Usefulness of lipoprotein ratios in assessing carotid atherosclerosis in Japanese type 2 diabetic patients

ObjectiveIt is indicated that total/HDL cholesterol and LDL/HDL cholesterol ratios have more predictive power for cardiovascular disease compared to classic lipid parameters. However, there have been few reports about the usefulness of these indices for the assessment of early stage atherosclerosis in Japanese type 2 diabetic subjects.MethodsWe examined the relation between various lipid parameters and carotid atherosclerosis in 934 type 2 diabetic subjects without apparent atherosclerotic diseases (males, 71.7%; age, 59.6 ± 10.5 years (mean ± SD)). Serum concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride were measured. LDL cholesterol (LDL-C) level was calculated using the Friedewald formula. The presence of carotid plaque and intima-media thickness (IMT) were evaluated by ultrasonography.ResultsA stepwise multivariate regression analysis demonstrated that HDL-C (β = ?0.110, p < 0.001), TC/HDL-C (β = 0.132, p < 0.001) and LDL-C/HDL-C ratios (β = 0.132, p < 0.001) were independent determinants of IMT even after adjustment of other conventional risk factors. However, there was no significant correlation between IMT and TC, triglyceride, LDL-C, and non-HDL-C levels. TC/HDL-C and LDL-C/HDL-C ratios and non-HDL-C levels were significantly higher, but HDL-C levels were significantly lower in patients with carotid plaque than those without it (p < 0.05). There was no significant difference between the groups regarding TC, LDL-C, and triglyceride levels. Furthermore, TC/HDL-C (OR; 1.34, p < 0.001) and LDL-C/HDL-C (OR; 1.54, p < 0.001) ratios showed a positive and linear relationship with the prevalence of carotid plaque, whether covariates were adjusted or not.ConclusionsTC/HDL-C and LDL-C/HDL-C ratios are useful as a tool to assess the risk of early stage atherosclerosis in Japanese type 2 diabetic patients.     

Porphyromonas gingivalis infection is associated with carotid atherosclerosis in non-obese Japanese type 2 diabetic patients

The aim of the present study was to investigate whether non-obese Japanese type 2 diabetic patients with porphyromonas gingivalis infection have atherosclerotic vascular diseases. A total of 134 non-obese Japanese type 2 diabetic patients (96 men and 38 women, aged 36 to 84 years, body mass index [BMI] 20.1 to 26.9 kg/m(2)) were studied. In conjunction with BMI, glycosylated hemoglobin (HbA(1c)), fasting glucose, and serum lipids (triglycerides, total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol) were measured. LDL cholesterol was calculated using the Friedewald formula. Using high-resolution B-mode ultrasound scan, we measured intimal medial thickness (IMT) in plaque-free segments of bilateral common carotid arteries, and the mean of IMT in 2 vessels was used for the analysis. Furthermore, we calculated the degree of stenosis in plaque segments of bilateral common carotid arteries. The degree of carotid atherosclerosis was expressed as a percentage ratio between the area of plaque and that of the lumen using the formula (Lumen Area Residual - Lumen Area)/Lumem Area x 100. Both the areas were automatically measured by the system on a frozen transverse scanning plane at the site of maximal narrowing. When 2 or more plaques were present in the vessel, only that causing the greatest degree of stenosis was considered for analysis. Values represent mean+/-SEM unless otherwise stated. Immunoglobulin G (IgG) titer against porphyromonas gingivalis was 245 +/- 65 (mean +/- 2 SD) in nondiabetic healthy subjects. In contrast, there was a wide variation in IgG titer against porphyromonas gingivalis in type 2 diabetic patients studied (range, 16 to 26,800). Thus, we classified our type 2 diabetic patients into 2 subpopulations according to the value of mean +/- 2 SD (= 310) of nondiabetic healthy subjects: one with high IgG titer against porphyromonas gingivalis (>310) (1,422 +/- 408) and the other with normal IgG titer against porphyromonas gingivalis (<310) (152 +/- 10, P =.002). The populations did not differ with respect to age, sex, BMI, fasting glucose, HbA(1c), serum triglycerides, total, HDL, and LDL cholesterol levels. Although the mean IMT in plaque-free segments was not different between the 2 groups (0.73 +/-0.03 v 0.68 +/- 0.02 mm, P =.098), the degree of stenosis in plaque segments was significantly higher in the high IgG titer group (12.0% +/- 2.2%) than in normal one (5.5% +/- 1.4%, P =.009). From these results, it can be concluded that porphyromonas gingivalis infection, although still a subclinical infection, is associated with atherosclerotic vascular disease in non-obese Japanese type 2 diabetic patients.     

