Diabetes & Metabolism Journal

Original Articles

Clinical Care/Education
Insulin Initiation in Insulin-Naïve Korean Type 2 Diabetic Patients Inadequately Controlled on Oral Antidiabetic Drugs in Real-World Practice: The Modality of Insulin Treatment Evaluation Study: Sang Soo Kim, In Joo Kim, Yong Ki Kim, Kun Ho Yoon, Ho Young Son, Sung Woo Park, Yeon Ah Sung, Hong Sun Baek; Diabetes Metab J. 2015;39(6):481-488. Published online November 25, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.481

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Background

The Modality of Insulin Treatment Evaluation (MOTIV) study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with oral hypoglycemic agents (OHAs).

Methods

This multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0%) who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice.

Results

A total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%). Basal insulin plus one OHA was the most frequently (51.0%) used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (P<0.001). Overall, 17.6% of patients experienced at least one hypoglycemic event.

Conclusion

In a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.

Citations

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Real-World Outcomes of Individualized Targeted Therapy with Insulin Glargine 300 Units/mL in Insulin-Naïve Korean People with Type 2 Diabetes: TOBE Study
Eun-Gyoung Hong, Kyung-Wan Min, Jung Soo Lim, Kyu-Jeung Ahn, Chul Woo Ahn, Jae-Myung Yu, Hye Soon Kim, Hyun Jin Kim, Won Kim, Dong Han Kim, Hak Chul Jang
Advances in Therapy.2024; 41(5): 1967. CrossRef
Clinical Evidence and Practice-Based Guidelines on the Utility of Basal Insulin Combined Oral Therapy (Metformin and Glimepiride) in the Current Era
Abhishek Shrivastava, Jothydev Kesavadev, Viswanathan Mohan, Banshi Saboo, Dina Shrestha, Anuj Maheshwari, Brij Mohan Makkar, Kirtikumar D. Modi, Ashok Kumar Das
Current Diabetes Reviews.2023;[Epub] CrossRef
Where to Initiate Basal Insulin Therapy: Inpatient or Outpatient Department? Real-World Observation in China
Minyuan Chen, Puhong Zhang, Yang Zhao, Nadila Duolikun, Linong Ji
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 3375. CrossRef
Therapeutic Effect of Quadruple Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus Who Have Insulin Limitations
Won Sang Yoo, Do Hee Kim, Hee Jin Kim, Hyun Kyung Chung
The Journal of Korean Diabetes.2019; 20(2): 117. CrossRef
Use of Insulin Glargine 100 U/mL for the Treatment of Type 2 Diabetes Mellitus in East Asians: A Review
Takahisa Hirose, Ching-Chu Chen, Kyu Jeung Ahn, Jacek Kiljański
Diabetes Therapy.2019; 10(3): 805. CrossRef
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Minyoung Lee, Jiyu Sun, Minkyung Han, Yongin Cho, Ji-Yeon Lee, Chung Mo Nam, Eun Seok Kang
Diabetes Care.2019; 42(11): 2057. CrossRef
Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017
Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
The Korean Journal of Internal Medicine.2017; 32(6): 967. CrossRef
Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017
Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
Diabetes & Metabolism Journal.2017; 41(5): 367. CrossRef
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Sunghwan Suh, Sun Ok Song, Jae Hyeon Kim, Hyungjin Cho, Woo Je Lee, Byung-Wan Lee
Journal of Diabetes Research.2017; 2017: 1. CrossRef
Comparison of Antidiabetic Regimens in Patients with Type 2 Diabetes Uncontrolled by Combination Therapy of Sulfonylurea and Metformin: Results of the MOHAS Disease Registry in Korea
Sung Hee Choi, Tae Jung Oh, Hak Chul Jang
Diabetes & Metabolism Journal.2017; 41(3): 170. CrossRef
Instauration d’une insulinothérapie chez le patient diabétique de type 2 en médecine générale : Comparaison de l’étude belge InsuStar avec quelques études françaises et internationales
A.-J. Scheen
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Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study: Kun Ho Yoon, Jeong Ah Shin, Hyuk Sang Kwon, Seung Hwan Lee, Kyung Wan Min, Yu Bae Ahn, Soon Jib Yoo, Kyu Jeung Ahn, Sung Woo Park, Kwan Woo Lee, Yeon Ah Sung, Tae Sun Park, Min Seon Kim, Yong Ki Kim, Moon Suk Nam, Hye Soon Kim, Ie Byung Park, Jong Suk Park, Jeong Taek Woo, Ho Young Son; Diabetes Metab J. 2011;35(1):26-33. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.26

