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Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus
Ji Hye Han, Kyong Hye Joung, Jun Choul Lee, Ok Soon Kim, Sorim Choung, Ji Min Kim, Yea Eun Kang, Hyon-Seung Yi, Ju Hee Lee, Bon Jeong Ku, Hyun Jin Kim
Diabetes Metab J. 2024;48(1):112-121.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2022.0402
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  • 1 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM.
Methods
A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment.
Results
The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups.
Conclusion
Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Citations

Citations to this article as recorded by  
  • Combining Ezetimibe and Rosuvastatin: Impacts on Insulin Sensitivity and Vascular Inflammation in Patients with Type 2 Diabetes Mellitus
    Eun Roh
    Diabetes & Metabolism Journal.2024; 48(1): 55.     CrossRef
  • Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?
    Il Rae Park, Jun Sung Moon
    Diabetes & Metabolism Journal.2024; 48(3): 387.     CrossRef
  • A Comparison of Rosuvastatin Monotherapy and Rosuvastatin Plus Ezetimibe Combination Therapy in Patients With Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials
    Samuel K Dadzie, Godfrey Tabowei, Mandeep Kaur, Saeed Ahmed, Aayushi Thakur, Khaldoun Khreis, Monika Bai, Adil Amin
    Cureus.2024;[Epub]     CrossRef
Drug Regimen
Article image
The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study
Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won
Diabetes Metab J. 2023;47(6):818-825.   Published online November 24, 2023
DOI: https://doi.org/10.4093/dmj.2023.0171
  • 2,992 View
  • 290 Download
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Citations

Citations to this article as recorded by  
  • Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?
    Il Rae Park, Jun Sung Moon
    Diabetes & Metabolism Journal.2024; 48(3): 387.     CrossRef
Review
Basic Research
Article image
Mitochondrial TFAM as a Signaling Regulator between Cellular Organelles: A Perspective on Metabolic Diseases
Jin-Ho Koh, Yong-Woon Kim, Dae-Yun Seo, Tae-Seo Sohn
Diabetes Metab J. 2021;45(6):853-865.   Published online November 22, 2021
DOI: https://doi.org/10.4093/dmj.2021.0138
  • 7,236 View
  • 287 Download
  • 16 Web of Science
  • 18 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Tissues actively involved in energy metabolism are more likely to face metabolic challenges from bioenergetic substrates and are susceptible to mitochondrial dysfunction, leading to metabolic diseases. The mitochondria receive signals regarding the metabolic states in cells and transmit them to the nucleus or endoplasmic reticulum (ER) using calcium (Ca2+) for appropriate responses. Overflux of Ca2+ in the mitochondria or dysregulation of the signaling to the nucleus and ER could increase the incidence of metabolic diseases including insulin resistance and type 2 diabetes mellitus. Mitochondrial transcription factor A (Tfam) may regulate Ca2+ flux via changing the mitochondrial membrane potential and signals to other organelles such as the nucleus and ER. Since Tfam is involved in metabolic function in the mitochondria, here, we discuss the contribution of Tfam in coordinating mitochondria-ER activities for Ca2+ flux and describe the mechanisms by which Tfam affects mitochondrial Ca2+ flux in response to metabolic challenges.

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    Bingjia Zhao, Qian Zhang, Yiqian He, Weifang Cao, Wei Song, Xiaochun Liang
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    Yan Wang, Jingwu Wang, Si‐Yu Tao, Zhengting Liang, Rong xie, Nan‐nan Liu, Ruxue Deng, Yuelin Zhang, Deqiang Deng, Guangjian Jiang
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    Yaqiong Li, Lei Tian, Siyuan Li, Xiaoniao Chen, Fengyang Lei, Jiayu Bao, Qianru Wu, Ya Wen, Ying Jie
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    Daria Shunkina, Anastasia Dakhnevich, Egor Shunkin, Olga Khaziakhmatova, Valeria Shupletsova, Maria Vulf, Alexandra Komar, Elena Kirienkova, Larisa Litvinova
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Original Article
Clinical Diabetes & Therapeutics
Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus
You-Cheol Hwang, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung
Diabetes Metab J. 2019;43(5):582-589.   Published online January 16, 2019
DOI: https://doi.org/10.4093/dmj.2018.0124
  • 7,140 View
  • 193 Download
  • 14 Web of Science
  • 13 Crossref
AbstractAbstract PDFPubReader   
Background

The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy.

Methods

This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks.

Results

After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation.

