Pituitary adenomas (PAs) are defined as benign monoclonal tumors in the pituitary gland that cause symptoms due to either hormonal hypersecretion or a space-occupying effect, and are classified as functioning or non-functioning. Because of their rarity and slow-growing with symptomless nature in most cases, it has been challenging to investigate the epidemiology of PAs. Considering their public health impact and association with increased morbidity and mortality, however, it is essential to understand the prevalence and incidence of PAs in order to improve patient outcomes and to minimize the resultant burden on the health care system. Fortunately, developments in imaging modalities and easier access to large-scale population data have enabled investigators to analyze the epidemiology of PAs more accurately. This review summarizes previously reported epidemiologic data on functioning PAs in Korea and other countries.

KSLA published our first version of treatment guidelines for dyslipidemia in 1996, which was based on health examination data gathered by the National Health Insurance Corperation in 1994. A number of academic societies including the Korean Endocrine Society, the Korean Society of Cardiology, the Korean Society for Laboratory Medicine, the Korean Society for Biochemistry and the Korean Nutrition Society participated in the development of this guideline. In 2003, the second version of our guidelines was published based on the Korean National Health and Nutrition Survey (KNHANES) data which was collected in 1998. In 2006, the second version was modified and expanded with using KNHANES data collected in 2005. This article summarizes the recommendations included in the expanded second version of treatment guidelines. The full version of treatment guidelines in Korean is available at the KSLA Homepage (http://www.lipid.or.kr).
Biochemistry ; Cardiology ; Dyslipidemias ; National Health Programs ; Nutrition Surveys

BACKGROUND: Previous studies have reported that glypican-4 (GPC4) regulates insulin signaling by interacting with insulin receptor and through adipocyte differentiation. However, GPC4 has not been studied with regard to its effects on clinical factors in patients with type 2 diabetes mellitus (T2DM). We aimed to identify factors associated with GPC4 level in T2DM. METHODS: Between January 2010 and December 2013, we selected 152 subjects with T2DM and collected serum and plasma into tubes pretreated with aprotinin and dipeptidyl peptidase-4 inhibitor to preserve active gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). GPC4, active GLP-1, active GIP, and other factors were measured in these plasma samples. We performed a linear regression analysis to identify factors associated with GPC4 level. RESULTS: The subjects had a mean age of 58.1 years, were mildly obese (mean body mass index [BMI], 26.1 kg/m2), had T2DM of long-duration (mean, 101.3 months), glycated hemoglobin 7.5%, low insulin secretion, and low insulin resistance (mean homeostatic model assessment of insulin resistance [HOMA-IR], 1.2). Their mean GPC4 was 2.0±0.2 ng/mL. In multivariate analysis, GPC4 was independently associated with age (β=0.224, P=0.009), and levels of active GLP-1 (β=0.171, P=0.049) and aspartate aminotransferase (AST; β=–0.176, P=0.043) after being adjusted for other clinical factors. CONCLUSION: GPC4 was independently associated with age, active GLP-1, and AST in T2DM patients, but was not associated with HOMA-IR and BMI, which are well known factors related to GPC4. Further study is needed to identify the mechanisms of the association between GPC4 and basal active GLP-1 levels.
Adipocytes ; Aprotinin ; Aspartate Aminotransferases ; Body Mass Index ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Gastric Inhibitory Polypeptide ; Glucagon-Like Peptide 1* ; Glypicans* ; Hemoglobin A, Glycosylated ; Humans ; Insulin ; Insulin Resistance ; Linear Models ; Multivariate Analysis ; Plasma ; Receptor, Insulin

BACKGROUND: The role of glycemic variability (GV) in development of cardiovascular diseases remains controversial, and factors that determine glucose fluctuation in patients with diabetes are unknown. We investigated relationships between GV indices, kinds of oral hypoglycemic agents (OHAs), and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). METHODS: We analyzed 209 patients with T2DM. The GV index (standard deviation [SD] and mean absolute glucose change [MAG]) were calculated from 7-point self-monitoring of blood glucose profiles. The patients were classified into four groups according to whether they take OHAs known as GV-lowering (A) and GV-increasing (B): 1 (A only), 2 (neither), 3 (both A and B), and 4 (B only). The 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Equations. RESULTS: GV indices were significantly higher in patients taking sulfonylureas (SUs), but lower in those taking dipeptidyl peptidase-4 inhibitors. In hierarchical regression analysis, the use of SUs remained independent correlates of the SD (beta=0.209, P=0.009) and MAG (beta=0.214, P=0.011). In four OHA groups, GV indices increased progressively from group 1 to group 4. However, these did not differ according to quartiles of 10-year ASCVD risk. CONCLUSION: GV indices correlated significantly with the use of OHAs, particularly SU, and differed significantly according to combination of OHAs. However, cardiovascular risk factors and 10-year ASCVD risk were not related to GV indices. These findings suggest that GV is largely determined by properties of OHAs and not to cardiovascular complications in patients with T2DM.
Blood Glucose ; Cardiovascular Diseases ; Cohort Studies ; Diabetes Mellitus, Type 2 ; Glucose ; Humans ; Hypoglycemic Agents* ; Risk Factors*

