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.

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.

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.

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.

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.

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.

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.

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.

Reappraisal of waist circumference cutoff value according to general obesity.

BACKGROUND: Current criterion of waist circumference (WC) for abdominal obesity is not enough to demonstrate characteristics of obese and non-obese populations defined by BMI. The aim of this study was to redefine the cutoff values of WC according to general obesity (BMI ≥ 25 kg/m(2)). METHODS: The receiver operating characteristic curve analysis was performed to determine cutoff values of WC for predicting atherosclerosis according to BMI in 1,063 non-diabetic subjects. To validate this new criterion, diabetic patients (n = 3,690) were divided into three groups based on the current (WC of 90/80 cm for men/women) and new cutoff values of WC: 1) group with WC below the lowest value of two criteria; 2) intermediate group defined as having a WC between them; and 3) group with WC more than the highest value of them. RESULTS: The new cutoff values of WC for predicting atherosclerosis in non-diabetic subjects were 84/76 cm for non-obese men/women, and 93/87 cm for obese men/women, respectively. Of non-obese diabetic patients, the intermediate group (WC 84 ~ 90/76 ~ 80 cm for men/women) was more insulin resistant and showed elevated odds ratio (OR) for having 2 or more metabolic risk factors compared to group with WC below 84/76 cm for men/women [OR 2.48 (95 % CI 1.89-3.25) in men, 2.01 (95% CI 1.45-2.78) in women]. In contrast, among obese diabetic patients, insulin resistance and the likelihood of having 2 or more metabolic risk factors were not different from the intermediate group (WC 90 ~ 93/80 ~ 87 cm for men/women) and group with WC below 90/80 cm for men/women. CONCLUSIONS: The current universal cutoff values of WC may under- or over-estimate the metabolic risks of intermediate groups. Therefore, the WC criteria for abdominal obesity should be applied differently depending on the BMI.

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.

Association between fish and shellfish, and omega-3 PUFAs intake and CVD risk factors in middle-aged female patients with type 2 diabetes.

BACKGROUND/OBJECTIVES: This study was performed to investigate the association between the dietary intake of fish and shellfish, and omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD) risk factors in the middle-aged Korean female patients with Type 2 diabetes (T2D). SUBJECTS/METHODS: A cross-sectional analysis was performed with 356 female patients (means age: 55.5 years), 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 and analyzed using the Computer Aided Nutritional Analysis program (CAN-Pro) version 4.0 software. RESULTS: In a multiple regression analysis after the adjustment for confounding factors such as age, BMI, duration of diagnosed T2D, alcohol consumption, fiber intake, sodium intake, and total energy intake, fish and shellfish intake of the subjects was negatively associated with triglyceride and pulse wave velocity (PWV). Omega-3 PUFAs intake was negatively associated with triglyceride, systolic blood pressures, diastolic blood pressures, and PWV. The multiple logistic regression analysis with the covariates showed a significant inverse relationship between the omega-3 PUFAs consumption and prevalence of hypertriglyceridemia [OR (95% CI) for greater than the median compared to less than the median: 0.395 (0.207-0.753)]. CONCLUSIONS: These results suggest that the consumption of fish and shellfish, good sources of omega-3 PUFAs, may reduce the risk factors for CVD in the middle-aged female patients with T2D.

Optimal Waist Circumference Cutoff Value Based on Insulin Resistance and Visceral Obesity in Koreans with Type 2 Diabetes.

BACKGROUND: Visceral obesity is the most powerful contributor to the development of metabolic syndrome (MetS) and cardiovascular diseases. In light of visceral obesity, however, there is a paucity of data on the appropriate cutoff point of waist circumference (WC) in subjects with type 2 diabetes. The aim of this study was to investigate the optimal cutoff value for WC that signals insulin resistance (IR) and visceral obesity in Koreans with type 2 diabetes. METHODS: We evaluated 4,252 patients with type 2 diabetes (male 2,220, female 2,032, mean age 57.24 years) who visited our clinic between January 2003 and June 2009. WC was measured at the midpoint between the lower rib and the iliac crest, and insulin sensitivity was assessed by the rate constant of plasma glucose disappearance (Kitt %/min) using an insulin tolerance test. Visceral fat thickness was measured using ultrasonography. Statistical analysis was performed using receiver operating characteristic curve. RESULTS: The optimal cutoff points for WC for identifying the presence of IR and visceral obesity, as well as two or more metabolic components, were 87 cm for men and 81 cm for women. Moreover, these cutoff points had the highest predictive powers for the presence of visceral obesity. The MetS defined by new criteria correlated with the increased carotid intima-media thickness in female subjects. CONCLUSION: Our results suggest that the optimal cutoff values for WC in Koreans with type 2 diabetes should be reestablished based on IR and visceral obesity.

Nonalcoholic Fatty liver disease is associated with increased carotid intima-media thickness only in type 2 diabetic subjects with insulin resistance.