Significantly higher incidence of carotid atherosclerosis found in Japanese type 2 diabetic patients with early nephropathy

We have tried to evaluate the clinical incidence of carotid atherosclerosis found in Japanese type 2 diabetic patients with early diabetic nephropathy. 123 diabetic patients with micro-albuminuria (group A) were investigated during 2-week hospitalization. As a control group, 50 diabetic patients without nephropathy (group B) were investigated. Carotid arteries were examined by B-mode ultrasonography (7.5 MHz), and peripheral arterial blood flow and pressure was examined at the same time with Doppler ultrasonography by a single examiner. Fasting blood samples and 24-h urine samples were taken to analyze biochemical data and urinary albumin excretion rate. In group A, 77 patients were found to have either carotid plaque lesions or increased thickness of carotid wall. And this was found significantly higher than in the control group B (18 cases, P < 0.01). To clarify the clinical risk factors for carotid atherosclerosis in diabetic patients with early nephropathy, 123 group A patients were divided into two groups with (group C, n = 76) or without carotid atherosclerosis (group D, n = 47) and comparative analysis was carried out. From this study, significantly higher incidence of carotid atherosclerosis was confirmed in the diabetic patients with early nephropathy. And it was suggested that the age, lipid levels, presence of hypertension would be important clinical risk factors for carotid atherosclerosis found in diabetic patients with early nephropathy.     

Plasma fatty acids and lipoproteins in type 2 diabetic patients

BACKGROUND: The dyslipidemia of type 2 diabetic patients is characterized by high VLDL, abnormal LDL composition and low HDL cholesterol concentrations. The aim of this study was to establish whether the type of dietary fats affects LDL size and density and HDL cholesterol concentrations in these patients. METHODS: Plasma phospholipid fatty acid composition, which reflects the type of dietary fatty acids, was quantified by gas chromatography. LDL relative flotation (LDL-Rf), a measure of LDL particle size and density, was determined by single vertical spin density gradient ultracentrifugation in 97 type 2 diabetic patients. RESULTS: By linear regression analysis of the data, plasma fatty acids were associated neither with LDL-cholesterol levels nor with LDL-Rf. The HDL cholesterol concentrations were negatively related with saturated fatty acids (r = -0.23; p = 0.02) but positively related with monounsaturated fatty acids (r = +0.20; p = 0.00). Furthermore, higher HDL concentrations were associated with large and buoyant LDL particles (HDL cholesterol vs LDL-Rf: r = +0.47; p = 0.00). In the multiple regression analysis, the LDL-Rf was significantly related both to triglycerides (beta coefficient = -0.55, p = 0.000) and HDL cholesterol (beta coefficient = 0.19, p = 0.034) concentrations. In a stepwise regression analysis including both triglycerides and HDL cholesterol, triglycerides alone explained the 43.0% of the LDL-Rf variability. CONCLUSIONS: A reduction of the dietary saturated fats and an increment of monounsaturated fats might increase HDL cholesterol concentrations in type 2 diabetic patients. Modifications of LDL composition might be expected from interventions aimed to reduce plasma triglycerides.     

Association of soluble CD40 ligand with carotid atherosclerosis in Japanese type 1 diabetic patients

Aims/hypothesis It has recently been shown that the soluble form of CD40 ligand (sCD40L) interacts with CD40 on vascular cells, leading to a variety of proinflammatory responses, and that serum sCD40L levels can be a predictive marker of cardiovascular events. The aim of this study was to estimate sCD40L levels in type 1 diabetic patients to examine a possible association with carotid atherosclerosis.Subjects and methods Human sCD40L levels in serum and intima–media thickness (IMT) of carotid artery were examined in 80 Japanese type 1 diabetic patients (27 men and 53 women, age 22.8±3.4 years (mean±SD), duration of diabetes 13.2±6.1 years) and 20 healthy age-matched non-diabetic individuals.Results Serum sCD40L levels were significantly (p=0.0185) higher in subjects with type 1 diabetes (2.10±1.33 ng/ml) compared with non-diabetic subjects (1.35±0.88 ng/ml). The greatest IMT (Max-IMT) and averaged IMT (Mean-IMT) were also significantly greater in patients with type 1 diabetes than in control subjects (0.73±0.14 vs 0.64±0.07 mm, p=0.0041, 0.63±0.09 vs 0.57±0.06 mm, p=0.0066, respectively). Levels of sCD40L were statistically significantly associated with Max-IMT (r=0.383, p<0.001) and Mean-IMT (r=0.275, p=0.0058). Furthermore, stepwise multivariate regression analyses demonstrated that sCD40L is a determinant of both Max- and Mean-IMT, independently of conventional risk factors.Conclusions/interpretation It is suggested that increased levels of serum sCD40L are associated with accelerated atherosclerotic change observed in young patients with type 1 diabetes.     

