Comparison of the Efficacy and Safety of Insulin Detemir Administered Once Daily According to Two Titration Algorithms (3-0-3 and 2-4-6-8) in Patients with Type 2 Diabetes Mellitus

BACKGROUND: This study was conducted to compare glycaemic control with insulin detemir administered according to two titration algorithms (3-0-3 and 2-4-6-8) after 20 weeks of treatment in subjects with type 2 diabetes mellitus inadequately controlled on metformin.METHODS: This was a 20-week, randomised, multicentre, open-labelled, treat-to-target trial. Forty-six patients were randomised in a 1:1 manner to either the 3-0-3 (G3, n=23) or 2-4-6-8 (G2, n=23) algorithm. The primary endpoint was change of haemoglobin A1c (HbA1c), and the secondary safety endpoint included hypoglycaemic events.RESULTS: After 20 weeks, HbA1c decreased similarly in the G3 and G2 groups, with a mean change of −0.9% from baseline. The mean change in fasting plasma glucose was numerically similar in both groups. The hypoglycaemia event rate per 100-patient-years of exposure (r) in the G2 group (r=1,427) was higher than that in the G3 group (r=807).CONCLUSION: Both treatment groups had numerically similar HbA1c reductions. A trend towards fewer hypoglycaemia episodes after dose stabilisation was seen with the simpler G3. Clinically, this may be an important observation, as a simpler titration algorithm may support self-management and maintenance of insulin therapy.

The Effect of Vildagliptin on Visfatin in Korean Patients with Type 2 Diabetes: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Prospective Study / 임상당뇨병

BACKGROUND: The effects of dipeptidyl peptidase-4 inhibitors on adipokines remain obscure. The aim of this study was to evaluate the effect of the addition of vildagliptin on visfatin, an adipokine that represents inflammatory biomarkers of adipose tissue, in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy. METHODS: In this 16-week, double-blind, randomized, parallel-group, placebo-controlled study, 71 patients were randomly assigned to vildagliptin 50 mg twice a day (n = 35) or placebo (n = 36) added to ongoing metformin therapy. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma lipids, and visfatin levels were measured at baseline and 16 weeks after treatment. RESULTS: After 16 weeks, significant reduction in HbA1c and FPG was observed with vildagliptin addon treatment compared to placebo (-0.54 +/- 0.52%, P = 0.001 and -14.80 +/- 19.21 mg/dL, P = 0.004, respectively). However, no other clinically meaningful changes in lipid parameters or visfatin were observed. CONCLUSION: Vildagliptin add-on to metformin significantly improved fasting blood glucose and HbA1c. However, in this study, no significant differences in lipid parameters or visfatin level were observed between the two groups.

An overview of the pathogenic mechanisms of autoimmune thyroid disorders / 고신대학교의과대학학술지

Objectives, recent epidemiologic studies in humans suggest an increased prevalence of thyroiditis associated with the excessive administration of iodine. More than three times of recommended daily intake of iodine was observed among people in North America. These people generally presented higher level of anti-thyroglobulin antibody, anti-thyroperoxidase antibody, serum thyroid-stimulating hormone and exacerbation of lymphocytic infiltration in thyroid, which indicated the overconsumption of iodine could induce hypothyroidism and enhance the autoimmune response. However, the precise mechanism of excessive iodine intake induced autoimmune thyroid disease remains largely unknown. Over half a century has elapsed since the 1956 identification of thyroglobulin antibodies and the devising of the first experimental model of autoimmune thyroiditis. Since then an incredible amount of experimental work has led to an ever deeper understanding of the nature of thyroid auto-antigens, the main immune mechanisms responsible for Hashimoto's thyroiditis and graves' disease, their genetics, and therir environmental risk factor. Yet, in the majority of genetically predisposed people the individual trigger of thyroid autoimmunity remains obscure. Similarly, effective prevention strategies still remain to be established and, hopefully, will be the target of future studies.

