Relationship between Serum Total Testosterone Concentration and Metabolic Syndrome in Premenopausal Obese Women.

Background: Men with low testosterone levels are at an increased risk of developing metabolic syndrome, irrespective of age or obesity. However, the relationship between metabolic syndrome and testosterone levels in women remains unclear. We compared the total testosterone concentrations between premenopausal obese women with and without metabolic syndrome and identified the factors affecting these concentrations. Methods: A single-center retrospective analysis was conducted using the medical records of 580 premenopausal women with obesity. The diagnostic criteria for metabolic syndrome were established using the National Cholesterol Education Program Adult Treatment Panel III guidelines. Results: The mean±standard deviation age, weight, and body mass index were 38.8±8.4 years, 78.0±11.8 kg, and 30.0±4.1 kg/m2, respectively. The mean total testosterone concentration was lower in the metabolic syndrome group than in the non-metabolic syndrome group (n=385 vs. n=195; 0.22±0.10 ng/mL vs. 0.24±0.11 ng/mL; P<0.001). In a model adjusted for age, body mass index, skeletal muscle mass, body fat mass, and body fat percentage, the odds ratio for metabolic syndrome with respect to the total testosterone level was 0.128 (P=0.028). Testosterone concentration was negatively correlated with age (r=-0.334), systolic blood pressure (r=-0.084), and triglyceride concentration (r=-0.093) but positively correlated with weight (r=0.144), body mass index (r=0.140), waist circumference (r=0.133), body fat mass (r=0.167), and body fat percentage (r=0.167). Stepwise regression analysis revealed that age (ß=-0.004, P<0.001), body mass index (ß=0.003, P=0.004), and high-density lipoprotein cholesterol concentration (ß=0.001, P=0.019) were independently associated with total testosterone concentration (adjusted R2=12.6%). Conclusion: Metabolic syndrome and obesity may be independently associated with testosterone levels in premenopausal women with obesity.

The efficacy and safety of tadalafil in the management of erectile dysfunction with diabetes and blood circulation issues.

BACKGROUND: Erectile dysfunction (ED) is a common diabetes-related complication. MATERIALS AND METHODS: This study examined the effect of daily low-dose tadalafil (5 mg) on patients' quality of life (including that of sex life) and blood circulation. Erectile dysfunction questionnaires were administered to 20 patients with type 2 diabetes (T2DM) and ED. The safety and efficacy of tadalafil were evaluated using laboratory tests, and the effect on blood circulation was measured through nail fold capillaroscopy. RESULTS: Daily tadalafil use by patients with T2DM and ED showed a statistically significant increase in the erectile reliability score from of 1.15 to 3.20 (p < .00012). Capillary blood circulation improvement tests showed a statistically significant increase in apical limb width from 13.1 to 14.64 µm (p = .04829) and flow from 9035 to 11946 µm3/s (p = .04405). Although not significant, increased capillary width and speed (rate of blood flow) confirmed improved blood circulation. There were no significant changes in the cardiac indicators (troponin, prostate-specific antigen, or electrocardiogram tests) before and after tadalafil administration, supporting the safety of its low-dose daily administration. CONCLUSIONS: A small dose of daily tadalafil was shown to safely improve erectile dysfunction and peripheral blood flow in patients with T2DM, in which peripheral arterial diseases should not be considered separately but rather as complex entities.

Frequency and Severity of Hypoglycemia in Type 2 Diabetes Mellitus Patients Treated with a Sulfonylurea-Based Regimen at University-Affiliated Hospitals in Korea: The Naturalistic Evaluation of Hypoglycemic Events in Diabetic Subjects Study.