Conclusion

A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Citations

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    Yura Kang, Jung Mi Park, Sang-Hak Lee
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  • A Comparison of Rosuvastatin Monotherapy and Rosuvastatin Plus Ezetimibe Combination Therapy in Patients With Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials
    Samuel K Dadzie, Godfrey Tabowei, Mandeep Kaur, Saeed Ahmed, Aayushi Thakur, Khaldoun Khreis, Monika Bai, Adil Amin
    Cureus.2024;[Epub]     CrossRef
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    Maya R Chilbert, Dylan VanDuyn, Sara Salah, Collin M Clark, Qing Ma
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    You-Cheol Hwang
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  • Letter: Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J2019;43:582–9)
    Tae Seo Sohn
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Review
Obesity and Metabolic Syndrome
Skeletal Muscle Thermogenesis and Its Role in Whole Body Energy Metabolism
Muthu Periasamy, Jose Luis Herrera, Felipe C. G. Reis
Diabetes Metab J. 2017;41(5):327-336.   Published online October 24, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.5.327
  • 9,566 View
  • 217 Download
  • 117 Web of Science
  • 123 Crossref
AbstractAbstract PDFPubReader   

Obesity and diabetes has become a major epidemic across the globe. Controlling obesity has been a challenge since this would require either increased physical activity or reduced caloric intake; both are difficult to enforce. There has been renewed interest in exploiting pathways such as uncoupling protein 1 (UCP1)-mediated uncoupling in brown adipose tissue (BAT) and white adipose tissue to increase energy expenditure to control weight gain. However, relying on UCP1-based thermogenesis alone may not be sufficient to control obesity in humans. On the other hand, skeletal muscle is the largest organ and a major contributor to basal metabolic rate and increasing energy expenditure in muscle through nonshivering thermogenic mechanisms, which can substantially affect whole body metabolism and weight gain. In this review we will describe the role of Sarcolipin-mediated uncoupling of Sarcoplasmic Reticulum Calcium ATPase (SERCA) as a potential mechanism for increased energy expenditure both during cold and diet-induced thermogenesis.

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Original Article
Obesity and Metabolic Syndrome
Serum Calcium and the Risk of Incident Metabolic Syndrome: A 4.3-Year Retrospective Longitudinal Study
Jong Ha Baek, Sang-Man Jin, Ji Cheol Bae, Jae Hwan Jee, Tae Yang Yu, Soo Kyoung Kim, Kyu Yeon Hur, Moon-Kyu Lee, Jae Hyeon Kim
Diabetes Metab J. 2017;41(1):60-68.   Published online December 26, 2016
DOI: https://doi.org/10.4093/dmj.2017.41.1.60
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AbstractAbstract PDFPubReader   
Background

An association between serum calcium level and risk of metabolic syndrome (MetS) has been suggested in cross-sectional studies. This study aimed to evaluate the association between baseline serum calcium level and risk of incident MetS in a longitudinal study.

Methods

We conducted a retrospective longitudinal study of 12,706 participants without MetS who participated in a health screening program, had normal range serum calcium level at baseline (mean age, 51 years), and were followed up for 4.3 years (18,925 person-years). The risk of developing MetS was analyzed according to the baseline serum calcium levels.

Results

A total of 3,448 incident cases (27.1%) of MetS developed during the follow-up period. The hazard ratio (HR) for incident MetS did not increase with increasing tertile of serum calcium level in an age- and sex-matched model (P for trend=0.915). The HRs (95% confidence interval [CI]) for incident MetS comparing the second and the third tertiles to the first tertile of baseline serum calcium level were 0.91 (95% CI, 0.84 to 0.99) and 0.85 (95% CI, 0.78 to 0.92) in a fully adjusted model, respectively (P for trend=0.001). A decreased risk of incident MetS in higher tertiles of serum calcium level was observed in subjects with central obesity and/or a metabolically unhealthy state at baseline.

Conclusion

There was no positive correlation between baseline serum calcium levels and incident risk of MetS in this longitudinal study. There was an association between higher serum calcium levels and decreased incident MetS in individuals with central obesity or two components of MetS at baseline.