Safety and Efficacy of Modern Insulin Analogues

BACKGROUND: A1chieve(R) was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. METHODS: Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. RESULTS: Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7+/-15.9 to 72.5+/-13.5) while the mean body weight was slightly increased (0.6+/-3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%+/-2.2%, 2.5+/-4.7 mmol/L, and 4.0+/-6.4 mmol/L, respectively. CONCLUSION: The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

Clinical Characteristics of Type 2 Diabetes Patients according to Family History of Diabetes / 당뇨병

BACKGROUND: Type 2 diabetes mellitus (T2DM) has a strong genetic component, and its prevalence is notably increased in the family members of T2DM patients. However, there are few studies about the family history of T2DM. We carried out this study to assess the influences of family history on clinical characteristics in T2DM patients. METHODS: This is a cross-sectional study involving 651 T2DM patients. Patient history and physical examination were performed and fasting blood was taken. If any first degree relative was diabetic, a family history of diabetes was considered to exist. RESULTS: Among the total 621 patients, 38.4% had a family history of diabetes. Patients with a family history had a younger age, higher weight, younger age at diagnosis and higher triglyceride level than did those without a family history. Dyslipidemia medication and metabolic syndrome were more prevalent in familial diabetes. Sex, blood pressure, previous treatment for diabetes, HbA1C, C-peptide, total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were not different between familial and non-familial diabetes. Upon multiple linear regression analysis, the family history of diabetes remained significantly associated with serum triglyceride level. CONCLUSION: In T2DM patients with a family history of diabetes, the disease tended to develop earlier. Metabolic syndrome and cardiovascular risk factors are more prevalent in familial T2DM than they were in non-familial T2DM. These results support the necessity of earlier screening for diabetes in family members of T2DM patients and more active prevention against cardiovascular disease in T2DM patients with a family history.

Peg-interferon induced autoimmune thyroiditis / 대한내과학회지

Peg-interferon is the main therapeutic agent in patients infected with the hepatitis C virus. It is rather safe, but it is known to induce production of autoantibodies and it can lead to the occurrence of autoimmune disease. Interferon induced thyroiditis is considered a major clinical problem for patients who receive interferon therapy. We recently experienced a 36 year-old woman who developed peg-interferon induced thyroiditis. To the best of our knowledge, this is a rare case report in Korea. We report here on this casea long with a review of the literature.

A case of idiopathic hyperaldosteronism vs. bilateral aldosterone producing adenoma / 대한내과학회지

In most cases, primary aldosteronism is due to a unilateral adrenal adenoma or bilateral hyperplasia of the adrenal cortex. However, a few bilateral adrenal tumors have also been reported in primary aldosteronism. In such cases, it is important to differentiate bilateral aldosterone-producing adenomas from bilateral adrenal hyperplasia so as to develop the optimal treatment plan. We report a case of idiopathic hyperaldosteronism due to bilateral adrenal hyperplasia that could have been misdiagnosed as a bilateral aldosterone-producing adenoma. An adrenal CT scan revealed bilateral adrenal tumors (1.5 cm [right] and 3.6 cm [left] in diameter). Idiopathic hyperaldosteronism was properly diagnosed using a posture test and selective adrenal venous sampling.

Hepatocyte nuclear factor 1-alpha mutation in normal glucose-tolerant subjects and early-onset type 2 diabetic patients