Correlations between homocysteine levels and atherosclerosis in Japanese type 2 diabetic patients

Elevated total plasma homocysteine (tHcy) level and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that tHcy correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 40 Japanese patients with type 2 diabetes mellitus and high tHcy levels (mean age +/- SD, 57 +/- 7 years) and a control group of 45 age-matched patients with normal tHcy levels (mean age +/- SD, 57 +/- 6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by an automatic oscillometric method. Brachial-ankle pulse wave velocity was used as an index of atherosclerosis. Body mass index values (P < .05), waist circumferences (P < .05), and the waist-to-hip ratios (P < .05) were larger in the high-tHcy group than in the normal-tHcy group. The BaPWV was higher in the high-tHcy group than in the normal-tHcy group (P < .0001). Fasting plasma glucose (P < .005) and insulin concentrations (P < .0001), and the homeostasis model assessment (HOMA) index (P < .0001) were higher in the high-tHcy group than in the normal-tHcy group. Multiple regression analysis showed that tHcy levels were independently predicted by BaPWV and the HOMA index. In conclusion, our results indicate that the elevated level of tHcy in Japanese patients with type 2 diabetes mellitus is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and the HOMA index are independent predictors of tHcy.     

Effects of glimepiride and glibenclamide on carotid atherosclerosis in type 2 diabetic patients

We performed a 3-year observation study of type 2 diabetic patients treated with glibenclamide or glimepiride and found that the annual progression of the maximum carotid intima-media thickness was significantly attenuated in the subjects treated with glimepiride (n = 20) as compared with those treated with glibenclamide (n = 20) (−0.044 ± 0.171 mm/year vs. 0.077 ± 0.203 mm/year, p = 0.0474).     

Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients

BACKGROUND: The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. MATERIAL AND METHODS: The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3-1.0 mg/dl, age: 57+/-5 years, mean+/-s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57+/-6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis. RESULTS: The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index. CONCLUSIONS: Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.     

Risk factors for asymptomatic atherosclerosis in Japanese type 2 diabetic patients without diabetic microvascular complications

Atherosclerotic vascular diseases are frequently associated with diabetes mellitus. There has been increasing evidence showing that the atherosclerotic diseases in diabetic patients are distinct from diabetic microvascular complications as to their pathophysiology and epidemiology. However, we have no information on the prevalence of asymptomatic atherosclerosis in diabetic patients before the onset of microvascular diseases. In the present investigation, we aimed to evaluate risk factors for the atherosclerosis in type 2 diabetic patients without the microvascular diseases. For this purpose, we evaluated atherosclerotic change of carotid arteries in 125 Japanese type 2 diabetic patients who had neither atherosclerotic vascular diseases nor diabetic microvascular complications. When atherosclerotic change was defined as the mean intima-media thickness (IMT) of >/= 1.1 mm and/or the presence of plaque lesion, 50% of patients had atherosclerosis of the carotid arteries. Risk factors for the carotid atherosclerosis were age, low-density lipoprotein (LDL)-cholesterol, hypertension, and diabetes treatment. Age and LDL-cholesterol were associated with mean IMT. Age, diabetes treatment, LDL-cholesterol, and hypertension were positively associated with plaque lesion, while high-density lipoprotein (HDL)-cholesterol was negatively associated with it. Fasting plasma glucose, glycosylated hemoglobin (HbA(1c)), and known diabetes duration remained unassociated with any parameters of asymptomatic atherosclerosis of the carotid arteries. These results indicate that glycemic control is unrelated with asymptomatic atherosclerosis in type 2 diabetic patients without diabetic microvascular complications. Conventional risk factors and diabetes treatment are independently associated with atherosclerosis of the carotid arteries in these patients.     

