Endocrinology and Metabolism

Original Articles

Diabetes
Retrospective Analysis of the Efficacy of Dapagliflozin in Patients with Type 2 Diabetes in a Primary Clinic in Korea: Sang Hyun Park, Young Ju Choi, Eun-Jung Rhee, Kab Bum Huh; Endocrinol Metab. 2019;34(1):70-79. Published online March 21, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.70

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Background

We aimed to retrospectively analyze the efficacy of 10 mg dapagliflozin (DAPA), which is a sodium-glucose cotransporter-2 inhibitor, in Korean patients with type 2 diabetes who visited a primary diabetes clinic.

Methods

In total, 83 patients with type 2 diabetes, who received treatment with DAPA for the first time in a primary diabetes clinic between January 2015 and October 2015, were included in the study. The effect of DAPA in lowering glycosylated hemoglobin (HbA1c) levels was evaluated via chart review at 6 months follow-up. The patients were categorized into five groups according to add-on to or switched from other glucose-lowering agents: add-on to metformin (MET, n=10), add-on to MET+dipeptidyl peptidase 4 inhibitor (DPP4i, n=12), switched from sulfonylurea (SU, n=13), switched from DPP4i (n=11), and switched from thiazolidinedione (TZD, n=37). All the participants had already used MET for their regimen.

Results

Treatment with DAPA reduced HbA1c level by 1.2%±0.8%. Moreover, a significant decrease was observed in all subgroups: add-on to MET, −1.2%±0.7%; add-on to MET+DPP4i, −1.4%±0.8%; switched from SU, −1.4%±0.7%; switched from DPP4i, −0.5%±0.7%; and switched from TZD, −1.2%±0.9% (P<0.01). A significant decrease in body weight (−3.1±2.6 kg, P<0.001) was observed after DAPA administration. Estimated glomerular filtration rate and urine microalbumin were significantly decreased after 6 months of treatment with DAPA (−4.0±13.5 mL/min/1.73 m², P=0.03; −23.6±45.9 mg/L, P<0.001).

Conclusion

Treatment with DAPA, whether added to or switched from other glucose-lowering agents, significantly decreased HbA1c levels in Korean patients with type 2 diabetes who visited a single primary diabetes clinic. DAPA can be considered as an optimal second-line treatment for patients with type 2 diabetes, as supported by real-world evidence studies.

Citations

Citations to this article as recorded by

The sodium glucose co-transporter 2 inhibitor dapagliflozin ameliorates the fluid-retaining effect of the endothelin A receptor antagonist zibotentan
Vandana Veenit, Hiddo J L Heerspink, Christine Ahlström, Peter J Greasley, Stanko Skritic, Natalie van Zuydam, Donald E Kohan, Pernille B L Hansen, Robert I Menzies
Nephrology Dialysis Transplantation.2023; 38(10): 2289. CrossRef

Phenotypic Variation of Polycystic Ovary Syndrome.: Gun Woo Pyun, Young Ju Choi, Hyejin Lee, Jee Young Oh, Young Sun Hong, Yeon Ah Sung, Hye Won Chung; J Korean Endocr Soc. 2007;22(5):326-331. Published online October 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.5.326

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Abstract PDF

BACKGROUND
Polycystic ovary syndrome (PCOS) is a common disorder in premenopausal women, but there has been little agreement on its diagnostic criteria due to its uncertain pathogenesis and the heterogeneity of symptoms. This study was performed in order to assess the differences in clinical, metabolic, and hormonal characteristics of women in the PCOS subgroups defined by ESHRE criteria. METHODS: Subjects were divided into four PCOS subgroups based on ESHRE criteria. The grouping groupings included: 1) hyperandrogenism, oligomenorrhea, and polycystic ovary morphology (HA + OM + PCO); 2) hyperandrogenism and oligomenorrhea (HA + OM); 3) hyperandrogenism and polycystic ovary morphology (HA + PCO); and 4) oligomenorrhea and polycystic ovary morphology (OM + PCO). Reproductive hormones and metabolic profiles were measured. RESULTS: Of the total number of subjects, 60 (40%) fulfilled the criteria for HA + OM + PCO, 50 (33%) for HA + OM, 11 (7%) for HA + PCO, and 30 (20%) for OM + PCO. There were no significant differences in clinical or metabolic features among the groups, except for LH, total cholesterol, and HDL cholesterol. CONCLUSION: In this population defined by ESHRE criteria, 73% of the patients met the former NIH definition for PCOS. Different phenotypes of PCOS cases were clinically or biochemically similar. Whether these women have an increased risk of infertility or metabolic complications remains to be determine.