BACKGROUND: We assessed the frequency and severity of hypoglycemia in type 2 diabetes mellitus patients treated with sulfonylurea monotherapy or sulfonylurea+metformin. METHODS: We conducted a retrospective, observational, cross-sectional study in 2011 and 2012 including patients with type 2 diabetes mellitus aged ≥30 years who were treated with ≥6 months of sulfonylurea monotherapy or sulfonylurea+metformin at 20 university-affiliated hospitals in Korea. At enrollment, glycated hemoglobin (HbA1c) was assessed; participants completed self-reported questionnaires describing hypoglycemia incidents over the past 6 months. A review of medical records up to 12 months before enrollment provided data on demographics, disease history, comorbidities, laboratory results, and drug usage. RESULTS: Of 726 enrolled patients, 719 were included (55.6% male); 31.7% and 68.3% were on sulfonylurea monotherapy and sulfonylurea+metformin, respectively. Mean±standard deviation age was 65.9±10.0 years; mean HbA1c level was 7.0%±1.0%; 77.8% of patients had hypertension (89.4% used antihypertensive medication); 60.5% had lipid disorders (72.5% used lipid-lowering medication); and 52.0% had one or more micro- or macrovascular diseases. Among patients with A1c measurement (n=717), 56.4% achieved therapeutic goals (HbA1c <7.0%); 42.4% (305/719) experienced hypoglycemia within 6 months of enrollment; and 38.8%, 12.9%, 12.7%, and 3.9% of patients experienced mild, moderate, severe, and very severe hypoglycemia symptoms, respectively. Several reported hypoglycemia frequency as 1-2 times over the last 6 months. The mean number of very severe hypoglycemia episodes was 3.5±5.5. CONCLUSION: Among type 2 diabetes mellitus patients treated with sulfonylurea-based regimens, glycemic levels were relatively well controlled but hypoglycemia remained a prevalent side effect.

Association of Fasting Glucose Level with Neutrophil-Lymphocyte Ratio Compared to Leukocyte Count and Serum C-Reactive Protein.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is often used as an inflammatory marker in chronic diseases such as cancer or cardiovascular diseases. However, there are few studies about the association between the NLR and diabetes mellitus (DM) or impaired fasting glucose (IFG) patients in Korea. This study investigated the association between the fasting plasma glucose (FPG) level and NLR in Koreans. METHODS: This cross-sectional retrospective study included 3,219 healthy subjects who visited Konyang University Hospital in South Korea for regular health examinations. Participants with a history of insulin administration, anti-diabetic drugs, anti-inflammatory drugs, or underlying diseases related to inflammation were excluded. RESULTS: All statistical evaluation was performed by dividing participants into males and females. Based on FPG levels, the subjects were classified into three groups, with normal fasting glucose (n=1,969), IFG (n=1,138), and DM (n=122). The NLR had no significant mean differences among these groups for both sexes. Multiple linear regression analysis between FPG level and NLR showed an independent and significantly negative association (ß±standard error, -0.67±0.24; P=0.006) in normal subjects after adjustment. Log(serum C-reactive protein [S-CRP]) showed an independently and significantly positive association with FPG in male IFG/DM patients. Total leukocyte (white blood cell [WBC]) showed an independently and significantly positive association with FPG in female IFG/DM patients. CONCLUSION: In normal subjects, NLR shows an independently and significantly negative association with FPG. In IFG/DM patients, NLR was not significantly related to FPG. WBC count in female patients and S-CRP level in male patients were significantly positively associated with FPG only in IFG/DM.

Relationship between coronary atherosclerosis in coronary computed tomography angiography and serum vitamin D level.

OBJECTIVES: Vitamin D deficiency has been shown to influence the development of some cardiovascular disease. In this study, the association between the existence of coronary artery plaque and vitamin D was examined among participants who were not previously diagnosed with coronary artery disease. METHODS: A total of 339 participants (246 men and 93 women) who visited a health examination center for check-up including blood test for serum vitamin D level and coronary computed tomography angiography (CCTA) were selected for this study. RESULTS: Among the total 339 participants, 106 displayed coronary artery plaques. The serum 25-hydroxy vitamin D (25(OH)D) level of the group with plaque was lower than that of the group without (17.7 ± 7.72 ng/mL vs. 19.6 ± 7.12 ng/mL, P = 0.0316). The group with plaque had higher incidence rates of diabetes mellitus, hypertension, and dyslipidemia than that without (P = 0.0078, P = 0.0065, and P = 0.0174, respectively). The former displayed higher serum glucose and glycated hemoglobin levels than the latter (P = 0.0055 and P = 0.0137, respectively). The group with plaque showed higher systolic and diastolic blood pressure than that without (P < 0.0001 and P = 0.0012, respectively). Stepwise multivariate logistic regression analysis revealed that 25(OH)D (coefficient, -0.06; odd ratio, 0.9433; 95% confidence interval, 0.8967-0.9924), age, and sex were independently related with presence of coronary artery plaque. CONCLUSIONS: Relatively low vitamin D level was observed among participants with plaque, which was determined through CCTA during a health examination. Plaque formation and serum 25(OH)D level showed inverse relationship.