Correlations of urinary albumin excretion and atherosclerosis in Japanese type 2 diabetic patients

Microalbuminuria and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the presence of microalbuminuria correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 36 Japanese patients with type 2 diabetes and microalbuminuria (age: 56+/-9 years, mean+/-S.D.) and a control group of 44 age-matched patients with normoalbuminuria (56+/-7 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method. BaPWV was used as an index of atherosclerosis. The BaPWV was higher in the microalbuminuria group than in the normoalbuminuria group (p<0.005). Fasting plasma glucose (p<0.05) and insulin concentrations (p<0.005), and the homeostasis model assessment (HOMA) index (p<0.0005), were higher in the microalbuminuria group than in the normoalbuminuria group. Multiple regression analysis showed that urinary albumin excretion was independently predicted by BaPWV and HOMA index. Our results indicate that the presence of microalbuminuria in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV, HOMA index are independent predictors of urine albumin excretion.     

2型糖尿病患者外周血管病变与颈动脉粥样硬化的关系

目的以踝肱指数（ABI）和颈动脉内中膜厚度（IMT）为主要研究参数,探讨2型糖尿病（T2DM）患者外周血管病变（PAD）与颈动脉粥样硬化之间的关系。方法观察对象分为两组：（1）糖尿病合并PAD组（PAD组）,59例;（2）糖尿病无PAD组,72例。比较两组IMT及颈动脉超声检测参数;并对ABI和IMT进行相关性分析。结果两组颈动脉斑块发生率相近（74.6%vs66.7%）。与无PAD组相比,PAD组IMT值较高,颈总动脉阻力指数升高,舒张期最大峰值流速及血流量显著下降。ABI与IMT呈显著负相关（r=-0.337,P〈0.01）。结论（1）糖尿病合并PAD患者,其颈动脉粥样硬化病变的程度重于糖尿病无PAD者,（2）糖尿病患者的IMT与ABI存在负相关。     

新诊断2型糖尿病患者内脂素、vaspin与颈动脉粥样硬化的相关性

目的 探讨初发2型糖尿病（T2DM）患者血清内脂素（visfatin）、vaspin水平与颈动脉粥样硬化（AS）的关系.方法 将100例初发2型糖尿病患者根据颈动脉内膜中层厚度（CIMT）分为非AS组,早期AS组和严重AS组,并配对选取33例无糖尿病的健康者为对照组.采用酶联免疫吸附试验（ELISA）测定血清visfatin、vaspin水平.结果 （1）糖尿病早期AS组和严重AS组的visfatin水平明显高于对照组和糖尿病非AS组（P＜0.01）;糖尿病非AS组和早期AS组的vaspin水平均高于对照组（P＜0.01）,严重AS组的vaspin水平明显低于糖尿病早期AS组（P＜0.05）.（2）偏相关分析显示visfatin与腰臀比（WHR）、三酰甘油（TG）、CIMT呈正相关（P＜0.05）,vaspin水平与HOMA-IR呈正相关（P＜0.05）,visfatin与vaspin无统计学关联（P＞0.05）.（3）Logistic回归分析结果显示,患者年龄、收缩压（SBP）、低密度脂蛋白胆固醇（LDL-C）、visfatin为CIMT的独立危险因素（P＜0.05）.结论 初发2型糖尿病患者血清visfatin和vaspin水平与肥胖、胰岛素抵抗密切相关;血清visfatin水平升高可能与颈AS形成密切相关.     

Metabolic syndrome, insulin resistance, and atherosclerosis in Japanese type 2 diabetic patients

The aim of the present study was to investigate the relationships between metabolic syndrome and atherosclerosis in 57 Japanese type 2 diabetic patients. Metabolic syndrome was diagnosed based on the criteria raised by the Japan Internal Medicine Society. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment. Ultrasonographically measured carotid atherosclerosis, brachial-ankle pulse wave velocity (ba-PWV), and ankle brachial index (ABI) were used to assess the degree of atherosclerosis. Of 57 patients, 25 were diagnosed as having metabolic syndrome. The patients with metabolic syndrome had significantly higher levels of waist circumference, insulin, insulin resistance index of homeostasis model assessment, systolic and diastolic blood pressures, and serum triglycerides, and lower concentrations of adiponectin. However, there was no significant difference in age, sex, glycosylated hemoglobin (hemoglobin A1c), fasting glucose, leptin, and tumor necrosis factor system activities including tumor necrosis factor alpha between the 2 groups. Furthermore, no significant difference was observed in the degree of carotid atherosclerosis (intimal-medial thickness in plaque-free segments: 0.72+/-0.03 vs 0.72+/-0.02 mm, P=.435; carotid stenosis in plaque segments: 6.6%+/-3.0% vs 6.6%+/-1.7%, P=.497), ba-PWV (1676+/-56 vs 1654+/-44, P=.380), and ABI (1.16+/-0.01 vs 1.15+/-0.01, P=.245) between the 2 groups. From these results, it can be suggested that metabolic syndrome, an insulin-resistant state, is not associated with carotid atherosclerosis, ba-PWV, or ABI in Japanese type 2 diabetic patients.     

