Susceptibility of low- and high-density lipoproteins from diabetic subjects to in vitro oxidative modification.

AIMS: To investigate the hypothesis that lipid peroxidation of both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) is important in the development of atherosclerosis. METHODS: We have investigated whether LDL and HDL from patients with Type 1 diabetes mellitus (DM, n = 16) and Type 2 DM (n = 15) is more susceptible to Cu2+ -induced lipid peroxidation than LDL and HDL from a similar number of nondiabetic controls matched for age, gender and serum cholesterol. RESULTS: The vitamin E content of LDL and HDL from both groups of diabetic patients was not significantly different from controls. The LDL from Type 2 diabetic patients and HDL from both diabetic groups were significantly richer in triglyceride than controls. Phospholipid was decreased in LDL from Type 2 diabetic patients and protein was decreased in HDL in Type 1 DM, but otherwise the composition of LDL and HDL in diabetic subjects was similar to controls. No significant differences were observed in the generation of conjugated dienes or lipid peroxides in either LDL or HDL when the two groups were compared with each other or with their respective controls. CONCLUSIONS: Increased lipid peroxidation occurring in vivo in diabetes is unlikely to be the result of increased susceptibility of lipoproteins to lipid peroxidation, but rather to increased generation of free radicals, to oxidation of lipids other than those present in serum lipoproteins or to decreases in antioxidant systems other than the fat-soluble antioxidants present in lipoproteins.     

Racial differences in lipid and lipoprotein levels in diabetes.

Racial differences in plasma lipid and lipoprotein levels were investigated in 145 patients with non-insulin-dependent diabetes mellitus (NIDDM). Black men had higher high-density lipoprotein (HDL) cholesterol levels, lower triglyceride levels, and an improved atherogenic index compared with white men. Premenopausal black women were also found to have higher HDL cholesterol levels, lower triglyceride levels, and a lower atherogenic index than their white counterparts. Adjustment for age, waist to hip ratio (WHR), hemoglobin A1c (HbA1c), and physical activity did not eliminate the significant differences found. There were no racial differences found regarding total and low-density lipoprotein (LDL) cholesterol. Metabolic control as measured by HbA1c was significantly correlated with the triglyceride level in black women. These data confirm that racial differences exist in plasma lipid levels among patients with NIDDM.     

Effects of vitamin C supplementation on antioxidants and lipid peroxidation markers in elderly subjects with type 2 diabetes

The objective of our study was to evaluate the effects of the administration of two dosages of vitamin C (Vit-C) (0.5 and 1g/day, vs. placebo) in elderly patients with type 2 diabetes mellitus on the intracellular levels of Vit-C and glutathione, and on the lipid peroxidation markers and vitamin E (Vit-E) content of low-density lipoprotein (LDL) and on LDL susceptibility to gamma radiolysis-induced peroxidation. Thirty-six patients were randomized into three groups. In patients on 0.5 g Vit-C/day versus the placebo group, a significant increase in cellular reduced glutathione level was observed (0.60+/-0.26 vs. 0.33+/-0.27). In patients on 1 g Vit-C/day versus placebo, a significant increase was also observed in cellular reduced glutathione (0.93+/-0.70 vs. 0.33+/-0.27), in Vit-C (5.66+/-2.00 vs. 2.72+/-1.88) and in vitamin E content of LDL (1.98+/-0.38 vs. 1.48+/-0.40). No change was observed in either group in basal levels of lipid peroxidation markers and in the susceptibility of LDL to peroxidation provoked by gamma-radiolysis. In conclusion, Vit-C has a dose-dependent effect on the cellular contents of antioxidants and on vitamin E content of LDL in elderly patients with type 2 DM. These changes are not sufficient to decrease the LDL susceptibility to peroxidation.     

