su Moon, Sung Wan Chun, Chong Hwa Kim, Ie Byung Park, In Joo Kim, Jihyun Lee, Bong Yun Cha, Tae Sun Park; Diabetes Metab J. 2020;44(4):542-554. Published online November 4, 2019; DOI: https://doi.org/10.4093/dmj.2019.0099

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Background

This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN).

Methods

This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS).

Results

Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was −0.65 (−1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ₁=0.51). For the TSS, the treatment difference was −0.05 (−1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ₂=0.054). There were no serious adverse events associated with the treatments.

Conclusion

GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.

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Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy
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Diyabet Tedavisinde Antioksidan Etki: Alfa Lipoik Asit
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Ranking Alpha Lipoic Acid and Gamma Linolenic Acid in Terms of Efficacy and Safety in the Management of Adults With Diabetic Peripheral Neuropathy: A Systematic Review and Network Meta-analysis
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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

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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
Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease
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Clinical and Molecular Hepatology.2020; 26(4): 430. CrossRef

Clinical Diabetes & Therapeutics
Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial: Tae Jung Oh, Jae Myung Yu, Kyung Wan Min, Hyun Shik Son, Moon Kyu Lee, Kun Ho Yoon, Young Duk Song, Joong Yeol Park, In Kyung Jeong, Bong Soo Cha, Yong Seong Kim, Sei Hyun Baik, In Joo Kim, Doo Man Kim, Sung Rae Kim, Kwan Woo Lee, Jeong Hyung Park, In Kyu Lee, Tae Sun Park, Sung Hee Choi, Sung Woo Park; Diabetes Metab J. 2019;43(3):276-286. Published online December 7, 2018; DOI: https://doi.org/10.4093/dmj.2018.0051

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Background

Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus.

Methods

A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24.

Results

The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039).

Conclusion

Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.

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Brief Reports

Complications
Effect of Empagliflozin, a Selective Sodium-Glucose Cotransporter 2 Inhibitor, on Kidney and Peripheral Nerves in Streptozotocin-Induced Diabetic Rats: Kyung Ae Lee, Heung Yong Jin, Na Young Lee, Yu Ji Kim, Tae Sun Park; Diabetes Metab J. 2018;42(4):338-342. Published online April 25, 2018; DOI: https://doi.org/10.4093/dmj.2017.0095

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The effect of sodium-glucose cotransporter 2 inhibitors on peripheral nerves and kidneys in diabetes mellitus (DM) remains unexplored. Therefore, this study aimed to explore the effect of empagliflozin in diabetic rats. DM in rats was induced by streptozotocin injection, and diabetic rats were treated with empagliflozin 3 or 10 mg/kg. Following 24-week treatment, response thresholds to four different stimuli were tested and found to be lower in diabetic rats than in normal rats. Empagliflozin significantly prevented hypersensitivity (P<0.05) and the loss of skin intraepidermal nerve fibers, and mesangial matrix expansion in diabetic rats. Results of this study demonstrate the potential therapeutic effects of empagliflozin for the treatment of diabetic peripheral neuropathy and nephropathy.

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Renal intrinsic cells remodeling in diabetic kidney disease and the regulatory effects of SGLT2 Inhibitors
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Sodium Glucose Cotransporter-2 Inhibitor Protects Against Diabetic Neuropathy and Nephropathy in Modestly Controlled Type 2 Diabetes: Follow-Up Study
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Protective effect of empagliflozin on gentamicin-induced acute renal injury via regulation of SIRT1/NF-κB signaling pathway
Sandy R. Botros, Asmaa I. Matouk, Aliaa Anter, Mohamed M.A. Khalifa, Gehan H. Heeba
Environmental Toxicology and Pharmacology.2022; 94: 103907. CrossRef
Empagliflozin mitigates type 2 diabetes-associated peripheral neuropathy: a glucose-independent effect through AMPK signaling
Noha F. Abdelkader, Marawan A. Elbaset, Passant E. Moustafa, Sherehan M. Ibrahim
Archives of Pharmacal Research.2022; 45(7): 475. CrossRef
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The Journal of Korean Diabetes.2022; 23(4): 222. CrossRef
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Adel T. Osman, Souty M.Z. Sharkawi, Mohamed I.A. Hassan, Amira M. Abo-youssef, Ramadan A.M. Hemeida
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Tushar Issar, Natalie C.G. Kwai, Ann M. Poynten, Ria Arnold, Kerry-Lee Milner, Arun V. Krishnan
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Effectiveness of Empagliflozin With Vitamin D Supplementation in Peripheral Neuropathy in Type 2 Diabetic Patients
Sanjana Mehta, Parminder Nain, Bimal K Agrawal, Rajinder P Singh, Jaspreet Kaur, Sabyasachi Maity, Aniruddha Bhattarcharjee, Jagannadha Peela, Shreya Nauhria, Samal Nauhria
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Frontiers in Physiology.2019;[Epub] CrossRef

