Non-alcoholic steatohepatitis and progression of carotid atherosclerosis in patients with type 2 diabetes: a Korean cohort study.

BACKGROUND: There is increasing concern regarding cardiovascular risk in individuals with non-alcoholic fatty liver disease. This study was conducted to evaluate whether hepatic steatosis with or without fibrosis is associated with the progression of carotid atherosclerosis in patients with type 2 diabetes. METHODS: From a longitudinal cohort, we enrolled 1120 patients with type 2 diabetes who underwent repeated carotid artery ultrasonography every 1-2 years. Ultrasonographic findings at baseline and after 6-8 years were compared. Presence of hepatic steatosis was mainly assessed by abdominal ultrasonography; patients with hepatic steatosis were further evaluated for hepatic fibrosis according to fibrosis-4 index. We investigated the association between liver status and atherosclerosis progression. RESULTS: Of 1120 patients, 636 (56.8%) were classified as having hepatic steatosis at baseline. After 6-8 years, 431 (38.5%) showed atherosclerosis progression. Hepatic steatosis was significantly associated with atherosclerosis progression (adjusted odds ratio[AOR]: 1.370, 95% CI 1.025-1.832; p < 0.05). Among patients with hepatic steatosis, only individuals with fibrosis showed significant association with atherosclerosis progression (AOR: 1.615, 95% CI 1.005-2.598; p < 0.05). The association between hepatic fibrosis and atherosclerosis progression was significant in all metabolic subgroups regardless of age, body mass index, presence of metabolic syndrome, or insulin sensitivity (all p < 0.05). Furthermore, subjects with hepatic steatosis & fibrosis and ≥ 4 components of metabolic syndrome criteria showed markedly increased risk of atherosclerosis progression (AOR: 2.430, 95% CI 1.087-5.458; p < 0.05). CONCLUSIONS: Hepatic steatosis with fibrosis is independently associated with the progression of carotid atherosclerosis in patients with type 2 diabetes.

Waist-to-calf circumstance ratio is an independent predictor of hepatic steatosis and fibrosis in patients with type 2 diabetes.

BACKGROUND AND AIM: Although a combination of central obesity and decreased skeletal muscle mass has been associated with various cardiometabolic disorders, its influence on the presence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D) is unclear. We investigated whether waist-to-calf circumference ratio (WCR) predicts NAFLD or hepatic fibrosis in T2D. METHODS: Patients with T2D (n = 5507) were enrolled in this study. Hepatic steatosis was diagnosed using abdominal ultrasound and predicting score. NAFLD was defined as 'hepatic steatosis absent other causes of chronic liver disease,' such as virus or alcoholism. Degree of hepatic fibrosis was calculated using non-invasive serum biomarker-based models. Insulin resistance was assessed by short insulin tolerance test. RESULTS: The prevalence of NAFLD and obesity (BMI ≥ 25 kg/m2 , Asian definition) were 46.4% and 38.9%, respectively. NAFLD prevalence was higher with increasing WCR tertiles: lowest tertile (36% in men, 28% in women) versus highest tertile (53.8% in men, 58.2% in women, both P < 0.001 after stratification by insulin resistance status. Increasing WCR tertiles were independently associated with presence of NAFLD: odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.22-1.68 and OR = 1.56, 95% CI = 1.31-1.86, in the middle and highest tertiles, respectively. Furthermore, patients with NAFLD and the highest WCR tertile had significant fibrosis (OR = 8.62, 95% CI = 1.39-53.36, P = 0.021). Also, WCR was correlated with risk of sarcopenia (OR = 3.18, 95% CI = 2.50-4.05, P < 0.001, highest tertile). CONCLUSIONS: Higher WCR is associated with increased risk of NAFLD and hepatic fibrosis independent of insulin resistance. This suggests that WCR may be a useful index to predict high risk of hepatic steatosis in T2D.

Carbohydrate intake interacts with SNP276G>T polymorphism in the adiponectin gene to affect fasting blood glucose, HbA1C, and HDL cholesterol in Korean patients with type 2 diabetes.