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Abstract PDF PubReader

Background

Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.

Methods

We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.

Results

HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.

Conclusion

The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

Citations

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Review

Insulin Resistance in Polycystic Ovary Syndrome.: Yeon Ah Sung; Korean Diabetes J. 2008;32(1):1-6. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.1

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Abstract PDF

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age and now recognized as an important metabolic and reproductive disorder. The majority of women with PCOS have insulin resistance and this is regarded to have a central etiological role in PCOS. Insulin resistance and concomitant hyperinsulinemia modifies reproductive function by driving androgen production, suppression of sex hormone-binding globulin (SHBG) and disruption of insulin signaling pathways in the central nervous system. Insulin resistance, together with defects in insulin secretion, confers markedly increased risk for type 2 diabetes mellitus and metabolic syndrome. There are post-binding defects in insulin receptor signaling, with selective resistance to insulin's metabolic actions and preserved other actions. Genetic and environmental abnormalities interact to produce peripheral insulin resistance in PCOS. The numerous in vivo and in vitro data supporting the central role of insulin resistance in the pathogenesis of PCOS have led a new therapy for PCOS with insulin-sensitizing agents.

Citations

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Epidemiology and Diagnostic Criteria of Polycystic Ovary Syndrome
Hyejin Lee, Yeon-Ah Sung
The Journal of Korean Diabetes.2015; 16(3): 189. CrossRef
Evaluation of Apelin and Insulin Resistance in Patients with PCOS and Therapeutic Effect of Drospirenone-Ethinylestradiol Plus Metformin
Xianchang Sun, Xingguo Wu, Yan Zhou, Xinyan Yu, Wenjuan Zhang
Medical Science Monitor.2015; 21: 2547. CrossRef
Hyperandrogenism in Women: Polycystic Ovary Syndrome
Yeon-Ah Sung
Hanyang Medical Reviews.2012; 32(4): 197. CrossRef
Adiponectin in Women with Polycystic Ovary Syndrome
Hyun-Young Shin, Duk-Chul Lee, Ji-Won Lee
Korean Journal of Family Medicine.2011; 32(4): 243. CrossRef
Polycystic Ovary Syndrome in Korean Women: Clinical Characteristics and Diagnostic Criteria
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Original Articles

Peroxisome Proliferator-activated Receptor-gamma (PPARgamma) Polymorphism in Korean Women with Polycystic Ovary Syndrome.: Jee Young Oh, Hyejin Lee, Young Sun Hong, Yeon Ah Sung, Hye Won Chung; Korean Diabetes J. 2007;31(6):480-487. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.480

