Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
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; Diabetes Metab J. 2024;48(4):730-739. Published online May 20, 2024; DOI: https://doi.org/10.4093/dmj.2023.0077

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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.

Citations

Citations to this article as recorded by

Real-world safety evaluation of atorvastatin: insights from the US FDA adverse event reporting system (FAERS)
Hongbing Wan, Xiuxiu Xu, Dasong Yi, Kexin Shuai
Expert Opinion on Drug Safety.2024; : 1. CrossRef

Correlations between Glucagon Stimulated C-peptide Levels and Microvascular Complications in Type 2 Diabetes Patients: Hye-Jin Yoon, Youn-Zoo Cho, Ji-young Kim, Byung-Joon Kim, Keun-Young Park, Gwan-Pyo Koh, Dae-Ho Lee, Dong-Mee Lim; Diabetes Metab J. 2012;36(5):379-387. Published online October 18, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.5.379

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Background

This study aimed to investigate whether stimulated C-peptide is associated with microvascular complications in type 2 diabetes mellitus (DM).

Methods

A cross-sectional study was conducted in 192 type 2 diabetic patients. Plasma basal C-peptide and stimulated C-peptide were measured before and 6 minutes after intravenous injection of 1 mg glucagon. The relationship between C-peptide and microvascular complications was statistically analyzed.

Results

In patients with retinopathy, basal C-peptide was 1.9±1.2 ng/mL, and stimulated C-peptide was 2.7±1.6 ng/mL; values were significantly lower compared with patients without retinopathy (P=0.031 and P=0.002, respectively). In patients with nephropathy, basal C-peptide was 1.6±0.9 ng/mL, and stimulated C-peptide was 2.8±1.6 ng/mL; values were significantly lower than those recorded in patients without nephropathy (P=0.020 and P=0.026, respectively). Stimulated C-peptide level was associated with increased prevalence of microvascular complications. Age-, DM duration-, and hemoglobin A1c-adjusted odds ratios for retinopathy in stimulated C-peptide value were 4.18 (95% confidence interval [CI], 1.40 to 12.51) and 3.35 (95% CI, 1.09 to 10.25), respectively. The multiple regression analysis between nephropathy and C-peptide showed that stimulated C-peptide was statistically correlated with nephropathy (P=0.03).

Conclusion

In patients with type 2 diabetes, the glucagon stimulation test was a relatively simple method of short duration for stimulating C-peptide response. Stimulated C-peptide values were associated with microvascular complications to a greater extent than basal C-peptides.

