Search

Introduction The aim of this study was to assess the efficacy and safety of switching to teneligliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM) inadequately controlled despite treatment with a stable dose of other DPP-4 inhibitors. Methods Patients with glycosylated hemoglobin (HbA1c) ≥ 7% despite taking DPP-4 inhibitors other than teneligliptin, with or without other antidiabetic agents, for at least 3 months were enrolled in this study. Patients on DPP-4 inhibitors administered prior to participation in this study were switched to 20 mg teneligliptin once daily and the dose was maintained for the 52-week study period. The primary endpoint was the change in HbA1c at week 12. Fasting plasma glucose (FPG) and the blood lipid profile were also evaluated. Adverse events were monitored for safety assessment. Results At weeks 12, 24, and 52, the HbA1c values significantly decreased by − 0.39, − 0.44, and − 0.52%, respectively, compared to the baseline value (p

Introduction Teneligliptin, an antidiabetic agent classified as a class III dipeptidyl peptidase-4 (DPP-4) inhibitor, has a unique structural feature that provides strong binding to DPP-4 enzymes. We investigated the efficacy and safety of switching patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control on a stable dose of other DPP-4 inhibitors to teneligliptin. Methods Patients with T2DM whose glycosylated hemoglobin (HbA1c) levels were ≥ 7% despite taking DPP-4 inhibitors other than teneligliptin, with or without other hypoglycemic agents, for at least 3 months were enrolled. The DPP-4 inhibitors taken before participating in the study were switched to 20 mg qd teneligliptin, and this was to be maintained for 52 weeks. The primary end point was the change in HbA1c levels after 12 weeks. Metabolic parameters including fasting plasma glucose (FPG) and blood lipids were assessed also. To assess safety, adverse and hypoglycemic events were monitored. The data from baseline to week 12 were used for analysis in this interim report. Results The mean change in HbA1c levels from baseline to week 12 was − 0.44%. At week 12, the percentage of patients achieving HbA1c

The effect of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the heat shock protein 90 inhibitor NVP-AUY922 (AUY922) on survival of thyroid carcinoma cells was elucidated. The SW1736 and TPC-1 human thyroid carcinoma cells were used. Cell viability, the percentage of viable cells, cytotoxic activity, the percentage of apoptotic cells, and mitochondrial membrane potential were measured. To evaluate the combined effect of gemigliptin with AUY922, the interactions were estimated by calculating combination index. Gemigliptin led to cell death in conjunction with overexpression of the phosphorylated protein levels of Akt, extracellular signal–regulated kinase 1/2, and adenosine monophosphate–activated protein kinase. In gemigliptin-treated cells, wortmannin augmented cell death, whereas AZD6244 and compound C did not affect cell survival. Wortmannin decreased phosphorylated adenosine monophosphate–activated protein kinase protein levels, and AZD6244 increased phosphorylated Akt protein levels. Meanwhile, cotreatment of both gemigliptin and AUY922, compared with treatment of AUY922 alone, potentiated cell death. All the combination index values were lower than 1.0, suggesting synergistic cytotoxicity of gemigliptin with AUY922. In treatment of both gemigliptin and AUY922, compared with AUY922 alone, the protein levels of total and phosphorylated Akt, phosphorylated extracellular signal–regulated kinase 1/2, and phosphorylated adenosine monophosphate–activated protein kinase increased without alteration in those of total extracellular signal–regulated kinase 1/2 and total adenosine monophosphate–activated protein kinase. The percentage of apoptotic cells increased. The protein levels of Bax and cleaved poly (ADP-ribose) polymerase increased, whereas Bcl2 protein levels were unchanged, resulting in increment of Bax/Bcl2 ratio. Transfection of Bax small interfering RNA did not cause any variation in cell viability, the percentage of viable cells and cytotoxic activity. Our results demonstrate that gemigliptin exerts a cytotoxic activity with concomitant alterations in expression of Akt, extracellular signal–regulated kinase 1/2, and adenosine monophosphate–activated protein kinase in thyroid carcinoma cells. Furthermore, gemigliptin synergizes with AUY922 in induction of cytotoxicity via regulation of Akt, extracellular signal–regulated kinase 1/2, and adenosine monophosphate–activated protein kinase as well as involvement of Bcl2 family proteins in thyroid carcinoma cells.

The influence of celastrol alone or in combination with paclitaxel on survival of anaplastic thyroid carcinoma cells was investigated. In 8505C and SW1736 cells, after treatment of celastrol, cell viability decreased, and cytotoxic activity increased. The protein levels of heat shock protein (hsp) 90, hsp70, Bax, death receptor 5, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase, phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-c-Jun N-terminal kinase (JNK) were elevated, and those of Bcl2, phospho-nuclear factor-kappaB (NF-κB), and total and phospho-Akt were reduced. The endoplasmic reticulum stress markers expression and reactive oxygen species production were enhanced. In celastrol-treated cells, N-acetylcysteine increased cell viability and phospho-NF-κB protein levels, and decreased reactive oxygen species production and cytotoxic activity. The protein levels of cyclooxygenase 2, phospho-ERK1/2, phospho-JNK and Bip were diminished. After treatment of both celastrol and paclitaxel, compared with paclitaxel alone, cell viability and the percentage of viable cells were reduced, and death rate and cytotoxic activity were elevated. The protein levels of phospho-ERK1/2, phospho-JNK, Bip, and cyclooxygenase 2, and reactive oxygen species production were enhanced. All of the Combination Index values calculated by Chou–Talalay equation were lower than 1.0, implying the synergism between celastrol and paclitaxel in induction of cell death. In conclusion, our results suggest that celastrol induces cytotoxicity through involvement of Bcl2 family proteins and death receptor, and modulation of phospho-NF-κB, Akt, and mitogen-activated protein kinase in association with endoplasmic reticulum stress and reactive oxygen species production in anaplastic thyroid carcinoma cells. Moreover, celastrol synergizes with paclitaxel in induction of cytotoxicity in anaplastic thyroid carcinoma cells.