Citations

Citations to this article as recorded by

Epidemiology and Diagnostic Criteria of Polycystic Ovary Syndrome
Hyejin Lee, Yeon-Ah Sung
The Journal of Korean Diabetes.2015; 16(3): 189. CrossRef
Hyperandrogenism in Women: Polycystic Ovary Syndrome
Yeon-Ah Sung
Hanyang Medical Reviews.2012; 32(4): 197. CrossRef
Polycystic Ovary Syndrome in Korean Women: Clinical Characteristics and Diagnostic Criteria
Yeon-Ah Sung
Endocrinology and Metabolism.2011; 26(3): 203. CrossRef
Clinical Manifestation of Polycysticv Ovary Syndrome
Yu-Bae Ahn
Journal of Korean Endocrine Society.2007; 22(5): 323. CrossRef

Therapeutic Effects of Metformin and Rosiglitazone in Korean Women with Polycystic Ovary Syndrome.: Jee Young Oh, Eun Kyung Byun, Hwi Ra Park, Young Ju Choi, Hyo Jung Kim, Hye Jin Lee, Young Sun Hong, Yeon Ah Sung, Hye Won Chung; J Korean Endocr Soc. 2005;20(5):467-475. Published online October 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.5.467

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Abstract PDF

BACKGROUND
Insulin resistance is a central feature of polycystic ovary syndrome (PCOS), and hyperinsulinemia contributes to anovulation, oligo or amenorrhea, hyperandrogenism and infertility in women with PCOS. The use of insulin sensitizers, such as metformin or thiazolidinedione, in PCOS is becoming increasingly accepted. The purpose of our study was to evaluate the therapeutic effects of metformin and rosiglitazone on the metabolic and reproductive derangement, and find parameters predicting their therapeutic efficacy in Korean PCOS women. METHODS: Sixty-two women with PCOS were recruited. The baseline characteristics, including BMI, glucose tolerance test, lipid profiles, sex hormones and hyperinsulinemic euglycemic clamp test, were assessed. After the administration of the insulin sensitizer (metformin 1.5g/day or rosiglitazone 4mg/day) for 3 months, the insulin sensitivity was reassessed. A drug response was defined as menstrual restoration or pregnancy. RESULTS: Of the 62 women with PCOS, 36 gained restored regular menstruation, and a further 5 conceived (a drug response rate of 66.7%). There were no significant clinical differences between responders and nonresponders. Twelve weeks after taking the drugs, the insulin sensitivity was significantly improved (M-value 4.7+/-0.2 vs. 5.5+/-0.4mg/kg/min, P<0.05), and the free testosterone levels(72.5+/-39.9 vs. 45.8 +/-3.8pmol/L, P<0.05) were significantly decreased, without significant weight reduction. CONCLUSION: Metformin and rosiglitazone restored menstruation in 66.1% of women with PCOS. Hyperandrogenemia and insulin sensitivity were significantly improved with the use of the two drugs. However, metabolic or hormonal markers for predicting the drug response could not be found.

Citations

Citations to this article as recorded by

Diagnosis and Treatment of Polycystic Ovary Syndrome
Hyejin Lee, Yeon-ah Sung
Journal of Korean Endocrine Society.2007; 22(4): 252. CrossRef

The Effects on Visceral Fat and Cardiovascular Risk Factors of Testosterone Replacement in Secondary Hypogonadal Men.: Eui Sil Hong, Sung Yeon Kim, Young Ju Choi, Sang Wan Kim, Chan Soo Shin, Kyong Soo Park, Hak Chul Jang, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2005;20(3):252-260. Published online June 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.3.252

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Abstract PDF

BACKGROUND
Increased body fat, abdominal obesity and insulin resistance are important clinical features in hypogonadal men. Several studies have demonstrated that a low testosterone concentration in men is associated with coronary heart disease, visceral obesity and insulin resistance. In this study, the effects of testosterone replacement therapy on the abdominal visceral fat and cardiovascular risk factors in hypogonadal men were investigated. METHODS: We selected 26 men with secondary hypogonadism (mean serum testosterone+/-SD 0.39+/- 0.57ng/mL), who were then treated with testosterone for 12 months. We measured the body composition, including the abdominal visceral fat area by abdominal CT at the L4 level, both before and 12 months after treatment, and the lipid profile, fasting plasma insulin, HOMA-IR and the serum homocysteine, CRP and IL-6 before and 6, 12 months after treatment. RESULTS: With respect to the body composition, the lean body mass had significantly increased 12 months after treatment(P= 0.002), but there were no significant changes in the body fat mass and abdominal visceral fat area. There was a trend toward a decreased fasting plasma insulin and HOMA-IR, but this did not reach statistical significance. The total cholesterol had decreased significantly at 12 months(P=0.04) and the HDL cholesterol decreased significantly over the course of study(P=0.02). There were no significant changes in the serum homocysteine, CRP and IL-6 after treatment. CONCLUSIONS: After 12 months testosterone replacement therapy in the 26 men with hypogonadism, the lean body mass had increased significantly, but there was no significant change on the abdominal visceral fat during the treatment period. Testosterone replacement had deleterious effect on HDL cholesterol, but not significant effects on insulin resistance and the serum homocysteine, CRP and IL-6. These results suggest that testosterone replacement therapy may have a few adverse effects on cardiovascular diseases in hypogonadal men. However, it will be necessary to examine the long-term effects of testosterone replacement on the incidence of cardiovascular events as well as the cardiovascular risk factors in men with hypogonadism