Low-density lipoprotein size and subclasses are markers of clinically apparent and non-apparent atherosclerosis in type 2 diabetes

The atherogenic lipoprotein phenotype is characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein (HDL), and the prevalence of small, dense low-density lipoprotein (LDL) particles. The present study investigated the clinical significance of LDL size and subclasses as markers of atherosclerosis in diabetes type 2. Thirty-eight patients with type 2 diabetes, total cholesterol of less than 6.5 mmol/L, and hemoglobin A1c (HbA1c) of less than 9% were studied. Median age was 61 years, mean (+/-SD) body mass index 29 +/- 4.3 kg/m2 , and mean HbA1c 7.1 +/- 0.9 %. Laboratory parameters included plasma lipids and lipoproteins, lipoprotein (a), apolipoprotein (apo) A-I, apo B-100, apo C-III, and high-sensitivity C-reactive protein. Low-density lipoprotein size and subclasses were measured by gradient gel electrophoresis and carotideal intima media thickness (IMT) by duplex ultrasound. By factor analysis, 10 out of 21 risk parameters were selected: age, body mass index, systolic blood pressure, smoking (in pack-years), HbA1c, high-sensitivity C-reactive protein, lipoprotein (a), LDL cholesterol, HDL cholesterol, and LDL particle size. Multivariate analysis of variance of these 10 risk parameters identified LDL particle size as the best risk predictor for the presence of coronary heart disease (P = .002). Smaller LDL particle size was associated with an increase in IMT (P = .03; cut-off >1 mm). Within the different lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apo B, apo A-I, apo C-III, LDL particle size), LDL particle size was most strongly associated with the presence of coronary heart disease (P = .002) and IMT (P = .03). It is concluded that LDL size is the strongest marker for clinically apparent as well as non-apparent atherosclerosis in diabetes type 2.     

Prevalence of 25-hydroxy vitamin D deficiency among type 2 diabetic subjects of South India

Vitamin D levels have been documented to have significant inverse relationship with type 2 diabetes. However, data on the extent of vitamin D deficiency among type 2 diabetes subjects of India is lacking. The present study was undertaken among diabetic subjects of South India to address this lacuna. This retrospective study was conducted among patients attending a diabetes specialty hospital who had established type 2 diabetes mellitus. Demographic data and data on laboratory parameters such as vitamin D, HbA1c, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and serum calcium were obtained from the hospital information system. Vitamin D levels were classified as normal (≥30 ng/mL), insufficient (>20 to 29.9 ng/mL), and deficient (≤20 ng/mL). We included 4628 subjects with diabetes. Among them, 71.4 % were vitamin D deficient, 15 % were vitamin D insufficient, and 13.6 % were found to have normal vitamin D levels. On comparing the two genders, it was seen that the percentage of men and women with these conditions were similar. The proportion of subjects with these conditions across different age groups (30–50, 50–70, >70) were also similar. BMI, age, calcium levels, and HbA1c were found to be the major confounders for vitamin D status. Our study, done among type 2 diabetes people, show that vitamin D deficiency was highly prevalent among them. Considering such high prevalence, screening of diabetic patients for vitamin D deficiency would be beneficial in this population.     

Impact of low-density lipoprotein particle size on carotid intima-media thickness in patients with type 2 diabetes mellitus

Small low-density lipoprotein (LDL) particles and modifications to LDL such as glycation and oxidation have been linked to the pathogenesis of atherosclerosis in patients with diabetes. We investigated whether LDL particle size, or the levels of glycated LDL or malondialdehyde-modified LDL (MDA-LDL) are associated with carotid intima-media thickness (IMT) in patients with type 2 diabetes mellitus. One hundred seventy-two patients with type 2 diabetes mellitus were enrolled. Carotid IMT was measured by high-resolution ultrasound, and LDL particle size and serum glycated LDL and MDA-LDL levels were determined. The 3 variables were significantly correlated with one another. Univariate analyses defined statistically significant correlations of carotid IMT with LDL size, hemoglobin A(1c), glycated LDL, MDA-LDL, high-density lipoprotein (HDL) cholesterol, and age. The strongest association of IMT was with LDL size (r = -0.406, P < .0001), followed by that with HDL cholesterol (r = -0.225, P = .004). A stepwise multiple regression analysis revealed that LDL size and HDL cholesterol are independent predictors of carotid IMT. Neither glycated LDL nor MDA-LDL had a significant independent contribution to the severity of carotid IMT in the multivariate model. Low-density lipoprotein particle size, but not the glycated LDL or MDA-LDL level, was independently associated with carotid IMT in patients with type 2 diabetes mellitus regardless of antidiabetic and lipid-lowering medications. These results suggest that the measurement of LDL size may be more useful than quantification of modified LDLs for assessing atherosclerosis in patients with type 2 diabetes mellitus. Small LDL particles may be the most important predictor for the risk of cardiovascular disease in diabetic patients.     