BACKGROUND/OBJECTIVE: The SNP276G>T polymorphism in the adiponectin gene has been reported to be associated with type 2 diabetes and impaired glucose tolerance. The objective of this study was to examine whether SNP276G>T polymorphism influences the blood glucose levels in relation to dietary carbohydrate intake. SUBJECTS/METHODS: In an ongoing, prospective study, 673 patients with type 2 diabetes (339 men and 334 women, aged 40-85 years) were recruited from one of two diabetes clinics in Seoul, Korea. The levels of carbohydrate intake were categorized as <55%, 55%-65%, and >65% of total energy intake. RESULTS: Significant gene-nutrient interactions between SNP276G>T polymorphism and the level of carbohydrate intake were found, which modulated plasma fasting blood glucose (p=0.0277), HbA1C (p=0.0407), and high-density lipoprotein (HDL) cholesterol (p=0.0134) concentrations. The G allele was associated with higher fasting blood glucose only in subjects consuming a low-carbohydrate diet (<55% of energy). However, when carbohydrate intake was intermediate (55%-65%), carriers of the T allele had greater fasting blood glucose and HbA1C concentrations. When carbohydrate intake was high (>65%), carriers of the T allele had greater HDL cholesterol concentrations. This interaction was significant even when carbohydrate intake was considered a continuous variable (p=0.0200 for fasting blood glucose, p=0.0408 for HbA1C, and p=0.0254 for HDL cholesterol), suggesting a strong dose-response relation. CONCLUSIONS: Our data show that the effect of the SNP276G>T polymorphism on plasma fasting blood glucose, HbA1C, and HDL cholesterol concentrations depends on dietary carbohydrate intake.

The association between non-alcoholic fatty liver disease and carotid atherosclerosis in subjects with within-reference range alanine aminotransferase levels.

Our aim was to investigate whether the evaluation of non-alcoholic fatty liver disease (NAFLD) by ultrasound provides additional benefit in assessing carotid atherosclerotic burden in subjects with alanine aminotransferase (ALT) concentrations within the reference range. This was a cross-sectional analysis of 769 healthy individuals (326 men and 443 women) with an ALT concentration ≤ 40 IU/L and alcohol consumption < 140 g/week. Mean carotid artery intima-media thickness (C-IMT) was measured using ultrasound. NAFLD was defined as a mild or greater degree of hepatic steatosis on ultrasound. Although all subjects had an ALT concentration within the reference range, the prevalence of NAFLD increased with increasing quartiles of ALT concentration (27.1%, 40.0%, 54.7%, 75.3% in men, P for trend < 0.001; 22.0%, 34.4%, 35.7%, 55.0% in women, P for trend < 0.001). In the 3rd and 4th quartiles of ALT concentration, women with NAFLD had a significantly higher C-IMT than those without NAFLD (0.671±0.019 mm vs. 0.742±0.025 mm, P=0.023 in Q3; 0.651±0.023 mm vs. 0.737±0.021 mm, P=0.005 in Q4). These differences remained significant even after adjusting for a broad spectrum of potential confounders. In contrast, although men with NAFLD tended to have a higher C-IMT than those without NAFLD in each quartile, these differences were not statistically significant. Women with an upper normal range ALT concentration showed increased C-IMT only when they had NAFLD. Therefore, in women with an elevated ALT level within the reference range, further evaluation for NAFLD, such as liver ultrasound, could potentially identify those patients at high risk for cardiovascular disease.

The association of insulin resistance and carotid atherosclerosis with thigh and calf circumference in patients with type 2 diabetes.