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Review
The Role of the Sweet Taste Receptor in Enteroendocrine Cells and Pancreatic β-Cells
Itaru Kojima, Yuko Nakagawa
Diabetes Metab J. 2011;35(5):451-457.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.451
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AbstractAbstract PDFPubReader   

The sweet taste receptor is expressed in taste cells located in taste buds of the tongue. This receptor senses sweet substances in the oral cavity, activates taste cells, and transmits the taste signals to adjacent neurons. The sweet taste receptor is a heterodimer of two G protein-coupled receptors, T1R2 and T1R3. Recent studies have shown that this receptor is also expressed in the extragustatory system, including the gastrointestinal tract, pancreatic β-cells, and glucose-responsive neurons in the brain. In the intestine, the sweet taste receptor regulates secretion of incretin hormones and glucose uptake from the lumen. In β-cells, activation of the sweet taste receptor leads to stimulation of insulin secretion. Collectively, the sweet taste receptor plays an important role in recognition and metabolism of energy sources in the body.

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Original Articles
Effects of Vitamin D and Calcium Intervention on the Improvement of Resistance in Patients with Type 2 Diabetes Mellitus.
Young Mee Choi, Jun Ho Lee, Ji Sook Han
Korean Diabetes J. 2009;33(4):324-334.   Published online August 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.4.324
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AbstractAbstract PDF
BACKGROUND
Recent reports suggest that the intake of vitamin D and calcium may influence insulin resistance. The aim of this study was to assess the effects of vitamin D and calcium intervention on the improvement of blood glucose and insulin resistance in patients with type 2 diabetes mellitus (DM). METHODS: Fasting blood glucose, glycosylated hemoglobin A1c (HbA1C), serum 25(OH)D3, serum lipid levels, insulin secretion, and activity and dietary surveys were analyzed in type 2 DM patients both before and after a 12-week vitamin D and calcium intake intervention. RESULTS: The serum 25(OH)D3 level was found to be negatively correlated with insulin resistance and fasting blood glucose. Calcium intake level was also negatively correlated with insulin resistance. Fasting blood glucose, HbA1C, and HOMA-IR decreased significantly (P <0.05) following vitamin D and calcium intake intervention in the medical nutrition therapy (MNT) group, while there was no such change observed in the control group. Dietary calcium and vitamin D intakes were significantly (P <0.05) higher in the MNT group than in the control group. The concentrations of serum 25(OH)D3 and insulin secretion increased slightly in the MNT group following the 12-week intervention; however, these results did not reach statistical significance. CONCLUSION: The results of the present study indicate that calcium and vitamin D intervention may be helpful in improving fasting blood glucose, HbA1C, serum 25(OH)D3 and HOMA-IR in patients with type 2 DM who have insufficient serum 25(OH)D3 concentrations.

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Relationship Between Serum Bilirubin Levels and Coronary Atherosclerosis in Patients with Type 2 Diabetes.
Jun Sung Moon, Woo Jin Chang, Chan Hee Lee, Ji Eun Lee, Kyung Ah Chun, Ji Sung Yoon, Ihn Ho Cho, Hyoung Woo Lee, Kyu Chang Won
Korean Diabetes J. 2008;32(4):338-345.   Published online August 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.4.338
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AbstractAbstract PDF
BACKGROUND
Lipid oxidation and formation of oxygen radicals have been identified to be the important factors of atherogenesis. Because bilirubin, a potent physiological antioxidant inhibits lipid oxidation, it is suggested that low serum concentrations of bilirubin is associated with atherosclerosis. The aim of this study was to evaluate the relationship between bilirubin levels and coronary atherosclerosis. METHODS: The coronary calcium score (CCS) of 172 subjects (male 63, mean age 60.5 +/- 1.0) with type 2 diabetes were evaluated in Yeungnam University Hospital between January 2005 and February 2007. The subjects were divided into two groups with CCS 10 as the cut off. RESULTS: Higher CCS was significantly associated with lower bilirubin (P < 0.05), but after adjusted with age, no longer correlation were seen (P = 0.121). To determine the relationship between subclinical coronary atherosclerosis and bilirubin, the subjects with previous history of cardiovascular disease were excluded. In 138 subjects (male 54, mean age 58.4 +/- 1.1), higher CCS was significantly associated with lower levels of bilirubin. After adjusted with age, duration of diabetes, and history of hypertension, CCS was also inversely related with bilirubin (P < 0.05). CONCLUSION: These results suggest that lower levels of bilirubin might be considered as a risk factor of coronary artery disease, especially in type 2 diabetics without cardiovascular disease.

