A Multicentre, Multinational, Open-Label, 52-Week Extension Study of Gemigliptin (LC15-0444) Monotherapy in Patients with Type 2 Diabetes Mellitus

The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (–0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was –0.9%±1.2% (P<0.0001). For the pbo-gemi group, HbA1c decreased after they were switched to gemigliptin, and the mean change in HbA1c at week 52 from baseline was –0.7%±1.2% (P<0.0001). Furthermore, the overall incidence of adverse events demonstrated that gemigliptin was safe and well tolerated up to 52 weeks.

A Multicentre, Multinational, Open-Label, 52-Week Extension Study of Gemigliptin (LC15-0444) Monotherapy in Patients with Type 2 Diabetes Mellitus

The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (–0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was –0.9%±1.2% (P<0.0001). For the pbo-gemi group, HbA1c decreased after they were switched to gemigliptin, and the mean change in HbA1c at week 52 from baseline was –0.7%±1.2% (P<0.0001). Furthermore, the overall incidence of adverse events demonstrated that gemigliptin was safe and well tolerated up to 52 weeks.

A Case of Fulminant Type 1 Diabetes Mellitus in an Elderly Patient / 임상당뇨병

Insulin deficiency due to destruction of pancreatic beta-cells is a typical characteristic of type 1 diabetes mellitus (DM). In 2000 Imagawa proposed a novel diagnostic model defining "fulminant type 1 DM" as developing rapidly without any evidence of autoimmunity, and ever since there have been many reports regarding the matter in Japan. In 2004, the first fulminant type 1 diabetes case was reported in Korea; however, there have been few reports since then. We present a case of a 60-year-old man who suffered from excessive thirst and polyuria after myalgia. Laboratory findings revealed a high blood glucose level and evidence of diabetic ketoacidosis, but the HbA1c level was within the normal range. The serum C-peptide level was very low and antibodies to glutamic acid decarboxylase were negative. These findings suggested fulminant type 1 diabetes. This patient has shown improvement in symptoms and examination results without complications after being treated with insulin therapy with hydration, throughout 6-months follow-up period.

Serum Magnesium Level Is Associated with Type 2 Diabetes in Women with a History of Gestational Diabetes Mellitus: The Korea National Diabetes Program Study

Gestational diabetes mellitus (GDM) is a strong predictor of postpartum prediabetes and transition to overt type 2 diabetes (T2DM). Although many reports indicate that low magnesium is correlated with deteriorated glucose tolerance, the association between postpartum serum magnesium level and the risk for T2DM in women with a history of GDM has not been evaluated. We analyzed postpartum serum magnesium levels and development of prediabetes and T2DM in women with prior GDM according to American Diabetes Association (ADA) criteria using the Korean National Diabetes Program (KNDP) GDM cohort. During a mean follow-up of 15.6+/-2.0 months after screening, 116 women were divided into three groups according to glucose tolerance status. Ultimately, eight patients (6.9%) were diagnosed with T2DM, 59 patients (50.9%) with prediabetes, and 49 patients (42.2%) with normal glucose tolerance (NGT) after follow-up. The T2DM group had the lowest serum magnesium level (0.65 [0.63-0.68] mM/L) in the postpartum period, but there was no significant difference between the prediabetes group (0.70 [0.65-0.70] mM/L) and the NGT group (0.70 [0.65-0.70] mM/L) (P=0.073) Multiple logistic regression analysis showed that postpartum HOMA-IR was a significant predictor of both prediabetes and T2DM. Moreover, we found that postpartum serum magnesium level was also a possible predictor for T2DM development. Serum magnesium level in the postpartum period may be a possible predictor for T2DM development in women with a history of GDM.

Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance

BACKGROUND/AIMS: The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). METHODS: A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose > or = 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). RESULTS: The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index beta-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p < or = 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p < 0.001 for all). Among the GIGT subjects, the 1-hour plasma glucose abnormal levels group showed significantly greater weight gain during pregnancy and higher values in the 50-g OGCT than the other two groups. Moreover, the 1-hour and 2-hour abnormal levels groups had poorer insulin secretion status than the 3-hour abnormal levels group. CONCLUSIONS: Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both beta-cell dysfunction and insulin resistance.