BACKGROUND: The relationship between body composition parameters such as thigh and calf circumference and insulin resistance or atherosclerosis in type 2 diabetes is poorly understood. The aim of this study was to investigate the relationship between insulin resistance, atherosclerosis, and thigh and calf circumference in patients with type 2 diabetes. METHODS: A total of 4,427 subjects with type 2 diabetes were enrolled in this study. Insulin sensitivity was assessed according the rate constant for plasma glucose disappearance (Kitt) determined via the short insulin tolerance test. Biochemical and anthropometric profiles were measured according to a standardized protocol. Visceral fat thickness and carotid intima media thickness (IMT) were measured by ultrasonography. RESULTS: Insulin sensitivity index (Kitt) was significantly correlated with weight adjusted thigh and calf circumference. Thigh circumference was inversely associated with IMT in men and women and calf circumference was negatively correlated with IMT in women. Multiple stepwise regression analysis revealed that thigh circumference was independently correlated with insulin sensitivity index (Kitt) and IMT. Furthermore, in multivariate logistic regression analysis, thigh circumference was an independent determinant factor for carotid atherosclerosis in patients with type 2 diabetes even after adjusting for other cardiovascular risk factors. CONCLUSIONS: Thigh and calf circumference were correlated with insulin resistance and carotid atherosclerosis, and thigh circumference was independently associated with insulin resistance and carotid atherosclerosis in patients with type 2 diabetes.

Hypoadiponectinemia is strongly associated with metabolic syndrome in Korean type 2 diabetes patients.

OBJECTIVE: To evaluate the relationship between serum adiponectin level, dietary intake, and metabolic syndrome (MetS) in type 2 diabetes mellitus (DM) patients, and to identify factors associated with serum adiponectin level. METHODS: A cross-sectional study was performed using 789 type 2 DM patients (406 men and 383 women) 40-80 years old. Subjects were classified into 3 groups on the basis of serum adiponectin level. General characteristics and anthropometric, hematologic, and dietary data were obtained for each subject. RESULTS: The prevalence of hypoadiponectinemia (<4.0 µg/mL) was 57.4% in men and 32.4% in women. Serum adiponectin level was negatively correlated with body mass index (BMI), waist circumference, body fat percentage, and serum concentrations of insulin and triglyceride, and was positively correlated with high-density lipoprotein (HDL)-cholesterol level. Even though the direct association of nutrient intake with serum adiponectin concentration was not strong, various contributing factors for hypoadiponectinemia were strongly correlated with micronutrient intake, such as calcium, iron, and niacin. Both sexes in the group with the lowest adiponectin concentration had a higher prevalence of MetS and MetS components than corresponding sexes in the group with the highest adiponectin concentration. CONCLUSIONS: Our findings show that hypoadiponectinemia is strongly associated with MetS in type 2 DM patients. Dietary intake may be indirectly associated with adiponectin levels through factors such as BMI, waist circumference, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, HDL-cholesterol, and blood pressure. Therefore, our results suggest that manipulation of the level of adiponectin may prevent MetS and reduce the risk of cardiovascular disease in type 2 DM patients.

Relationships between Thigh and Waist Circumference, Hemoglobin Glycation Index, and Carotid Plaque in Patients with Type 2 Diabetes.

BACKGROUND: This study investigated the relationships of thigh and waist circumference with the hemoglobin glycation index (HGI) and carotid atherosclerosis in patients with type 2 diabetes. METHODS: This observational study included 3,075 Korean patients with type 2 diabetes, in whom anthropometric measurements and carotid ultrasonography were conducted. HGI was defined as the measured hemoglobin A1c (HbA1c) level minus the predicted HbA1c level, which was calculated using the linear relationship between HbA1c and fasting plasma glucose levels. Carotid atherosclerosis was defined as a clearly isolated focal plaque or focal wall thickening >50% of the surrounding intima-media thickness. RESULTS: The frequency of a positive HGI decreased with increasing thigh circumference in men and increased with increasing waist circumference in women after adjusting for potential confounding variables. Thigh and waist circumference had a combined augmentative effect on the likelihood of positive HGI, which was dramatically higher in patients in higher waist-to-thigh ratio quartiles (adjusted odds ratios for the highest compared to the lowest quartile: 1.595 in men and 1.570 in women). Additionally, the larger the thigh circumference, the lower the risk of carotid atherosclerosis, although in women, this relationship lacked significance after adjustment for potential confounders. CONCLUSION: HGI was associated with thigh circumference in men and waist circumference in women. In addition, the combination of low thigh circumference and high waist circumference was strongly associated with a higher HGI in Korean patients with type 2 diabetes. In particular, thigh circumference was associated with carotid atherosclerosis in men. However, further longitudinal studies are warranted.

Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus.

BACKGROUND: Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM. METHODS: We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography. RESULTS: LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002). CONCLUSIONS: Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

Association Between Serum Bilirubin and the Progression of Carotid Atherosclerosis in Type 2 Diabetes.

OBJECTIVE: This study investigated whether serum bilirubin levels can predict the progression of carotid atherosclerosis in individuals with type 2 diabetes mellitus (T2DM). METHODS: This observational study included 1,381 subjects with T2DM in whom serial measurements of carotid intima-media thickness (CIMT) were made at 1- to 2-year intervals for 6-8 years. The progression of carotid atherosclerosis was defined as newly detected plaque lesions on repeat ultrasonography. After dividing total serum bilirubin levels into tertiles, the association between total serum bilirubin at baseline and plaque progression status was analyzed. RESULTS: Among 1,381 T2DM patients, 599 (43.4%) were categorized as having plaque progression in their carotid arteries. Those with plaque progression were significantly older; showed a higher prevalence of hypertension, abdominal obesity, and chronic kidney disease; and had a longer duration of T2DM, higher levels of total cholesterol (TC), triglycerides, and insulin resistance, and lower total bilirubin concentrations than those with no plaque progression. When total serum bilirubin levels were divided into tertiles, the highest tertile group was younger than the lowest tertile group, with higher levels of TC and high-density lipoprotein cholesterol. Multiple logistic regression analysis demonstrated that higher serum bilirubin levels were associated with a significantly lower risk of CIMT progression (odds ratio, 0.584; 95% confidence interval, 0.392-0.870; p=0.008). Age (p<0.001), body mass index (p=0.023), and TC (p=0.019) were also associated with the progression of carotid atherosclerosis in T2DM patients. CONCLUSION: Total serum bilirubin is independently associated with progression of atherosclerosis in the carotid arteries in T2DM patients.

Serum adiponectin as a useful marker for metabolic syndrome in type 2 diabetic patients.

BACKGROUND: Although adiponectin is generally known as a predictor of metabolic syndrome, potential of adiponectin as a predictor for metabolic syndrome in type 2 diabetes is debated. The purpose of this study is to determine the association between adiponectin and metabolic syndrome in patients with type 2 diabetes. METHODS: Adiponectin and the risk of metabolic syndrome were examined among 1013 type 2 diabetes patients who visited Huh's Diabetes Center from January 2003 to June 2006. Adiponectin levels were classified into quartile groups, and metabolic syndrome was defined according to the standard of National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III. Insulin sensitivity was directly assessed using the short insulin tolerance test (SITT) (Kitt: %/ min). RESULTS: Adiponectin was significantly correlated with metabolic syndrome components. The age-adjusted correlations between adiponectin and clinical parameters including metabolic components were significant; adiponectin was negatively correlated with waist circumference, diastolic blood pressure and triglyceride, and positively correlated with high-density lipoprotein (HDL) cholesterol. Subjects with metabolic syndrome showed lower adiponectin levels than those without metabolic syndrome. After multivariate adjustment, participants with lower adiponectin levels also had a higher risk for metabolic syndrome (OR for lowest quartiles 2.21; 95% CI, 1.51-3.24). Metabolic syndrome risk was stronger among those with low adiponectin and severe insulin resistance simultaneously. This study has shown additive effects of adiponectin and insulin resistance on metabolic syndrome. CONCLUSIONS: In type 2 diabetic patients, the adiponectin was a useful predictor of metabolic syndrome independent of potential confounding variables.

Staged diabetes management according to individual patient insulin resistance and beta-cell function ameliorates glycaemic control in type 2 diabetes mellitus.