Citations

Citations to this article as recorded by

The Association of Level of Testosterone and Parameters of Obesity
Chong Hwa Kim
The Korean Journal of Obesity.2015; 24(1): 28. CrossRef
The Relationship between Various Obesity Indices and Level of Male Hormone according to Different Age Groups
Yoo-Jung Lee, Hyeon-Ju Kim, Mi-Hee Kong
The Korean Journal of Obesity.2014; 23(4): 245. CrossRef
Androgen Receptor Gene CAG Repeat Polymorphism and Effect of Testosterone Therapy in Hypogonadal Men in Korea
Min Joo Kim, Jin Taek Kim, Sun Wook Cho, Sang Wan Kim, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim
Endocrinology and Metabolism.2011; 26(3): 225. CrossRef
Effects of Androgen on the Cardiovascular System in the Aging Male
Jin Wook Kim, Je Jong Kim, Du Geon Moon
Korean Journal of Andrology.2011; 29(1): 10. CrossRef

The Clinical Characteristics of Macroprolactinemia.: Young Ju Choi, Jun Goo Kang, Sung Yeon Kim, Eui Sil Hong, Sang Wan Kim, Chan Soo Shin, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2005;20(3):216-223. Published online June 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.3.216

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Abstract PDF: BACKGROUND
Prolactin has been identified by gel chromatography to exist is three different forms in human serum; monomeric prolactin(molecular mass 23kDa), big prolactin (molecular mass 50~60 kDa) and big big prolactin, otherwise known as macroprolactin(molecular mass 150~170kDa). The predominance of macroprolactinemia has long been known in idiopathic hyperprolactinemic patients with maintained fertility. In recent reports, 24% of microprolactinoma patients showed no menstrual disturbances, which was suggestive of macroprolactinemia. The purpose of this study was to evaluate: (1) the frequency of macroprolactinemia among idiopathic hyperprolactinemia and prolactinoma patients, (2) the difference in the clinical characteristics between hyperprolactinemia, with and without macroprolactinemia, among idiopathic hyperprolactinemia and prolactinoma patients, and (3) the follow-up prolactin level using the bromocriptine response. METHODS: We retrospectively analyzed the clinical characteristics and prolactin levels in 43 idiopathic hyperprolactinemia and 51 prolactinoma patients with a poor bromocriptine response. Macroprolactinemia was identified by the prolactin recovery of < 40% using the polyethylene glycol(PEG) precipitation test. RESULTS: (1) Of the 43 idiopathic hyperprolactinemia and 51 prolactinoma patients, 17(39.5%) and 9(17.6%), respectively, were macroprolactinemic(P<0.05). (2) Among the idiopathic hyperprolactinemia patients, galactorrhea combined with amenorrhea was significantly less frequent (P<0.05), with the 1- and 2-year follow-up prolactin levels being significantly higher in those with macroprolactinemia than monomeric prolactinemia(P<0.05). (3) Among the prolactinoma patients, amenorrhea was significantly less frequent(P<0.05), but asymptomatic cases were more frequent in those with macroprolactinemia than monomeric prolactinemia(P <0.05). The 1- and 2-year follow-up prolactin levels were significantly higher in those with macroprolactinemia than monomeric prolactinemia(P<0.05). CONCLUSION: The screening of macroprolactinemia should be considered in idiopathic hyperprolactinemia and prolactinoma patients with a poor bromocriptine response

High-Dose Hook Effect in Patients with Macroprolactinoma.: Sung Yeon Kim, Chul Gu Park, Young Ju Choi, Eui Sil Hong, Sang Wan Kim, Chan Soo Shin, Hak Chul Jang, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2005;20(2):148-153. Published online April 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.2.148