Prevalence of Sexual Dysfunction and Associated Risk Factors in Middle-Aged and Elderly Korean Men in Primary Care.

Although several studies have individually investigated the risk factors for erectile dysfunction (ED), premature ejaculation (PE), and late-onset hypogonadism (LOH), few studies have considered ED, PE, and LOH as categories of sexual dysfunction (SD) within the same population. We therefore aimed to investigate the prevalence of SD and its associated risk factors among men in primary care. Study participants were enrolled by 18 family physicians from 15 hospital-based family practices in Korea between August 2010 and May 2011. Participants answered a questionnaire regarding their demographic characteristics and lifestyle factors as well as the Korean versions of the Androgen Deficiency in the Aging Male, the International Index of Erectile Function, and the Premature Ejaculation Diagnostic Tool questionnaires. SD prevalence was 64.9% among study participants who were ≥ 40 years of age. ED prevalence was 43.7%, PE prevalence was 38.6%, and LOH prevalence was 16.8%. SD prevalence was significantly associated with increased age, overweight, hypertension, diabetes, and depression. These findings highlight the importance of screening questions for SD in primary care, especially among older male patients with the identified risk factors.

The Effect of Sleep Quality on the Development of Type 2 Diabetes in Primary Care Patients.

Sleep has important effects on physical and mental health, and sleep disorders are associated with increased mortality and morbidity. This study was conducted to evaluate the relationship between sleep duration or sleep quality and the risk of type 2 diabetes. The FACTS (FAmily CohorT Study in primary care) was established to investigate the relations between familial environment and health which was conducted at 22 family medicine outpatient clinics in general hospitals. Total 563 patients without diabetes who received ≥1 year follow-up examination were included in the analysis. We used the Pittsburgh Sleep Quality Index to determine sleep quality, and a score of ≥5 was considered to define poor sleep quality. Patients taking oral hypoglycemic agents, having a fasting glucose level of >126 mg/dL, or diagnosed with diabetes by physicians were classified as having diabetes. The median follow-up period was 2.5 years. Poor sleep quality was associated with a higher risk of diabetes after adjusting for age, sex, body mass index, income, physical activity, and family history of diabetes (relative risk=2.64; 95% confidence interval, 1.03-6.78). As a risk factor for the development of diabetes, poor sleep quality may independently increase the incidence of diabetes.

The Relationship between a Spouse's Alcohol Use Disorder and Family Communication.

BACKGROUND: Alcohol use disorder (AUD) affects not only an individual's health but also their family. This study was conducted to examine effects of a spouse's AUD on family functioning and family communication. METHODS: We conducted a cross-sectional study using data from 890 participants (445 couples) in a Korean family cohort in primary care. Participants with Alcohol Use Disorders Identification Test in Korea scores of 8 or greater were classified into an AUD group. Family functioning was classified into three groups (balanced, midrange, and extreme) using the Family Adaptability and Cohesion Scale (FACES)-III questionnaire, and then reclassified into two groups (appropriate and extreme groups) for binominal analyses. Family communication was classified into three groups (high, moderate, and low) using the Family Communication Scale, FACES-IV, and also reclassified into two groups (good and poor). RESULTS: There was no significant difference in adaptability and cohesion between both male and female participants with a spouse with AUD and participants with a spouse without AUD. Using multivariate logistic regression to adjust for potential confounders, there was no significant difference in family type and communication between the two groups in males. However, there was a significant decrease in family communication (odds ratio, 2.14; 95% confidence interval, 1.29 to 3.58) in females with a spouse with AUD compared to females with a spouse without AUD, even after adjusting for the participant's own AUD. CONCLUSION: In females, family communication is significantly worse when spouses have AUD. This suggests that a husband's alcohol consumption has negative effects on his wife's family communication.

