Low serum creatinine to cystatin C ratio is independently associated with sarcopenia and high carotid plaque score in patients with type 2 diabetes.

BACKGROUND AND AIMS: Low serum creatinine (Cr) to cystatin C (cysC) ratio has been suggested to be associated with low muscle mass and strength and poor prognosis in various chronic disease. We investigated the associations of CCR with sarcopenia and carotid plaque score (PS) in patients with type 2 diabetes mellitus. METHODS AND RESULTS: A total of 1577 patients with type 2 diabetes were enrolled. High PS was defined as PS ≥ 3. Sarcopenia was assessed by the measurement of appendicular skeletal muscle mass (ASM) and grip strength (GS). Compared to the highest CCR group, the lowest tertile group was older; had higher C-reactive protein levels, CIMT, and PS, but lower cysC-based estimated glomerular filtration rate (cysC-eGFR), ASM/BMI, and GS. Positive correlations between CCR and ASM/BMI (r = 0.239 in men and 0.303 in women, p < 0.001) and GS (r = 0.282 in men and 0.270 in women, p < 0.001) were observed in both genders. Odds ratios and 95% confidence intervals for high PS after adjusting for age and sex were 1.22 (0.92-1.61, p = 0.18) in the middle and 1.74 (1.31-2.30, p < 0.001) in the lowest tertiles, respectively, with those of the lowest tertile remaining significant after further adjusting for multiple confounders. CONCLUSIONS: Low CCR was independently associated with sarcopenia and high PS in patients with type 2 diabetes mellitus, especially after adjusting for ASM/BMI and GS.

Muscle mass and grip strength in relation to carotid intima-media thickness and plaque score in patients with type 2 diabetes.

BACKGROUND AND AIMS: In this study, we examined the relationships of appendicular skeletal muscle mass (ASM) and grip strength (GS) with carotid intima-media thickness (CIMT) and plaque score (PS) in patients with type 2 diabetes. METHODS AND RESULTS: A total of 1185 patients were recruited. High CIMT and high PS were defined as ≥ 75 percentile of maximal CIMT of each sex and PS ≥ 3. Patients in the lowest ASM/body mass index (BMI) or GS/BMI tertile were older and had lower HDL cholesterol, and eGFR, but higher BMI, waist circumference (WC), HOMA-IR, and C-reactive protein than those in the highest tertile. Meanwhile, individuals in the lowest ASM or GS tertile group had lower BMI and WC than those in the highest one. CIMT and PS and the prevalence of high CIMT, carotid plaques, and high PS gradually increased with decreasing tertiles of ASM, ASM/BMI, GS, and GS/BMI (p < 0.001). After adjusting for age and sex, odds ratios (ORs) and 95% confidence intervals (CIs) for high CIMT and high PS were 0.98 (0.68-1.42), 1.64 (1.14-2.36), 2.000 (1.33-3.01), and 1.77 (1.22-2.58) and 1.63 (1.16-2.30), 1.78 (1.28-2.54), 1.91 (1.33-2.75), and 1.61 (1.13-2.28) in the lowest tertile of ASM, ASM/BMI, GS, and GS/BMI, respectively. After further adjusting for potential confounders, ORs and 95% CI for high CIMT and high PS remained significant in the lowest tertile group. CONCLUSIONS: Low ASM and low GS may be independent risk factors for high CIMT and high PS in patients with type 2 diabetes.

Combined association of skeletal muscle mass and grip strength with cardiovascular diseases in patients with type 2 diabetes.