Effect of combination therapy of benidipine hydrochloride and candesartan cilexetil on serum lipid metabolism and blood pressure in elderly hypertensive patients with type 2 diabetes mellitus

The effects of combination therapy of angiotensin II receptor blockers (ARBs) and a calcium antagonist, benidipine hydrochloride, on glucose and lipid metabolism and pulse pressure were studied in elderly hypertensive patients with type 2 diabetes mellitus. Twenty-five hypertensive diabetic patients aged 65 years or older, who had been receiving candesartan cilexetil, were administered benidipine hydrochloride (4 mg/day) and followed for 4 months. After 4 months, systolic and diastolic blood pressure decreased significantly from 154/91 mmHg to 139/78 mmHg (p<0.01 versus before benidipine hydrochloride administration). Body mass index (BMI) and glycosylated hemoglobin (HbA1c) were apparently reduced but the changes were not statistically significant. The serum lipid profile showed no significant changes in serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Serum lipoprotein lipase mass levels (preheparin LPL mass) increased significantly from 51 to 59 ng/dl (p<0.01 versus before benidipine hydrochloride administration), and the LDL/HDL motility ratio calculated from PAG disc electrophoresis decreased significantly (p<0.05 versus before benidipine hydrochloride administration). When patients were divided into a systolic hypertension group (systolic blood pressure > or =140 mmHg and diastolic blood pressure <90 mmHg) and non-systolic hypertension group (others), preheparin LPL mass was significantly lower in the systolic hypertension group, and the decrease in pulse pressure and increase in preheparin LPL mass were significantly greater in the systolic hypertension group. Stepwise regression analysis showed that low preheparin LPL mass at baseline was associated with a decrease in pulse pressure. Add-on benidipine hydrochloride therapy in elderly hypertensive patients with type 2 diabetes mellitus significantly decreases the LDL/HDL motility ratio and pulse pressure, and significantly increases preheparin LPL mass, in addition to improving blood pressure control. These findings suggest that combination therapy with benidipine hydrochloride and candesartan cilexetil may contribute to the suppression of arteriosclerosis and may be useful for elderly hypertensive patients with diabetes mellitus.     

Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes.

The sulfonylurea gliclazide and the biguanide metformin have different mechanisms to reduce glycemia. We performed a randomized study to compare these two agents with respect to glycemic control and effects on lipid peroxidation markers in 36 adult patients with type 2 diabetes. Both agents significantly decreased glycosylated hemoglobin ([HbA1c] P < .05), fructosamine (P < .05), and the glucose-excursion curve during the oral glucose tolerance test ([OGTT] P < .01). With regard to the insulin curve during this test, no significant change was observed with metformin and a significant increase was measured with gliclazide (P < .05). Considering the small number of events, no significant difference was detected in the number of hypoglycemic episodes between the two agents. More upper-gastrointestinal (GI) symptoms were observed with metformin compared with gliclazide (P < .05). Even with no change in the standard lipid profile, both agents increased serum vitamin E (P < .01 for gliclazide and P < .05 for metformin) and decreased the level of lipid peroxidation markers in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (P < .05). Despite different mechanisms of action, gliclazide and metformin demonstrated comparable levels of efficacy and complementary effects on lipid peroxidation markers.     

Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages

Argan oil is rich in unsaturated fatty acids, tocopherol and phenolic compounds. These protective molecules make further study of its cardiovascular diseases (CVDs) action interesting. Furthermore, no previous study has explored the antioxidant activity of argan oil in comparison with olive oil. The present study was conducted to evaluate the beneficial properties of Virgin argan oil phenolic extracts (VAO-PE) towards CVD by: (A) protecting human (low-density lipoprotein, LDL) against lipid peroxidation and (B) promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. Human LDLs were oxidized by incubation with CuSO(4) in the presence of different concentrations of VAO-PE (0-320mug/ml). LDL lipid peroxidation was evaluated by conjugated diene and MDA formation as well as Vitamin E disappearance. Incubation of LDL with VAO-PE significantly prolonged the lag-phase and lowered the progression rate of lipid peroxidation (P<0.01) and reduced the disappearance of Vitamin E in a concentration-dependent manner. Incubation of HDL with VAO-PE significantly increased the fluidity of the HDL phospholipidic bilayer (P=0.0004) and HDL-mediated cholesterol efflux from THP-1 macrophages. These results suggest that Virgin argan oil provides a source of dietary phenolic antioxidants, which prevent cardiovascular diseases by inhibiting LDL-oxidation and enhancing reverse cholesterol transport. These properties increase the anti-atherogenic potential of HDL.     

Low serum adiponectin is associated with high circulating oxidized low-density lipoprotein in patients with type 2 diabetes mellitus and coronary artery disease

Decrease in adiponectin level, a common feature in patients with type 2 diabetes mellitus, is considered to predict cardiovascular events. Elevated oxidized low-density lipoprotein (oxLDL), formed within the arterial wall, is commonly seen as part of the atherogenic profile. We investigated the association of adiponectin and oxLDL in 58 patients with type 2 diabetes mellitus and ischemic coronary artery disease. In addition to adiponectin, the serum lipid profile (including oxLDL), plasminogen activator inhibitor 1, high-sensitivity C-reactive protein, and whole-body glucose uptake determined by euglycemic-hyperinsulinemic clamp were evaluated. The average adiponectin level was 7.1 +/- 3.5 microg/mL and was higher in female than in male patients (P = .011). Adiponectin level correlated with whole-body glucose uptake (P = .037) and high-density lipoprotein (HDL) cholesterol concentration (P = .007) and was inversely associated with oxLDL (P = .005), triglycerides (P = .010), and plasminogen activator inhibitor 1 (P = .004). No association was found between adiponectin and high-sensitivity C-reactive protein or LDL cholesterol levels. In multiple linear regression analysis, adiponectin contributed to oxLDL concentration, whereas total cholesterol, LDL and HDL cholesterol, and triglycerides did not. In conclusion, our results suggest that low adiponectin concentration indicates increased oxidative state in the arterial wall, which further supports previous data on the role of adipose tissue in atherogenesis.     

Lipid profile correlates with glycemic control in young patients with type 1 diabetes mellitus

Data on dyslipidemia in type 1 diabetes is scarce. The authors aimed to evaluate the lipid profile in patients with type 1 diabetes and its correlation to glycemic control. Ninety-four subjects (53.2% males), aged 15.4+/-4.7 (3.6-21.9 years), with disease duration of 5.0+/-3.6 years (0.3-17 years) were evaluated for heart rate, blood pressure, height, and weight. Laboratory data included total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs), glycemia, glycosylated hemoglobin (HbA1c), creatinine, thyroid-stimulating hormone, antithyroid antibodies, and 24-hour microalbuminuria. Correlations were performed by the Spearman rank correlation test, and the significance level was <0.05. Mean values were TC, 168.6+/-46.6 mg/d; HDL, 43.1+/-15.3 mg/dL; LDL, 110.9+/-40.6 mg/dL; TGs, 78.3+/-48.6 mg/dL; glycemia, 204.6+/-116.7 mg/dL; and HbA1c, 11.2%+/-2.9%. High TC (43.9% vs. 10.7%; p<0.002) and LDL (51.5% vs. 10.7%; p<0.01) were more prevalent in patients 19 years and younger (n=66). HbA1c correlated with TC (r=0.30; p=0.004), LDL (r=0.28; p=0.008), TG (r=0.31; p=0.003), and TG/HDL ratio (r=0.25; p=0.01). Duration of diabetes correlated with LDL (r=0.21; p=0.04) and insulin daily doses with TG (r=0.23; p=0.04) and body mass index expressed as z scores (r=-0.28; p=0.007). There was a high prevalence of hypercholesterolemia (54.6%) in these diabetic patients, and lipid fraction levels were correlated with HbA1c. Good management of diabetes seems to be of paramount importance in controlling dyslipidemia.     