A coronary heart disease prediction model: the Korean Heart Study.

OBJECTIVE: The objectives of this study were to develop a coronary heart disease (CHD) risk model among the Korean Heart Study (KHS) population and compare it with the Framingham CHD risk score. DESIGN: A prospective cohort study within a national insurance system. SETTING: 18 health promotion centres nationwide between 1996 and 2001 in Korea. PARTICIPANTS: 268 315 Koreans between the ages of 30 and 74 years without CHD at baseline. OUTCOME MEASURE: Non-fatal or fatal CHD events between 1997 and 2011. During an 11.6-year median follow-up, 2596 CHD events (1903 non-fatal and 693 fatal) occurred in the cohort. The optimal CHD model was created by adding high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides to the basic CHD model, evaluating using the area under the receiver operating characteristic curve (ROC) and continuous net reclassification index (NRI). RESULTS: The optimal CHD models for men and women included HDL-cholesterol (NRI=0.284) and triglycerides (NRI=0.207) from the basic CHD model, respectively. The discrimination using the CHD model in the Korean cohort was high: the areas under ROC were 0.764 (95% CI 0.752 to 0.774) for men and 0.815 (95% CI 0.795 to 0.835) for women. The Framingham risk function predicted 3-6 times as many CHD events than observed. Recalibration of the Framingham function using the mean values of risk factors and mean CHD incidence rates of the KHS cohort substantially improved the performance of the Framingham functions in the KHS cohort. CONCLUSIONS: The present study provides the first evidence that the Framingham risk function overestimates the risk of CHD in the Korean population where CHD incidence is low. The Korean CHD risk model is well-calculated alternations which can be used to predict an individual's risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans.

The Korean Heart Study: rationale, objectives, protocol, and preliminary results for a new prospective cohort study of 430,920 men and women.

BACKGROUND: To describe the rationale, objectives, protocol, and preliminary results for a new prospective cohort study of cardiovascular disease (CVD) risk factors in South Korea. METHODS: Study members were recruited from participants in routine health assessments at health promotion centres across South Korea. Established and emerging CVD risk factors were measured. Eighteen centres holding electronic health records agreed to linkage of participants' records to future health insurance claims for monitoring of disease events. The recruitment of 430,920 participants (266,782 men, 164,138 women), aged 30-74 years, provides broad geographical reach across South Korea. RESULTS: Risk factor prevalence was more favourable in women than men, and, in general, in the younger rather than older study members. There was also close similarity between the characteristics of the present sample and the Korean National Health and Nutrition Examination Survey. The expected associations between risk factors and both CVD and death were also apparent. CONCLUSIONS: Data from the present sample, based on data linkage, show close agreement with South Korea-wide surveys (for risk factor prevalence) and the extant literature (for risk factor associations). These findings gives confidence in future results anticipated from this cohort study of east Asians - a group that has been traditionally under-researched.

Achieving recommended low density lipoprotein cholesterol goals and the factors associated with target achievement of hypercholesterolemia patients with rosuvastatin in primary care.