BACKGROUND: Appendicular skeletal muscle mass (ASM) and grip strength (GS) have been suggested to be related to cardiovascular diseases (CVDs), but their association with type 2 diabetes (T2D) remains unclear. Therefore, we examined the combined association of ASM and GS with the prevalence of CVD in patients with T2D. METHODS: A total of 1230 patients with T2D were recruited and divided into four groups based on the sex-specific median values of ASM adjusted for body mass index (ASM/BMI; short: SM) and GS: high SM/high GS (HSM/HGS), high SM/low GS (HSM/LGS), low SM/high GS (LSM/HGS), and low SM/low GS (LSM/LGS). RESULTS: The LSM/LGS group was older and had higher values of systolic blood pressure, homeostasis model assessment of insulin resistance, waist circumference, and C-reactive protein but lower high-density lipoprotein cholesterol concentrations than the HSM/HGS group. After adjusting for potential confounders, the odds ratios (ORs) and 95% CIs for CVD, coronary heart disease (CHD), ischemic stroke, and peripheral arterial disease (PAD) in the LSM/LGS group were 2.90 (1.89-4.47), 2.39 (1.46-3.92), 1.77 (0.84-3.71), and 5.83 (1.58-21.48), respectively. After adjusting for variable confounders among patients with higher glycosylated hemoglobin (HbA1c) (≥7.1%), the ORs and 95% CIs for CVD and CHD in the LSM/LGS group were 7.27 (3.37-15.67) and 6.17 (2.65-14.37), respectively. CONCLUSIONS: The combination of low SM and GS was strongly associated with CVD, CHD, and PAD in patients with T2D, especially in those with higher HbA1c levels.

Relationship between Regional Body Fat Distribution and Diabetes Mellitus: 2008 to 2010 Korean National Health and Nutrition Examination Surveys.

BACKGROUND: The aim of this study was to investigate the association between regional body fat distribution, especially leg fat mass, and the prevalence of diabetes mellitus (DM) in adult populations. METHODS: A total of 3,181 men and 3,827 postmenopausal women aged 50 years or older were analyzed based on Korea National Health and Nutrition Examination Surveys (2008 to 2010). Body compositions including muscle mass and regional fat mass were measured using dual-energy X-ray absorptiometry. RESULTS: The odds ratios (ORs) for DM was higher with increasing truncal fat mass and arm fat mass, while it was lower with increasing leg fat mass. In a partial correlation analysis adjusted for age, leg fat mass was negatively associated with glycosylated hemoglobin in both sexes and fasting glucose in women. Leg fat mass was positively correlated with appendicular skeletal muscle mass and homeostasis model assessment of ß cell. In addition, after adjusting for confounding factors, the OR for DM decreased gradually with increasing leg fat mass quartiles in both genders. When we subdivided the participants into four groups based on the median values of leg fat mass and leg muscle mass, higher leg fat mass significantly lowered the risk of DM even though they have smaller leg muscle mass in both genders (P<0.001). CONCLUSION: The relationship between fat mass and the prevalence of DM is different according to regional body fat distribution. Higher leg fat mass was associated with a lower risk of DM in Korean populations. Maintaining leg fat mass may be important in preventing impaired glucose tolerance.

High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis.

BACKGROUND: Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans. METHODS: We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008-2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka's equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD. RESULTS: The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26-1.55, in HSI; OR 1.75, CI 1.39-2.20, in FLI, both P < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values. CONCLUSIONS: High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis.

Lower Serum Creatinine Is Associated with Low Bone Mineral Density in Subjects without Overt Nephropathy.