Serum lipid profile in diabetic macular edema

PurposeTo evaluate the correlation of lipid profile and clinical presentation of macular edema in Type 2 diabetes mellitus (DM) patients.Materials and MethodsThe study included 20 patients with chronic diabetic macular edema and plaque-like hard exudates (Group 1), 20 patients with diabetic macular edema (Group 2), and 20 DM patients but without retinopathy (Group 3). Diabetic retinopathy was classified according to the Early Treatment Diabetic Retinopathy Study grading system. Sample t test was used to evaluate the association between the fasting serum lipid [total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL)], glycosylated hemoglobin (HbA1c), fasting blood glucose, creatinine levels, and the clinical findings. P values <.05 were considered statistically significant.ResultsThere was no difference between fasting serum lipids and HbA1c levels. Duration of diabetes was shorter in Group 3 than in Groups 1 and 2. Patients in Group 1 had longer duration of diabetes than others (P<.05). Creatinine levels in Group 1 were higher than in other groups (P<.05). Although there was no correlation between fasting blood glucose and HbA1c levels, HbA1c was higher in all three groups from the baseline-normal limits (P<.05).ConclusionNo correlation was found between serum lipid levels and macular edema severity, but the duration of diabetes was demonstrated as a significant factor in the progression of macular edema. High HbA1c levels in all patients highlight the importance of intense glycemic control in diabetic patients.     

Decreased protection by HDL from poorly controlled type 2 diabetic subjects against LDL oxidation may Be due to the abnormal composition of HDL.

High plasma triglyceride concentrations in diabetic subjects increase their risk for developing coronary heart disease. Numerous studies have shown that the high density lipoprotein (HDL) composition is abnormal in type 2 diabetic subjects. One study has shown that HDL (lipoprotein A-I) isolated from subjects with non-insulin-dependent diabetes mellitus exhibits a decreased capacity to induce cholesterol efflux. The current study examined the effect of HDL(2) and HDL(3) subfractions from poorly controlled type 2 diabetic and control subjects on THP-1 macrophage-mediated low density lipoprotein (LDL) oxidation. The composition and protective effects of HDL(2), but not of HDL(3), differed significantly between control and diabetic subjects. HDL(2) from diabetics were triglyceride enriched and cholesterol depleted compared with those from controls. Control HDL(2) inhibited LDL oxidation, as assessed by lipid peroxides and electrophoretic mobility, significantly (P<0.05) more than did diabetic HDL(2) in both the fasting and postprandial state. In addition, HDL(2) from diabetics did not protect against apolipoprotein B-100 fragmentation in LDL. Cross-linking in apolipoprotein A-I, oxidized in the presence of LDL, was extensive in HDL(2) from diabetics compared with that from controls. Serum triglyceride concentrations were negatively correlated with protection by HDL(2) (r=-0.673, P<0.05) in diabetic but not in control subjects. HDL(2)-associated platelet-activating factor acetylhydrolase activity was positively correlated with protection by HDL(2) in control (r=0.872, P<0.002) but not in diabetic subjects. In conclusion, compositional alterations in HDL(2) from poorly controlled type 2 diabetic subjects may reduce its antiatherogenic properties.     