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Abstract PDF: BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine disease affecting 5~10% of women with reproductive age. Familial aggregation suggests the evidence supporting a genetic basis for PCOS. The mode of inheritance of PCOS is not yet clear, however, probably polygenic and might be related to insulin resistance. Polymorphism of peroxisome proliferator-activated receptor (PPAR)-gamma gene is a susceptible gene for the development of obesity and diabetes. In this study, we examined the frequency and genetic effect of PPAR-gamma polymorphism on insulin resistance or hyperandrogenemia in Korean women with PCOS. METHODS: One-hundred twenty five Korean women with PCOS were evaluated for their metabolic and reproductive hormonal status. PPAR-gamma polymorphism was analyzed. RESULTS: Genetic frequency of PPAR-gamma was not significantly different between women with PCOS (n = 125) and those with regular menstrual cycles (n = 344). PCOS with Pro12Ala polymorphism had significantly higher levels of waist circumference and subcutaneous fat area compared with those with Pro12Pro genotype. They also had tendency of higher levels of fasting glucose concentration, body mass index (BMI) and visceral fat area. After BMI adjustment, this polymorphism was related to lower fasting insulin and higher insulin sensitivity index, and higher sex hormone binding globulin and lower free testosterone levels. CONCLUSION: Pro12Ala polymorphism of PPAR-gamma gene might be associated with obesity. However, after BMI adjustment, it may have favorable effect on insulin resistance and hyperandrogenemia. Because this study has limitations to conclude the genetic causality, further study is needed to support these findings.

The Appropriate Distance and Duration of Walking for Exercise in Patients with Type 2 Diabetes Mellitus.: Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Kyung Ah Han, Hyun Shik Son, Hyo Jeong Kim, Chul Woo Ahn, Yeon Ah Sung, Kyung Wan Min, Sei Hyun Baik, Jae Myeong Yu, Sung Woo Park; Korean Diabetes J. 2007;31(2):157-162. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.157

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Abstract PDF

BACKGROUND
For decades, exercise has been considered a cornerstone of diabetes managements, along with diet and medication. Many studies have shown that regular physical activity improves quality of life, reduces the risk of mortality from all causes, and is particularly advantageous in subjects with impaired glucose tolerance or type 2 diabetes mellitus. However, high-quality evidence and basic data on the importance of exercise and physical fitness in Korean diabetic patients were lacking until recent years. METHOD: This study included 240 diabetic patients (122 men, 118 women) recruited from 6 diabetic centers in Korea. To measure step length and walking velocity at normal walking speed, we made the patient walk 12 meter at normal speed. The patients wore the pedometer for 7 days and we got the equation between the walking steps per day and calorie expenditure for 7 days. From the equation, we calculated appropriate steps, distance and duration of walking in type 2 diabetic patients as exercise program RESULTS: In men, the walking velocity was 4.4 +/- 0.6 km/h and step length was 67.6 +/- 7.3 cm at normal walking speed. In women, the walking velocity was 4.0 +/- 0.6 km/h and step length was 58.4 +/- 5.5 cm at normal walking speed. The equation between kcal per week and steps per day was that kcal/week = (steps/day) x 0.268 + 64.074 (R2 = 0.854, P < 0.01) in men and kcal/week in women = (steps/day) x 0.256 - 39.005 (R2 = 0.890, P < 0.01). The steps/day, walking distance and walking duration which correspond to 700 kcal/week was 2,373 steps/day, 21.9 minutes and 1,604 meter in men, and 2,887 steps/day, 25.3 minutes and 1,690 meter in women at normal walking speed. CONCLUSION: To exert at least 700 kcal/week with exercise, it is recommended that type 2 diabetic patients walk at least 25 minutes/day or 1,700 meter/day or 2,500 steps/day in men and 30 minutes/day or 1,800 meter/day or 3,000 steps/day in women at normal walking speed.

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Effects of Tai Chi Exercise on Glucose Control, Neuropathy Scores, Balance, and Quality of Life in Patients with Type 2 Diabetes and Neuropathy
Sukhee Ahn, Rhayun Song
The Journal of Alternative and Complementary Medicine.2012; 18(12): 1172. CrossRef
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Hee Jung Ahn, Kyung Ah Han, Jin Young Jang, Jae Hyuk Lee, Kang Seo Park, Kyung Wan Min
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Hee-Jung Ahn, Boo-Kyung Koo, Ji-Yeon Jung, Hwi-Ryun Kwon, Hyun-Jin Kim, Kang-Seo Park, Kyung-Ah Han, Kyung-Wan Min
Korean Diabetes Journal.2009; 33(2): 155. CrossRef