BACKGROUND: Low skeletal muscle mass is associated with deterioration of bone mineral density. Because serum creatinine can serve as a marker of muscle mass, we evaluated the relationship between serum creatinine and bone mineral density in an older population with normal renal function. METHODS: Data from a total of 8,648 participants (4,573 men and 4,075 postmenopausal women) aged 45-95 years with an estimated glomerular filtration rate >60 ml/min/1.73 m2 were analyzed from the Fourth Korea National Health and Nutrition Examination Survey (2008-2010). Bone mineral density (BMD) and appendicular muscle mass (ASM) were measured using dual-energy X-ray absorptiometry. Receiver operating characteristic curve analysis revealed that the cut points of serum creatinine for sarcopenia were below 0.88 mg/dl in men and 0.75 mg/dl in women. Subjects were divided into two groups: low creatinine and upper normal creatinine according to the cut point value of serum creatinine for sarcopenia. RESULTS: In partial correlation analysis adjusted for age, serum creatinine was positively associated with both BMD and ASM. Subjects with low serum creatinine were at a higher risk for low BMD (T-score ≤ -1.0) at the femur neck, total hip and lumbar spine in men, and at the total hip and lumbar spine in women after adjustment for confounding factors. Each standard deviation increase in serum creatinine was significantly associated with reduction in the likelihood of low BMD at the total hip and lumbar spine in both sexes (men: odds ratio (OR) = 0.84 [95% CI = 0.74-0.96] at the total hip, OR = 0.8 [95% CI = 0.68-0.96] at the lumbar spine; women: OR = 0.83 [95% CI = 0.73-0.95] at the total hip, OR=0.81 [95% CI = 0.67-0.99] at the lumbar spine). CONCLUSIONS: Serum creatinine reflected muscle mass, and low serum creatinine was independently associated with low bone mineral density in subjects with normal kidney function.

Maternal age at first delivery is associated with the risk of metabolic syndrome in postmenopausal women: from 2008-2010 Korean National Health and Nutrition Examination Survey.

BACKGROUND: Recent cross-sectional studies demonstrated that earlier maternal age at first childbirth is correlated with a higher risk of diabetes in postmenopausal women. In this study, we evaluated whether the age at first delivery is associated with the risk of metabolic syndrome (MetS) in postmenopausal women. METHODS: A total of 4,261 postmenopausal women aged 45 years or older were analyzed using data generated from Korea National Health and Nutrition Examination Surveys (2008-2010). Subjects were divided into three groups according to the maternal age at first delivery as follows: ≤ 20 years (n=878), 21-25 years (n=2314), and ≥ 26 years (n=1069). RESULTS: Approximately 37% of subjects had MetS. The prevalence of MetS showed a gradual increase as maternal age at first delivery decreased (≥ 26 years = 30.9% vs. 21-25 years = 39.9% vs. ≤ 20 years = 50.8%, respectively, p < 0.001). Central obesity indices such as trunk fat mass and waist circumference were significantly higher in the group aged ≤ 20 years than other groups. After adjustments for confounding factors, the odds ratios (ORs) for predicting the presence of MetS increased gradually as first delivery age decreased (≥ 26 years vs. 21-25 years vs. ≤ 20 years: OR [95% CI] = 1 vs. 1.324 [1.118-1.567] vs. 1.641 [1.322-2.036], respectively). Among components of MetS, younger maternal age at first delivery (≤ 20 years) was significantly associated with increased waist circumference (OR [95% CI] = 1.735 [1.41-2.13]), elevated blood pressure (1.261 [1.02-1.57]), high triglyceride (1.333 [1.072-1.659]), and low HDL-cholesterol (1.335[1.084-1.643]). CONCLUSIONS: Our findings suggest that younger maternal age at first delivery is independently associated with a higher risk of central obesity and MetS in postmenopausal women.

Gender-specific association between urinary sodium excretion and body composition: Analysis of the 2008-2010 Korean National Health and Nutrition Examination Surveys.

OBJECTIVE: Few studies have reported the relationship between sarcopenia and the estimated amount of sodium excreted in 24 h, as measured by the spot urine test (E24UNA), in a community-dwelling cohort. We investigated the gender specific association between E24UNA values and body composition indices. MATERIALS AND METHODS: Data from a total of 7162 participants (3545 men and 3617 postmenopausal women) aged 45 years or older were obtained from multiple Korea National Health and Nutrition Examination Surveys (2008-2010) and analyzed. The total amount of sodium excreted in the urine in a 24-h period was estimated with spot urine specimens. Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight (ASM/Wt) that was less than 1 standard deviation below the sex-specific mean for young adults. RESULTS: E24UNA values were positively correlated with body mass index, waist circumference, total fat mass, and blood pressure; in contrast, E24UNA values were negatively correlated with ASM/Wt in both sexes. Compared with those in the lowest E24UNA tertile, participants in the highest E24UNA tertile were at higher risk for sarcopenia (men: odds ratio (OR)=1.3 [95% confidence interval (CI)=1.07-1.59]; women: OR=1.41 [95% CI=1.16-1.73]). Further classification of subjects with sarcopenia into sarcopenic obese and sarcopenic nonobese groups revealed that the highest E24UNA values were found in the sarcopenic obese group; this difference was statistically significant. The next highest levels were found in the sarcopenic nonobese group, followed by the nonsarcopenic group. This trend was observed in both sexes. CONCLUSION: High E24UNA values were independently associated with both sarcopenia and obesity in Korean individuals older than 45 years. These results suggest that high salt intake may have a deleterious effect on body composition.

