정혜원, 김대중, 김하동, 최성희, 안철우, 차봉수, 이현철, 허갑범

Background: The prevalence of obesity is known to be lower in Asian population than that in Europe. But, the health risks associated with obesity occur at a lower body mass index (BMI) in Asian. The aim of this study was to assess the prevalence of the metabolic syndrome and its components in Korean adult population according to the new criteria for obesity proposed in Asia-Pacific Perspective. Methods: From individuls, who participated in medical check-up of Korean Association of Health (KAH), 1,230 individuals were included in the analysis. In patients with type 2 diabetes (n=131), subjects with impaired fasting glucose (IFG) (n=84), or individuals who have insulin-resistance but show normal fasting glucose (NFG) (n=1015), the metabolic syndrome was defined as presence of at least two of the following components; hypertension, dyslipidemia, and obesity. Results: Metabolic syndrome was present in 19% of men and 16% of women. In detail, about 10% in NFG, 50% in IFG, and 70% of patients with type 2 diabetes fulfilled the criteria of metabolic syndrome. In comparison with the lowest tertile of waist circumference and BMI, the prevalence of the metabolic syndrome increased about 13 fold in subjects with the highest tertile. Using a multiple regression analysis, HOMA-IR was associated with an increased risk for the metabolic syndrome (RR=2.23, p=0.001). Conclusion: The metabolic syndrome, according to the new criteria for obesity in Asian-Pacific Perspective in Korean adult population, is seen as much as Western countries. Insulin resistance and hyperinsulinemia can be suggested as the main causes of the metabolic syndrome.ope

Proteinuria is Associated with Carotid Artery Atherosclerosis in Non-Albuminuric Type 2 Diabetes: A Cross-Sectional Study

The association of specific urinary proteins other than albumin with cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) has been shown. In this respect, CV outcomes may differ in non-albuminuric T2D patients who were considered as a low risk group, according to the presence of proteinuria. We investigated the association between proteinuria and atherosclerosis assessed by carotid artery intima-media thickness (CIMT) in non-albuminuric T2D patients. 2047 T2D patients whose urine albumin-to-creatinine ratio was below 30 mg/g were recruited and classified into a non-proteinuria (NP, uPCR < 150 mg/g, n = 1865) group and a non-albuminuric proteinuria (NAP, uPCR ≥ 150 mg/g, n = 182) group. CIMT was compared between the two groups and logistic regression analysis was conducted to verify whether proteinuria could predict deteriorated CIMT status. In this cross-sectional study, mean CIMT of the NAP group were significantly thicker than those of the NP group (0.73 ± 0.16 vs. 0.70 ± 0.14, p = 0.016). The presence of proteinuria is associated with deteriorated CIMT after the adjustment for conventional risk factors (odds ratio, 2.342; 95% confidence interval, 1.082-5.070, p = 0.030) in regression analysis. We postulated that the measurement of urinary protein in conjunction with albumin might be helpful for predicting atherosclerosis, especially for non-albuminuric patients.ope

Reduction in microalbuminuria by calcium channel blockers in patients with type 2 diabetes mellitus and hypertension-A randomized, open-label, active-controlled, superiority, parallel-group clinical trial

Background: It has been suggested that renoprotection with calcium channel blockers (CCBs) may differ. This study aimed to compare the anti-proteinuric effect of different CCBs in patients with type 2 diabetes (T2D). Methods: A multicentre, randomized, open-label, active-controlled study was performed in seven centres in Korea. A total of 74 patients with T2D and microalbuminuria treated with renin-angiotensin system (RAS) blockers were randomized to a cilnidipine 10 mg treatment (n=38) or amlodipine 5 mg treatment (n=36). Results: Urine albumin to creatinine ratio (ACR) reduction was similar between the two groups at 12 weeks (-53.0±123.2 mg/g in cilnidipine group and -35.7±83.6 mg/g in amlodipine group, P=.29) or 24 weeks (-57.3±106.9 mg/g in cilnidipine group and -20.0±110.4 mg/g in amlodipine group, P=.24). In a subgroup analysis, cilnidipine treatment showed a larger ACR reduction than amlodipine treatment at 12 weeks (-84.7±106.8 mg/g in cilnidipine group and -9.5±79.2 mg/g in amlodipine group, P=.01) and 24 weeks (-84.0±111.7 mg/g in cilnidipine group and 14.6±119.4 mg/g in amlodipine group, P=.008), particularly in patients with a longer duration of diabetes more than 10 years. Conclusions: Cilnidipine did not show any additional anti-albuminuric effect compared with amlodipine in patients with T2D and microalbuminuria treated with an RAS blocker. However, the anti-albuminuric effect of cilnidipine might differ according to the duration of diabetes.ope