Pedometer-Determined Physical Activity in Type 2 Diabetes in Korea.: Sang Ah Chang, Jung Min Lee, Tae Seo Sohn, Hyun Shik Son, Sung Woo Park, Sei Hyun Baik, Jae Myung Yu, Yeon Ah Sung, Chul Woo Ahn, Kyung Wan Min, Kyung Ah Han; Korean Diabetes J. 2007;31(1):83-88. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.83

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Abstract PDF: BACKGROUND
Walking is a popular, convenient and relatively safe form of exercise. However, there is few objective data for walking exercise. The aim of this study was to evaluate pedometer-determined physical activity defined as steps/day in type 2 diabetes mellitus. Therefore, it could be the basic data for programming walking exercise in diabetes mellitus. METHODS: Participants with type 2 diabetes who visited in 6 university hospitals on February, 2006 in Seoul and Kyung-gi area were recruited. The participants were asked their ambulatory activity with the given pedometer and calorimeter for 1 week. Total 240 (Male 122, Female 118) subjects who walked above 1000 steps/day were analyzed. We also collected their biochemical data from the medical records. RESULTS: Participants took 8532 +/- 4130 steps for day (step/day) and energy expenditure were 320 +/- 161 Cal/day. Steps/day was not significantly different between male and female, but energy expenditure was higher in male than female ( P < 0.05). Steps/day was significantly lower in obese patients than non-obese patients (P < 0.001). BMI (r = -0.325, P < 0.001), waist circumference (r = -0.287, P < 0.001), triglyceride (r = 0.164, P < 0.018) showed significant inverse correlation with steps/day, but BUN (r = 0.165, P = 0.019) and HDL-cholesterol (r = 0.164, P = 0.018) were positive correlated with steps/day significantly. BMI (r = -0.14, P < 0.032) and cholesterol (r = -0.139, P < 0.041) showed significantly inverse correlation with energy expenditure and BUN (r = 0.187, P = 0.008) and HDL cholesterol (r = 0.145, P < 0.037) positively correlated with energy expenditure. Pedometer-determined steps/day was positively associated with energy expenditure (r2 = 0.824, P < 0.001). CONCLUSION: This study showed the objective quantification of physical activity measured by simple and inexpensive pedometers. It could be used to recommend walking exercise since the practitioners can estimate steps/day for required energy expenditure.

Prevalence of Metabolic Syndrome in Young Korean Women with Polycystic Ovary Syndrome.: Hyejin Lee, Jee Young Oh, Youngsun Hong, Yeon Ah Sung, Hyewon Chung; Korean Diabetes J. 2006;30(4):285-291. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.285

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Abstract PDF

BACKGROUND
Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and consequent hyperinsulinemia. Insulin resistance plays an important role in the development of metabolic syndrome (MS). We conducted a cross-sectional study to determine the prevalence of the MS and whether the insulin resistance or hyperandrogenemia is related to the MS in young Korean women with PCOS. METHODS: 143 women with PCOS (mean age 26+/-5 years) were studied to evaluate the prevalence of MS by modified Adult Treatment Panel III. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp technique. RESULTS: The prevalence of MS in women with PCOS was 11.9%, 2.8-fold higher than age matched women in Korean urban population. The most frequent component of MS was low HDL cholesterol (39.4%), and the least frequent one was high fasting serum glucose levels (6.7%). The frequency of MS was 40.7% in obese PCOS (BMI > or = 25 kg/m2, n = 38), 10.0% in overweight PCOS (BMI 23~24.9 kg/m2, n = 13), and 0% in lean PCOS (BMI < 23 kg/m2, n = 92). The frequency of MS was 26.1% in insulin resistant PCOS (insulin mediated glucose uptake, IMGU < lowest 10th percentile of lean controls, n = 65), whereas no one had MS in insulin sensitive PCOS (IMGU > or = lowest 10th percentile of lean controls, n = 78). CONCLUSION: MS is frequent in young women with PCOS, and obesity and insulin resistance might be essential for the development of MS in this study group.

