Endocrinology and Metabolism

Original Articles

Diabetes, obesity and metabolism
Efficacy of Gemigliptin Add-on to Dapagliflozin and Metformin in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Study (SOLUTION): Byung Wan Lee, KyungWan Min, Eun-Gyoung Hong, Bon Jeong Ku, Jun Goo Kang, Suk Chon, Won-Young Lee, Mi Kyoung Park, Jae Hyeon Kim, Sang Yong Kim, Keeho Song, Soon Jib Yoo; Endocrinol Metab. 2023;38(3):328-337. Published online June 28, 2023; DOI: https://doi.org/10.3803/EnM.2023.1688

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Abstract PDF Supplementary Material PubReader ePub: Background
This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin.
Methods
In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks.
Results
The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted.
Conclusion
Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Clinical Study
Relationships between Thigh and Waist Circumference, Hemoglobin Glycation Index, and Carotid Plaque in Patients with Type 2 Diabetes: Myung Ki Yoon, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm, Kap Bum Huh, Chul Sik Kim; Endocrinol Metab. 2020;35(2):319-328. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.319

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Background
This study investigated the relationships of thigh and waist circumference with the hemoglobin glycation index (HGI) and carotid atherosclerosis in patients with type 2 diabetes.
Methods
This observational study included 3,075 Korean patients with type 2 diabetes, in whom anthropometric measurements and carotid ultrasonography were conducted. HGI was defined as the measured hemoglobin A1c (HbA1c) level minus the predicted HbA1c level, which was calculated using the linear relationship between HbA1c and fasting plasma glucose levels. Carotid atherosclerosis was defined as a clearly isolated focal plaque or focal wall thickening >50% of the surrounding intima-media thickness.
Results
The frequency of a positive HGI decreased with increasing thigh circumference in men and increased with increasing waist circumference in women after adjusting for potential confounding variables. Thigh and waist circumference had a combined augmentative effect on the likelihood of positive HGI, which was dramatically higher in patients in higher waist-to-thigh ratio quartiles (adjusted odds ratios for the highest compared to the lowest quartile: 1.595 in men and 1.570 in women). Additionally, the larger the thigh circumference, the lower the risk of carotid atherosclerosis, although in women, this relationship lacked significance after adjustment for potential confounders.
Conclusion
HGI was associated with thigh circumference in men and waist circumference in women. In addition, the combination of low thigh circumference and high waist circumference was strongly associated with a higher HGI in Korean patients with type 2 diabetes. In particular, thigh circumference was associated with carotid atherosclerosis in men. However, further longitudinal studies are warranted.

Citations

Citations to this article as recorded by

Association between hemoglobin glycation index and subclinical myocardial injury in the general population free from cardiovascular disease
Zhenwei Wang, Yihai Liu, Jing Xie, Nai-Feng Liu
Nutrition, Metabolism and Cardiovascular Diseases.2022; 32(2): 469. CrossRef
Association of Hemoglobin Glycation Index With Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography: A Retrospective Study
Zhezhe Chen, Duanbin Li, Maoning Lin, Hangpan Jiang, Tian Xu, Yu Shan, Guosheng Fu, Min Wang, Wenbin Zhang
Frontiers in Physiology.2022;[Epub] CrossRef
Associations of continuous glucose monitoring-assessed glucose variability with intima-media thickness and ultrasonic tissue characteristics of the carotid arteries: a cross-sectional analysis in patients with type 2 diabetes
Naohiro Taya, Naoto Katakami, Tomoya Mita, Yosuke Okada, Satomi Wakasugi, Hidenori Yoshii, Toshihiko Shiraiwa, Akihito Otsuka, Yutaka Umayahara, Kayoko Ryomoto, Masahiro Hatazaki, Tetsuyuki Yasuda, Tsunehiko Yamamoto, Masahiko Gosho, Iichiro Shimomura, Hi
Cardiovascular Diabetology.2021;[Epub] CrossRef

Impact of Serum Adiponectin Concentration on Progression of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.: Chul Sik Kim, Ju Ri Park, Sung Hoon Yu, Jun Goo Kang, Ohk Hyun Ryu, Seong Jin Lee, Eun Gyung Hong, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo; Endocrinol Metab. 2012;27(1):31-38. Published online March 1, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.1.31