OBJECTIVE: Hypercholesterolemia is a major risk factor for cardiovascular disease and requires continuous management. The role of primary physicians in this regard is important, yet the factors associated with successful lipid lowering treatments in primary clinics have not been clearly identified. We aimed to evaluate the rate of successful hypercholesterolemia treatment in Korean primary care, and to identify the factors associated with achieving low density lipoprotein cholesterol (LDL-C) targets. METHODS: We prospectively recruited and retrospectively assessed 1851 Korean patients with hypercholesterolemia who visited family physicians and were prescribed rosuvastatin for the first time. LDL-C lowering targets, defined according to NCEP ATP III guidelines, were evaluated at 6 months after the first prescription. The factors associated with achieving these targets were also assessed. RESULTS: Overall, 87.6% of our participants attained their LDL-C goals. In multiple logistic regression analysis, good adherence to medication was strongly associated with the achievement of target LDL-C levels, whereas higher cardiovascular risk factors including diabetes (in both sexes), low high density lipoprotein, and current smoking status (in males), and hypertension (in females) were related to LDL-C target level failures. CONCLUSION: Our observations of the short period for hypercholesterolemia in Korean primary care has revealed that the rate of achieving target LDL-C levels was high in these patients, whereas patients at higher risk for cardiovascular disease tended to have lower LDL-C achievement outcomes. Primary care physicians should pay more attention to patients showing higher cardiovascular risk and stress the need for good adherence and management regimens in these individuals.

Models for estimating the biological age of five organs using clinical biomarkers that are commonly measured in clinical practice settings.

OBJECTIVES: To date, no worldwide studies have been conducted to estimate the biological age of five organs using clinical biomarkers that are associated with the aging status. Therefore, we conducted this study to develop the models for estimating the biological age of five organs (heart, lung, liver, pancreas, and kidney) using clinical biomarkers which are commonly measured in clinical practice. DESIGN: A cross sectional study. METHODS: Subjects were recruited from the routine health check-up centers in Korea from 2004 through 2010. Data obtained from 121,189 subjects (66,168 men and 55,021 women) were used for clinical evaluation and statistical analysis. We examined the relations between clinical biomarkers associated with five organs and the chronological age and proposed a model for estimating the biological age of five organs. RESULTS: In the models for predicting the biological ages of the heart, lung, liver, pancreas and kidney in men, 12, 2, 8, 3, and 5 parameters were respectively included (R(2)=0.652, 0.427, 0.107, 0.245, and 0.651). In contrast to men, 10, 2, 8, 3, and 5 parameters in women were respectively included (R(2)=0.780, 0.435, 0.140, 0.384, and 0.501). CONCLUSION: We first proposed the models for predicting the biological age of five organs in the current study. We developed those using clinical parameters that can be easily obtained in clinical practice settings. Our biological age prediction models may be used as supplementary tools to assess the aging status of five organs in clinical practice settings.

The efficacy and safety of a combined alendronate and calcitriol agent (maxmarvil): a postmarketing surveillance study in korean postmenopausal women with osteoporosis.

BACKGROUND: Combined therapy with alendronate and calcitriol may have additive effects on bone density. An observational study was performed to evaluate the efficacy and safety of Maxmarvil, a combinative agent of alendronate (5 mg) and calcitriol (0.5 µg), and to identify factors associated with efficacy. METHODS: A total of 568 postmenopausal women with osteoporosis were enrolled by family physicians in 12 hospitals. The study subjects took Maxmarvil daily for 12 months. Questionnaires about baseline characteristics, socioeconomic status, and daily calcium intake were completed at the first visit. Adverse events were recorded every 3 months and bone mineral density (BMD) in the lumbar spine was measured using dual-energy X-ray absorptiometry at baseline and after 12 months. We evaluated the efficacy and safety of Maxmarvil, and the factors related to BMD improvement. RESULTS: A total of 370 patients were included in final analysis. The median BMD was 0.81 ± 0.12 g/cm(2) at pre-treatment and 0.84 ± 0.13 g/cm(2) after one year. The average BMD improvement was 3.4% ± 6.4% (P < 0.05), and 167 (45.1%) patients showed improvement. Factors associated with improved BMD were continuation of treatment (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.15 to 5.07) and good compliance (OR, 2.54; 95% CI, 1.29 to 5.00). Adverse events were reported by 35 of the 568 patients, with the most common being abdominal pain and dyspepsia. CONCLUSION: Maxmarvil was found to be safe, well tolerated and effective in osteoporosis treatment. Continuation of treatment and good compliance were the factors associated with efficacy.

Comparison of visceral fat and liver fat as risk factors of metabolic syndrome.