OBJECTIVE: The current consensus algorithm for management of type 2 diabetes is based on the fasting glucose concentration and glycated haemoglobin A(1c) (HbA(1c)) level. We applied a new therapeutic strategy by assessing insulin secretion and insulin resistance, in addition to glucose concentrations in individual patients. DESIGN AND PATIENTS: We enrolled 193 patients with type 2 diabetes. The patients were assigned to one of six groups according to insulin secretion measured by the serum fasting C-peptide concentration and insulin resistance measured by an insulin tolerance test (ITT). The two groups were treated differently: 108 patients were treated using a new staged diabetes management (SDM) strategy and 85 patients continued with conventional therapy. MEASUREMENTS: We compared metabolic variables in the two groups at baseline and 12 months after enrollment. RESULTS: In patients treated with the SDM strategy, fasting glucose concentration decreased from 9.8 +/- 2.1 to 8.2 +/- 1.7 mmol/l (P < 0.001). Postprandial 2-h glucose concentration decreased from 14.19 +/- 3.34 to 12.27 +/- 3.24 mmol/l (P < 0.001). HbA(1c) level decreased from 8.37 +/- 1.42% to 7.72 +/- 1.39% (P < 0.001). About 43% of the new SDM group achieved an HbA(1c) of < 7.0% compared with 25% of patients in the conventional treatment group. CONCLUSIONS: The new SDM strategy, based on individual data on insulin resistance and insulin secretion, may provide valuable clinical benefits in non-obese Korean patients with type 2 diabetes.

ApoB/ApoA-I ratio is independently associated with carotid atherosclerosis in type 2 diabetes mellitus with well-controlled LDL cholesterol levels.

BACKGROUND/AIMS: This study aimed to investigate whether the apolipoprotein (Apo) B/ApoA-I ratio is associated with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM) subjects with low density lipoprotein cholesterol (LDL-C) levels less than 100 mg/dL. METHODS: This cross-sectional study included 845 subjects aged with T2DM 40 to 75 years who had visited Huh's Diabetes Center in Seoul, Republic of Korea for CIMT measurement. Traditional fasting lipid profiles, ApoB and ApoA-I levels were examined. CIMT was measured at three points on the far wall of 1 cm long section of the common carotid artery in the proximity of the carotid bulb. The mean value of six measurements from right and left carotid arteries were used as the mean CIMT. In this study, carotid atherosclerosis was defined as having a focal plaque or diffuse thickening of the carotid wall (mean CIMT ≥ 1.0 mm). RESULTS: The prevalence of carotid atherosclerosis increased with ApoB/ApoA-I ratio. The ApoB/ApoA-I ratio, expressed as both quartiles (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.21 to 3.79; p for trend = 0.014) and continuous values (OR, 10.05; 95% CI, 3.26 to 30.97; p < 0.001), was significantly associated with a higher risk for carotid atherosclerosis, regardless of conventional cardiovascular disease risk factors. The optimal ApoB/ApoA-I ratio cutoff value for detecting carotid atherosclerosis was 0.57, based on receiver operating characteristic curve analysis with a sensitivity of 58.0% and a specificity of 55.1%. CONCLUSIONS: A high ApoB/ApoA-I ratio was significantly associated with carotid atherosclerosis in T2DM patients with LDL-C levels less than 100 mg/dL.

Color Doppler Ultrasonography Is a Useful Tool for Diagnosis of Peripheral Artery Disease in Type 2 Diabetes Mellitus Patients with Ankle-Brachial Index 0.91 to 1.40.

BACKGROUND: The clinical utility of ankle-brachial index (ABI) is not clear in subjects with less severe or calcified vessel. Therefore, we investigated the usefulness of color Doppler ultrasonography for diagnosing peripheral artery disease (PAD) in type 2 diabetes mellitus (T2DM) subjects. METHODS: We analyzed 324 T2DM patients who concurrently underwent ABI and carotid intima-media thickness (CIMT) measurements and color Doppler ultrasonography from 2003 to 2006. The degree of stenosis in patients with PAD was determined according to Jager's criteria, and PAD was defined as grade III (50% to 99% stenosis) or IV stenosis (100% stenosis) by color Doppler ultrasonography. Logistic regression analysis and receiver operating characteristic curve analysis were performed to evaluate the risk factors for PAD in patients with ABI 0.91 to 1.40. RESULTS: Among the 324 patients, 77 (23.8%) had ABI 0.91 to 1.40 but were diagnosed with PAD. Color Doppler ultrasonography demonstrated that suprapopliteal arterial stenosis, bilateral lesions, and multivessel involvement were less common in PAD patients with ABI 0.91 to 1.40 than in those with ABI ≤0.90. A multivariate logistic regression analysis demonstrated that older age, current smoking status, presence of leg symptoms, and high CIMT were significantly associated with the presence of PAD in patients with ABI 0.91 to 1.40 after adjusting for conventional risk factors. CIMT showed significant power in predicting the presence of PAD in patients with ABI 0.91 to 1.40. CONCLUSION: Color Doppler ultrasonography is a useful tool for the detection of PAD in T2DM patients with ABI 0.91 to 1.40 but a high CIMT.