Citations

Citations to this article as recorded by

A Nomogram for Predicting Vision-Threatening Diabetic Retinopathy Among Mild Diabetic Retinopathy Patients: A Case–Control and Prospective Study of Type 2 Diabetes
Jing Ke, Kun Li, Bin Cao
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 275. CrossRef
The average 30-minute post-prandial C-peptide predicted diabetic retinopathy progress: a retro-prospective study
Ting Pan, Jie Gao, Xinghua Cai, Huihui Zhang, Jun Lu, Tao Lei
BMC Endocrine Disorders.2023;[Epub] CrossRef
Dysregulation of miR-374a is involved in the progression of diabetic retinopathy and regulates the proliferation and migration of retinal microvascular endothelial cells
Zhanhong Wang, Xiao Zhang, Yanjun Wang, Dailing Xiao
Clinical and Experimental Optometry.2022; 105(3): 287. CrossRef
The Relationship between the Lipid Accumulation Product and Beta-cell Function in Korean Adults with or without Type 2 Diabetes Mellitus: The 2015 Korea National Health and Nutrition Examination Survey
Hye Eun Cho, Seung Bum Yang, Mi Young Gi, Ju Ae Cha, so Young Park, Hyun Yoon
Endocrine Research.2022; 47(2): 80. CrossRef
Effects of Serum C‐Peptide Level on Blood Lipid and Cardiovascular and Cerebrovascular Injury in Patients with Type 2 Diabetes Mellitus: A Meta‐Analysis
Juan Qin, Rongli Sun, Ding Ding, Yuvaraja Teekaraman
Contrast Media & Molecular Imaging.2022;[Epub] CrossRef
Investigation of Diabetes Complication Risk Perception and Diabetes Self-Management Skills in Individuals with Diabetes
Mehmet AYTEMUR, Bahar İNKAYA
Turkish Journal of Diabetes and Obesity.2022; 6(2): 121. CrossRef
Diabetic Retinopathy and Insulin Insufficiency: Beta Cell Replacement as a Strategy to Prevent Blindness
Eli Ipp
Frontiers in Endocrinology.2021;[Epub] CrossRef
Association of C-peptide with diabetic vascular complications in type 2 diabetes
Y. Wang, H. Wan, Y. Chen, F. Xia, W. Zhang, C. Wang, S. Fang, K. Zhang, Q. Li, N. Wang, Y. Lu
Diabetes & Metabolism.2020; 46(1): 33. CrossRef
Variations in glucose/C-peptide ratio in patients with type 2 diabetes associated with renal function
John A. D'Elia, Christopher Mulla, Jiankang Liu, Larry A. Weinrauch
Diabetes Research and Clinical Practice.2019; 150: 1. CrossRef
The pharmacokinetics of porcine C‐peptide after intraperitoneal injection
Naho Iizuka, Masuhiro Nishimura, Yasutaka Fujita, Osamu Sawamoto, Shinichi Matsumoto
Xenotransplantation.2019;[Epub] CrossRef
Association of KCNJ11(RS5219) gene polymorphism with biochemical markers of glycemic status and insulin resistance in gestational diabetes mellitus
Lenin M, Ramesh Ramasamy, Sweta Kulkarani, Seetesh Ghose, Srinivasan A.R.S., Sathish Babu M
Meta Gene.2018; 16: 134. CrossRef
Glucagon secretion is increased in patients with Type 2 diabetic nephropathy
Xiaoyu Wang, Juhong Yang, Baocheng Chang, Chunyan Shan, Yanguang Xu, Miaoyan Zheng, Ying Wang, Huizhu Ren, Liming Chen
Journal of Diabetes and its Complications.2016; 30(3): 488. CrossRef
Relationship between serum C-peptide level and diabetic retinopathy according to estimated glomerular filtration rate in patients with type 2 diabetes
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
Journal of Diabetes and its Complications.2015; 29(3): 350. CrossRef
Independent association between serum C‐peptide levels and fat mass‐to‐lean mass ratio in the aging process
Ying Li, Lian Shun Zheng, Yue Li, Duo Duo Zhao, Lu Meng
Geriatrics & Gerontology International.2015; 15(7): 918. CrossRef
Relationship Between β-Cell Function, Metabolic Control, and Microvascular Complications in Type 2 Diabetes Mellitus
Lihua Zhao, Jing Ma, Shaoxin Wang, Yun Xie
Diabetes Technology & Therapeutics.2015; 17(1): 29. CrossRef
Association of fasting insulin and C peptide with diabetic retinopathy in Latinos with type 2 diabetes
Jane Z Kuo, Xiuqing Guo, Ronald Klein, Barbara E Klein, Robert N Weinreb, Pauline Genter, Fone-Ching Hsiao, Mark O Goodarzi, Jerome I Rotter, Yii-Der Ida Chen, Eli Ipp
BMJ Open Diabetes Research & Care.2014; 2(1): e000027. CrossRef
Association between physical activity and serum C‐peptide levels among the elderly
Ying Li, Lu Meng, QianQian Miao, Yasuto Sato
Geriatrics & Gerontology International.2014; 14(3): 647. CrossRef
Age at Diagnosis and C-Peptide Level Are Associated with Diabetic Retinopathy in Chinese
Xiaoling Cai, Xueyao Han, Simin Zhang, Yingying Luo, Yingli Chen, Linong Ji, Alfred S. Lewin
PLoS ONE.2014; 9(3): e91174. CrossRef
Prevalence and risk factors for diabetic retinopathy in Asian Indians with young onset Type 1 and Type 2 Diabetes
Ramachandran Rajalakshmi, Anandakumar Amutha, Harish Ranjani, Mohammed K. Ali, Ranjit Unnikrishnan, Ranjit Mohan Anjana, K.M. Venkat Narayan, Viswanathan Mohan
Journal of Diabetes and its Complications.2014; 28(3): 291. CrossRef
Prediction of response to GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes
Kenjiro Imai, Tetsuro Tsujimoto, Atsushi Goto, Maki Goto, Miyako Kishimoto, Ritsuko Yamamoto-Honda, Hiroshi Noto, Hiroshi Kajio, Mitsuhiko Noda
Diabetology & Metabolic Syndrome.2014;[Epub] CrossRef
The Association between the Serum C-Peptide Level and Bone Mineral Density
Ying Li, Hua Liu, Yasuto Sato, Bin He
PLoS ONE.2013; 8(12): e83107. CrossRef
C-Peptide and Its Career from Innocent Bystander to Active Player in Diabetic Atherogenesis
Corinna Lebherz, Nikolaus Marx
Current Atherosclerosis Reports.2013;[Epub] CrossRef
C-Peptide and Vascular Complications in Type 2 Diabetic Subjects
Seok Man Son
Diabetes & Metabolism Journal.2012; 36(5): 345. CrossRef