Impaired fatty acid metabolism in type 2 diabetic skeletal muscle cells is reversed by PPARγ agonists

The impact of type 2 diabetes on the ability of muscle to accumulate and dispose of fatty acids and triglycerides was evaluated in cultured muscle cells from nondiabetic (ND) and type 2 diabetic (T2D) subjects. In the presence of 5 μM palmitate, T2D muscle cells accumulated less lipid than ND cells (11.5 ± 1.2 vs. 15.1 ± 1.4 nmol/mg protein, P < 0.05). Chronic treatment (4 days) with the peroxisome proliferator-activated receptor-γ (PPARγ) agonist troglitazone increased palmitate accumulation, normalizing uptake in T2D cells. There were no significant differences between groups with regard to the relative incorporation of palmitate into neutral lipid species. This distribution was also unaffected by troglitazone treatment. β-Oxidation of both long-chain (palmitate) and medium-chain (octanoate) fatty acids in T2D muscle cells was reduced by ∼40% compared with ND cells. Palmitate oxidation occurred primarily in mitochondrial (∼40–50% of total) and peroxisomal (20–30%) compartments. The diabetes-related defect in palmitate oxidation was localized to the mitochondrial component. Both palmitate and octanoate oxidation were stimulated by a series of thiazolidinediones. Oxidation in T2D muscle cells was normalized after treatment. Troglitazone increased the mitochondrial component of palmitate oxidation. Skeletal muscle cells from T2D subjects express defects in free fatty acid metabolism that are retained in vitro, most importantly defects in β-oxidation. These defects can be corrected by treatment with PPARγ agonists. Augmentation of fatty acid disposal in skeletal muscle, potentially reducing intramyocellular triglyceride content, may represent one mechanism for the lipid-lowering and insulin-sensitizing effects of thiazolidinediones.ope

Neonatal Tetany Caused by Hyperparathyroidism Undetected During Pregnancy

Primary hyperparathyroidism is rarely encountered during pregnancy but its prompt diagnosis and treatment if encountered during pregnancy is important because it can carry considerable morbidity not only for the mother but also for the fetus. It tends to remain undiagnosed because 50~80% of the patients are asymptomatic. Even if they do demonstrate symptoms, those are often nonspecific. The other reason for non-diagnosis is masking of hypercalcemia due to the change of calcium homeostasis during pregnancy. Neonatal tetany can be a clue for the presence and diagnosis maternal hyperparathyroidism. The asymptomatic patient who is diagnosed postpartum when her newborn is symptomatic should undergo elective parathyroidectomy to avoid future complication. We experienced a woman with undiagnosed primary hyperparathyroidism during pregnancy whose two children suffered neonatal tetany. We report this case along with a review of literature on primary hyperparathyroidism in pregnancy and calcium homeostasis during pregnancy.ope

Efficacy and safety of ipragliflozin as an add-on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial

AIM: To evaluate the efficacy and safety of ipragliflozin vs placebo as add-on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: This double-blind, placebo-controlled, multi-centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT). RESULTS: In total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add-on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were -0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference -0.83% [95% CI -1.07 to -0.59]; P < .0001). More ipragliflozin-treated patients than placebo-treated patients achieved HbA1c target levels of <7.0% (44.4% vs 12.1%) and < 6.5% (12.5% vs 1.5%) at EOT (P < .05 for both). Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference -1.64 mmol/L, -1.50 μU/mL, -1.72 kg, and -0.99, respectively; P < .05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted. CONCLUSIONS: Ipragliflozin as add-on to metformin and sitagliptin significantly improved glycaemic variables and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM.ope

A Case of panhypopituitarism Due to Craniopharyngioma with Slipped Capitalis Femoral Epiphysis