Hyperglycemia is not identified as a significant prognostic factor for idiopathic sudden sensorineural hearing loss in any literature. Therefore, we investigated the prognostic value of hyperglycemia in predicting hearing recovery.A retrospective cohort study.Tertiary university hospital.Patients were classified into 3 groups according to their glucose tolerance using the 75-gram oral glucose tolerance test and hemoglobin A1c test as follows: (1) a normal glucose tolerance group, (2) a prediabetes group, which included patients with impaired glucose tolerance and/or impaired fasting glucose levels, and (3) a diabetes mellitus group.Among 94 patients with idiopathic sudden sensorineural hearing loss, 45 were classified into the normal glucose tolerance group, 28 into the prediabetes group, and 21 into the diabetes mellitus group. The recovery rate of the normal glucose tolerance group was not higher than that of the diabetes mellitus group (P = .140). However, when the prediabetes and diabetes mellitus groups were collectively defined as the impaired glucose regulation (hyperglycemia) group, the hearing recovery rate of the normal glucose tolerance (normoglycemia) group was significantly better than that of the impaired glucose regulation group (P = .038).We suggest that hyperglycemia may be a potential negative prognostic factor for hearing recovery in idiopathic sudden sensorineural hearing loss. Further interventional studies should be followed to determine whether hearing outcomes of the impaired glucose regulation group may be improved to the same extent as those of the normal glucose tolerance group after strict glycemic control.

Epidemiologic studies have shown that low vitamin D levels are associated with reduced insulin sensitivity and increased risk of developing type 2 diabetes mellitus (T2DM). However, there is little evidence that vitamin D supplementation improves glucose intolerance. We evaluated the glucose-lowering effect of vitamin D in Korean T2DM subjects. We enrolled 158 T2DM patients who had stable glycemic control [hemoglobin A1c (HbA1c)

The possible involvement of glucocorticoid system in interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. In the first experiment, mice were treated intrathecally (i.t.) with IL-1β (100 pg). Corticotrophin releasing hormone (CRH) mRNA (hypothalamus) and c-Fos mRNA (pituitary gland, spinal cord, and the adrenal gland) levels were measured at 30, 60 and 120 min after IL-1β administration. We found that i.t. injection with IL-1β increased CRH mRNA level in the hypothalamus. The IL-1β administered i.t. elevated c-Fos mRNA levels in the spinal cord, pituitary and adrenal glands. Furthermore, i.t. administration of IL-1β significantly increased the plasma corticosterone level up to 60 min. In addition, the adrenalectomy caused the reductions of the blood glucose level and pain behavior induced by IL-1β injected i.t. in normal and D -glucose-fed groups. Furthermore, intraperitoneal (i.p.) pretreatment with RU486 (100 mg/kg) attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. in normal and D -glucose-fed groups. Our results suggest that IL-1β administered i.t. increases the blood glucose level and pain behavior via an activation of the glucocorticoid system.

We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.

The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABAB receptor agonist; 1-10 μg/5 μl) or bicuculline (a GABAA receptor antagonist; 1-10 μg/5 μl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABAA receptor agonist; 1-5 μg/5 μl) or phaclofen (a GABAB receptor antagonist; 5-10 μg/5 μl) administered i.t. did not affect the blood glucose level. Baclofen-induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 μg/5 μl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABAB receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABAA receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.

The relationship between pain stimulation and the blood glucose level was studied in ICR mice. We examined the possible change of the blood glucose level after the pain stimulation induced by acetic acid injected intraperitoneally (i.p.),, formalin injected subcutaneously (s.c.) into the hind paw, or substance P (SP), glutamate, and pro-inflammatory cytokines (TNF-α and IFN-γ) injected intrathecally (i.t.). We found in the present study that acetic acid, formalin, SP, TNF-α, and IFN-γ increased the blood glucose level. The blood glucose level reached at maximal state 30 min and returned to normal level 2 h after the pain stimulation in a fasting group. Furthermore, acetic acid, formalin, SP, TNF-α, and IFN-γ caused the elevation of the blood glucose level in d-glucose-fed group only in an additive manner. However, i.t. injection of glutamate did not alter the blood glucose level in a fasting group. In contrast, i.t. injection of glutamate enhanced the blood glucose level in the d-glucose-fed grou...

Background In the present study, the possible anti-diabetic action of biguanide and thiazolidinediones administered supraspinally or spinally was studied in ICR mice. Methods Mice were intracerebroventricular (i.c.v.) or intrathecal (i.t.) treated with 20 or 30 μg metformin, pioglitazone and rosiglitazone in d -glucose fed and streptozotocin-treated models, and blood glucose levels was measured at 30, 60 and 120 min after i.c.v. or i.t. administration. Results We found that i.c.v. injection with metformin or rosiglitazone slightly attenuated the blood glucose level in d -glucose fed model, whereas pioglitazone showed no effect on the blood glucose level in d -glucose fed model. The i.t. administration with metformin, pioglitazone or rosiglitazone did not alter the blood glucose level in d -glucose fed model. We also assessed the possible roles of biguanide and thiazolidinedione in the regulation of the blood glucose level in streptozotocin-treated model. We found in the present study that i.c.v. or i.t. administration with metformin caused a pronounced attenuation of the blood glucose level in streptozotocin-treated model. However, rosiglitazone administered i.c.v. did not affect the blood glucose level in streptozotocin-treated model. Conclusions Our results suggest that the anti-diabetic actions of metformin and rosiglitazone appear to be mediated via the brain regions as revealed in d -glucose fed animal model. Furthermore, metformin administered supraspinally or spinally may be effective for treating type I diabetes mellitus as revealed in streptozotocin-treated mouse model.

The relationship between interleukin-1β (IL‐1β)‐induced nociception and the blood glucose level was studied in ICR mice. We found in the present study that intrathecal (i.t.) injection of IL‐1β increased pain behavior. In addition, i.t. IL‐1β injection caused an elevation of the blood glucose level. The time‐course study showed that maximal blood glucose level was observed 30 and 60 min after i.t. IL‐1β administration. Furthermore, i.t. injection of IL‐1β enhanced the blood glucose level when mice were orally fed with d ‐glucose. The i.t. administration of IL‐1β antagonist (AF12198) inhibited the hyperglycemia and pain behaviors induced by IL‐1β. We found in the present study that adrenal tyrosine hydroxylase (TH) mRNA level was also increased by i.t. IL‐1β injection. Furthermore, intraperitoneal (i.p.) pretreatment with phentolamine (an α1‐adrenergic blocker) or yohimbine (an α2‐adrenergic blocker) significantly attenuated the blood glucose level and pain behavior induced by IL‐1β administered i.t. However, the blood glucose level and pain behavior were not affected by butoxamine (a β2-adrenergic blocker), whereas metoprolol (a β2-adrenergic blocker) enhanced IL‐1β-induced blood glucose level and pain behavior in mice fed with d ‐glucose. However, its effect was not statistically significant. Our results suggest that IL‐1β administered i.t. increases the blood glucose level via an activation of α adrenergic nervous system.