Complication
Morphologic Comparison of Peripheral Nerves in Adipocyte Tissue from db/db Diabetic versus Normal Mice: Kyung Ae Lee, Na Young Lee, Tae Sun Park, Heung Yong Jin; Diabetes Metab J. 2018;42(2):169-172. Published online March 21, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.169

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Abstract PDF PubReader: Present study investigated the morphologic changes of autonomic nerves in the adipose tissue in diabetic animal model. Male obese type 2 diabetic db/db mice and age matched non-diabetic db/m control mice were used. Epididymal adipose tissue from diabetic db/db mice with that from control heterozygous db/m mice was compared using confocal microscopy-based method to visualize intact whole adipose tissue. Immunohistochemistry with tyrosine hydroxylase for sympathetic (SP), choline acetyltransferase for parasympathetic (PSP), and protein gene product 9.5 (PGP 9.5) for whole autonomic nerves was performed. The quantity of immunostained portion of SP, PSP, and PGP 9.5 stained nerve fibers showed decreased trend in diabetic group; however, the ratio of SP/PSP of adipose tissue was higher in diabetic group compared with control group as follows (0.70±0.30 vs. 0.95±0.25, P<0.05; normal vs. diabetic, respectively). Both SP and PSP nerve fibers were observed in white adipose tissue and PSP nerve fibers were suggested as more decreased in diabetes based on our observation.

Original Article

Epidemiology
Dietary Sodium Intake in People with Diabetes in Korea: The Korean National Health and Nutrition Examination Survey for 2008 to 2010: Myung Shin Kang, Chong Hwa Kim, Su Jin Jeong, Tae Sun Park; Diabetes Metab J. 2016;40(4):290-296. Published online June 23, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.4.290

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Background

Diabetics are likely to receive advice from their physicians concerning lifestyle changes. To understand how much sodium is consumed by diabetics in Korea, we compared the average daily sodium intake between diabetics and non-diabetics after controlling for confounding factors.

Methods

We obtained the sodium intake data for 13,957 individuals who participated in the Korean National Health and Nutrition Examination Survey (KNHANES), 2008 to 2010, which consisted of a health interview and behavioral and nutritional surveys. The KNHANES uses a stratified, multistage, probability-sampling design, and weighting adjustments were conducted to represent the entire population.

Results

Our analysis revealed that, overall, diabetics tended to have lower sodium intake (4,910.2 mg) than healthy individuals (5,188.2 mg). However, both diabetic and healthy individuals reported higher sodium intake than is recommended by the World Health Organization (WHO). Stratified subgroup analyses revealed that the sodium intake (4,314.2 mg) among newly diagnosed diabetics was higher among women when compared to patients with known diabetes (3,812.5 mg, P=0.035). Female diabetics with cardiovascular disease had lower average sodium intake compared to those without cardiovascular disease after adjusting for sex, age, body mass index, and total energy intake (P=0.058). Sodium intake among male diabetics with hypercholesterolemia (P=0.011) and female diabetics with hypertriglyceridemia (P=0.067) tended to be higher than that among those who without dyslipidemia.

Conclusion

The average sodium intake of diabetics in Korea was higher than the WHO recommends. Sodium intake in newly diagnosed diabetics was significantly higher than that in non-diabetics and previously diagnosed diabetics among females. Prospective studies are needed to identify the exact sodium intake.