Craniopharyngioma accounts for 3% to 5% of intracranial tumors and is the second most common neoplasm in the sellar region. Panhypopituitarism associated with craniopharyngioma has been reported in 7% of all patients with craniopharyngioma. Slipped capital femoral epiphysis is the condition in which the femoral head slips downward and backward on the femoral neck at the epiphyseal plate due to growth disturbance of capital physis, the actual cause of which is unknown. It is a disease of adolescence, during which many physiologic hormonal changes occur. The clinical association between slipped capital femoral epiphysis and endocrine disease is well known. There have been four cases of slipped capital femoral epiphysis associated with endocrine disorders in Korea. This is the first Korean case report of slipped capital femoral epiphysis combined with craniopharyngioma caused by hypopituitarism.ope

Randomized, Open Label, Multicenter Clinical Trial about the Effect of Cilazapril on Vascular Endothelial Function in Patients with Type 2 Diabetes Combined with Hypertension

Background: The angiotensin converting enzyme inhibitor (ACEi) improves the vascular endothelial cell function and has a better clinical outcome by decreasing the LDL cholesterol oxidation, hypercoagulability, oxidative stress and improving the level of endothelial nitric oxide synthesis in patients with type 2 diabetes and hypertension. However, the correlations between the ACEi and the serum markers for the vascular endothelial function in previous studies were not consistent. Subjects and Methods: Between July 2003 and April 2005, 104 type 2 diabetes patients with hypertension, who had been admitted to 9 major university hospitals in Korea, were examined. The subjects were randomly allocated to the cilazapril (2.5~5 mg/day) and atenolol (50~100 mg/day) treatment group and given a combination of hydrochlorothiazide and amlodipine. The lipid profile and the markers for endothelial function, such as vWF, VCAM, E-selectin, tPA, fibrinogen, adiponectin, hsCRP, nitrotyrosine were evaluated and the differences in the variables were compared with those obtained 6 months later. Results: A total 56 subjects completed the 6-months follow up period. Regarding the baseline characteristics, there were no significant differences in the variables observed in the two groups except for HbA1c (P = 0.037), vWF (P = 0.048), and hsCRP (P = 0.038). After 6 months, both groups showed a significant and identical decrease in the systolic and diastolic blood pressure compared with the baseline (P < 0.002). However, there were no significant differences in the endothelial markers between each group. On the other hand, there was some deterioration in the triglyceride (P = 0.009) and HbA1c (P = 0.017) levels in the atenolol treatment groups. Conclusions: There were no significant differences in the endothelial function markers observed between the cilazapril and atenolol groups. However, cilazapril had an identical effect on the blood pressure reduction compared with atenolol but had fewer adverse effects on the glucose and lipid metabolism.ope

Cost-effectiveness analysis of low density lipoprotein cholesterol-lowering therapy in hypertensive patients with type 2 diabetes in Korea: single-pill regimen (amlodipine/atorvastatin) versus double-pill regimen (amlodipine+atorvastatin).

OBJECTIVES: Single-pill combination therapy (amlodipine/atorvastatin) might be more effective than double-pill therapy (amlodipine+atorvastatin) in patients with diabetes and concomitant hypertension requiring statin therapy. We compared the cost-effectiveness of a single-pill with that of double-pill for control of low density lipoprotein cholesterol (LDL-C) levels, with the ultimate goal of cardiovascular disease prevention, in these patients using a cost-effectiveness analysis model that considered medication adherence. METHODS: Effectiveness was defined as the percentage (%) attainment of target LDL-C levels (<100 mg/dL) based on adherence for each therapy. Adherence was defined as compliance to medication (≥80% proportion of days covered). A systematic review of the literature was conducted to determine the proportion of patients who were adherent and target goal attainment based on adherence level. The annual medication costs were based on the adherence levels for each regimen. The average cost-effectiveness ratio (ACER) was calculated as the cost per % attainment of the target LDL-C level. RESULTS: The ACER for the single-pill regimen was lower than for the double-pill regimen (4,123 vs. 6,062 Korean won per 1% achievement of target goal). Compared with the double-pill, the medication costs were approximately 32% lower with the single-pill. CONCLUSION: A single-pill for reductions in LDL-C is cost-effective compared with double-pill in hypertensive patients with type 2 diabetes.ope

Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2 Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial

BACKGROUND: This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin. METHODS: This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea. RESULTS: Eighty-two Korean patients received ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were -0.97% in the ipragliflozin group and -0.31% in the placebo group, with an adjusted between-group difference of -0.60% (P<0.001). Compared to placebo, FPG and body weight also decreased significantly (both P<0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of -21.4 mg/dL and -1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection. CONCLUSION: Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.ope