BACKGROUND Little is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients. METHODS Among type 2 diabetic patients who visited Hallym University Sacred Heart Hospital from March 2007 to September 2009, 120 patients who had carotid artery IMT measured annually and A1C checked every three months for at least one year were analyzed. Individual A1C variability was defined as the standard deviation (SD) of five A1C levels taken every three months for approximately one year. Change in IMT was defined as an increase in IMT on follow-up measurement. The association between the SD of A1C and changes in IMT was evaluated. RESULTS With greater A1C variability, there was a greater increase in the mean IMT (r = 0.350, P < 0.001) of the carotid artery. After adjusting for confounding factors that may influence IMT, A1C variability was significantly associated with the progression of IMT (r = 0.222, P = 0.034). However, the SD of A1C was not a significant independent risk factor for the progression of IMT in multiple regression analysis (beta = 0.158, P = 0.093). CONCLUSION Higher A1C variability is associated with IMT progression in type 2 diabetic patients; however, it is not an independent predictor of IMT progression. Overall glycemic control is the most important factor in the progression of IMT.

In diabetic nephropathy, transforming growth factor beta1 (TGFbeta1) is related to p38 mitogen-activated protein kinase (MAPK) that induces production of fibronectin in mesangial cells. We investigated the effects of alpha-lipoic acid (ALA), a potent antioxidant, on proteinuria and TGFbeta1-p38 MAPK-fibronectin pathway in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After ALA treatment for 5 weeks in OLETF rats at 30 weeks of age, plasma malondialdehyde, urinary protein excretion, renal cortical TGFbeta1, and fibronectin protein levels were decreased; and urinary protein excretion was positively correlated with renal cortical TGFbeta1 and fibronectin protein levels. Phospho-form but not total-form levels as well as fold activations of each protein consisting of p38 MAPK pathway were also attenuated. These results suggest that ALA ameliorates proteinuria by attenuating expressions of TGFbeta1 and fibronectin proteins, and these favorable effects are related to inhibition of phosphorylating activation of p38 MAPK pathway in renal cortex of OLETF rats.

Background. We investigated the cardiac effects of TSH (thyroid-stimulating hormone) oversuppression in women with thyroidectomized differentiated thyroid cancer (DTC) during levothyroxine suppression therapy.Methods. Fourteen young female patients with DTC were enrolled. The duration of TSH-suppressive therapy was 5 to 9 years. They satisfied the following criteria: (1) a serum level of TSH < 0.1 mU/L in the intermediate-risk or TSH < 0.3 mU/L in the low-recurrence-risk group and (2) having been receiving a fixed dose of LT4 before the study. Controls matched for age, sex, and body mass index (BMI) were compared in terms of the levels of serum free T4, free T3, TSH, plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and cardiac functions and structures.Results. DTC patients and control subjects were well matched in heart rate and blood pressure. There were marked differences in serum TSH (P=0.001) and free T4 (P=0.002). However, there were no differences between the groups in serum free T3 and plasma NT-pro-BNP. Furthermore, there were nonsignificant differences in cardiac functions and structures between the groups.Conclusions. This study shows that TSH suppression therapy in women with DTC may be safe with respect to cardiac functions and structures despite intermittent oversuppression of TSH during long-term suppressive therapy.Trial Registration. This trial is registered with clinicaltrials.gov identifierNCT02645786.

Knowledge about the current status of diabetes management is indispensable for the improvement of diabetes management. We performed a survey to investigate the current trend of diabetes management in elderly Koreans, at eight hospitals located throughout the country. A total of 539 patients with type 2 diabetes older than 65 years (men=224, women=315) were recruited. Their mean age was 71.5+/-4.9 years and BMI 24.3+/-3.4 (men=23.6+/-2.8, women=24.9+/-3.7)kg/m(2), and 38.2% of the patients were obese (BMIor =25 kg/m(2), men=29.5%, women=44.4%). The mean duration of the diabetes was 13.1+/-9.2 years. Although 37.3% of the patients had A1C below 7.0%, 33.8% of the patients had A1C more than 8.0%. Three hundred and sixty three patients (67.4%) were treated with oral hypoglycemic agents and 175 patients (32.5%) were treated with insulin or combination with oral agents. The glycemic control was better in patients treated with oral agents (oral agent group=7.7+/-4.6%, insulin group=8.5+/-1.9%). Although mean SBP and DBP were 131.4+/-16.7 and 75.9+/-10.4 mmHg, respectively, 67.4% of the patients had hypertension and 38.2% of the patients with hypertension did not reach the goal (130/80 mmHg). Of 539 elderly patients, 253 patients (47.4%) had dyslipidemia (LDL-Cor =4.1 mmol/l and/or triglycerideor =2.5 mmol/l and/or HDL-C1.1 mmol/l) and 72.7% of the patients with dyslipidemia took the lipid lowering agents. However, 47.4% of them did not achieve the goal (LDL-C2.6 mmol/l and/or triglyceride1.7 mmol/l and/or HDL-C1.1 mmol/l). Twenty-eight patients (5.5%) had been admitted to the hospital because of severe hypoglycemia. Half of the patients (57%) had microvascular complications (retinopathy, neuropathy or overt proteinuria), and 28% of the patients had macro-vascular complications (CVD, stroke or peripheral vascular disease). As elderly diabetic patients are usually polymorbid, diabetes mellitus in old age is needed a more comprehensive approach to not only the treatment of hyperglycemia but also of hypertension, dyslipidemia and other associated diseases.