The principal objective of this study was to determine whether visceral fat or liver fat is a more relevant risk factor for metabolic syndrome. A total of 98 subjects aged 18-65 yr, who visited a health promotion center in a university hospital, were enrolled in this study. Metabolic syndrome was diagnosed based on the modified National Cholesterol Education Program's Adult Treatment Panel III report (NCEP-ATPIII) criteria. We defined the visceral obesity as a visceral fat area of ≥ 100 cm(2) which was acquired by CT at the L4-5 level. To evaluate fatty liver, we applied a liver-to-spleen attenuation ratio ≤ 1.1 as measured by CT at the T12 level. We employed binary logistic regression models that used the presence or absence of metabolic syndrome as a dependent variable and age, sex, and the presence or absence of visceral obesity and fatty liver as independent variables. Visceral obesity was not found to be an independent variable as a risk factor of metabolic syndrome (odds ratio 2.7; 95% confidence interval 0.55-13.30), but fatty liver was found to be significant in this model (odds ratio 71.3; 95% CI 13.04-389.53). Our study suggests that liver fat may be a more important risk factor than visceral fat in terms of its association with metabolic syndrome.

Development of models for predicting biological age (BA) with physical, biochemical, and hormonal parameters.

Individual differences are the hallmark of aging. Chronological age (CHA) is known that fails to provide an accurate indicator of the aging but biological age (BA) estimates the functional status of an individual in reference to his or her chronological peers on the basis of how well he or she functions in comparison with others of the same CHA. Therefore, we developed models for predicting BA that can be applicable in clinical practice settings. This was a community-based cross-sectional study. Subjects were recruited from the health promotion center in Korea from 2001 to 2005. Among these, data obtained from the 3575 participants (1302 men and 2273 women) was used for clinical evaluation and statistical analysis. For our test battery we selected 25 parameters among the routine tests. For males, the best models were developed using 15, 7, 5, and 4 of the 25 chosen parameters for total, physical, biochemical and hormonal characteristics, respectively (R(2)=0.62, 0.38, 0.33, and 0.36, respectively). Similar to males, for the females, 14, 6, 8, and 3 parameters were developed as the models (R(2)=0.66, 0.40, 0.42, and 0.37, respectively). Our BA prediction models may be used as supplementary tools adding knowledge in the evaluation of aging status.

Relationship of serum adiponectin and resistin levels with breast cancer risk.

Obesity is one of the well-known risk factors of breast cancer. We evaluated the relationship between serum adiponectin and resistin levels and breast cancer risk in 41 biopsy-proven breast cancer patients and 43 age- and body mass index-matched controls. The mean serum adiponectin level was lower in the breast cancer group than the control group (6.93+/-3.2 microg/mL, vs. 7.60+/-3.5 microg/mL), but this difference did not reach statistical significance (p=0.37). There was a statistically significant difference in serum resistin levels between the groups (breast cancer group 5.23+/-6.9 ng/mL vs. control 1.46+/-2.0 ng/mL; p<0.001). The risk of breast cancer was significantly increased in the highest tertile group for serum resistin level compared to the lowest tertile group (adjusted odds ratio 2.77 [95% CI 1.40-5.50]). The lymph node metastasis was significantly increased in the patients with less than the median adiponectin level (p=0.017). In the patients whose resistin level was higher than the median, the frequency of tumor with the highest histological grade was significantly increased (p=0.025). In conclusions, both the low serum adiponectin levels and high resistin levels are likely to be associated with increased breast cancer risk in Korean women.

Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell.

Recently, it was reported that reduction in serum adiponectin levels is correlated with the incidence of breast cancer. As an effort to explain this, we screened various human breast cancer cell lines to identify those in which proliferation is directly controlled by adiponectin. Among the five tested cell lines, proliferation of MDA-MB-231 cancer cell was significantly suppressed by adiponectin within the range of physiological concentration. Furthermore, prolonged adiponectin treatment caused cell growth arrest and even apoptosis of MDA-MB-231. This result is the first to show that adiponectin can directly control cancer cell growth and provides a rationale for the theory that reduction in plasma adiponectin levels could be a risk factor for breast cancer.