Serum cystatin C levels are associated with asymptomatic peripheral arterial disease in type 2 diabetes mellitus patients without overt nephropathy.

AIMS: We investigated the association between serum cystatin C and asymptomatic peripheral artery disease (PAD) in type 2 diabetes mellitus patients with normal renal function or mild renal impairment and we compared cystatin C with albuminuria and estimated glomerular filtration rate (eGFR) for prediction of PAD. METHODS: We enrolled 272 patients with type 2 diabetes. Patients were excluded if they had an eGFR<60mL/min per 1.73m(2), 24-h urine albumin (24h-uAlb)≥300mg/day, serum creatinine (Cr)>1.3mg/dL, or previous history of cardiovascular disease. PAD was defined as having an ankle brachial index (ABI)≤0.9. RESULTS: Patients with PAD were more likely to have a lower eGFR and higher values of 24h-uAlb, cystatin C, and serum Cr than subjects without PAD. Cystatin C was independently associated with age, current smoking, HDL, eGFR, and PAD. Odds ratios (ORs) for PAD after adjustment for age, gender, smoking, and hypertension were 1.71 (95% CI, 1.02-2.85), 1.51 (95% CI, 0.93-2.44), and 0.78 (95% CI, 0.41-1.49) for a one standard deviation increase in cystatin C, 24h-uAlb, and eGFR, respectively. CONCLUSIONS: Cystatin C was independently associated with PAD in type 2 diabetes mellitus patients without overt nephropathy.

Bone mineral density and bone turnover markers in patients on long-term suppressive levothyroxine therapy for differentiated thyroid cancer.

PURPOSE: Current management for patients with differentiated thyroid cancer includes near total thyroidectomy and radioactive iodine therapy followed by administration of supraphysiological doses of levothyroxine (L-T4). Although hyperthyroidism is a well known risk factor for osteoporosis, the effects of L-T4 treatment on bone mineral density (BMD) in patients with thyroid cancer do not appear to be as significant as with endogenous hyperthyroidism. In this study, we evaluated the impact of long-term suppressive therapy with L-T4 on BMD and bone turn over markers in Korean female patients receiving L-T4 suppressive therapy. METHODS: We enrolled 94 female subjects (mean age, 50.84 ± 11.43 years) receiving L-T4 after total or near total thyroidectomy and radioactive iodine therapy for thyroid cancer (mean follow-up period, 12.17 ± 4.27 years). The subjects were divided into three groups by thyroid stimulating hormone (TSH) level (group 1 with TSH level ≤0.001 µIU/mL, group 2 with TSH level between 0.001 and 0.17 µIU/mL, group 3 with TSH level >0.17 µIU/mL) and four groups by quartile of free T4 level. L-T4 dosage, BMD (examined by dual-energy x-ray absorptiometry), and bone turnover markers were evaluated according to TSH and free T4 levels. RESULTS: No significant decrease was detected in BMD or bone turnover markers according to TSH level or free T4 level. Also, the prevalence of osteoporosis and osteopenia was not different among groups. CONCLUSION: Long-term L-T4 suppressive therapy after thyroid cancer management did not affect bone density or increase the prevalence of osteoporosis even though TSH levels were supraphysiologically suppressed.

Egg consumption in relation to risk of cardiovascular disease and diabetes: a systematic review and meta-analysis.