Comparative analysis of biochemical parameters in diabetic and non-diabetic acute myocardial infarction patients

BackgroundDiabetes is a metabolic disorder characterized by enhanced production of free radicals hence oxidative stress. The aim of this study was to evaluate the activity of cardiac and antioxidant enzymes in diabetic and non-diabetic acute myocardial infarction (AMI) patients.MethodsThis case–control study was conducted on 450 subjects (70–85 years). Subjects were divided into three groups (Normal, N; Non-diabetic AMI, N-AMI; and Diabetic AMI, D-AMI). Each individual was subjected to a detailed history, clinical examination, and cardiovascular parameters analysis (fasting blood sugar, HbA1c, systolic and diasystolic blood pressure, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), TC/HDL and LDL/HDL ratios). Cardiac markers (Troponin-I, creatine phosphokinase (CPK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP) and aspartate aminotransferase (AST)) and oxidative stress markers (superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT)) were also assessed. All these parameters were compared between diabetic and non-diabetic AMI patients.ResultsD-AMI individuals had high level of TC, TG, LDL, and low level of HDL in comparison to N-AMI individuals. Study suggests that cardiac markers such as Troponin I, CPK, CK-MB, AST, LDH, and CRP levels were significantly increased in patients suffering from myocardial infarction with diabetes mellitus (DM) compared to patients of myocardial infarction without DM. The activity levels of antioxidant SOD and GSH were lower in D-AMI patients than in N-AMI. However, levels of MDA and CAT were higher in D-AMI than in N-AMI controls.ConclusionStudy suggests elevated cardiac markers and reduced antioxidants in D-AMI patients compared to N-AMI patients.     

Postprandial lipidemia is normal in non-obese type 2 diabetic patients with relatively preserved insulin secretion

To assess postprandial lipidemia in normotriglyceridaemic type 2 diabetic patients treated with diet only, 12 non-obese patients (8 males, hemoglobin A(1c) [HbA(1c)] 6.80 +/- 0.67%) and 14 controls of similar age, body mass index (BMI), and fasting triglyceride (Tg) were given a test meal (58 g fat, 100,000 IU vitamin A). Fasting low-density lipoprotein (LDL) cholesterol (LDLc), high-density lipoprotein (HDL) cholesterol (HDLc), free fatty acids, and apolipoprotein B (apoB), and fasting and postprandial Tg, retinylpalmitate (RP), LDL size, glucose, and insulin were measured. The homeostasis assessment model (HOMA) index and lipoprotein (Lpl) and hepatic (HL) lipase activities were estimated. Patients showed lower fasting HDLc (1.12 +/- 0.26 v 1.40 +/- 0.28 mmol/L, P =.02) and a trend towards smaller LDL particles, which was significant 4 hours postprandially (25.86 +/- 0.40 v 26.16 +/- 0.30 nm, P =.04). The area under the curve of Tg (AUC-Tg) and RP, and Lpl were similar, but HL was higher in patients (156.63 +/- 23.89 v 118 +/- 43.27 U/L, P =.011). HL correlated inversely with LDL size and directly with the HOMA index. In conclusion, normotriglyceridemic type 2 diabetic patients with insulin resistance but relatively preserved insulin secretion show low fasting HDLc and increased HL, but normal postprandial lipidemia.     

Relationship of regional adiposity to insulin resistance and serum triglyceride levels in nonobese Japanese type 2 diabetic patients

The aim of this study was to investigate the relationships between insulin resistance and regional abdominal fat area, body mass index (BMI), and serum lipid profile in nonobese Japanese type 2 diabetic patients. A total of 63 nonobese Japanese type 2 diabetic patients aged 45 to 83 years were examined. The duration of diabetes was 8.4 +/- 0.8 years. BMI, glycosylated hemoglobin (HbA(1c)) levels, and fasting concentrations of plasma glucose, serum lipids (total cholesterol, high-density lipoprotein [HDL] cholesterol, and triglycerides), and serum insulin were measured. The low-density lipoprotein (LDL) cholesterol level was calculated using the Friedewald formula (LDL cholesterol = total cholesterol - HDL cholesterol - 1/5 triglycerides). Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). Computed tomography (CT) was used to measure cross-sectional abdominal subcutaneous and visceral fat areas in all the patients. Adipose tissue areas were determined at the umbilical level. Subcutaneous and visceral abdominal fat areas were 136.5 +/- 6.0 and 86.0 +/- 4.1 cm(2), respectively. Univariate regression analysis showed that insulin resistance was positively correlated with subcutaneous (r =.544, P <.001) and visceral (r =.408, P =.001) fat areas, BMI (r =.324, P =.009), HbA(1c) (r =.254, P =.001), serum triglycerides (r =.419, P <.001), and serum LDL cholesterol (r =.290, P =.019) levels and was negatively correlated with serum HDL cholesterol level (r =.254, P =.041). Multiple regression analyses showed that insulin resistance was independently predicted by the areas of subcutaneous (F = 6.76, P <.001) and visceral (F = 4.61, P <.001) abdominal fat and serum triglycerides (F = 8.88, P <.001) level, which explained 36.9% of the variability of insulin resistance. Moreover, the present study demonstrated that whereas BMI was positively correlated with visceral (r =.510, P <.001) and subcutaneous (r =.553, P <.001) fat areas, serum triglyceride level was positively associated with visceral (r =.302, P =.015), but not with subcutaneous (r =.222, P =.074) fat area. From these results, it can be suggested that (1) both subcutaneous and visceral abdominal fat areas are independently associated with insulin resistance and (2) visceral fat area, but not the subcutaneous one, is associated with serum triglyceride levels in our nonobese Japanese type 2 diabetic patients.     