BACKGROUND: Air pollution causes many diseases and deaths. It is important to see how air pollution affects obesity, which is common worldwide. Therefore, we analyzed data from a smartphone application for intentional weight loss, and then we validated them. METHODS: Our analysis was structured in two parts. We analyzed data from a cohort registered to a smartphone application in 10 large cities of the world and matched it with the annual pollution values. We validated these results using daily pollution data in United States and matching them with user information. Body mass index (BMI) variation between final and initial login time was considered as outcome in the first part, and daily BMI in the validation. We analyzed: daily calories intake, daily weight, daily physical activity, geographical coordinates, seasons, age, gender. Weather Underground application programming interface provided daily climatic values. Annual and daily values of particulate matter PM10 and PM2.5 were extracted. In the first part of the analysis, we used 2,608 users and then 995 users located in United States. RESULTS: Air pollution was highest in Seoul and lowest in Detroit. Users decreased BMI by 2.14 kg/m2 in average (95% confidence interval, −2.26 to −2.04). From a multilevel model, PM10 (β=0.04, P=0.002) and PM2.5 (β=0.08, P < 0.001) had a significant negative effect on weight loss when collected per year. The results were confirmed with the validation (βAQI*time=1.5×10–5; P < 0.001) by mixed effects model. CONCLUSION: This is the first study that shows how air pollution affects intentional weight loss applied on wider area of the world.
Air Pollution* ; Body Mass Index ; Cohort Studies ; Mobile Applications ; Motor Activity ; Obesity ; Particulate Matter ; Seasons ; Seoul ; Smartphone ; United States ; Weather ; Weight Loss

Patients with diabetes have many different kinds of complications involving multiple organs, but those involving the musculoskeletal system are relatively uncommon. Diabetic muscle infarction (DMI) is a rare, painful, and potentially serious condition in patients with poorly controlled diabetes mellitus. A 35-year-old man diagnosed with type 2 diabetes eight years ago, visited with severe muscle pain in the right anteromedial thigh without any event of trauma. He had been treated with metformin, but his glycemic control was very poor with a glycated hemoglobin of 14.5%. Evaluation of his painful thigh lesion did not reveal any evidence of infection or vasculitis, but the magnetic resonance imaging and bone scan showed findings of DMI at vastus medialis muscle and an insufficiency fracture at the right medial tibial condyle. He was diagnosed with retinopathy, neuropathy and microalbuminuria but not macrovascular complications. We also diagnosed his diabetes as latent autoimmune diabetes in adults (LADA) based on his low C-peptide level, positive anti-glutamic acid decarboxylase (GAD) antibody and early onset diabetes. Instead of antibiotics, bed rest, analgesics and strict blood glucose control with multiple daily insulin injections led to symptom improvement. This is an unusual case of a young man with LADA experiencing severe musculoskeletal complication of DMI and insufficiency fracture. If a poorly controlled diabetic patient appears to have unaccounted soft tissue pain, musculoskeletal complications such as DMI associated with hyperglycemia should be considered.
Adult* ; Analgesics ; Anti-Bacterial Agents ; Bed Rest ; Blood Glucose ; C-Peptide ; Diabetes Mellitus ; Diabetes Mellitus, Type 1* ; Fractures, Stress ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Infarction ; Insulin ; Magnetic Resonance Imaging ; Metformin ; Musculoskeletal System ; Myalgia ; Nociceptive Pain ; Quadriceps Muscle ; Thigh ; Vasculitis