CONTEXT: The association between nonalcoholic fatty liver disease (NAFLD) and subclinical atherosclerosis in type 2 diabetes is controversial. OBJECTIVE: The objective of the study was to investigate the participation of insulin resistance in the association of NAFLD and the carotid atherosclerotic burden in a large cohort of patients with type 2 diabetes. DESIGN, SETTING, AND PATIENTS: This was an observational study performed in 4437 consecutively enrolled patients with type 2 diabetes. MAIN OUTCOMES MEASURES: Hepatic steatosis and mean carotid intima-media thickness (C-IMT) were measured using ultrasonography. Insulin resistance was assessed using the short insulin tolerance test. RESULTS: The prevalence of NAFLD was 72.7% in the whole study population. Among subjects with NAFLD, 23.2% were not insulin resistant. There were significant differences in C-IMT and the frequency of carotid atherosclerosis between groups classified by insulin resistance within the same NAFLD strata. C-IMT was highest in subjects with both NAFLD and insulin resistance [0.844 ± 0.004 (mean ± SE) mm vs 0.786 ± 0.008, 0.821 ± 0.007, and 0.807 ± 0.006 mm, P for trend <.001, respectively, in insulin sensitive subjects without NAFLD, insulin resistant subjects without NAFLD, and insulin sensitive subjects with NAFLD]. These differences remained after adjusting for potential confounders. However, C-IMT in subjects having only NAFLD or insulin resistance was not higher than that in those with neither NAFLD nor insulin resistance. CONCLUSIONS: NAFLD is very common in subjects with type 2 diabetes, but NAFLD not accompanied by insulin resistance is not associated with a carotid atherosclerotic burden. However, having both NAFLD and insulin resistance seemed to be an independent predictor of increased C-IMT.

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.

Serum adiponectin and type 2 diabetes: a 6-year follow-up cohort study.

BACKGROUND: Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. METHODS: A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. RESULTS: Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders. CONCLUSION: A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.

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.

Relationship between milk and calcium intake and lipid metabolism in female patients with type 2 diabetes.

PURPOSE: This study was conducted to determine the association between intake of milk and dairy products as well as calcium and biomarkers related to lipid metabolism in Korean female patients with type 2 diabetes. MATERIALS AND METHODS: A cohort of 509 female subjects (mean age: 59.0 years; range: 35-80 years) was recruited from Huh's Diabetes Clinic in Seoul between 2005 and 2010. Dietary intake was assessed using a validated food-frequency questionnaire. Subjects were divided into three groups on the basis of their daily intake of milk and dairy products [<50 g/day (0<50 g/day), 50-200 g/day, and >200 g/day (>200-1201 g/day)] and then further divided into two groups according to their daily calcium intake: below and above the estimated average requirement (EAR). RESULTS: After adjustment for age, body mass index, energy intake, exercise, use of nutritional supplements and cholesterol medication, the level of serum high-density lipoprotein (HDL)-cholesterol was significantly higher in subjects with milk and dairy products consumption of >200 g/day than in subjects in the other two groups. Those subjects with a milk and dairy products consumption of >200 g/day had significantly higher levels of apolipoprotein A-1 and a significantly lower atherogenic index than the other two groups. Patients with a calcium intake above the EAR exhibited a significantly greater serum HDL-cholesterol level than those with a calcium intake below the EAR. CONCLUSION: Milk and dairy products, good sources of calcium, play a positive role in lipid profiles in female patients with type 2 diabetes.

Adiponectin as predictor for diabetes among pre-diabetic groups.

Adiponectin is found to associate with diabetes in studies apart from cohort studies. This prospective cohort study is to evaluate the predictive role of adiponectin in diabetes among participants with impaired fasting glucose (IFG). A total of 42,845 participants who visited 7 health examination centers located in Seoul and Kyunggi province, South Korea, during 2004-2008 were first included. Of the 42,845 participants, 5,085 participants had IFG. IFG was categorized as stage 1 (fasting glucose 100-109 mg/dL) or stage 2 (110-125 mg/dL). The incidence rates of diabetes were followed up to December, 2011. Hazard ratios (HRs) and 95 % confidence intervals (CI) were performed by Cox proportional hazard model. Of the 5,085 participants, 652 participants developed diabetes during a mean follow-up of 4.4 years. Low adiponectin was associated with diabetes among men with stage 2 IFG (HR, 1.78; 95 %CI, 1.33-2.38) while it was associated with diabetes among women with stage 1 IFG (HR, 2.64; 95 %CI, 1.38-5.03) and stage 2 IFG (HR, 2.17; 95 %CI, 1.07-4.42). When combined men and women, the association between adiponectin and diabetes was statistically significant in stage 2 IFG with an increase of about 82 % (HR, 1.82; 95 %CI, 1.40-2.39) after adjusting for age, sex, body mass index, waist circumference, and fasting serum glucose. There was an interaction by sex and stage 1 IFG in the association between adiponectin and risk of diabetes (P < 0.001). Adiponectin was independently associated with diabetes among participants with IFG. This association was apparent in stage 2 IFG. Adiponectin may be used as a predictor of diabetes in patients having IFG.

Smoking is associated with abdominal obesity, not overall obesity, in men with type 2 diabetes.

OBJECTIVES: Abdominal obesity increases mortality and morbidity from cardiovascular disease and there is a possibility that smoking effects obesity. However, previous studies concerning the effects of smoking on obesity are inconsistent. The objective of this study was to examine whether smoking is positively related to abdominal obesity in men with type 2 diabetes. METHODS: Subjects consisted of 2197 type 2 diabetic patients who visited Huh's Diabetes Center from 2003 to 2009. Indices of abdominal obesity were defined as visceral fat thickness (VFT) measured by ultrasonography and waist circumference (WC). Overall obesity was defined as body mass index (BMI). RESULTS: Statistically significant differences in WC and VFT by smoking status were identified. However, there was no statistical difference in BMI according to smoking status. Means of WC and VFT were not significantly higher in heavy smokers and lower in mild smokers. Compared to nonsmokers, the BMI confounder adjusted odds ratio and 95% confidence interval for VFT in ex-smokers and current-smokers were 1.70 (1.21 to 2.39) and 1.86 (1.27 to 2.73), respectively. CONCLUSIONS: Smoking status was positively associated with abdominal obesity in type 2 diabetic patients.

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.