Clinical characteristics of Korean type 2 diabetic patients in 2005.

Korean type 2 diabetics differ from Western diabetics in showing non-obese but centrally obese anthropometry and relatively more insulin secretory defects than insulin resistance. We assessed insulin secretion based on fasting serum C-peptide level and insulin resistance using the short insulin tolerance test (Kitt; rate constant for plasma glucose disappearance) in 1601 type 2 diabetic Korean patients (831 men and 770 women). Insulin secretory defects were catergorized as severe (C-peptide<1.10 ng/ml), moderate (C-peptide 1.10-1.69 ng/ml), and mild to non-secretory defect (C-peptide> or=1.70 ng/ml). Groups with a Kitt value of less than 2.5%/min were considered insulin-resistant, while those with a Kitt value > or =2.5%/min were considered insulin-sensitive. Overall, 42.5% of patients had a BMI>or =25.0 kg/m(2), and 70.2% had a BMI> or =23.0 kg/m(2); 45.2% (41.7% of men and 58.3% of women) were abdominally obese (waist> or =90 cm in men and 80 cm in women); mean fasting serum C-peptide level was 1.93+/-0.90 ng/ml, and the mean Kitt value was 2.03+/-0.96%/min. Accordingly, 13, 33, and 54% of patients showed a severe, moderate, and mild to non-secretory defect, respectively; 70.6% were insulin-resistant; and 29.4% were insulin-sensitive. Obese type 2 diabetes is recently increasing in Korea, indicating a shift from insulin secretory defects to insulin resistance.

The level of 2-h post-challenge glucose is an independent risk factor of carotid intima-media thickness progression in Korean type 2 diabetic patients.

OBJECTIVE: To evaluate the relationship between the metabolic abnormalities commonly associated with diabetes and the changes in carotid intima-media thickness (IMT) in Korean type 2 diabetic patients who do not have clinically manifest cardiovascular disease (CVD). DESIGN: In a prospective study, a total of 152 type 2 diabetic patients were recruited from a group of outpatients at the Yonsei University Hospital. MATERIALS AND METHODS: The carotid IMTs of 152 subjects with type 2 diabetes (mean age 63.5+/-7.0 years) were determined at baseline and after a mean follow-up time of 23.7+/-3.7 months. Fasting plasma glucose, serum total cholesterol (TC), serum triglyceride, high-density lipoprotein cholesterol (HDL-C), HbA1c, oral glucose tolerance test (OGTT) results for 2-h post-challenge glucose (2hPG), and blood pressure measurements were collected every 3 months and averaged. RESULTS: The highest quartiles of baseline C-peptide and homeostatic model assessment (HOMA) index showed more IMT progression than the lowest quartiles. The change in the mean IMT correlated with average values of HbA1c (r=.219, P=.007), the 2-h post-challenge glucose (r=.239, P=.003), HDL-C (r=-.228, P=.005), LDL-C (r=.175, P=.033), and non-HDL-C (r=.194, P=.016). Multiple regression analysis demonstrated that the independent risk factor for the mean IMT change in diabetic patients was the average 2hPG level (P=.004). The change in the mean IMT of those in the lowest quartile of average 2hPG (<11.1 mmol/l) was 823+/-176 to 841+/-146 microm (P=.276). In the highest quartile (2hPG >15.3 mmol/l), however, the mean IMT increased from 794+/-127 to 882+/-153 microm (P<.001). CONCLUSION: The 2hPG parameter among the various metabolic parameters exerts the greatest influence upon the prevention of carotid IMT progression in type 2 diabetic subjects. The level of 2hPG is an independent risk factor for the progression of carotid IMT in Korean type 2 diabetic patients.