BACKGROUND/AIMS: The prevalence of diabetes in Korea is reported to be approximately 10%, but cases of maturity-onset diabetes of the young (MODY) are rare in Korea. A diagnostic technique for autosomal dominant MODY is being actively sought. In this regard, we used a DNA chip to investigate the frequency of mutations of the MODY3 gene (hepatocyte nuclear factor-1alpha) in Korean patients with early-onset type 2 diabetes. METHODS: The genomic DNA of 30 normal individuals [age, 24.9+/-8.6 years] and 25 patients with early-onset type 2 diabetes (age, 27+/-5.9 years) was extracted, and the MODY3 gene was amplified. The amplified DNA was hybridized onto a MODY3 chip, which has oligonucleotides of 15-25 bases, representing wild-type and mutant MODY3 sequences in both forward and reverse orientations, immobilized on its surface. RESULTS: Among the normal subjects, there was no mutation of MODY3. Among those with early-onset type 2 diabetes, there was one case of MODY3 mutation. CONCLUSIONS: Our results indicate that MODY3 mutations are not rare in Korean early-onset type 2 diabetes patients in Korea and suggest that MODY3 mutations in patients with early-onset type 2 diabetes need to be further evaluated.

Morphological Changes in Vasopressin-immunoreactive Neurons in the Hypothalamus of the Aged Rats / 체질인류학회지

The role of neuropeptides in the central nervous system (CNS) has received increasing attention. Numerous peptide molecules are found in the mammalian CNS and many of them are thought to act as either neurotransmitters or neuromodulators. The neuropeptides found in high concentration in the hypothalamus include vasopressin (VP), vasoactive intestinal polypeptide, somatostatin, and oxytocin. The main approches to assess the involvement of neuropeptides can be focused on functions affecting the aging of the brain. Morphological aging of the CNS has been characterized by degenerative changes of fiber connections and cell loss, although degeneration does not always occur to the same extent throughout various parts of the brain and, moreover, varies for different cell types. Despite of many studies in VP containing neurons , there exist discrepancies in results about the changes of aged rat brain. The aim of the present study is, therefore, to investigative possible changes in the number and morphology of VPimmunoreactive neurons with aging in each area of the hypothalmus of the aged rats. As a result, the number of VP-immunoreactive neurons was decreased in hypothalamus nucleus of aged group. Especially, in VP-immunoreactive neurons of hypothalamus, the size of neuronal cell body and nuclei in aged group is larger than in young group and the fiber density of immunoreactivity neurons of median eminance (ME) in aged group is stronger than in young group. But, the total number of VP-immunoreactive neurons in the suprachiasmatic nucleus (SCN) of the aged group is larger than in the young group. These studies indicate the involvement of VP-immunoreactive neurons in aging process of hypothalamus, and aging process may affect the synthesis of VP in the neurons of hypothalamic nuclei. Whereas, in VP expression, aging process induces an enlargement of the cell size of surviving neurons to compensate.

A Case of a Composite Adrenal Medullary Tumor of Pheochromocytoma and Ganglioneuroma Masquerading as Acute Pancreatitis

Composite adrenal medullary tumors, composed of both pheochromocytoma and ganglioneuroma, are extremely rare, as are pheochromocytomas masquerading as acute relapsing pancreatitis. We recently experienced a case of a 48-year-old male with both these phenomena. The patient complained of an acute onset of intense abdominal discomfort. At the same time, pancreatic enzymes were increased in concentration. An abdominal computed tomographic scan revealed an enlarged pancreas and a 3-cm left adrenal incidentaloma. Biochemical and 131I-MIBG scintigraphic findings were compatible with a pheochromocytoma. Yet, he had no clinical manifestations suggesting pheochromocytoma. An adrenalectomy was performed and a composite adrenal medullary tumor of pheochromocytoma and ganglioneuroma was confirmed during a pathologic examination. This case illustrates two points: 1) acute abdominal intense discomfort and hyperamylasemia may be unusual presentations of pheochromocytomas; and 2) the possibility of the pheochromocytoma, albeit rare, should be considered when a relapsing pancreatitis of uncertain etiology develops.