Several single-nucleotide polymorphisms of genes related to oxidative stress have been evaluated because intracellular reactive oxygen species are associated with development of diabetes and its microvascular complications. We performed a case-control study to investigate whether V16A polymorphism of manganese superoxide dismutase (Mn-SOD) gene is related to pathogenesis of diabetes and whether the polymorphism is associated with stages of albuminuria in Korean type 2 diabetic patients. Genotype distributions were studied in 178 nondiabetic subjects and 371 type 2 diabetic patients of 3 groups with a normoalbuminuria group (Normo group, n = 244), a microalbuminuria group (Micro group, n = 86), and an overt albuminuria group (Macro group, n = 41). The albumin/creatinine ratio (ACR) was defined as a urinary albumin/creatinine ratio. V16A genotypes were determined with polymerase chain reaction-restriction fragment length polymorphism method. Between nondiabetic subjects and type 2 diabetic patients, Mn-SOD genotype distribution (VV/VA + AA, 146/32 vs 314/57) and A allele frequency (0.121 vs 0.104) were not different. Patients with nephropathy, Micro and Macro groups, had significantly lower A allele frequency, longer diabetic duration, higher prevalence of hypertension, and greater ACR than those of patients without nephropathy (P < .05). A allele was significantly less frequent with progression of nephropathy (Normo group, 0.119; Micro group, 0.073; Macro group, 0.03; P < .05). In type 2 diabetic patients, A allele carriers had significantly lower prevalence of hypertension and lesser ACR than those of A allele noncarriers (P < .01). In multivariate analysis, hypertension, duration of diabetes, serum total cholesterol level, and A allele of Mn-SOD gene were independently associated with stages of albuminuria. These results suggest that V16A polymorphism of Mn-SOD gene is not related to pathogenesis of diabetes but is associated with stages of albuminuria in Korean type 2 diabetes.

Body weight is a significant predictor of bone mass. Hormonal factors such as sex hormones, insulin, leptin and adiponectin are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. However, contradictory results have been reported for the association between serum adipocytokines and bone mineral density (BMD). We therefore examined whether the serum adipocytokine and ghrelin levels, markers of fat metabolism, are associated with BMD in male adults.For 80 male adults (average age 54.5 +/- 6.4 years; average body mass index (BMI) 24.4 +/- 2.5 kg/m2), the correlations between serum resistin, leptin, adiponectin and ghrelin levels with BMD were investigated.Among the adipocytokines, serum resistin levels were negatively correlated with lumbar spine BMD (r = -0.237, P = 0.05). After adjustment was made for age and BMI, log-transformed serum leptin showed a significant negative correlation with lumbar spine BMD, which was not seen on bivariate analysis (r = -0.237, P = 0.039). Femoral neck BMD was marginally associated only with serum adiponectin levels (r = -0.226, P = 0.062). In multiple regression analyses, among the adipokines, only resistin was a significant determinant of lumbar spine BMD, although the variance was small (R2 = 0.256). Serum ghrelin levels were not correlated with the BMD of either body site.Serum resistin level showed a significant negative correlation with lumbar spine BMD, although the variance was small. Further studies are needed to elucidate the role of adipocytokines in bone metabolism.

Summary Objective Osteoporosis is a growing health problem in males as well as in females. Sex hormones and insulin-like growth factor-I (IGF-I) have been shown to be the major determinants in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF-κB ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis. However, the relationship between the OPG-RANKL system and male bone status in human populations are unclear. Thus, the aim of this study was to investigate the relationship between the OPG-RANKL system and bone mineral metabolism in males. Patients and Measurements Serum concentrations of OPG, RANKL, oestradiol, total testosterone and IGF-I and bone mineral density (BMD) were measured in 80 Korean males aged 42–70 (mean age, 54·5 year). Enzyme-linked immunosorbent assays were used to determine the serum concentrations of OPG and RANKL. Serum concentrations of oestradiol, total testosterone, IGF-I and bone turnover markers were determined using standard methods. BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Results We observed a significant negative correlation between the serum OPG levels and lumbar spine BMD (r =−0·259, P

Summary objective Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the RANK ligand. Moreover, OPG has been shown to be an important inhibitor of osteoclastogenesis in animal models. However, the relationship between circulating OPG levels and female bone status in human populations is unclear. In this study we undertook to investigate the relationship between circulating OPG levels and bone mineral metabolism in healthy women. patients and measurements Our subjects were 287 women aged 37–73 years (mean age 51·5 years). The serum concentrations of OPG were determined by enzyme-linked immunosorbent assay (ELISA). The biochemical markers of bone turnover and FSH were measured using standard methods. Bone mineral densities at the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. results Postmenopausal women had a significantly higher mean value of serum OPG than premenopausal women (1358·5 ± 32·5 pg/ml vs. 1228·8 ± 33·3 pg/ml, P

Background: Since its reemergence in 1993, a number of cases of Plasmodium vivax malaria have been reported in Korea. We analyzed the cases of malaria patients living in Chuncheon and its neighboring communities, to characterize its clinical manifestations and laboratory findings, and to identify any differences between our clinical findings and those of previous studies. Methods: We reviewed the clinical records of cases that were confirmed as malaria by peripheral blood smear at Chuncheon Sacred Heart Hospital from July 1998 to September 2001. Results: Forty-four cases were included in the study. All patients were infected with Plasmodium vivax, and presented with high fever; however, tertian fever developed in only 15 patients (35.7%). A number of cases showed various symptoms, which included headache, abdominal pain, nausea and vomiting. Of the 44 cases identified, 41 (93.2%) developed malaria between June and September. Thrombocytopenia was a prominent finding in 75% of the cases at diagnosis, but resolved during or after therapy. Other laboratory abnormalities such as, anemia, elevated transamines, coagulopathies, and elevated lactose dehydrogenase (LDH) were also noted. Cerebrospinal fluid (CSF), studies were performed in five cases, one of which showed pleocytosis in the CSF. Conclusion: We noted only 15 patients (35.7%) with tertian fever; the other patients showed variable fever patterns. Thrombocytopenia was the most prominent laboratory finding. Therefore, we suggest that malaria should be included in the differential diagnosis of febrile diseases with an onset between June to and September, regardless of the pattern of the fever.