Response

Response: Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:41-9): Sung-Tae Kim, Byung-Joon Kim, Dong-Mee Lim, In-Geol Song, Jang-Han Jung, Kang-Woo Lee, Keun-Young Park, Youn-Zoo Cho, Dae-Ho Lee, Gwan-Pyo Koh; Diabetes Metab J. 2011;35(2):190-191. Published online April 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.2.190

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Original Article

Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients: Sung-Tae Kim, Byung-Joon Kim, Dong-Mee Lim, In-Geol Song, Jang-Han Jung, Kang-Woo Lee, Keun-Young Park, Youn-Zoo Cho, Dae-Ho Lee, Gwan-Pyo Koh; Diabetes Metab J. 2011;35(1):41-49. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.41

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Abstract PDF PubReader

Background

Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients.

Methods

Data was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed.

Results

A simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029). The multiple regression analysis between intima-media thickness (IMT) and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043), while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226).

Conclusion

Basal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease.

Citations

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Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients
Regina Esze, László Balkay, Sándor Barna, Lilla Szatmáriné Egeresi, Miklós Emri, Dénes Páll, György Paragh, Liliána Rajnai, Sándor Somodi, Zita Képes, Ildikó Garai, Miklós Káplár
Journal of Clinical Medicine.2024; 13(10): 2900. CrossRef
The Correlation Between C-Peptide and Severity of Peripheral Atherosclerosis in Type 2 Diabetes Mellitus
Maisa A Wahab, Alshaymaa Alhabibi, Ahmed Khairy Sakr, Mohamed Yahia Zakaria, Ola I Saleh, Inass Hassan Ahmad, Eman Abdelrahman, Randa Taha, Fayka Karem Abdel Azeem Ahmed, Bothayna Ismail, Lamiaa Hosney Azel, Asmaa S Hassan, Hanaa Mohammed Eid El Sayed, Sa
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 2617. CrossRef
Blood C‐peptide concentration as a proxy marker of cardiovascular disease: An observational cross‐sectional study
Laurinda Adusu‐Donkor, Emmanuel Kwaku Ofori, Fleischer C. N. Kotey, Francis Kwaku Dogodzi, Wormenor Dziedzorm, Alfred Buabeng, Segla Kwame Bernard, Seth K. Amponsah, Henry Asare‐Anane
Health Science Reports.2023;[Epub] CrossRef
The impact of insulin induced lipohypertrophy on carotid intima-media thickness in patients with type 2 diabetes mellitus
Cem Onur Kirac, Vehbi Sirikci, Huseyin Avni Findikli
Medicine.2023; 102(39): e34696. CrossRef
Effects of Serum C‐Peptide Level on Blood Lipid and Cardiovascular and Cerebrovascular Injury in Patients with Type 2 Diabetes Mellitus: A Meta‐Analysis
Juan Qin, Rongli Sun, Ding Ding, Yuvaraja Teekaraman
Contrast Media & Molecular Imaging.2022;[Epub] CrossRef
Correlation between serum C-peptide-releasing effects and the risk of elevated uric acid in type 2 diabetes mellitus
Yanyan Liu, Xue Zhao, Zequn Yang, Shurui Wang, Cong Han, Huijuan Zhang
Endocrine Journal.2022; 69(7): 773. CrossRef
Human C-peptide is a ligand of the elastin-receptor-complex and therewith central to human vascular remodelling and disease in metabolic syndrome
Gert Wensvoort
Medical Hypotheses.2022; 168: 110964. CrossRef
Influence of blood glucose fluctuation, C-peptide level and conventional risk factors on carotid artery intima–media thickness in Chinese Han patients with type 2 diabetes mellitus
Min Liu, Li Ao, Xinyu Hu, Jianning Ma, Kena Bao, Ye Gu, Jing Zhao, Weiping Huang
European Journal of Medical Research.2019;[Epub] CrossRef