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Proliferation and Differentiation of Pancreatic beta Cells in L-type Calcium Channel alpha(1D) Subunit (Ca(v)1.3) Heterozygous Knock Out Mice After Partial Pancreatectomy.
Yoon Hee Choi, Il Hee Yun, Sun Hee Suh, Dong Jun Lim, Jae Hyuung Cho, Hyuk Sang Kwon, Bong Yun Cha, Ho Young Son, Chung Gyu Park, Kun Ho Yoon
Korean Diabetes J. 2007;31(3):208-219.   Published online May 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.3.208
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AbstractAbstract PDF
BACKGROUND
S: L-type voltage-dependent calcium channel (LTCC) plays a crucial role in insulin secretion from pancreatic beta cells through Ca2+ influx. In the recent report, LTCC Ca(v)1.3 subtype homozygous knock out mice showed impairment of postnatal pancreatic beta cell development as well as insulin secretion. METHODS: We performed 90% partial pancreatectomy in heterozygous Ca(v)1.3 knock out mice to investigate the effect of partial deficiency of Ca(v)1.3 gene on beta cell regeneration in the adult. Glucose homeostasis, metabolic profiles including serum insulin and lipid levels and morphologic changes of pancreatic islets were studied. RESULTS: 90% Partial pancreatectomy induced glucose intolerance only in the heterozygous knock out mice at 8 weeks after surgery. Distribution of islet size was significantly different between two groups after partial pancreatectomy; median value of islet size of heterozygote was larger than that of wild type (642.8 micrometer2 vs 1459.8 micrometer2, P < 0.01). The frequency of single beta cell unit, considered as a unit of beta cell neogenesis, was much lower in heterozygote than that of wild type (41% vs 23.3%, P < 0.05). CONCLUSION: These data suggest that Ca(v)1.3 gene deficiency is specifically associated with impairment of beta cell regeneration, especially neogensis and eventual glucose intolerance in the 90% partial pancreatectomized mice.
Value of Coronary Calcium Score in Type 2 Diabetics.
Ji Eun Lee, Mi Jung Eun, Kyung Ah Chun, Jae Hong Kim, Ji Sung Yoon, Ihn Ho Cho, Kyu Chang Won, Hyoung Woo Lee
Korean Diabetes J. 2006;30(4):303-311.   Published online July 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.4.303
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BACKGROUND
Cardiovascular disease including coronary heart disease (CHD) is the most common cause of morbidity and mortality in patients with diabetes. But traditional risk factor assessment is limited to predict CHD in asymptomatic high-risk individuals. In this study, relationship between coronary calcium score (CCS) and CHD was evaluated to determine value of coronary artery calcification detected by multi-slice spiral computed tomography to predict CHD in high risk asymptomatic patients with type 2 diabetes. METHODS: 127 patients were enrolled who admitted in Yeungnam University Hospital between December 2004 and May 2005. Standard cardiovascular risk factors and the CCS measured by multi-slice spiral computed tomography were assessed. RESULTS: Enrolled subjects were consisted of 56 subjects with diabetes and 71 subjects without diabetes. The mean CCS was significantly greater in patients with diabetes than without diabetics (P < 0.01). In both groups, patients with higher CCS had higher prevalence of CHD (P < 0.05). In all subjects, LDL cholesterol levels and CCS were significantly associated in multi-variate analysis (P < 0.05). In patients without diabetes, age was only associated with presence of CHD (P < 0.05). CCS was only associated with CHD in patients with diabetes, even after adjusting for the effects of age, LDL cholesterol and CRP (P < 0.05). CONCLUSION: Therefore, multi-slice spiral computed tomography can non-invasively and accurately detect coronary calcification. By detection of coronary artery calcification, it may be possible to predict coronary heart disease early in high-risk asymptomatic patients with type 2 diabetes.
Association of High Intracellular Calcium Levels with Insulin Resistance in Women with Polycystic Ovary Syndrome.
Jee Young Oh, Hye Jin Lee, Young Sun Hong, Hye Won Chung, Yeon Ah Sung
Korean Diabetes J. 2004;28(2):101-110.   Published online April 1, 2004
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BACKGROUND