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Abstract PDF: BACKGROUND
Increased cardiovascular events, which is the leading cause of death in type 2 diabetic patients, are mainly caused by accelerated atherosclerosis. Adiponectin has been suggested as a risk factor for cardiovascular diseases in cross-sectional studies. However, little is known about the impact of adiponectin on the progression of carotid atherosclerosis in type 2 diabetic patients. This study was conducted to evaluate the impact of early adiponectin levels on the progression of carotid atherosclerosis. METHODS: From March 2009, 150 patients with type 2 diabetes were consecutively enrolled in our affiliated outpatient clinic. Anthropometric and biochemical data, including adiponectin levels, were measured in each participant. We measured the carotid intima-media thickness (CIMT) at baseline and at 1-year follow-up (n = 111). Then, we prospectively studied the relationship between the serum adiponectin levels and the progression of CIMT for 1 year. RESULTS: Adiponectin levels negatively correlated with CIMT (r = -0.219, P = 0.015). Moreover, mean progression of CIMT was 0.016 +/- 0.040 mm. However, there was no correlation between adiponectin levels and the progression of CIMT within 1-year follow-up period (r = -0.156, P = 0.080). Age (beta = 0.556, P = 0.004), LDL cholesterol (beta = 0.276, P = 0.042), and A1C (beta = 0.309, P = 0.038) were found to be independent risk factors for CIMT. However, A1C (beta = 0.311, P = 0.042) was found to be the only independent risk factor for the progression of CIMT. CONCLUSION: In our study, adiponectin levels were negatively associated with CIMT. However, it did not affect the progression of CIMT at 1-year follow-up. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.

Case Reports

A Case of Thyrotoxic Periodic Paralysis with Rhabdomyolysis.: Seo Hee Lee, Seong Yeol Kim, Hae Ri Lee, Jun Goo Kang, Ohk Hyun Ryu, Chul Sik Kim, Byung Wan Lee, Seong Jin Lee, Eun Gyoung Hong, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yu, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo; J Korean Endocr Soc. 2008;23(6):425-429. Published online December 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.6.425

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Abstract PDF: Hyperthyroidism combined with rhabdomyolysis is extremely rare. There are only 6 reported cases of hyperthyroidism accompanied with rhabdomyolysis in the medical literature. Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle, and this causes myoglobin and intracellular protein to leak into the circulation. The causes of rhabdomyolysis include trauma, electrolyte abnormality, infection, drug, toxin and hypothyroidism. We report here on a patient who presented with thyrotoxic periodic paralysis and rhabdomyolysis with hypokalemia. He complained of lower leg paralysis along with muscle tenderness, and the laboratory findings showed elevated creatine kinase (CK) levels. After treatment by hydration, potassium replacement and drug medication, including propylthiouracil and beta-blocker, his CK levels were normalized and his symptoms were much improved. For patient with thyrotoxic periodic paralysis and muscle tenderness, the possibility of rhabdomyolysis should be clarified by examining the CK levels.

A Case of Unilateral Exophthalmos Caused by a Dural Arteriovenous Malformation in Thyroid-Associated Ophthalmopathy.: Sun Ryoung Choi, Seong Jin Lee, Hae Ri Lee, Jun Goo Kang, Ohk Hyun Ryu, Chul Sik Kim, Byung Wan Lee, Eun Gyung Hong, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo; J Korean Endocr Soc. 2008;23(1):51-55. Published online February 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.1.51

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Abstract PDF

Thyroid-associated ophthalmopathy is associated with thyroid dysfunction, particularly Graves' disease, and is manifested as eye signs, including proptosis. In cases of unilateral exophthalmos with thyroid-associated ophthalmopathy, other causes such as orbital neoplasm, carotid-cavernous fistula, cavernous sinus thrombosis, and dural arteriovenous malformation (AVM) should be excluded. Dural AVM, an abnormal dural arteriovenous connection, is a rare neurovascular entity that mimics thyroid-associated ophthalmopathy. When eye involvement is unilateral or asymmetric, dural AVM can be considered in the differential diagnosis of thyroid-associated ophthalmopathy. A twenty-six year-old woman presented with unilateral exophthalmos in Graves' disease. By orbital magnetic resonance imaging and cerebral angiography, thyroid-associated ophthalmopathy and dural AVM were diagnosed. The unilateral exophthalmos improved after coil embolization of the dural AVM. In summary, we report the first case of a dural AVM with Graves' disease and thyroid-associated ophthalmopathy.