Seroepidemiological Characteristics of Haemorrhagic Fever with Renal Syndrome from 1996 to 2005 in Korea

Haemorrhagic fever with renal syndrome (HFRS) caused by Hantaan viruses has been one of the principal acute febrile disease in Korea. To analysis the sero-epidemiological patterns of HFRS, 4,177 patient sera of acute febrile illness submitted for serological assay to National Institute of Health from Community Health Centers, Institutes of Health and Environment and hospitals from 1996 to 2005 were examined for antibodies against Hantaan virus by indirect immunofluorescent assay (IFA). Serum samples with greater than 1:32 antibody titer were considered positive. The results were analyzed seroepidemiologically by annual, sexual, seasonal, age and regional distribution of HFRS patients. Out of 4,177 serum samples tested, 1,415 samples (33.9%) were positive to Hantaan virus. The ratio of males (48.2%, 682/1,415) to females (38.2%, 541/1,415) was 1.3:1. Seasonal incidence showed that 69.5% (985/1,415) of cases occurred from October to December, resulting with higher prevalence in November (41.3%, 584/1,415). Regionally, seropositive rates of samples collected in Gyenggi, Gangwon and Chungbuk were 39.9% (564/1,415), 19.3% (274/1,415) and 8.5% (120/1,1415), respectively. Age distributions of seropositive of HFRS were detected from 20 to 79 years (78%).

Apoptotic Neuronal Death in the Mouse Brain Induced by Experimental Japanese Encephalitis Virus Infection / 대한해부학회지

Japanese encephalitis virus (JEV)may cause acute encephalitis in humans and induce severe cytopathic effects in various types of cultured cells. To investigate whether JEV infection induces apoptosis, we examined DNA fragmentation and apoptosis in the specific region of the JEV infected mouse brain by DNA oligonucleosomal laddering and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)technique and immunohistochemical study. JEV infections in the mouse brain were detected in the telencephalon, the diencephalons, and the brain stem, but not in the cerebellum and the hippocampus. Fragmentation of cellular DNA into oligonucleosome-length ladders was only observed in tissue samples prepared from the cerebral cortex. In addition, the large number of TUNEL-positive cells was observed in the cerebral cortex. Double-labeling experiment with TUNEL staining and immunostaining for the JEV showed that TUNEL-positive neurons containing JEV immunoreactivity. These results suggest that JEV infection may evoke apoptotic neuronal death in the mouse brain, which plays an important role in the pathogenesis of Japanese encephalitis.

A Case Of Transient Hyporeninemic Hypoaldosteronism After Unilateral Adrenalrectomy for Aldosterone-Producing Adenoma / 대한내분비학회지

Primary aldosteronism is due to either a unilateral adrenal adenoma or bilateral hyperplasia of the adrenal cortex in most cases. A unilateral adrenalectomy in hypertensive and hypokalemic patients, with a well-documented adrenal adenoma, is usually followed by the correction of hypokalemia in all subjects, with the cure of hypertension in 60 to 87% of patients. Here, a unique case, in which a unilateral adrenalectomy for the removal of an adrenal adenoma was followed by severe hyperkalemia, low levels of plasma renin activity and serum aldosterone, suggestive of chronic suppression of the renin-aldosterone axis, is reported. In a follow-up Lasix stimulation test on the 70th day after surgery, the suppression of the renin-aldosterone axis was resolved, indicating the suppression was transient. Patients undergoing a unilateral adrenalectomy for an aldosterone-producing adenoma should be closely followed up to avoid severe hyperkalemia.

A Case of Graves' Disease associated with Idiopathic Thrombocytopenic Purpura / 대한내분비학회지