Background and Purpose Diabetes is associated with cognitive decline as well as the development of dementia. Although mean blood glucose levels are typically used to assess the status of diabetic patients, glucose variability is also involved in the manifestation of macro- and microvascular complications in this population. Thus, the present study sought to determine whether visit-to-visit glucose variability contributes to cognitive decline in patients with type 2 diabetes. Methods The present study assessed 68 patients with type 2 diabetes using several validated neuropsychological measures. All patients had no cerebrovascular disease, history of hypoglycemia, psychiatric conditions, or other medical illnesses. Standard deviations (SDs) and coefficients of variance (CVs) of the patients’ blood glucose (after fasting and 2 hours postprandial; FBS and PP2), and glycated hemoglobin (HbA1c) values were used as indices of glucose variability. The cognitive outcome parameters were transformed with z-scores and entered into a multiple linear regression model that included educational status, age, sex, vascular risk factors, and mean glucose parameters as covariates. Results The mean age of the total patient population was 70.9 years; 46 (67.6%) of the patients were men, and the median follow-up duration at our endocrinology outpatient clinic was 4.8 years. The mean FBS and PP2 glucose levels of the patients were 132 mg/dL and 199 mg/dL, respectively, and the mean HbA1c level was 8.0%. A univariable analysis revealed that only the PP2 value was associated with the Mini-Mental State Examination (MMSE) score, and multivariable analysis revealed that a high SD and/or CV for PP2 glucose were associated with low scores on the Rey Complex Figure Copy test and/or the Verbal Learning Test. Additionally, a high SD and a higher CV for HbA1c level were significantly associated with low MMSE and Digit Span test scores even after adjusting for mean HbA1c values. Conclusions The present data indicate that a greater degree of visit-to-visit glucose variability influenced specific types of cognitive function in type 2 diabetic patients independently of mean blood glucose levels. Future studies should focus on whether reductions in glycemic variability will improve the cognitive decline observed in type 2 diabetic patients.

Seasonal variations in lifestyle, such as food intake and physical activity, have been reported. Glycemic control in type 2 diabetes mellitus (T2DM) may be affected by such changes. We investigated seasonal variations in glycemic control, food intake, and physical activity in type 2 diabetic patients. This prospective observational study included 37 Korean female patients who had

Purpose Chemerin has been suggested to be linked to insulin resistance and type 2 diabetes mellitus (T2DM). However, the relationship between visceral adiposity and chemerin levels remains unclear in subjects with T2DM. In this study, we investigated the relationship between serum chemerin levels and visceral adiposity. Materials and Methods This study included 102 subjects newly diagnosed with T2DM. The relationships between serum chemerin levels and clinical and biochemical parameters were examined. Multiple linear regression analysis was performed to determine the predictable factors of serum chemerin levels. Results Serum chemerin levels showed significant positive correlations with body mass index (BMI), waist circumference (WC), visceral fat thickness (VFT), insulin levels, the homeostasis model assessment of insulin resistance, and levels of triglycerides (log-transformed) and high-sensitivity C-reactive protein, while showing significant negative correlations with high-density lipoprotein cholesterol. After adjusting for BMI and WC, VFT showed a significant relationship with serum chemerin levels (r=0.222, p=0.027). Moreover, VFT was an independent predictive factor of serum chemerin levels (β=0.242, p=0.041). Conclusion We demonstrated that chemerin is linked to metabolic syndrome components. Moreover, serum chemerin levels were associated significantly with obesity, especially visceral adipose tissue, in subjects with T2DM.

In the present study, the effect of intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration with cholera toxin (CTX) on the blood glucose level was examined in ICR mice. The i.t. treatment with CTX alone for 24 h dose-dependently increased the blood glucose level. However, i.c.v. treatment with CTX for 24 h did not affect the blood glucose level. When mice were orally fed with D-glucose (2 g/kg), the blood glucose level reached to a maximum level at 30 min and almost returned to the control level at 120 min after D-glucose feeding. I.c.v. pretreatment with CTX increased the blood glucose level in a potentiative manner, whereas i.t. pretreatment with CTX increased the blood glucose level in an additive manner in a D-glucose fed group. In addition, the blood glucose level was increased in formalin-induced pain animal model. I.c.v. pretreatment with CTX enhanced the blood glucose level in a potentiative manner in formalin-induced pain animal model. On the other hand, i.t. pretreatment with CTX increased the blood glucose level in an additive manner in formalin-induced pain animal model. Our results suggest that CTX administered supraspinally or spinally differentially modulates the regulation of the blood glucose level in D-glucose fed model as well as in formalin-induced pain model.

ObjectiveThis study aimed to investigate thyroid hormone (TH) status and its relationship with myocardial function as well as clinical and biochemical parameters in stress cardiomyopathy (CMP).MethodsForty-five patients with stress CMP (the patient group), 31 patients without stress CMP (the control II group), and 58 healthy subjects (the control I group) were included. Sick euthyroid syndrome (SES) was defined as low total triiodothyronine (T3) with normal TSH levels.ResultsIn the patient group at admission, prevalence of SES was 62.2%. Compared with the control I group, the patient group had a decrease in left ventricular ejection fraction (LVEF) and systolic blood pressure (BP) and an increase in troponin-I, CK-MB, and B-type natriuretic peptide (BNP) levels. Total T3 levels were reduced, and anti-thyroid peroxidase antibody (anti-TPO Ab) positivity, C-reactive protein (CRP) and cortisol levels were elevated. Total T3 levels were associated with acute physiology and chronic health evaluation II (APACHE II) score, LVEF, systolic BP, and cortisol levels in multivariate analysis. In the control II group, total T3 levels were not associated with any variables. In the SES (n=28) and myocardial dysfunction (MDys, n=27) subgroups, increased APACHE II score and BNP levels as well as decreased LVEF and systolic BP were significant. Total T3 levels were reduced, and CRP, cortisol and catecholamines levels were elevated. In the MDys subgroup, anti-TPO Ab positivity and titer were increased.ConclusionThese results suggest that total T3 levels may be associated with myocardial contractility, clinical severity, and cortisol levels. Thyroid autoimmunity may influence myocardial contractility in stress CMP.

We investigated the effects of Amadori-glycated serum albumin (GSA) on cell proliferation as well as expressions of antioxidant enzyme genes and marker genes associated with signal transduction pathways in rat aortic vascular smooth muscle cells (VSMCs). Quiescent VSMCs treated with GSA (0-500 microg/mL, 48 h) exhibited a dose-dependent increase in proliferation that was prevented by PD98059 (25 microM), suggesting a MAPK-dependent signaling pathway. Compared with bovine serum albumin (BSA)-treated cells, the GSA (500 microg/mL, 24~h)-treated VSMCs showed a higher superoxide dismutase 2 gene expression in quantitative RT-PCR, suggesting the involvement of oxidative stress. In a focused oligonucleotide array containing 96 signal transduction-related genes, expression of inhibitor of apoptosis protein-1 (IAP-1), nerve growth factor-gamma (NGF-gamma), and c-jun genes was significantly higher in the GSA-treated VSMCs. These results suggest that induction of antiapoptotic proteins like IAP-1 and strong mitogens like NGF-gamma by GSA might further contribute to the VSMC proliferation and accelerated vascular remodeling in diabetes.