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Abstract PDF

BACKGROUND
Large amounts of antigen may produce false low values on immunoradiometric assays due to the so-called high-dose hook effect. The physicians' awareness of the possibility of the "high-dose hook effect" will prevent preoperative misdiagnosis. The study was designed to identify the frequency and clinical features of patients with pituitary macroadenomas in whom a high-dose PRL hook effect was documented. METHODS: Our retrospective study involved 42 patients with non-functioning pituitary adenomas (tumor diameter >30mm) who underwent transsphenoidal microsurgery from between Jan 1999 to Aug 2004, and 6 patients with non-functioning pituitary adenoma(tumor diameter>30mm) were selected for prospective study from Sep 2003 to Feb 2004. Our retrospective study also involved 13 patients with macroprolactinoma for the comparison of the clinical features. RESULTS: 1) The presence of a high-dose hook effect was retrospectively suggested when the PRL levels increased in 4 out of the 42 patients with non- functioning adenomas(tumor diameter >30mm) after surgery. Post-operative immunohistochemical staining of their pituitary specimens revealed the tumors to be prolactinoma. 2) Prospectively, dilution testing of the specimens obtained before surgery was done in the 6 patients, and one patient presented with a case of the hook effect. The patient's prolactin level was measured at 53.1ng/mL before dilution and this was increased up to 22,600ng/mL upon the 1:1000 dilution. 3) Conclusively, the hook effect was seen in 5 of the 48 patients(10.4%) with non-functioning pituitary adenoma(tumor diameter >30mm) 4) Compared with other 2 patient groups(the macroprolactinoma(N=13) group, and the non-functioning pituitary tumor(N=43) group), the high-dose PRL hook effect is more likely to be observed in male patients with large pituitary tumors. CONCLUSION: In order to avoid the high-dose hook effect, PRL should be assayed at 1:100~1:200 or even higher dilutions of serum from all patients(and especially the male patients) with large pituitary tumors

Citations

Citations to this article as recorded by

Multiple Endocrine Neoplasia Type 1 Presenting with an Invasive Giant Prolactinoma
Jinhoon Cha, Jin Seo Kim, Jung Suk Han, Yeon Won Park, Min Joo Kim, Yun Hyi Ku, Hong Il Kim
The Korean Journal of Medicine.2016; 91(3): 300. CrossRef

Sex Hormone-Binding Globulin and Oxidative Stress in Korean Premenopausal Women.: Young Ju Choi, Jee Young Oh, Young Sun Hong, Yeon Ah Sung; J Korean Endocr Soc. 2004;19(1):48-57. Published online February 1, 2004

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Abstract PDF: BACKGROUND
Low levels of sex hormone-binding globulin(SHBG), an indirect index of androgenicity, are associated with insulin resistance and cardiovascular risk factors. The risk factors of the cardiovascular disease are known to be related to oxidative stress. In recent reports, sex hormones were associated with oxidative stress in women with polycystic ovarian syndrome(PCOS), which is characterized by increased androgenicity and insulin resistance. METHODS: To investigate the relationship between sex hormones and oxidative stress, we examined the association of malondialdehyde(MDA), total antioxidant status(TAS), oxidized low density lipoprotein cholesterol(ox-LDL), and SHBG in 46 Korean premenopausal women. RESULTS: 1. SHBG and MDA levels were not significantly different among the women with NGT and IGT. But, TAS was significantly lower(p=0.034) in the subjects with IGT than in the subjects with NGT. 2. The SHBG level was significantly lower(p=0.036) in obese women than in non-obese women. 3.The SHBG level was significantly inversely correlated with BMI(r=-0.394, p=0.007), post challenge glucose(r=-0.326, p=0.027), waist size(r=-0.323, p=0.029), waist-to-thigh ratio(WTR) (r=-0.308, p=0.037), fasting insulin level(r=-0.387, p=0.008), visceral fat area(VFA)(r=-0.339, p=0.021), and was significantly positively correlated with SI(r=0.397, p=0.008). 4. The SHBG level was significantly inversely correlated with levels of MDA(r=-0.357, p=0.015) and ox-LDL(r=-0.367, p=0.014). 5. In a multiple linear regression analysis, the SHBG level was a significant and independent factor for both MDA and ox-LDL. For TAS, the fasting insulin level and post challenge glucose were significant and independent factors. CONCLUSION: Increased androgenicity assessed by the decrease in serum SHBG levels is associated with the increase in MDA and ox-LDL. These results suggest that increased androgenicity in premenopausal women can contribute to the development of cardiovascular diseases via increased oxidative stress.

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