Increased Selenoprotein P Levels in Subjects with Visceral Obesity and Nonalcoholic Fatty Liver Disease

BACKGROUND: Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD). METHODS: We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected from participants of the Korean Sarcopenic Obesity Study. In addition, we evaluated the relationship between SeP and cardiometabolic risk factors, including homeostasis model of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), adiponectin values, and brachial-ankle pulse wave velocity (baPWV). RESULTS: Subjects with NAFLD showed increased levels of HOMA-IR, hsCRP, VFA, and several components of metabolic syndrome and decreased levels of adiponectin and high density lipoprotein cholesterol than those of controls. Serum SeP levels were positively correlated with VFA, hsCRP, and baPWV and negatively correlated with the liver attenuation index. Not only subjects with visceral obesity but also those with NAFLD exhibited significantly increased SeP levels (P<0.001). In multiple logistic regression analysis, the subjects in the highest SeP tertile showed a higher risk for NAFLD than those in the lowest SeP tertile, even after adjusting for potential confounding factors (odds ratio, 7.48; 95% confidence interval, 1.72 to 32.60; P=0.007). CONCLUSION: Circulating SeP levels were increased in subjects with NAFLD as well as in those with visceral obesity and may be a novel biomarker for NAFLD.

Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats

BACKGROUND: Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats. METHODS: Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks. RESULTS: Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-beta1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups. CONCLUSION: Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.

Hyperprolactinemia-Associated Breast Uptake of Radioiodine Following 131I Postablation Scan in Differentiated Thyroid Cancer

Scanning with whole-body 131I scintigraphy after surgery has been a valuable diagnostic modality in the surveillance of patients with differentiated thyroid cancer. Radioiodine uptake is rarely observed in non-lactating breast tissue, which mimics thyroid cancer metastasis. We now report a case of a 45-year-old female thyroid cancer patient who underwent radioiodine therapy, and in whom breast uptake of radioiodine was observed on a post-therapy whole body scan. Her serum prolactin level was elevated to 328 ng/mL at the time of the radioiodine uptake, and the hyperprolactinemia was induced by her antipsychotic medications. Six months after she discontinued that medication, her serum prolactin level was normalized to 12.6 ng/mL and breast uptake of iodine was no longer present in a follow-up whole body scan.

Effect of Exercise on Cardiovascular Disease in Patients with Diabetes Mellitus (Aerobic vs. Resistance) / 임상당뇨병

The beneficial effects of exercise in patients with type 2 diabetes mellitus (T2DM) are caused by improvement of various cardiovascular risk factors. Previous studies have shown that there is a dose-dependent negative relationship between aerobic exercise and risk of cardiovascular disease (CVD). Furthermore, many recent studies reported that both aerobic and resistance exercise are equally beneficial for improvement of diverse CVD risk factors as well as better glucose control. Exercise especially improves HbA1c, HDL-cholesterol, blood pressure, and central obesity.Aerobic exercise that uses large muscle structure leads to improve aerobic fitness (VO2max). Increase of VO2max and improvement of insulin sensitivity is strongly correlated. On the other hand, resistance exercise induces a hypertrophy of muscle and muscle-fiber type shifting. Therefore, resistance training is beneficial for increment of muscle mass. These changes allow potential increase of glucose utilization. In patients with type 2 diabetes, exercise training is useful for controlling glucose and other metabolic risk factors. However, exercise training must be implemented with proper pre-assessment of cardiovascular risk.

Klebsiella pneumoniae Orbital Cellulitis with Extensive Vascular Occlusions in a Patient with Type 2 Diabetes

A 39-year-old woman visited the emergency room complaining of right eye pain and swelling over the preceding three days. The ophthalmologist's examination revealed orbital cellulitis and diabetic retinopathy in the right eye, although the patient had no prior diagnosis of diabetes. It was therefore suspected that she had diabetes and orbital cellulitis, and she was started on multiple antibiotic therapies initially. She then underwent computed tomography scans of the orbit and neck and magnetic resonance imaging of the brain. These studies showed an aggravated orbital cellulitis with abscess formation, associated with venous thrombophlebitis, thrombosis of the internal carotid artery, and mucosal thickening of maxillary sinus with multiple paranasal abscesses. Three days later, initial blood culture grew Klebsiella pneumoniae. She recovered after incision and drainage and antibiotic therapy for 37 days.