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Relationship between flavonoids intake and metabolic syndrome in Korean women with polycystic ovary syndrome
Ji Soo Oh, Mi Jin Ahn, Chan Jung Han, Hyesook Kim, Oran Kwon, Hye Won Chung, Namsoo Chang
Journal of Nutrition and Health.2014; 47(3): 176. CrossRef
Inappropriate gonadotropin secretion in polycystic ovary syndrome: The relationship with clinical, hormonal and metabolic characteristics
A Ra Shim, Yu Im Hwang, Kyung Jin Lim, Young Mi Choi, Young Eun Jeon, Seok Kyo Seo, Si Hyun Cho, Young Sik Choi, Byung Seok Lee
Korean Journal of Obstetrics & Gynecology.2011; 54(11): 659. CrossRef
Diagnosis and Treatment of Polycystic Ovary Syndrome
Hyejin Lee, Yeon-ah Sung
Journal of Korean Endocrine Society.2007; 22(4): 252. CrossRef

Usefulness of Insulin Sensitivity Indexes derived from Oral Glucose Tolerance Test in Women with Polycystic Ovary Syndrome.: Hyo Jeong Kim, Eun Kyung Byun, Jee Young Oh, Yeon Ah Sung, Hye Won Chung; Korean Diabetes J. 2006;30(4):277-284. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.277

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Abstract PDF

BACKGROUND
Insulin resistance is prevalent in women with polycystic ovary syndrome (PCOS), and it makes them to have high risk for development of type 2 diabetes. Evaluation of insulin sensitivity would be important to predict their risks. Although the euglycemic-hyperinsulinemic clamp technique is the gold standard for measuring insulin sensitivity, it is too hard to practice in large epidemiologic studies. The aim of this study is to verify the validity of various insulin sensitivity indexes from oral glucose tolerance test (OGTT) in women with PCOS. METHODS: We performed euglycemic-hyperinsulinemic clamp (target glucose; 90 mg/dL, insulin ;~1 mU/kg.min) to obtain insulin-mediated glucose disposal rate (M-value) in 62 non-diabetic women with PCOS (BMI < 23 kg/m2; n = 37, BMI > or = 23 kg/m2; n = 25). Homeostasis model assessment [HOMA(IR)], quantitative insulin sensitivity check index (QUICKI), glucose to insulin ratio (G/I ratio), whole body insulin sensitivity index [ISI(COMP)], metabolic clearance rate of glucose [MCR(est)-OGTT(1,2)], and insulin sensitivity indexes [ISI(est)-OGTT(1,2)] were calculated from plasma glucose and insulin levels from standard 75-g OGTT. The correlations of various insulin sensitivity indexes from OGTT with M-value were evaluated. RESULTS: In lean women with PCOS (BMI < 23 kg/m2, n = 37), ISI(COMP) (r = 0.36, P < 0.05), MCRest-OGTT1 (r = 0.49, P < 0.01), ISI(est)-OGTT(1) (r = 0.50, P < 0.01), MCR(est)-OGTT(2) (r = 0.45, P < 0.01) and ISI(est)-OGTT(2) (r = 0.40, P < 0.05) were significantly correlated with M-value. In overweight and obese women with PCOS (BMI > or = 23 kg/m2, n = 25), HOMA(IR) (r = -0.40, P < 0.05), QUICKI (r = 0.40, P < 0.05), MCR(est)-OGTT(1) (r = 0.76, P < 0.001), ISI(est)-OGTT(1) (r = 0.63, P < 0.001), MCR(est)-OGTT(2) (r = 0.58, P < 0.01) and ISI(est)-OGTT(2) (r = 0.42, P < 0.05) showed significant correlations with M-value. CONCLUSION: MCR(est)-OGTT(1) and ISI(est)-OGTT(1) were the most reliable and easily accessible insulin sensitivity indexes obtained from OGTT for measuring of insulin sensitivity in women with PCOS regardless of obesity.