BACKGROUND: The associations of egg consumption with cardiovascular disease (CVD) and diabetes are still unclear. OBJECTIVE: We aimed to quantitatively summarize the literature on egg consumption and risk of CVD, cardiac mortality, and type 2 diabetes by conducting a meta-analysis of prospective cohort studies. DESIGN: A systematic literature review was conducted for published studies in PubMed and EMBASE through March 2012. Additional information was retrieved through Google or a hand review of the reference from relevant articles. Studies were included if they had a prospective study design, were published in English-language journals, and provided HRs and 95% CIs for the associations of interest. Data were independently extracted by 2 investigators, and the weighted HRs and 95% CIs for the associations of interest were estimated by using a random-effects model. RESULTS: A total of 22 independent cohorts from 16 studies were identified, including participants ranging in number from 1600 to 90,735 and in follow-up time from 5.8 to 20.0 y. Comparison of the highest category (≥1 egg/d) of egg consumption with the lowest (<1 egg/wk or never) resulted in a pooled HR (95% CI) of 0.96 (0.88, 1.05) for overall CVD, 0.97 (0.86, 1.09) for ischemic heart disease, 0.93 (0.81, 1.07) for stroke, 0.98 (0.77, 1.24) for ischemic heart disease mortality, 0.92 (0.56, 1.50) for stroke mortality, and 1.42 (1.09, 1.86) for type 2 diabetes. Of the studies conducted in diabetic patients, the pooled HR (95% CI) was 1.69 (1.09, 2.62) for overall CVD. CONCLUSIONS: This meta-analysis suggests that egg consumption is not associated with the risk of CVD and cardiac mortality in the general population. However, egg consumption may be associated with an increased incidence of type 2 diabetes among the general population and CVD comorbidity among diabetic patients.

Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism.

Although peroxisome proliferator receptor (PPAR)-α and PPAR-γ agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-δ has not been fully investigated. In this study, we examined the effects of the PPAR-δ agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-δ agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-γ coactivator (PGC)-1α gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-α and MCP-1 was also examined in supernatant of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-α, MCP-1, and PGC-1α were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-δ agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1α gene expression, and improvement of insulin signaling.

Role of HbA1c in the Screening of Diabetes Mellitus in a Korean Rural Community.

BACKGROUND: Recently, the measurement of glycated hemoglobin (HbA1c) was recommended as an alternative to fasting plasma glucose or oral glucose tolerance tests for diagnosing diabetes mellitus (DM). In this study, we analyzed HbA1c levels for diabetes mellitus screening in a Korean rural population. METHODS: We analyzed data from 10,111 subjects from a Korean Rural Genomic Cohort study and generated a receiver operating characteristic curve to determine an appropriate HbA1c cutoff value for diabetes. RESULTS: The mean age of the subjects was 56.3±8.1 years. Fasting plasma glucose and 2-hour plasma glucose after 75 g oral glucose tolerance tests were 97.5±25.6 and 138.3±67.1 mg/dL, respectively. The mean HbA1c level of the subjects was 5.7±0.9%. There were 8,809 non-DM patients (87.1%) and 1,302 DM patients (12.9%). A positive relationship between HbA1c and plasma glucose levels and between HbA1c and 2-hour plasma glucose levels after oral glucose tolerance tests was found in a scatter plot of the data. Using Youden's index, the proper cutoff level of HbA1c for diabetes mellitus screening was 5.95% (sensitivity, 77%; specificity, 89.4%). CONCLUSION: Our results suggest that the optimal HbA1c level for DM screening is 5.95%.

Serum sex hormone-binding globulin levels are independently associated with nonalcoholic fatty liver disease in people with type 2 diabetes.