Relationship between carotid atherosclerosis and erythrocyte membrane cholesterol oxidation products in type 2 diabetic patients

Oxidative stress is well known to play a critical role in atherosclerosis. This study investigated an appropriate marker of in vivo oxidative stress and whether it could predict macroangiopathy in diabetes. The lipid composition of erythrocyte membranes was analyzed in 64 type 2 diabetic patients using gas chromatography-mass spectrometry (GC/MS). After 3,5,7-cholestatriene (a cholesterol oxidation product) was detected, the peak height ratio of 3,5,7-cholestatriene to cholesterol was calculated. Carotid artery intima-media thickness (IMT) was measured to evaluate atherosclerosis. The IMT was independently associated with 3,5,7-cholestatriene (P<0.0001), age (P=0.0001), and HbA1c (P=0.05) by stepwise multiple regression analysis (R2=0.416, P<0.0001). When the subjects were divided into groups with or without carotid atherosclerosis, the 3,5,7-cholestatriene level was significantly higher in 37 subjects with atherosclerosis than in 27 subjects without it (0.41+/-0.22 vs. 0.16+/-0.16%, P<0.0001). Among 38 subjects with no clinical manifestations of macroangiopathy and long-term good glycemic control, the 3,5,7-cholestatriene level was also significantly higher in the patients with carotid atherosclerosis than in those without it (0.40+/-0.20 vs. 0.18+/-0.12%, P=0.0003). These data suggest that the 3,5,7-cholestatriene level in erythrocyte membrane lipids may be a useful predictor of subclinical atherosclerosis.     

老年2型糖尿病患者血糖漂移幅度与颈动脉粥样硬化的相关性分析

目的 探讨2型糖尿病（T2DM）患者血糖漂移水平的差异与颈动脉内膜中层厚度（IMT）的关系。方法 采用动态血糖监测系统（continuous glucose monitoring system,CGMS）对43例正常人及87例2型糖尿病患者进行连续71±10）h的血糖监测,分析日内不同时段的血糖水平、平均血糖漂移幅度（MAGE）及日间血糖平均色对差（MODD）;并用多普超声观察颈动脉粥样硬化斑块的发生率及内中膜厚度,将糖尿病者分为A组（IMT〈0．8mm）和B组（IMT≥0．8mm）,与对照组C组进行比较。结果 （1）糖尿病组的血压、血糖、血脂、糖化血红蛋白（HbAlc）及体质量指数（BMI）均高于对照组（P〈0．05或P〈0．01）,而高密度脂蛋白（HDL—C）则降低（P〈0．01）;B组冠心病及脑血管病的百分比、糖尿病病程、收缩压、HbAlC、BMI及低密度脂蛋白（LDL—C）较A组有增高（P〈0．05或P〈0．01）;IMT与负2h血糖的相关性最强（r=0,88,P〈0．01）,而与胰岛素敏感指数（ISI）呈负相关。（2）T2DM组的颈动脉粥样硬化斑块的发生率及IMT增加（P〈0．001）;而CGMS显示的24hMBG、MAGE与IMT的相关性强（r=0．181,P〈0．01）.（3）HbAlc与MBG呈正相关（r=0．82,P〈0．01）,而与MAGE、NGE及MODD均不相关。（4）研究还证明：CGMS观测值与血浆葡萄糖值及指端毛细血管血糖均呈正相关（r=0．93,r=0．95,P均〈0．001）。结论 T2DM患者的颈动脉粥样硬化不仅与血压、血糖、血脂、HbAlc及IMT有关,而且与血糖漂移水平的差异密切关联,相似的HbAlc水平其血糖漂移的程度可以不同,而血糖漂移幅度大的患者发生慢性并发症的危险性高。     

Role of nonesterified unsaturated fatty acids in the pathophysiological processes of leptospiral infection