This study was designed to investigate whether V16A polymorphism of the manganese superoxide dismutase (Mn-SOD) gene is associated with the development of type 2 diabetes mellitus and with progression of diabetic retinopathy (DR) and diabetic macular edema (DME). We simultaneously analyzed insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene in the 16th intron to avoid its confounding effect. A total of 192 nondiabetic subjects and 304 type 2 diabetic patients were included in the study. Diabetic retinopathy was classified as nonretinopathy, nonproliferative retinopathy, and proliferative retinopathy. Diabetic macular edema was defined as thickening of the retina and/or hard exudates within a 1-disk diameter of the center of the macula. Diabetic macular edema was further classified into focal, diffuse, and ischemic types. The A allele frequency of the Mn-SOD gene was not different between nondiabetic and type 2 diabetic subjects, between the normotensive and hypertensive groups, between the DR (-) and DR (+) groups, and among the stages of DR. In the DR (+) group, the DME (+) group had a lower A allele frequency than that of the DME (-) group. In the DME (+) group, focal, diffuse, and ischemic types were found in 8, 23, and 6 patients, respectively. The A allele frequency of each type was 0.188, 0.109, and 0.0. The D allele frequency of the angiotensin-converting enzyme gene did not differ in any of the comparisons. Clinical and laboratory parameters of the A allele carriers were not different from those of the noncarriers except for the prevalence of hypertension and DME. Hypertension, diabetic duration, and insulin therapy were related to DR. The A allele, hypertension, and insulin therapy were associated with DME. In conclusion, our results suggest that V16A polymorphism of the Mn-SOD gene is not related to the development of diabetes and progression of DR, but is associated with DME in Korean type 2 diabetic patients.

Background Osteoporosis associated with thyroid dysfunction has been traditionally viewed as a secondary consequence of altered thyroid function, but there was recently a report about the direct effects of thyroid-stimulating hormone (TSH) on bone remodeling, which was mediated via the TSH receptor found on osteoblast and osteoclast precursor cells. Endogenous subclinical thyroid dysfunction seems to be an appropriate model to examine the direct effect of TSH on bone metabolism while ruling out the direct effect of thyroid hormone on bone metabolism. Thus, we aimed to investigate the relationship between subclinical thyroid dysfunction and bone mineral metabolism in women. Methods We enrolled 413 women (mean age: 52.2 ± 6.6 years) in our study. Serum levels of TSH, free T 4 and the biochemical markers of bone turnover were measured by the standard methods. BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Results Femoral neck BMD was significantly reduced both in the subclinical hyperthyroid group and in the subclinical hypothyroid group as compared with the euthyroid group (one-way ANOVA, p p = 0.041, p = 0.033). In contrast to the femoral neck BMD, the lumbar spine BMD showed no difference between the two groups. Additionally, serum calcium and alkaline phosphatase levels, urine deoxypyridinoline levels, and urine calcium to creatinine ratio showed no differences between the two groups. Conclusions Women having subclinical hyperthyroidism and women with subclinical hypothyroidsm have reduced femoral neck BMD. Additional studies are required to elucidate the mechanism for this finding.

Osteoporosis is a growing health problem in women and in men. This cross-sectional study examined the association of anthropometric, lifestyle, and hormonal factors with bone mineral density (BMD) in 152 healthy Korean middle-aged men. Smoking habits and alcohol consumption were assessed by interview. Serum testosterone and insulin-like growth factor-I (IGF-I) levels were measured by radioimmunoassay, and serum growth hormone (GH) levels were measured by immunoradiometric assay. GH stimulation tests were performed after the ingestion of 500 mg of L-dopa. BMD was measured at the lumbar spine and at the femoral neck by dual-energy X-ray absorptiometry. Of the middle-aged men, 3.9% were osteoporotic and 28.3% were osteopenic at the lumbar spine site, and 5.9% were osteoporotic and 45.4% were osteopenic at the femoral neck site. Lumbar spine BMD correlated significantly with body mass index (BMI), and femoral neck BMD correlated significantly with age, BMI, and serum IGF-I levels. The lowest quartile group for serum IGF-I levels showed the lowest femoral neck BMD. Osteoporotic men by lumbar spine BMD showed significant differences from the normal BMD group in terms of BMI and smoking habits. Also, osteoporotic men by femoral neck BMD were significantly different for mean age, BMI, and serum IGF-I levels compared with the normal BMD group. On multiple regression analysis, BMI was found to be the only independent predictor of lumbar spine BMD, whereas both BMI and serum IGF-I levels were found to be the independent predictors of femoral neck BMD. Overall, 28.3%-45.4% of middle-aged Korean men were osteopenic. We suggest that higher age, a lower BMI, current smoking history, and lower serum IGF-I levels are risk factors for lower BMD in middle-aged Korean men; however, serum testosterone levels and GH secretory capacity were not found to be correlated with BMD.

Objectives: Type 2 diabetes, a leading cause of cardiovascular disease, is well known for its association with accelerated atherosclerosis. Adiponectin and tumor necrosis factor alpha (TNF-α), which are produced and secreted in adipose tissue, have been suggested as predictors for cardiovascular disease. However, little is known about the influence of adiponectin and TNF-α ratio on the progression of carotid atherosclerosis in newly diagnosed type 2 diabetic patients. This study was conducted to evaluate the influence of serum adiponectin/TNF-α levels on the progression of carotid atherosclerosis. Methods: One hundred eleven newly diagnosed type 2 diabetes patients were enrolled. Anthropometric and biochemical data including serum adiponectin, TNF-α were measured for each participant. Also we measured carotid intima-media thickness (CIMT) at baseline and at 1 year follow-up (n=81). We finally examined the relationship among serum adiponectin over TNF-α levels (ADPN/TNF-α), baseline CIMT, and progression of CIMT at 1 year. Results: ADPN/TNF-α negatively correlated with baseline CIMT (r=-0.231, p=0.025). Moreover, progression of CIMT was significant at 1 year (0.011±0.138 mm). There was a negative correlation between ADPN/TNF-α and progression of CIMT at 1 year (r=-0.172, p=0.038). In multiple regression analysis, age and HbA1c were found to be independent risk factors for baseline CIMT. However, only HbA1c was an independent risk factor for the progression of CIMT. Conclusion: ADPN/TNF-α was negatively associated with baseline CIMT and the progression of CIMT at 1 year. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.