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Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes
Flavia Tosi, Enzo Bonora, Paolo Moghetti
Human Reproduction.2017; 32(12): 2515. CrossRef

Insulin Resistance in Normal Weight Women with Polycystic Ovary Syndrome.: Eun Kyung Byun, Hye Jin Lee, Jee Young Oh, Young Sun Hong, Hye Won Chung, Yeon Ah Sung; Korean Diabetes J. 2004;28(4):315-323. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Insulin resistance is considered a regular component of polycystic ovary syndrome (PCOS). However, several studies have failed to confirm insulin resistance in non-obese women with PCOS. The aim of the study was to identify whether insulin resistance is present in normal weight women with PCOS and the factors associated with insulin sensitivity. METHODS: Twenty-two normal weight (body mass index, BMI < 25 kg/m2) women with PCOS, and 16 age and BMI comparable control women with regular menstrual cycles were examined during their early follicular phase. The levels of serum hormones and lipids were measured. The visceral fat area was assessed by computed tomography at umbilical level. The standard 75g oral glucose tolerance test was performed to determine the glucose tolerance status. The insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp technique (target glucose 90 mg/dL, insulin~1 mu/kg/min). RESULTS: The levels of free testosterone (1.9+/-0.6 pg/mL vs. 0.8+/-0.3 pg/mL, p<0.001), androstenedione (14.5+/-3.7 nmol/L vs. 8.8+/-1.3 nmol/L, p<0.001), LH (10.7+/-4.5 IU/L vs 4.6+/-4.8 IU/L, p<0.001) and FSH (5.8+/-1.7 IU/L vs. 4.2+/-2.4 IU/L, p<0.05) of the women with PCOS were significantly higher than those of the control subjects. The fasting plasma glucose (4.92+/-0.31 mmol/L vs. 4.42+/-0.61 mmol/L, p<0.01) and post glucose load plasma insulin (233.2+/-119.5pmol/L vs. 109.0+/-46.4 pmol/L, p<001) levels of women with PCOS were significantly higher than those of the control subjects. The glucose disposal rate (M value) was significantly lower in women with PCOS compared to the controls (5.3+/-1.2 mg/kg min vs. 6.7+/-1.6 mg/kg min, p<0.05), even after adjusting for age and BMI. There was no significant correlation of the M value with the anthropometric and a metabolic indices, and a multiple regression analysis of the M value showed no significant variables. CONCLUSION: Our non-obese women with PCOS showed significant insulin resistance compared to their age and BMI comparable control subjects, and-their insulin resistance may be an intrinsic defect not associated with other features, such as hyperandrogenemia or body fat distribution patterns.

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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Abstract PDF: 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.

Association between Hyperleptinemia and Metabolic Syndrome in an Urban Korean Community.: Jee Young Oh, Young Sun Hong, Yeon Ah Sung; Korean Diabetes J. 2003;27(4):313-322. Published online August 1, 2003