The aim of this study was to investigate the relationship between somatostatinergic tone (SST) and the size of growth hormone (GH)-producing pituitary tumors. GH levels of 29 patients with newly diagnosed acromegaly were measured using a 75-gram oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), and an octreotide suppression test (OST). Differences between GH levels during the ITT and the OGTT (DeltaGH(IO)), and between the OGTT and the OST at the same time point (DeltaGH(OS)) were compared according to the size of the tumor and the response pattern to the OST. DeltaGH(IO) of macroadenomas (n=22) was non-significantly higher than those of microadenomas while DeltaGH(OS) of macroadenomas were significantly higher than those of microadenomas. According to further analyses of macroadenomas based on the response pattern to the OST, GH levels during the ITT were significantly higher in non-responders. DeltaGH(OS) showed near-significant differences between responders and non-responders. In conclusion, as the size of the pituitary tumor increases, the effect of glucose on SST appears to be attenuated. Macroadenomas that are non-responders to the OST possess a portion of GH secretion exceeding the range of regulation by SST.
Acromegaly/*diagnosis/*pathology ; Adenoma/drug therapy/*pathology ; Adult ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Female ; Glucose Tolerance Test ; Human Growth Hormone/*blood/secretion ; Humans ; Insulin/blood ; Insulin-Like Growth Factor I/analysis ; Male ; Middle Aged ; Octreotide/therapeutic use ; Pituitary Neoplasms/drug therapy/*pathology

Background: Acromegaly is a rare, slowly progressive disease. Its mechanism is not fully understood, and epidemiological research on Korean patients with acromegaly is scarce.The purpose of this study was to determine the incidence and prevalence of acromegaly and assess the comorbidities and survival benefits based on treatment options. Methods: This nationwide population-based cohort study was conducted using data of the Korean Health Insurance Review and Assessment claims database to evaluate the incidence of newly diagnosed acromegaly cases during 2013–2017. Results: During the 5-year period, 1,093 patients were newly diagnosed with acromegaly.The average annual incidence was 4.2 cases per million per year, and the prevalence was 32.1 cases per million during this period. The incidence of hypertension was low after medical treatment (hazard ratio, 0.257; 95% confidence interval, 0.082–0.808; P = 0.020), but the incidence of diabetes showed no significant difference across treatment modalities. Over a period of 6 years since diagnosis, we found that patients treated for acromegaly had a significantly higher survival rate than those untreated (P < 0.001). Conclusion The annual incidence rate of Korean patients with acromegaly was similar to that reported in previous studies. Using nationwide population data, our study emphasized the importance of treatment in acromegaly patients.

Background: Methylglyoxal (MG) is associated with the pathogenesis of age- and diabetes-related complications. Spironolactone is a competitive antagonist of aldosterone that is widely employed in the treatment of hypertension and heart failure. This study examined the effects of spironolactone on MG-induced cellular dysfunction in MC3T3-E1 osteoblastic cells. Methods: MC3T3-E1 cells were treated with spironolactone in the presence of MG. The mitochondrial function, bone formation activity, oxidative damage, inflammatory cytokines, glyoxalase I activity, and glutathione (GSH) were measured. Results: Pretreatment of MC3T3-E1 osteoblastic cells with spironolactone prevented MG-induced cell death, and improved bone formation activity. Spironolactone reduced MG-induced endoplasmic reticulum stress, production of intracellular reactive oxygen species, mitochondrial superoxides, cardiolipin peroxidation, and inflammatory cytokines. Pretreatment with spironolactone also increased the level of reduced GSH and the activity of glyoxalase I. MG induced mitochondrial dysfunction, but markers of mitochondrial biogenesis such as mitochondrial membrane potential, adenosine triphosphate, proliferator-activated receptor gamma coactivator 1α, and nitric oxide were significantly improved by treatment of spironolactone. Conclusion Spironolactone could prevent MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells by reduction of oxidative stress. The oxidative stress reduction was explained by spironolactone's inhibition of advanced glycation end-product formation, restoring mitochondrial dysfunction, and anti-inflammatory effect.

Background: Only a few studies have established the epidemiology of prolactinoma and Cushing’s disease in Korea. Furthermore, the incidence of these disease are increasing than before associated with the development of technologies. This study was designed to evaluate the epidemiology of prolactinoma and Cushing’s disease and their survival analysis according to treatment. Methods: The nationwide, population-based study evaluated incidence and prevalence of prolactinoma and Cushing’s disease using de-identified claims data in The Korean Health Insurance Review and Assessment Service database between 2013 and 2017. The survival analysis investigated regarding treatment over a period of 6 years. A log-rank test and Cox proportional hazard regression analysis were used. Results: The 6,056 patients with newly diagnosed prolactinoma and 584 patients with Cushing’s disease were recorded between 2013 and 2017. The annual incidence of prolactinoma was 23.5 cases per million, and its prevalence was 82.5 cases per million, and 2.3 cases per million/year and 9.8 cases per million for Cushing’s disease. The survival benefit was insignificant in prolactinoma according to treatment, but treatment of Cushing’s disease ameliorated the survival rate significantly. Conclusion Overall, the incidence of prolactinoma and Cushing’s disease was similar with those found previously, but the prevalence of two diseases were inconsistent when compared with the early studies. The present study also proposed necessity of treatment in Cushing’s disease for improving the survival rate.