The association of Graves' disease and idiopathic thrombocytopenic purpura(ITP) is a rather rare, but well documented condition, and has also been reported a few times in Korea. At present, two main hypothetical mechanisms are used to explain the association of the two diseases; the presence of autoimmunity, which leads to both diseases, and activation of the reticuloendothelial system by thyroid hormone. A 33 year old female patient visited our hospital with mucosal bleeding and purpura over her entire body of 3 days duration. Her initial platelet count was 2x109/L, and the thyroid function tests showed a suppressed TSH level of 0.09 mU/L(0.4~3.1) and elevated levels of triiodothyronine and free thyroxine. The levels of anti-thyroglobulin Ab anti-TPO Ab, and anti-TSH receptor Ab were also elevated. The clinical, laboratory and bone marrow findings were compatible with Graves' disease associated with ITP. She was treated with methylprednisolone and propylthiouracil, after which her platelet count increased and thyroid function normalized. We report a case of Graves' disease associated with ITP, which was treated well by glucocorticoid and antithyroid medications

A Case of Thyroid Abscess Associated with Lymphocytic Thyroidits / 대한내분비학회지

No Abstract available.

Positive Rate of Antibody Against Dengue Virus for Korean Who Traveled to Dengue Epidemic Area

BACKGROUND: Recently, dengue fever has increased throughout tropical regions and emerged as the most important vector borne viral disease in human. 4 serotypes of viruses are circulating concurrently in these regions and thus it may be anticipated to increase risk of dengue hemorrhagic fever. Even though dengue fever is still not endemic in Korea, it is necessary to test antibodies against dengue viruses because the number of Koreans who have visited these regions is continuously increasing. MATERIALS AND METHODS: Serum specimens from persons with suspected dengue fever had been collected. Commercial kit, immunochromatographic test (ICA), and the IgM capture enzyme-linked immunosorbent assay (MAC-ELISA) were employed for dengue fever detection in these studies. For confirmation randomized 25 specimens among total of 99 specimens were selected and compared with those results from commercial kit and IFA. RESULTS: 33 (33.3%) among 99 specimens showed positive antibody against dengue virus by commercial kit. Positive rate of traveller who have visited Indonesia, Philippines, Malaysia, Thiland was 54.5%. To compare the efficiency of test methods, 25 randomly selected specimens were tested by the MAC-ELISA and IFA simultaneously. 9 specimens showed postive results with the MAC-ELISA method whereas 13 speciments were positive with the IFA methods. CONCLUSION: Confirming the diagnosis of dengue fever with antibody against dengue virus was attempted for the first time in Korea. The results from our study indicate that establishing a national surveillance and/or laboratory diagnostic system in Korea are necessary. In addtion, antibody test strategies for national surveillance system should be carefully considered.

Positive Rate of Antibody Against Dengue Virus for Korean Who Traveled to Dengue Epidemic Area

BACKGROUND: Recently, dengue fever has increased throughout tropical regions and emerged as the most important vector borne viral disease in human. 4 serotypes of viruses are circulating concurrently in these regions and thus it may be anticipated to increase risk of dengue hemorrhagic fever. Even though dengue fever is still not endemic in Korea, it is necessary to test antibodies against dengue viruses because the number of Koreans who have visited these regions is continuously increasing. MATERIALS AND METHODS: Serum specimens from persons with suspected dengue fever had been collected. Commercial kit, immunochromatographic test (ICA), and the IgM capture enzyme-linked immunosorbent assay (MAC-ELISA) were employed for dengue fever detection in these studies. For confirmation randomized 25 specimens among total of 99 specimens were selected and compared with those results from commercial kit and IFA. RESULTS: 33 (33.3%) among 99 specimens showed positive antibody against dengue virus by commercial kit. Positive rate of traveller who have visited Indonesia, Philippines, Malaysia, Thiland was 54.5%. To compare the efficiency of test methods, 25 randomly selected specimens were tested by the MAC-ELISA and IFA simultaneously. 9 specimens showed postive results with the MAC-ELISA method whereas 13 speciments were positive with the IFA methods. CONCLUSION: Confirming the diagnosis of dengue fever with antibody against dengue virus was attempted for the first time in Korea. The results from our study indicate that establishing a national surveillance and/or laboratory diagnostic system in Korea are necessary. In addtion, antibody test strategies for national surveillance system should be carefully considered.