Organ malfunctions in patients with leptospirosis have been associated with the bacterial glycolipoprotein endotoxin and with its nonesterified unsaturated fatty acid (NEUFA) components. We examined the involvement of NEUFAs in the pathophysiological processes of leptospirosis. Patients showed a moderate increase in serum concentrations of oleic and linoleic acids but an important decrease in serum concentrations of albumin. A highly significant correlation between serum concentrations of creatinine or total bilirubin and the oleic-plus-linoleic acid : albumin ratio was revealed. We used the Na(+),K(+)-ATPase inhibitory property of NEUFAs to test the capacity of serum to prevent the cytotoxic effects of NEUFAs in vitro. Albumin solutions and serum samples from healthy volunteers, but not serum samples from severely affected patients, were able to revert the Na(+),K(+)-ATPase inhibition by oleic acid. On the basis of these data, we defined a "serum protection factor" that can be helpful in predicting NEUFA toxicity. Our data support the concept that the administration of human albumin to patients may be helpful in severe leptospirosis cases.     

Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients.

Fifteen patients with Type 2 diabetes were given two diets rich in either saturated fat or polyunsaturated fat in alternate order over two consecutive 3-week periods on a metabolic ward. Both diets contained the same amount of fat, protein, carbohydrates, dietary fibre, and cholesterol. The proportions of saturated, monounsaturated and polyunsaturated fatty acids in the saturated fat diet were 16, 10, and 5%-energy and in the polyunsaturated fat diet (PUFA) 9, 10, and 12%-energy. The PUFA diet contained a high proportion of n-3 fatty acids. Metabolic control improved significantly in both dietary periods, due to both qualitative dietary changes and a negative energy balance. The serum lipoprotein concentrations decreased on both diets but the serum lipids were significantly lower after the PUFA diet (serum triglycerides -20%, p = 0.001; serum cholesterol -5%, p = 0.03; VLDL-triglycerides -29%, p less than 0.001; and VLDL-cholesterol -31%, p = 0.001) than after the saturated fat diet. Average blood glucose concentrations during the third week were significantly higher fasting (+15%, p less than 0.01), and during the day at 1100 h (+18%, p less than 0.001) and 1500 h (+17%, p = 0.002) on PUFA than on the saturated fat diet. Significantly higher blood glucose levels were also recorded with a standard breakfast, while the sum of the insulin values was lower (-19%, p = 0.01). HbA1c did not differ significantly between the two dietary periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors responsible for the evolution of insulin resistance in Japanese type 2 diabetic patients: association with atherosclerosis

Type 2 diabetes is a heterogeneous syndrome characterized by defective insulin secretion and/or insulin resistance. In distinct from Caucasian populations, Japanese type 2 diabetic patients are divided into two categories: one with insulin resistance and the other with normal insulin sensitivity. This unique feature allows us to explore the factors responsible for the evolution of insulin resistance in Japanese type 2 diabetic patients. In this article, we describe the factors responsible for insulin resistance in Japanese type 2 diabetic patients and discuss the relationships between these factors and atherosclerosis. Japanese type 2 diabetic patients with insulin resistance had significantly higher concentrations of triglyceride, remnant-like particle cholesterol, subcutaneous and visceral abdominal fat areas, leptin, high sensitive C-reactive protein (hs-CRP), and soluble E-selectin and lower concentration of adiponectin when compared to those with normal insulin sensitivity. There were, however, no significant difference in tumor necrosis factor (TNF)-alpha and soluble TNF receptors between the two groups. Serum triglyceride was positively correlated to visceral abdominal fat area, while serum leptin was positively correlated with subcutaneous abdominal fat area. In contrast, serum adiponectin was negatively correlated to visceral abdominal fat area. High sensitive CRP was positively correlated to BMI, triglyceride, and leptin, but was negatively correlated to adiponectin. Tumor necrosis factor-alpha and soluble TNF receptors, however, were not associated with any of these factors. Thus, it may be hypothesized that Japanese type 2 diabetic patients are divided into two categories: one with normal insulin sensitivity and the other with insulin resistance. The former group has a low cardiovascular risk factor, whereas the latter one has a markedly increased cardiovascular disease risk factor. Furthermore, abdominal fat related insulin resistance seems to be associated with insulin resistance in Japanese type 2 diabetic patients. In this section, we would like to focus on the factors contributing to insulin resistance and discuss the association of these factors with atherosclerosis in Japanese type 2 diabetic patients.