We investigated the frequency of sleep disturbances and the association between sleep disturbances and glucoregulation in type 2 diabetic patients. The frequency of sleep disturbances in 614 type 2 diabetic patients was investigated using validated sleep questionnaires. There were 381 male and 233 female patients. The mean age was 59.7 ± 11.1 yr; the mean body mass index was 24.9 ± 4.4 kg/m(2); the mean HbA1c was 7.8% ± 1.5%; and the mean duration of diabetes was 10.3 ± 8.4 yr. The questionnaires revealed insomnia in 48.2% of the patients while 8.5% reported excessive daytime sleepiness. A total of 49% of the patients was poor sleepers, while 28.5% had depression. Multivariate logistic regression analysis showed that there was no significant association between HbA1c and other sleep disturbances, such as poor sleep, insomnia, and short duration of sleep. Sleep disturbances were very common in patients with type 2 diabetes mellitus, whereas there was no association between poor or short sleep and glucoregulation. Awareness and identifying sleep complaints in such patients are necessary to improve their quality of daily life.

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (α-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with α-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, α-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 µg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

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. An thropometric 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 be tween 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 (β = 0.556, P = 0.004), LDL cholesterol (β = 0.276, P = 0.042), and A1C (β = 0.309, P = 0.038) were found to be independent risk factors for CIMT. However, A1C (β = 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. (Endocrinol Metab 27:31-38, 2012)

Background: The average duration of diabetes and predictive factors of macrovascular complications in Korean diabetic patients remain to be elucidated. This study ex amines the average duration of diabetes up to the onset of macrovascular complications and clinically important factors of early development of these complications in Korean type 2 diabetic patients. Methods: Clinical characteristics in type 2 diabetics with (n = 121) and without macrovascular complications (n = 115) were analyzed. In addition, early onset (≤ 5 years, n = 54) and late onset groups (> 5 years, n = 67) were compared, as were the clinical characteristics between male and female patients in the macrovascular complications group. Results: The average duration of diabetes was 8.7 ± 7.8 years in the macrovascular complications group. Average age, systolic and diastolic blood pressures and smoking history were all higher in the macrovascular complications group than the control group. However, HbA1c levels and prevalence of microvascular complications were higher in the controls. Average age was lowe r in the early onset group and many more patients of that group had a smoking history. In the analysis based on sex, marcrovascular complications developed earlier in male patients. In addition, the prevalence of family history of diabetes was higher in males and 77.8% of male patients had a smoking history (female: 3.4%). Conclusion: Our study confirms that older age, high blood pressure and smoking history are major risk factors for the development of macrovascular complications. Mor eover, a smoking history in males can be both risk and predictive factors for earlier development of macrovascular complications in Korean type 2 diabetic patients. We also found that several clinical characteristics including age, family history of diabetes, hypertension and smoking history, vary between the sexes, and these findings can provide useful indices for the prevention of macrovascular complications. (Korean Diabetes J 33:134-142, 2009)

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. (J Korean Endocr Soc

Background and Objectives: Prehypertension (preHT) is considered to a precursor of hypertension and it is a predictor of excessive cardiovascular risk. We investigated the rates and determinants of progression to hypertension (HT) among local residents aged 45 or over, and we compared the differences in demographic factors, anthropometric measurements, life styles and metabolic profiles between the progression individuals and non-progression individuals. Subjects and Methods: Data from the Hallym Aging Study, which was conducted 3 years apart were used to form the sample of 489 adults. PreHT was defined by the Joint National Committee (JNC-7) criteria. We conducted interviews to determine the life style (alcohol, smoking and exercise) and the measured obesity indices. The metabolic profiles were fasting blood sugar (FBS), cholesterol, triglyceride and high density lipoprotein (HDL)-Cholesterol. The factors related to progression to HT were examined by using multiple logistic regression analysis. Results: The progression rate to HT was 56.4% (56.9% in men, 55.9% in women). The presence of metabolic syndrome was significantly greater and the body mass index (BMI) and systolic blood pressure were significantly higher in the progression group compared with the non-progression group (p=0.0475, p=0.0099, p=0.0082, respectively). Important determinants of progression to HT are a BMI≥25 kg/m 2 [

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 ext racted 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. (J Kor Endocrine Soc 22:118~124, 2007)

Background: With the extension of human life span, the prevalence of diabetes in elderly population is increasing. The glycemic control is also important in elderly diabetics because the life expectancy in elderly is steadily increased. In this study, we investigated the role of family support on glycemic control in elderly type diabetic patients. Methods: This study was conducted with 126 type 2 diabetic patients over 60 years of age who were enrolled between March and December, 2005. The data for glycemic control, family characteristics, and family support were collected by structured questionnaire, personal interview, and medical record review. We used total supportive index scores to evaluate family support. We evaluated the relationship between family support and glycemic control. Results: Fasting plasma glucose was positively correlated with duration of diabetes (r = 0.277, P = 0.003). Postprandial 2 hour plasma glucose was negatively correlated wi th monthly incomes (r = -0.357, P = 0.002), assessment support (r = -0.201, P = 0.029). Hemoglobin A1c was positively correlated with duration with diabetes (r = 0.294, P = 0.002) and insulin use (r = 0.259, P = 0.004), but it was negatively correlated with diabetic self-management education (r = -0.190, P = 0.036). Adjusted for age, sex, duration of diabetes, and monthly incomes, there were no significant associations between glycemic control and family support. Conclusion: In this study, there were no significant associations between glycemic control and family support. More large prospective studies will be followed to exactly evaluate the role of family support in diabetic patients. (J Kor Diabetes Assoc 31:435~443, 2007)

Background: Diabetes mellitus (DM) is equivalent as well a risk factor of cardiovascular disease. We analyzed the effects of DM on clinical risk factors of acute coronary syndrome by comparing DM group with Non-DM group. Methods: A total of 847 (514 males and 333 females) patients with acute coronary syndrome was selected from 1664 patients who had undergone coronary angiography (CAG). These patients comprised 105 subjects with non-ST elevation myocardial infarction (MI), 313 with ST elevation MI and 429 with unstable angina. According to the presence of DM, we retrospectively reviewed the measured basic demographics, biochemical markers and coronary angiographic findings. Results: In the multivariated analysis, history of hypertension (P = 0.001), C-reactive protein (CRP) level (P = 0.001) and triglyceride level (P = 0.018) were independent risk factors in type 2 diabetic group. Also the frequency of multiple coronary vessel disease was higher in DM group than non-DM group on the coronary angiographic finding Conclusions: Classic risk factors for acute coronary syndrome are strong predictors in patients with type 2 DM. Among these factors, the most important powerful risk factor is history of hypertension.