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Abstract PDF: BACKGROUND
To determine whether hyperleptinemia is a principal component of metabolic syndrome in a Korean population using factor analysis. METHODS: Metabolic syndrome was defined by the NCEP-ATP III guideline. An oral glucose tolerance test was performed, and plasma samples for leptin and lipid profiles were collected from 199 men and 426 women who had no history of diabetes, hypertension, dyslipidemia, or of taking lipid-lowering, antihypertensive, or antihyperglycemic medications. RESULTS: Leptin level was correlated with overall and central obesity, blood pressure, and glucose or insulin levels in men and women aged 30 to 83. Before and after adjustment for BMI, leptin level was significantly and positively correlated, in women only, with insulin and with insulin resistance, as assessed by a homeostasis model assessment (HOMA) (Ps<0.0001). Factor analysis identified the following four factors from among the metabolic syndrome variables; an obesity/hyperinsulinemia factor, a glucose intolerance factor, a hypertension factor, and a dyslipidemia factor in men. Leptin was clustered as an obesity/ hyperinsulinemia and a dyslipidemia factor in men. In women, four different groups were found: an obesity/hypertension factor, a glucose intolerance factor, an obesity/dyslipidemia factor, and an obesity/hyperinsulinemia factor. Leptin was clustered as an obesity/hyperinsulinemia factor in women. CONCLUSION: Our research suggests that leptin level is associated with metabolic syndrome in relation to obesity and hyperinsulinemia. Moreover, obesity, as opposed to hyperinsulinemia, is related to hypertension or dyslipidemia in women only, and this gender differences may reflect different roles of central adiposity on metabolic abnormalities.

The Prevalence and Incidence of Diabetes in Mokdong, Seoul.: Jee Young Oh, Hye Jin Lee, Eun Soon Hong, Young Sun Hong, Yeon Ah Sung, Sun Hee Lee; Korean Diabetes J. 2003;27(1):73-83. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Diabetes has recently become a major public health problem due to the socioeconomic changes in Korea. Epidemiological data for diabetes are needed to establish disease control and health improvement programs in the community. Considering the tendency for larger concentrations of the population in the urban areas of Korea, epidemiological studies in these areas are essential. This this was performed to determine the epidemiologic characteristics, prevalence, and incidence of diabetes in Korean urban communities. METHODS: The target cohort of this study was randomly selected from 20,222 residents living in the Mokdong apartment areas one, two, five and six, Yangcheon-Gu, Seoul. Of the 20,222 residents, 1,011 were residents, of which 766 (male 264, female 502) subjects participated and 372 subjects without diabetes at baseline examination followed up for 2 years. At the baseline and follow-up examination, all subjects underwent a 75g oral glucose tolerance test (OGTT) and anthropometric measurements (height, weight, waist to hip ratio, pulse rate, blood pressure, and subcutaneous skin fold thickness) were performed. RESULTS: There was an 8.5% prevalence of diabetes and 7.8% with impaired glucose regulation (IGR), including impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). The age-adjusted prevalence of diabetes IGR were 8.4% and 7.1%, respectively. The prevalence of diabetes or IGR increased with increasing age. The prevalence of diabetes was associated with aging, family history of diabetes, and high levels of waist to hip ratio. The age-adjusted annual incidence rate of diabetes for subjects over 40 years of age at the baseline was 1.3%. The risk factors for the development of incident diabetes, from a multiple logistic regression analysis, were the waist to hip ratio and the 2-hour postload serum glucose concentrations. CONCLUSION: The prevalence of diabetes in the Mokdong apartment area was slightly higher than in Yonchon, Jungup, or Beijing. The annual incidence of diabetes was lower than that found in the studies in Yonchon or in Pima Indian, but higher than those of Caucasians or American Hispanics.