Insulin resistance is an intrinsic defect of polycystic ovary syndrome (PCOS), and elevated levels of cytosolic free calcium in insulin target cells may cause insulin resistance. To our knowledge, the relationship between intracellular calcium and insulin resistance in PCOS has not been investigated. The purpose of this study was to determine whether the levels of intracelluar calcium are changed and if they have any association with insulin resistance in women with PCOS. METHODS: The intracellular calcium levels in the platelets and the insulin sensitivity were measured by fluorescent spectrophotometry and the euglycemic hyperinsulinemic clamp technique, respectively, in 16 women with PCOS and 6 normal cycling women. A 2h, 75 g oral glucose tolerance test was performed to determine the glucose tolerance. RESULTS: The insulin sensitivity measured by the glucose disposal rate(the M-value), was significantly lower in women with PCOS(4.6+/-1.5mg/kg/min vs. 7.0+/-1.3mg/kg/min, p<0.01), but the intracellular calcium levels were significantly higher in women with PCOS compared to the controls(122.7+/-36.7 vs 59.1+/-29.3mmol/L, p<0.01). When the women with PCOS were divided into the overweight or obese(n=9, BMI ?23kg/m2) and lean(n=7, BMI<23kg/m2) groups, both groups had significantly lower M values compared to the control subjects(3.9+/-1.3, 5.5+/-1.2 vs. 7.0+/-1.3mumg/kg/min, p<0.001), and these levels between the overweight/obese and lean PCOS groups showed a significant difference(p<0.001). The overweight/ obese and lean women with PCOS had significantly higher levels of intracellular calcium compared to the control subjects(131.3+/-39.6, 111.7+/-31.8 vs. 59.1+/-29.3nmol/L, p<0.01), but these levels did not differ significantly between the overweight/obese and lean women with PCOS. The intracellular calcium levels showed a significant positive correlation with age, and a negative correlation with the M value(r=-0.55, p<0.05). The BMI-adjusted partial correlation showed marginal significance between elevated levels of intracellular calcium and insulin sensitivity (r=-0.47, p=0.07). CONCLUSION: Women with PCOS showed both insulin resistance and increased levels of intracellular calcium compared to the control subjects. Increased levels of intracellular calcium were associated with insulin resistance in women with PCOS.
Effect of Glucose Concentrations on the Cell Proliferation and Expression of L-type Calcium Channel mRNA in Cultured Rat Aortic Vascular Smooth Muscle Cells.
Young Jung Cho, Hyung Joon Yoo, Hong Woo Nam, Ji Young Suh, In Kyung Jeong, Sung Hee Ihm, Hyeon Kyu Kim, Cheol Young Park, Jae Myung Yoo, Doo Man Kim, Moon Gi Choi, Sung Woo Park
Korean Diabetes J. 2003;27(3):253-259.   Published online June 1, 2003
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BACKGROUND
Vascular smooth muscle cell (VSMC) proliferation is one of the major pathogenic mechanisms for atherosclerosis. It is known that L-type calcium channels play a role in VSMC proliferation in diabetic rats. However, there have been no studies that show an association between the L-type calcium channels and the VSMC proliferation due to various glucose concentrations in the culture media. Therefore, the association between the voltage-dependent L-type calcium channels of the VSMCs, and the growth of vascular smooth muscle cells, was examined. METHODS: Rat aortic VSMCs were isolated from the aorta of Sprague-Dawley and OLETF rats, using an enzymic method. The VSMCs were cultured in various concentrations of glucose (5.5, 11.0, 16.6, 25, 30 and 40 mM). The VSMCs (1x10(4) cells in 24-well plates) were incubated in the presence of Bay K 8644 (10(-6)M), both with and without verapamil (10(-6)M), for 48 hours. The proliferation was then assessed by the MTT (methylthiazole tetrazolium) assay, and the expression of L-type calcium channel mRNA by RT-PCR. RESULTS: The vascular smooth muscle cell proliferation was significantly increased, in a dose-dependent manner, with glucose concentrations below 25 mM in both in a dose-dependent manner, with glucose concentrations below 25 mM in both kinds of rat. However, the increase in the VSMC proliferation of the OLETF rat was significantly higher than in the Sprague-Dawley rat. After the Bay K 8644 treatment, with the same glucose concentration, the VSMC proliferation and the expression of L-type calcium channel mRNA were significantly increased in both kinds of rat. After treatment with verapamil, the increased VSMC proliferation and expression of L-type calcium channel mRNA, due to the Bay K 8644, were suppressed to control levels in both kinds of rat. CONCLUSION: The results suggest that below certain concentrations of glucose, 25 mM, the L-type calcium channels may play a role in the VSMC proliferation of OLETF and Sprague-Dawley rats. The growth of the VSMCs in OLETF rats, due to various glucose concentrations (< 25 mM), was significantly higher than in the Sprague-Dawley rats.

Diabetes Metab J : Diabetes & Metabolism Journal
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