Human chorionic gonadotropin (HCG) is a member of the glycoproteins family synthesized by the placenta, which consists of 2 noncovalently joined subunits (alpha(α) and beta(β)). The α- and β-subunits have a structural homology with the α- and β-subunits of TSH and LH. The thyrotropic action of HCG results from its structural similarity to TSH, so β-HCG can bind to the TSH receptor in the thyroid gland. A high level of HCG accompanied by an increased thyroid hormone level, can be observed in gestational trophoblastic disease (GTD), such as a hydatidiform mole or a choriocarcinoma, but the clinical symptoms of hyperthyroidism are rarely observed. We experienced a case of Hashimoto's thyroiditis, where the patient was diagnosed with T3-thyrotoxicosis, which had initially been induced by excess β -HCG due to an H-mole; after evacuation of the H-mole, the condition was diagnosed as hypothyroidism. It has been speculated that a patient with Hashimoto's thyroiditis could have hyperthyroidism, induced by β-HCG, due to an H-mole (J Kor Soc Endocrinol 20:294～298, 2005).

Background: Radioiodine treatment is effective for the removal of remnant thyroid tissues after thyroi- dectomy in patients with differentiated thyroid carcinoma. To induce the elevation of serum TSH level which facilitates the uptake of radioiodine into remnants, a 4 to 6 week interval between thyroidectomy and radioio- dine administration has been established. During the period of preparation, most patients have experienced overt symptoms of hypothyroidism which have led to the development of alternative strategies. Some reports have suggested that the interval could be reduced to about 3 weeks with less symptoms. We reevaluated the adequate time needed for the elevation of serum TSH level above 30μU/mL after thyroidectomy. Methods: Forty five patients who had undergone total thyroidectomy for differentiated thyroid carcinoma were investigated. Serum TSH and free T4 levels were measured one or more times within 3 weeks after operation (total 97 blood samples). Eighty nine blood samples were obtained within 15 days. Results: In 41 patients (91.1%) serum TSH levels increased to 30 μU/mL until 15 days after operation. Until postoperative 21 days, serum TSH levels in all the other patients reached 30 μU/mL. In linear equation, the daily increment of serum TSH levels was 2.62 μU/mL for the first 8 days after operation and 5.34 μU/mL for the next 7 days. The half-life of serum free T 4 levels showed marked individual variations. Conclusion: Measurement of serum TSH level at about 15 days after total thyroidectomy for differentiated thyroid carcinoma may be useful in determining the time of radioiodine administration (J Kor Soc Endocrinol 20:460~466, 2005).

Background: Osteoprotegerin (OPG) is a recently identified cytokine, which acts as a decoy receptor for the receptor activator of the NF-κB ligand (RANKL), and has also been shown to be an important inhibitor of osteoclastogenesis in animal models. However, the relationship between OPG gene polymorphism and female bone stati in human populations is unclear. In this study, the relationship between OPG gene polymorphisms and bone mineral metabolism in healthy Korean women was investigated. Methods: We observed 251 healthy women (mean age, 51.3 ± 6.9 yr). The serum OPG concentrations were determined using ELISA, and the biochemical markers of bone turnover and FSH measured using standard methods. The bone mineral densities at the lumbar spine and femoral neck were measured by dual energy χ-ray absorptiometry. The A163G, G209A, T245G and T950C polymorphisms of the OPG gene were analyzed by allelic discrimination using the 5 nuclease polymerase chain reaction assay. Results: The lumbar spine BMD of premenopausal women was marginally decreased in the variant allele group compared to the wild type group (A163G, 0.98 ± 0.14 g/cm 2 (GG +G A) vs. 1.05± 0.15 g/cm 2 (AA), P = 0.070; T245G, 0.97 ± 0.13 g/cm

Leptin serves an important role in suppressing appetite in mice and is known to be elevated in chronic renal failure (CRF) patients. But clinical significance of leptin as an appetite-reducing uremic toxin, remains to be determined. So we studied the relationship between plasma leptin and nutritional status in 46 chronic hemodialysis (HD) patients. Pre HD leptin was measured and divided by body mass index (BMI) to give adjusted leptin levels. KT/Vurea (K, dialyzer urea clearance; T, duration of HD; V, volume of distribution of urea), C-reactive protein (CRP), plasma insulin and nutritional parameters such as serum albumin, normalized protein catabolic rate (nPCR), subjective global assessment (SGA), BMI and mid-arm muscle circumference (MAMC) were also measured. Mean plasma leptin levels were 8.13+/-2.91 ng/mL (male 3.15+/-0.70; female 14.07+/-6.14, p

125I-insulin binding to erythrocytes was measured to evaluate the role of insulin receptors in the mechanism of insulin resistance in partients with chronic liver disease (CLD). Patients with CLD were divided into two groups by the fasting plasma glucose level (FBS) and the glucose disappearance rate (k-glucose) during intravenous glucose tolerance tests: one with normal FBS and normal k-glucose (group I), and the other with higher FBS and lower k-glucose (group II). Insulin receptor bindings were reduced in group I patients compared with those of normal controls, but were not reduced in group II patients. Fasting insulin levels were significantly higher in group I patients than those in normal subjects, and down-regulation by hyperinsulinemia might be the cause of reduced insulin receptor bindings in these patients. However down-regulation of insulin receptors was not associated with glucose intolerance. So it is suggested that insulin resistance in CLD is not due to a primary defect of insulin receptors in peripheral tissues, and down-regulation of insulin receptors is an epiphenomenon of hyperinsulinemia.