Application of Hantavirus N Protein Expressed by E. coli System

Hantaan viruses cause haemorrhagic fever with renal syndrome (HFRS), resulting in severe morbidity and mortality in humans. The genome of Hantaan virus is composed of three segmented and single stranded negative sense RNA genome. In this study, we expressed nucleocapsid (N) proteins of Hantaan 76-118, Seoul 80-39 and Hantaan virus isolated in Korea (01-23) using E. coli system. These N proteins were fused with a thioredoxin protein for secretion of the expressed protein. The antigenicity of each expressed N proteins was examined in Western blot with sera from HFRS patients and normal controls. The expressed N proteins did not show any cross-reactivity with sera obtained from patients with leptospirosis and tsutsugamushi disease. These results suggest that our recombinant N proteins can be used for the development of diagnostic system to distinguish between HFRS and leptospirosis or tsutsugamushi.

In vivo Study on the Japanese Encephalitis: Viral Localization and Histopathology in the Mouse Brain / 대한해부학회지

Japanese encephalitis is a potentially lethal disease of the central nervous system caused by infection with Japanese encephalitis virus (JEV). JEV is the most common cause of encephalitis over a large part of eastern Asia. To establish and characterize in vivo model to study the Japanese encephalitis, the immunohistochemical localization of JEV and the histopathological finding were investigated in the brains of young adult mice infected with JEV by intraperitoneal inoculation. JEV was localized to neurons in discrete regions of the brain. Histopathological finding showed typical pattern of acute viral encephalitis, such as inflammatory cell infiltration in brain parenchyme and perivascular cuffs of mononuclear cells. These results suggest that this in vivo system can be used to study the mechanism of virus entry into the brain, cell specific tropism, and pathophysiology in Japanese encephalitis.

Usefulness of ankle brachial pressure index measured using photoplethysmography and automated blood pressure measurement device / 대한내과학회지

BACKGROUND: Resting ankle brachial pressure index is a non-invasive method to assess the patency of lower extremity arterial system and it can be measured using traditional Doppler method or photoplethysmography. Automated blood pressure measurement is a easy and quick method for measurement of ankle brachial pressure index, but usefulness of this method have not been investigated. So we evaluated the accuracy of Automated blood pressure measurement device as flow detector in determining the ankle brachial pressure index in comparison to photoplethysmography. METHODS: A total 136 subjects containing 117 diabetic patients and 19 volunteers were included in the study. With each subject in the supine position, dorsalis pedis arterial pulses were palpated by examiner. And the brachial and ankle systolic blood pressure were recorded using photoplethysmography (Rheoscreen, Medis, Germany) and automated blood pressure measurement device (MD-800, Meditec, Korea). Ankle brachial pressure index for each leg was separately calculated by dividing the ankle systolic pressure by the higher brachial systolic pressure. Statistical analyses were performed by SPSS for Windows (version 10.0 SPSS Inc.) RESULTS: Brachial and ankle systolic pressure measured using automated blood pressure measurement device were higher than photoplethysmography and correlations between both method were significant (r=0.886, r=0.844). Ankle brachial pressure index derived using automated blood pressure measurement have a better correlation with photoplethysmography method (r=0.622) than pulse palpation (r=0.255). The subject was considered to have peripheral arterial disease if either leg ABI was 0.9 or less. Peripheral arterial disease was more frequent when it was defined using photoplethysmography (13.8%) vs automated blood pressure measurement device (6.3%). The sensitivity of the automated blood pressure measurement is 32.4%, the specificity is 97.8% and the accuracy is 88.8% for peripheral arterial disease defined using photoplethysmography. CONCLUSION: Automated blood pressure measurement was easier and quicker and less expensive as compared with photoplethysmography. Automated blood pressure measurement was not sensitive but more accurate as compared with pulse palpation. So we recommend that it be used on a routine screening basis of peripheral arterial disease in primary care.