Effects of folic acid supplementation on serum homocysteine levels, lipid profiles, and vascular parameters in post-menopausal Korean women with type 2 diabetes mellitus.

BACKGROUND/OBJECTIVES: Complications of diabetes, such as cardiovascular disease, are associated with increased mortality among type 2 diabetes mellitus patients. Homocysteine has been recently identified as a predictor of cardiovascular disease-related complications in diabetes. We investigated whether or not supplementation with folic acid tablets can lower homocysteine levels and improve parameters related with vascular complications. SUBJECTS/METHODS: We conducted a non-randomized 8-week trial involving postmenopausal diabetic women (n = 25) supplemented with 800 µg of folic acid (400 µg twice a day) daily. Subjects' serum levels of folate, homocysteine, and vitamin B12 were measured, along with vascular function and brachial-ankle pulse wave velocity. RESULTS: Folic acid supplementation significantly increased serum folate levels (P < 0.0001), reduced homocysteine levels (P < 0.0001), and increased vitamin B12 levels (P = 0.0063). There were significant decreases in low-density lipoprotein cholesterol levels as well as the ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol and total cholesterol to high-density lipoprotein cholesterol. Brachial-ankle pulse wave velocities were not altered by supplementation. Changes in serum vitamin B12 after folic acid supplementation were negatively correlated with changes in brachial-ankle pulse wave velocity. CONCLUSIONS: In this study on postmenopausal Korean women with type 2 diabetes mellitus, folic acid supplementation reduced serum homocysteine levels, increased serum folate and vitamin B12 levels, and lowered lipid parameters.

Clinical and biochemical characteristics of nonobese type 2 diabetic patients with glutamic acid decarboxylase antibody in Korea.

We evaluated the prevalence of glutamic acid decarboxylase autoantibody (GADA) in nonobese patients with type 2 diabetes mellitus in Korea and investigated the characteristics of GADA-positive and GADA-negative patients. Two years later, we assessed the progression of beta-cell function in these patients. Of the 647 nonobese patients with type 2 diabetes mellitus enrolled in the study, 10.1% was positive for GADA. Glutamic acid decarboxylase antibody-positive patients had lower fasting and stimulated C-peptide levels compared with GADA-negative patients (1.70 +/- 0.72 vs 1.24 +/- 0.59 microg/L, P < .001; 2.59 +/- 1.51 vs 1.99 +/- 0.82 microg/L, P < .001). Patients treated with insulin had lower fasting and stimulated C-peptide levels than those not treated (1.13 +/- 0.52 vs 1.66 +/- 0.73 microg/L, P = .002; 1.85 +/- 0.69 vs 2.49 +/- 0.91 microg/L, P = .004) and had higher titers of GADA (30.5 +/- 7.3 vs 6.0 +/- 4.8 U/mL, P < .001). In terms of progression of beta-cell function, fasting and stimulated C-peptide levels were significantly lower in GADA-positive patients after 2 years (from 1.24 +/- 0.59 to 0.95 +/- 0.54 microg/L, P = .004; from 1.99 +/- 0.82 to 1.61 +/- 0.77 microg/L, P = .007), whereas no such difference was observed in the GADA-negative patients. We demonstrate that a significant proportion of Korean patients may be positive for GADA; this is consistent with studies of white subjects, although disagrees with previous reports on Korean subjects. By assessing the presence of GADA in Korean type 2 diabetic patients, we are able to predict their course of beta-cell function and identify in advance those who are likely to require insulin treatment.

Normative values of carotid artery intima-media thickness in healthy Korean adults and estimation of macrovascular diseases relative risk using this data in type 2 diabetes patients.