Sex Hormone Binding Globulin, Body Fat Distribution and Insulin Resistance in Premenopausal Women.: Young Sook Lee, Hye Jin Lee, Jee Young Oh, Young Sun Hong, Yeon Ah Sung; Korean Diabetes J. 2003;27(1):63-72. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Low levels of sex-hormone binding globulin (SHBG), an indirect index of androgenicity, have been reported to be associated with obesity, especially central obesity. In women, increased androgenicity is related to hyperinsulinemia, impaired glucose tolerance and the development of type 2 diabetes mellitus. Recent studies have suggested that the relationship between SHBG and insulin resistance was mediated by the change in total or visceral adiposity, and that ethnical differences in the relationship between sex hormone and body fat distribution might exist. METHODS: We examined the associations of SHBG to the body fat distribution and insulin resistance in Korean premenopausal women. The fasting serum level of SHBG was measured by RIA, and the insulin sensitivity by the minimal model derived sensitivity index (SI), using the insulin modified intravenous glucose tolerance test. The amount of body fat, and its distribution, were assessed by anthropometric measurement, bioelectric impedance analyses, and computed tomography at the level of the umbilicus. RESULTS: 1. SHBG was significantly inversely correlated with the body mass index (BMI), waist circumference, visceral fat area, and fasting insulin levels, and was significantly positively correlated to the SI. 2. SHBG was significantly lower in premenopausal women with an impaired glucose tolerance, compared to those with a normal glucose tolerance, and significantly lower in those with hypertension (systolic BP> or =140 mmHg or diastolic BP> or =90 mmHg), compared to those with normal blood pressure. SHBG was also significantly lower in persons with central obesity(waist circumference > or = 80 cm) compared to those without. 3. In a multiple linear regression analysis, the SI was significantly associated with SHBG, after adjustment for age, BMI, systolic blood pressure, triglycerides, HDL- cholesterol, and percentage body fat, but this association disappeared after additional adjustment for visceral fat area. 4. In a multiple linear regression analysis, the fasting plasma insulin, BMI and percentage body fat were significant independent factors associated with SHBG. CONCLUSION: Increased androgenicity as assessed by decreased serum SHBG concentrations, is strongly associated with an unfavorable body fat distribution, hypertension, glucose intolerance, hyperinsulinemia, and insulin resistance.

Impaired Insulin Secretion in Normoglycemic Offspring of Patients with Type 2 Diabetes.: Eun Kyung Byun, Young Sun Hong, Jee Young Oh, Yeon Ah Sung, Yeon Jin Jang; Korean Diabetes J. 2003;27(1):39-48. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Although it is well known that insulin secretory defects and insulin resistance are major pathogenetic factors of type 2 diabetes, their relative importance still remains controversial in various ethnic groups. Increased levels of proinsulin, and the proinsulin/insulin (PI/I) ratio, are considered markers of pancreatic dysfunction, and predictors for the development of type 2 diabetes. To reveal which pathogenetic abnormality is most prominent in Koreans with type 2 diabetes, we measured the insulin sensitivity and secretory capacity in the normal glucose tolerant offspring of patients with type 2 diabetes. METHODS: Sixty-two offspring, with normal glucose tolerance (mean age 40.4+/-6.5 BMI 23.4+/-2.7 kg/m2), of type 2 diabetes parents, were compared with and 20, age and BMI-matched control subjects, with on family history of diabetes. We measured the serum levels of proinsulin (PI), specific insulin (I), and C-peptide(C) and calculated the PI/I and C/I ratios, as parameters of hepatic insulin clearance. The insulin sensitivity index (SI) was measured by the intravenous glucose tolerance test (IVGTT) using the MINMOD program, as a marker of insulin sensitivity. The acute insulin response to glucose (AIRg), AIRg by product, SI and the area under the insulin curve (AUCinsulin) were measured by IVGTT, and used as a marker of the insulin secretory capacity. We also evaluated the association between the proinsulin and insulin secretory capacities. RESULTS: Offspring of the type 2 diabetic patients had significantly lower AIRg SI and AUCinsulin (p<0.05), and tended to have lower AIRg (p=0.06), than the control subjects. However, there was no significant difference in the SI between the two groups. However, with the proinsulin, and the insulin, PI/I and C/I ratios, not significant differences were found between the offspring and the control subjects, and the PI/I ratio was not correlated with AIRg, AIRg x SI or SI. CONCLUSION: Insulin secretory defect could be a more prominent factor in the development of type 2 diabetes in Koreans, with no change in the proinsulin secretion.

Review

Sex Hormone and Action of Insulin.: Yeon Ah Sung; Korean Diabetes J. 2002;26(4):229-237. Published online August 1, 2002

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Abstract PDF: No abstract available.

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