AIM: To clarify the association between serum sex hormone-binding globulin (SHBG) levels and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes. METHODS: Two hundred seventy nine patients with type 2 diabetes were consecutively enrolled and metabolic parameters were checked. High-grade NAFLD was defined as moderate or severe fatty liver disease, measured using liver ultrasound. SHBG, testosterone, and estradiol levels were measured. RESULTS: SHBG levels were lower in patients with high-grade NAFLD than in those with normal ultrasound and decreased significantly based on the severity of fatty liver disease. SHBG levels were negatively correlated with hypertension, body mass index (BMI), waist circumference, high-grade NAFLD, triglycerides, alanine aminotransferase (ALT), γ-glutamyltransferase (γGT), homeostasis model assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein (CRP) and were positively correlated with testosterone and estradiol levels. The odds ratios (ORs) predicting the presence of high-grade NAFLD in men and women decreased significantly with increasing SHBG tertile. The ORs remained significant even after further adjusting for BMI, waist circumference, hypertension, triglycerides, γGT, ALT, CRP, HOMA-IR, testosterone, estradiol, and anti-diabetic medications. CONCLUSIONS: Serum SHBG levels were independently associated with the high-grade NAFLD in patients with type 2 diabetes.

Effects of spironolactone and losartan on diabetic nephropathy in a type 2 diabetic rat model.

BACKGROUND: While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model. METHODS: Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9). RESULTS: At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-ß, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups. CONCLUSION: These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-ß and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

Optimal waist circumference cutoff values for metabolic syndrome diagnostic criteria in a Korean rural population.

The Korean Society for the Study of Obesity (KSSO) has defined the waist circumference cutoff value of central obesity as 90 cm for men and 85 cm for women. The purpose of this investigation was to determine the corresponding waist circumference values. A total of 3,508 persons in the Korean Rural Genomic Cohort Study were enrolled in this survey. Receiver operating characteristic (ROC) curve analysis was used to find appropriate waist circumference cutoff values in relation to insulin resistance determined by homeostasis model assessment for insulin resistance (HOMA-IR), body mass index (BMI), and components of metabolic syndrome. The optimal waist circumference cutoff values were 87 cm for men and 83 cm for women by ROC analysis to HOMA-IR and 86 cm for men and 83 cm for women by ROC analysis to value with more than two components of metaobolic syndrome. By using a BMI > or =25 kg/m(2), 86 cm for men and 82 cm for women were optimal waist circumference cutoff values. In this study, we suggest that the most reasonable waist circumference cutoff values are 86-87 cm for men and 82-83 cm for women.

Association between alcohol intake amount and prevalence of metabolic syndrome in Korean rural male population.

Moderate alcohol consumption is known to be associated with a reduced risk of cardiovascular disease and mortality. However, few studies reported that long-term alcohol drinking may increase the prevalence of central obesity, and cardiovascular disease. We examined the association between metabolic syndrome, nutritional factors and alcohol intake amount in Korean male rural population. We performed a cross-sectional analysis on data from Korean Rural Genomic Cohort (KRGC) study. We used multiple logistic regression analysis to estimate the adjusted odds ratio of metabolic syndrome according to alcohol intake amount categories (never, 0-16 g/day, 16-40 g/day, and >40 g/day). The age adjusted odds ratio for the prevalence of metabolic syndrome was significantly increased in the quartile with the highest alcohol consumption compared to the non-alcohol drinking group (1.33; C.I., 1.11-1.59). These results were similar in the high energy intake group, but not in the low energy intake group. Waist circumference, blood pressure, and serum triglyceride levels were significantly higher in the quartile with the highest alcohol consumption compared to the non-alcohol drinking group. These results suggest that large alcohol consumption is associated with metabolic syndrome and may be a modifiable risk factor of metabolic syndrome especially in subjects with high calorie intake.

Elevated serum gamma-glutamyltransferase levels are independently associated with insulin resistance in non-diabetic subjects.