The objectives of this study were to determine normative values of carotid intima-media thickness (IMT) in healthy Korean subjects and to use these values to estimate the relative risk of macrovascular diseases in patients with type 2 diabetes mellitus (T2DM). High-resolution B-mode ultrasonography was performed in 1,229 healthy subjects and 830 T2DM patients. Height, weight, blood pressure, fasting plasma glucose, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, and fasting insulin level were measured. Subjects were classified as healthy subjects; T2DM patients without ischemic heart disease (IHD), stroke, and peripheral arterial occlusive diseases (PAOD); T2DM patients with IHD, stroke, or PAOD. IMT was significantly increased as age increased. Patients with T2DM had higher IMTs compared to healthy subjects. Independent risk factors of IMT were age, systolic blood pressure, BMI for healthy subjects, and age, duration of diabetes, LDL-cholesterol for T2DM subjects. According to presence of increased IMT, the relative risks of IHD, stroke, and PAOD in diabetic subjects, were 2.34 (CI; 1.32-4.14), 2.95 (CI; 1.46-5.54), and 3.64 (CI; 1.66-7.40), respectively. This study suggests normative values that can be used as an index for carotid artery IMT of healthy Korean subjects, and that IMT data reflects the risk of macrovascular diseases in T2DM.

The relation between birth weight and insulin resistance in Korean adolescents.

Low birth weight is associated with insulin resistance and type 2 diabetes in adults. The fetal programming hypothesis has shown that insulin resistance and its associated metabolic disturbances result from a poor gestational environment, for which low birth weight is a surrogate. An at-home questionnaire survey was performed on 660 middle school students (12-15 years) in Seoul, Korea, and 152 cases were randomly selected based on their birth weight. Subjects were divided into three groups according to birth weight. We recorded their birth weight and measured their current anthropometric data, blood pressure, lipid profile, HOMA-IR, and HOMA-beta, and compared these parameters among the groups. The relation of birth weight to physiological characteristics in adolescence was examined. Systolic blood pressure, lipid profiles, and fasting plasma glucose, HOMA-beta were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C-peptide, and HOMA-IR were higher in the lower birth weight tertile. After adjustment for confounding factors, birth weight was inversely related to diastolic blood pressure, insulin, C-peptide, and HOMA-IR. We conclude that low birth weight may predict the risk of the insulin resistance and its progression over age, and that adequate gestational nutrition is therefore necessary to prevent low birth weight.

Association between dietary flavanones intake and lipid profiles according to the presence of metabolic syndrome in Korean women with type 2 diabetes mellitus.

BACKGROUND/OBJECTIVES: This study was aimed at examining the association between dietary flavanones intake and lipid profiles according to the presence of metabolic syndrome (MetS) in Korean women with type 2 diabetes mellitus (T2DM). SUBJECTS/METHODS: A cross-sectional analysis was performed among 502 female T2DM patients (non-MetS group; n = 129, MetS group; n = 373) who were recruited from the Huh's Diabetes Clinic in Seoul, Korea between 2005 and 2011. The dietary intake was assessed by a validated semi-quantitative food frequency questionnaire (FFQ) and the data was analyzed using the Computer Aided Nutritional Analysis program (CAN-Pro) version 4.0 software. The intake of flavanones was estimated on the basis of the flavonoid database. RESULTS: In the multiple linear regression analysis after adjustment for confounding factors, daily flavanones intake was negatively associated with CVD risk factors such as total cholesterol, LDL-cholesterol, and apoB and apoB/apoA1 ratio only in the MetS group but not in the non-MetS group. Multiple logistic regression analysis revealed that the odds ratio for a higher apoB/apoA1 ratio above the median (≥ 0.74) was significantly low in the 4(th) quartile compared to that in the 1(st) quartile of dietary flavanones intake [OR: 0.477, 95% CI: 0.255-0.894, P for trend = 0.0377] in the MetS group. CONCLUSIONS: Dietary flavanones intake was inversely associated with the apoB/apoA1 ratio, suggesting a potential protective effect of flavanones against CVD in T2DM women with MetS.