Citations

Citations to this article as recorded by

Proptosis as a Primary Symptom of Brain Arteriovenous Malformation
Jong Eun Lee, Jin Sook Yoon, Keun Young Park
Ophthalmic Plastic & Reconstructive Surgery.2020; 36(2): e53. CrossRef
Ophthalmopathy Induced by Bilateral Carotid Cavernous Fistula in a Patient with Graves' Disease
Jong Kun Ha, Ji Hye Suk, A Ra Jo, Chan Woo Jung, Bong Jae Kim, Seong Oh Park, Sang Su Kim, Mi Kyung Kim
Endocrinology and Metabolism.2011; 26(4): 335. CrossRef

Original Article

The Clinical Significance of Retinoic Acid Receptor beta Expressions in Primary and Recurred Metastatic Lymph Node Papillary Thyroid Carcinomas.: Jae Pil Han, Seong Jin Lee, Kyung Chan Choi, Young Euy Park, Hae Ri Lee, Jun Goo Kang, Ohk Hyun Ryu, Chul Sik Kim, Byung Wan Lee, Eun Gyung Hong, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Hyung Joon Yoo, Moon Gi Choi; J Korean Endocr Soc. 2007;22(6):419-427. Published online December 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.6.419

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Abstract PDF: BACKGROUND
The present study was designed to investigate the correlations of retinoic acid receptor beta(RARbeta) expression for primary and recurred metastatic lymph node (LN) papillary thyroid carcinoma (PTC) tissues and the correlations of RARbeta expression with the uptake of I(131) as detected on a whole body scan (WBS). METHODS: Primary and metastatic LN PTC tissues were examined by immunohistochemical methods. Staining positivity was calculated, and staining intensity was graded as negative (0), weak (1+), moderate (2+) and strong (3+). Nuclear staining intensity (NSI) of cells from tissues was also examined. RESULTS: Seventeen patients who had regional cervical LN metastasis without distant metastasis were included in the study, and 13 patients had the abnormal uptake of I(131) as detected on a WBS. In primary PTC tissues, RARbeta staining positivity and intensity of carcinoma cells were significantly higher than those of normal cells but NSI was significantly higher in normal cells than carcinoma cells. Between primary and metastatic LN PTC tissues, RARbeta staining intensity was correlated after controlling for age. Primary PTC tissues from 14 (82.4%) out of 17 patients were concordant between NSI and the uptake of I(131) as detected on a WBS. NSI predicted the I(131) uptake as detected on a WBS with 81.3% positive predicted value (PPV) and 100% negative predicted value. Metastatic LN PTC tissues from 13 (76.5%) out of 17 patients were concordant between NSI and the uptake of I(131) as detected on a WBS. NSI predicted the uptake of I(131) as detected on a WBS with 76.5% PPV. When the results of NSI taken either as positive or negative were correlated with those of the uptake of I(131) as detected on a WBS in primary and metastatic LN PTC tissues, the correlation was not significant after controlling for age. CONCLUSION: Our results demonstrate that nuclear RARbeta expression may be decreased in PTC tissues than normal thyroid tissues, and RARbeta expression in primary PTC tissues as well as in recurred metastatic LN PTC tissues may predict the uptake of I(131) as detected on a WBS.

Case Reports

A Case of Kallmann's Syndrome Mildly Presenting as Secondary Amenorrhea.: Na Rae Joo, Cheol Young Park, Hong Ju Moon, Jun Goo Kang, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Yul Lee, Ki Won Oh, Sung woo Park; J Korean Endocr Soc. 2007;22(2):130-134. Published online April 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.2.130

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Abstract PDF: Kallmann's syndrome is very rare congenital defect in GnRH (gonadotrophin releasing hormone) secretion involving both sexes. The mode of inheritance has not been fully understood. But, including X-linked inheritance, the ratio of incidence between male versus female is 5:1, and there is a few case reports of female Kallmann's syndrome in Korea, especially in internal medicine department. We report a case of 35 year-old female Kallmann's syndrome presenting secondary amenorrhea as a mild presentation.

A Novel Mutation of the Vasopressin-Neurophysin II Gene in a Familial Neurohypophyseal Diabetes Insipidus.: Mi Jung Kim, Byung Wan Lee, In Kyung Jeong, Jun Goo Kang, Seong Jin Lee, Eun Gyung Hong, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo; J Korean Endocr Soc. 2007;22(2):118-124. Published online April 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.2.118

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Abstract PDF: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare form of central diabetes insipidus (DI), and this malady is clinically characterized by polydipsia and polyuria, and it is caused by mutation in the vasopressin-neurophysin II. We identified a Korean family that suffered with adFNDI and we found a novel mutation in the NP II molecule. The index subject's DI symptoms dated to childhood, and his familial history was consistent with autosomal transmission. The diagnosis of central DI was done by performing a water deprivation test and a vasopressin challenge test. For molecular analysis, the genomic DNA was extracted and the AVP-NP II gene was amplified by polymerase chain reaction from four clinically-affected members and seven clinically-nonaffected members. Genetic analysis of AVP-NP II revealed new a heterozygous missense mutation in exon 2 of the AVP-NP II gene (+1692C > A) and this amino acid substitution (Cys105Stop) was predicted to have occurred in four clinically-affected subjects. In summary, in the present study we have described a novel mutation of the AVP-NPII gene in a Korean family suffering with adFNDI.