Serum C peptide and carotid intima-medial thickness are independent markers of glucose intolerance among patients with ischemic cerebrovascular stroke
Nearmeen M. Rashad, Ghada M. Samir, Hanan M. Sabry, Nesreen M. Mohy, Shereen M. El Shabrawy
The Egyptian Journal of Internal Medicine.2019; 31(3): 368. CrossRef
Biomarker potential of C-peptide for screening of insulin resistance in diabetic and non-diabetic individuals
Haseeb A. Khan, Samia H. Sobki, Aishah Ekhzaimy, Isra Khan, Mona A. Almusawi
Saudi Journal of Biological Sciences.2018; 25(8): 1729. CrossRef
SERUM C-PEPTIDE LEVEL IN OBESE AND NON-OBESE PATIENTS WITH TYPE 2 DIABETES MELLITUS
Shamha Beegum Mariyam, Saboora Beegum Muthubeevi, Sandhya Chandrasekharan Vasantha
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Mechanisms of action and therapeutic potential of proinsulin C-peptide
A. O. Shpakov
Journal of Evolutionary Biochemistry and Physiology.2017; 53(3): 180. CrossRef
Hemolysis Affects C‐Peptide Immunoassay
Zhi‐Qi Wu, Ju Lu, Hua‐Guo Xu
Journal of Clinical Laboratory Analysis.2016; 30(6): 1232. CrossRef
Lipid and inflammatory biomarker profiles in early insulin resistance
Itahisa Marcelino Rodríguez, José Oliva García, José Juan Alemán Sánchez, Delia Almeida González, Santiago Domínguez Coello, Buenaventura Brito Díaz, Fadoua Gannar, María del Cristo Rodríguez Pérez, Roberto Elosua, Antonio Cabrera de León
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C-Peptide Is Independently Associated with an Increased Risk of Coronary Artery Disease in T2DM Subjects: A Cross-Sectional Study
Lingshu Wang, Peng Lin, Aixia Ma, Huizhen Zheng, Kexin Wang, Wenjuan Li, Chuan Wang, Ruxing Zhao, Kai Liang, Fuqiang Liu, Xinguo Hou, Jun Song, Yiran Lu, Ping Zhu, Yu Sun, Li Chen, Marta Letizia Hribal
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C-peptide as a risk factor of coronary artery disease in the general population
Antonio Cabrera de León, José Gregorio Oliva García, Itahisa Marcelino Rodríguez, Delia Almeida González, José Juan Alemán Sánchez, Buenaventura Brito Díaz, Santiago Domínguez Coello, Vicente Bertomeu Martínez, Armando Aguirre Jaime, María del Cristo Rodr
Diabetes and Vascular Disease Research.2015; 12(3): 199. CrossRef
Gender differences in the association of insulin resistance and high-sensitivity c-reactive protein in obese adolescents
Ramin Alemzadeh, Jessica Kichler
Journal of Diabetes & Metabolic Disorders.2014;[Epub] CrossRef
Cytokinome Profile of Patients with Type 2 Diabetes and/or Chronic Hepatitis C Infection
Susan Costantini, Francesca Capone, Eliana Guerriero, Raffaele Marfella, Angela Sorice, Patrizia Maio, Michele Di Stasio, Giuseppe Paolisso, Giuseppe Castello, Giovanni Colonna, Patricia Fitzgerald-Bocarsly
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Serum glycated albumin predicts the progression of carotid arterial atherosclerosis
Sun Ok Song, Kwang Joon Kim, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee
Atherosclerosis.2012; 225(2): 450. CrossRef
C-Peptide: A New Mediator of Atherosclerosis in Diabetes
Dusica Vasic, Daniel Walcher
Mediators of Inflammation.2012; 2012: 1. CrossRef
Letter: Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetes Patients (Diabetes Metab J 2011;35:41-9)
Min Suk Lee, Hae Jin Kim
Diabetes & Metabolism Journal.2011; 35(2): 188. CrossRef
Response: Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:41-9)
Sung-Tae Kim, Byung-Joon Kim, Dong-Mee Lim, In-Geol Song, Jang-Han Jung, Kang-Woo Lee, Keun-Young Park, Youn-Zoo Cho, Dae-Ho Lee, Gwan-Pyo Koh
Diabetes & Metabolism Journal.2011; 35(2): 190. CrossRef

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