We investigated the associations of gamma-glutamyltransferase (GGT) with visceral obesity, adiponectin and retinol binding protein 4 (RBP4), and insulin resistance (IR) and compared these associations with other liver enzymes in non-diabetes. We enrolled 94 healthy subjects 30-69 years old. Clinical and biochemical metabolic parameters were measured. Adiponectin and RBP4 were determined by ELISA. IR was examined by HOMA-IR. Visceral fat was determined by computed tomography scan. GGT and alanine aminotransferase (ALT) were positively correlated with waist circumference (WC), waist-to-hip ratio (WHR), visceral fat area (VFA), visceral-to-subcutaneous fat area ratio (VSR), HOMA-IR, and RBP4, but was negatively correlated with adiponectin (p<0.05). In multivariate regression, GGT was associated with male sex, HOMA-IR, and RBP4 (R(2)=0.48, p<0.05) and ALT was associated with HOMA-IR (R(2)=0.22, p<0.05). By logistic regression after adjusted for age and sex, the odds ratio (OR) for IR in the highest tertile of sex-specific GGT and ALT were significantly increased compared to those in the lowest [OR (95% CI); 6.90 (2.08-22.82), 3.38 (1.08-10.57), respectively]. However, these relationships after further adjustments for RBP4, adiponectin, VFA, VSR, WHR, WC, TG, and HDL remained significant in only GGT. In conclusions, GGT may be a useful marker of IR in non-diabetes.

Serum adipocyte fatty acid-binding protein levels are associated with nonalcoholic fatty liver disease in type 2 diabetic patients.

OBJECTIVE: Adipocyte fatty acid-binding protein (A-FABP) is a major cytoplasmic protein in adipocytes and macrophages and is closely associated with metabolic syndrome, type 2 diabetes, and atherosclerosis. Here, we investigated whether A-FABP was associated with nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes. RESEARCH DESIGN AND METHODS: We enrolled 181 type 2 diabetic patients. Clinical and biochemical metabolic parameters were measured. The severity of NAFLD was measured by ultrasound. A-FABP, adiponectin, and retinol-binding protein-4 (RBP-4) were determined by enzyme-linked immunosorbent assay. RESULTS: A-FABP levels, defined as more than a moderate degree of fatty liver compared with men, those without metabolic syndrome, and those without NAFLD, were higher in women, patients with metabolic syndrome, and patients with overt NAFLD, respectively. Adiponectin was decreased according to the severity of NAFLD, but RBP-4 showed no difference. Age- and sex-adjusted A-FABP showed positive correlations with BMI, waist-to-hip ratio, waist circumference, triglycerides, gamma-glutamyltransferase, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), A1C, and C-reactive protein (CRP) but showed negative correlation with HDL cholesterol. The odds ratio (OR) for the risk of overt NAFLD with increasing levels of sex-specific A-FABP was significantly increased (OR 2.90 [95% CI 1.15-7.29] vs. 7.87 [3.20-19.38]). The OR in the highest tertile of A-FABP remained significant after adjustments for BMI, waist circumference, A1C, HDL cholesterol, triglycerides, HOMA-IR, CRP, and hepatic enzymes. CONCLUSIONS: Our study demonstrates that serum A-FABP is significantly associated with NAFLD in type 2 diabetes, independent of BMI, waist circumference, HOMA-IR, A1C, triglycerides, HDL cholesterol, and CRP.

Effects of NADPH oxidase inhibitor on diabetic nephropathy in OLETF rats: the role of reducing oxidative stress in its protective property.

Diabetic nephropathy is the most serious complication in diabetes mellitus. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway play critical roles in the development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka (LETO) were divided into the following three groups: LETO rats (n=9), control OLETF rats (n=7) and apocynin-treated OLETF rats (n=9). We examined body weights, plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24h urinary 8-OHdG (8-hydroxy-2'-deoxyguanosine) and MDA (malondialdehyde). Urinary protein and albumin excretions were reduced after apocynin treatment, though apocynin could not significantly decrease serum glucose levels. There were improvements of glomerular and mesangial expansion in the apocynin-treated OLETF rats. Apocynin significantly decreased optical density of glomerular VEGF expression in immunohistochemical stain and reduced the concentration of 24h urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may have the potential to protect against diabetic nephropathy via amelioration of oxidative stress.