Original Article

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

Case Reports

A Case of Sporadic Nonfamilial Hypophosphatemic Osteomalacia.: Jun Goo Kang, Dong Sun Kim, Chan Bum Choi, Tae Jong Kim, Jong Pyo Kim, Chang Beom Lee, Yong Soo Park, You Hern Ahn, Tae Wha Kim, Sang Cheol Bae, Chan Gum Park; J Korean Endocr Soc. 2002;17(4):610-616. Published online August 1, 2002

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Abstract PDF: Acquired hypophosphatemic rickets, or osteomalacia, requires the recognition of the typical clinical and radiological features of osteomalacia in association with hypophosphatemia, which is caused by the decrease in intestinal absorption or impaired renal tubular phosphate reabsorption. The latter form may either be hereditary or acquired. Acquired hypophosphatemic osteomalacia includes oncogenic osteomalacia, neurofibromatosis, fibrous dysplasia, renal tubular acidosis and sporadic nonfamilial hypophosphatemic osteomalacia. A 33-year-old man presented with bone pain, progressive severe muscle weakness and a height loss of more than 10 cm over a 5 year period. The familiy history was negative for bone disease or other renal tubular defects. He was found to have hypophosphatemia, impaired phosphate reabsorption, normocalcemia, normal vitamin D metabolite levels, normal PTH and elevated alkaline phophatase. A bone biopsy showed thickened unmineralized osteoid compared to pelvic bone in control cases. Clinical symptoms, such as bone pain and muscle weakness, were improved after supplementation of oral phosphorus and calcitriol, although the serum phosphorus level did not normalize.

A Case of Thyroid Storm Developed after Dilatation and Curettage for Invasive Molar Pregnancy.: Joon Sung Park, Jun Goo Kang, Chang Beom Lee, Yong Soo Park, Dong Sun Kim, Tae Wha Kim, Joon Soo Hahm, Jung Han Lee, Jung Hyae Hwang, Seung Ryong Kim, You Hern Ahn; J Korean Endocr Soc. 2002;17(4):589-595. Published online August 1, 2002

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Abstract PDF: Thyroid dysfunction is one of the more prevalent clinical situations encountered by primary care physicians. Thyroid storm is defined as a life-threatening exacerbation of the hyperthyroid state in which there is evidence of decompensation of one or more organ systems. Common precipitants include infection, surgery, diabetic ketoacidosis, vascular accidents, non-compliance with antithyroid medication, and emotional stress, but rarely develop in invasive molar pregnancy. An 18-year-old woman presented to the emergency department complaining of lower abdominal pain and vaginal spotting. She had no previous history of hyperthyroidism. Under the diagnosis of invasive molar pregnancy, dilatation and curettage was performed. However, right after the procedure the patient developed a semi-coma metal status, high grade fever, and tachycardia. Prompt diagnosis of thyroid storm was made and treatment followed immediately. We present a case of thyroid storm and a review of thyroid storm precipitated by invasive molar pregnancy.

A Case of Steroid induced Myopathy in Patient with Iatrogenic Cushing Syndrome.: Jun Goo Kang, You Hern Ahn, Joon Sung Park, Chang Beom Lee, Yong Soo Park, Dong Sun Kim, Woong Hwan Choi, Tae Wha Kim, Joon Soo Hahm, Yong Wook Park, Eun Kyung Hong; J Korean Endocr Soc. 2002;17(2):275-279. Published online April 1, 2002

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Abstract PDF: Many endocrinologic diseases can induce muscular diseases. Myopathy caused by exogenous steroid is a common problem in patients prescribed steroids as therapy. We report a case of iatrogenic steroid myopathy in a 55-year-old female who had taken steroids under her own volition at a local pharmacy for more than 3 months due to skin rash and itching. She complained of severe proximal muscle wasting and weakness in the lower extremities and also exhibited other stigmata of Cushing's syndrome such as moon face, buffalo hump or easy bruising. Needle electromyography showed the typical pattern of myopathy. Muscle biopsy revealed intermixed numerous, markedly atrophic and angulated basophilic fibers and a few fat cells without inflammation. In addition there was marked and selective atrophy of type II fiber on ATPase staining in pH 9.4 buffer. After discontinuation of steroid treatment, she has experienced slow improvement through physical therapy, including isotonic exercise.

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