Therapeutic effects of a long-acting formulation of lanreotide in Korean patients with acromegaly / 대한내과학회지

BACKGROUND: The present study was conducted to examine the effects of a long-acting formulation of lanreotide (Somatulin-Autogel(R)) in Korean acromegalic patients who had undergone surgery. METHODS: The subjects in the study were 11 acromegalic patients (5 men and 6 women) who had undergone transsphenoidal tumor resection at Korea University Guro Hospital. The anthropometric parameters, blood pressure, fasting blood glucose (FBG), IGF-1, HbA1C, mass size and GH level following a 75 gm oral glucose tolerance test (OGTT) were measured in each subject before and after treatment with a long-acting formulation of lanreotide. RESULTS: The median age of the subjects was 41 yrs (range: 28-52 yrs) (Table 1). The mean pre-operative levels of serum IGF-1 in the 11 patients was 1185+/-323.58 ng/mL, and post-operatively it was 862+/-314.06 ng/mL. The mean serum IGF-1 concentration decreased from 862+/-314.06 ng/mL to 549+/-371.62 ng/mL after 6 months treatment with the long-acting formulation of lanreotide (p=0.003, vs baseline, n=11), and it decreased further to 439+/-342.53 ng/mL after 12 months treatment (p=0.005 vs baseline, n=10) (Table 3). Two patients achieved the target level of IGF-1. The HbA1C measured before and after lanreotide treatment was 5.8+/-0.5% and 5.9+/-0.3%, respectively. CONCLUSIONS: This study showed that a long-acting formulation of lanreotide decreased the IGF-1 and GH levels without significant side effects. In spite of the small number of subjects in this study, these findings suggest that this formulation of lanreotide is effective for the post-operative management of acromegaly.

The prevalence of microalbuminuria and associated factors in newly diagnosed type 2 diabetes mellitus in Korea / 대한내과학회지

BACKGROUND: To determine the prevalence and the associated factors of microalbuminuria in Korean subjects with newly diagnosed type 2 diabetes mellitus. METHODS: A total of 304 patients with newly diagnosed type 2 diabetes mellitus that visited Anam Hospital, Korea University Medical Center, were studied cross-sectionally for the presence of microalbuminuria and other micro- and macrovascular complications. Microalbuminuria was calculated by the amount of albumin excretion in the urine for 24 hrs (30-299 mg/24hr) or by the albumin creatinine ratio in a spot urine sample (30-299 mg/g creatinine). Subjects were divided into two groups: the normoalbuminuria group and the microalbuminuria group. RESULTS: The prevalence of microalbuminuria, normoalbuminuria and overt proteinuria in patients with newly diagnosed type 2 diabetes mellitus was 17.1%, 80.3% and 2.6%. respectively. Microalbuminuria was significantly correlated with the body mass index (BMI), fasting insulin level, fasting C-peptide level and triglyceride level. The number of metabolic syndrome components was significantly correlated with the amount of microalbuminuria. In patients with microalbuminuria and without retinopathy, the correlation of microalbuminuria and the presence of metabolic syndrome was also significant. CONCLUSIONS: The prevalence of microalbuminuria in 304 Korean patients with newly diagnosed type 2 diabetes mellitus was 17.1%, and microalbuminuria had a correlation with the BMI, fasting insulin level, fasting C-peptide level, HOMA level, triglyceride level and the presence of metabolic syndrome.

A Case of Sheehan's Syndrome Presenting Central Diabetes Insipidus / 대한내분비학회지

Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. The manifestations of this clinical syndrome are most often caused by a deficiency in the hormones produced by the anterior pituitary gland, whereas the neurohypophysis is usually preserved but can be involved in severe cases that manifest as diabetes insipidus. This is a report of Sheehan's syndrome that manifested with diabetes insipidus as presenting symptom 2 month's after delivery. The patient suffered massive bleeding, so received a blood transfusion. A combined pituitary stimulation and water deprivation test revealed deficiencies of not only anterior pituitary hormones, such as growth hormone and prolactin, but also of anti-diuretic hormone. We report this case, with a review of the literature.

A Case of Sheehan's Syndrome Presenting Central Diabetes Insipidus / 대한내분비학회지

Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. The manifestations of this clinical syndrome are most often caused by a deficiency in the hormones produced by the anterior pituitary gland, whereas the neurohypophysis is usually preserved but can be involved in severe cases that manifest as diabetes insipidus. This is a report of Sheehan's syndrome that manifested with diabetes insipidus as presenting symptom 2 month's after delivery. The patient suffered massive bleeding, so received a blood transfusion. A combined pituitary stimulation and water deprivation test revealed deficiencies of not only anterior pituitary hormones, such as growth hormone and prolactin, but also of anti-diuretic hormone. We report this case, with a review of the literature.