Citations

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Natália Gonçalves Ribeiro, Deborah F. Lelis, Rosane H. Griep, Sandhi M. Barreto, Maria del Carmen B Molina, Maria I. Schmidt, Bruce B. Duncan, Isabela Bensenor, Paulo A. Lotufo, José G. Mill, Marcelo Perim Baldo
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Review

Pathophysiology
Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy: Heung Yong Jin, Hong Sun Baek, Tae Sun Park; Diabetes Metab J. 2015;39(6):461-467. Published online December 11, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.461

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Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN). Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.

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Original Articles

The Relationship between Anemia and the Initiation of Dialysis in Patients with Type 2 Diabetic Nephropathy: Sun Hee Kim, Kyung Ae Lee, Heung Yong Jin, Hong Sun Baek, Tae Sun Park; Diabetes Metab J. 2015;39(3):240-246. Published online April 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.3.240

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Background

Anemia is associated with various poor clinical outcomes in chronic kidney disease patients. The aim of this study was to investigate the relationship between anemia and the initiation degree and time of dialysis in type 2 diabetic nephropathy patients.

Methods

This observational retrospective study included 130 type 2 diabetic nephropathy patients in Korea. The existence of anemia, the degree and time of dialysis initiation were reviewed. Clinical characteristics and variables were also compared.

Results

The levels of hemoglobin and serum creatinine were significantly correlated with the dialysis initiation (P<0.05) during the 10-year follow-up period. Patients with anemia showed rapid decline of renal function, causing significantly more dialysis initiation (54.1% vs. 5.4%, P<0.05) compare to the patients without anemia. Average time to initiate dialysis in patients with anemia was 45.1 months (range, 8.0 to 115.8 months), which was significantly faster than that (68.3 months [range, 23.3 to 108.8 months]) in patients without anemia (P<0.01). The risk to dialysis initiation was significantly increased in patients with anemia compared to the patients without anemia (adjusted hazard ratio, 8.1; 95% confidence interval, 2.4 to 27.0; P<0.05).

Conclusion

Anemia is associated with rapid decline of renal dysfunction and faster initiation of dialysis in diabetic nephropathy patients. Therefore, clinicians should pay an earlier attention to anemia during the management of diabetes.

Citations

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Sohaib Asghar, Shoaib Asghar, Tayyab Mahmood, Syed Muhammad Hassan Bukhari, Muhammad Habib Mumtaz, Ali Rasheed
Cureus.2023;[Epub] CrossRef
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Relationship between the Korean Version Survey of the Autonomic Symptoms Score and Cardiac Autonomic Neuropathy Parameters in Patients with Diabetic Peripheral Neuropathy: Sun Hee Kim, Kyung Ae Lee, Heung Yong Jin, Hong Sun Baek, Tae Sun Park; Diabetes Metab J. 2014;38(5):349-355. Published online October 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.5.349

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Abstract PDF PubReader

Background

The Survey of Autonomic Symptom (SAS) scale was reported as an easy instrument to assess the autonomic symptoms in patients with early diabetic neuropathy. In this study, we investigated the relationship between the SAS scale and the parameters of cardiac autonomic neuropathy (CAN) in Korean patients with diabetic peripheral neuropathy (DPN).

Methods

The SAS scale was tested in 30 healthy controls and 73 patients with DPN at Chonbuk National University Hospital, in Korea. The SAS score was compared to the parameters of the CAN test and the total symptom score (TSS) for DPN in patients with DPN.

Results

The SAS symptom score and total impact score were increased in patients with DPN compared to the control group (P=0.01), particularly in sudomotor dysfunction (P=0.01), and vasomotor dysfunction (P=0.01). The SAS score was increased in patients with CAN compared to patients without CAN (P<0.05). Among the diverse CAN parameters, the valsalva ratio and postural hypotension were associated with the SAS score (P<0.05). However, there was no association between the SAS scale and TSS for DPN, and TSS for DPN did not differ between patients with and without CAN.

Conclusion

SAS is a simple instrument that can be used to assess autonomic symptoms in patients with diabetes and can be used as a screening tool for autonomic neuropathy, particularly for CAN.

Citations

Citations to this article as recorded by

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