Effect of ciprofibrate on lipoprotein metabolism and oxidative stress parameters in patients with type 2 diabetes mellitus and atherogenic lipoprotein phenotype

The effect of ciprofibrate therapy on plasma lipids and lipoproteins, HDL and LDL subfraction profile, fractional esterification rate of HDL cholesterol (FER_HDL) and the resistance of LDL and serum lipids to oxidation was studied in 24 males with type 2 diabetes and atherogenic lipoprotein phenotype (ALP). We also examined the effect of ciprofibrate therapy on oxidative DNA damage in peripheral lymphocytes. No differences in glucose, HbA1C and BMI levels were found after three months of ciprofibrate therapy. Ciprofibrate significantly decreased total cholesterol and triglyceride levels by 5.5% and 50% (p = 0.05; 0.001, respectively) and increased HDL-cholesterol levels by 8.5% (p = 0.05). FER_HDL and LDL subfraction profile were also favorably affected, However, no effect on HDL subclasses was found. There were no statistically significant differences in lipid resistance to oxidation measured in serum and in LDL (lag time and V_max) before and after therapy. No significant effect of ciprofibrate was found on oxidative DNA damage. The evaluation of the relationship between oxidative damage purines with lag time in LDL and maximal rate of serum lipid oxidation showed significant correlations after therapy (r = −0.58; 0.47, p = 0.01; 0.05, respectively), but only trends before starting ciprofibrate treatment. Type 2 diabetes mellitus represents a complex metabolic disorder expressed in glucose and lipoprotein disturbances and increased oxidative stress. Ciprofibrate therapy favorably affected major features of lipid abnormalities of diabetic patients, but the level of oxidative stress assessed by in vitro and in vivo methods was not changed. The evaluation of expected logical correlations between the parameters of lipoprotein metabolism, lipid resistance in serum and LDL, and oxidative DNA damage showed that those correlations were more relevant and significant after ciprofibrate treatment and were not related with glucose homeostasis. Received: 13 March 2000 / Accepted in revised form: 7 November 2000     

Variations in erythrocyte antioxidant levels and lipid peroxidation status and in serum lipid profile parameters in relation to blood haemoglobin A1c values in individuals with type 2 diabetes mellitus

Aims

The present study aimed to evaluate the antioxidant and lipid peroxidation status in erythrocytes and serum lipid profile parameters, in relation to haemoglobin A1c (HbA1c) concentrations, in patients with type 2 diabetes mellitus and in normal healthy individuals.

Methods

Sixty test individuals with diabetes and 15 control individuals were categorized as: Group I, control (non-diabetes); Group II, individuals with diabetes with HbA1c levels ≤7.0% (53 mmol/mol); Group III, individuals with diabetes with HbA1c levels between 7.1 and 8.0% (54 and 64 mmol/mol); Group IV, individuals with diabetes with HbA1c levels between 8.1 and 9.0% (65 and 75 mmol/mol); Group V, individuals with diabetes with HbA1c levels >9.0% (75 mmol/mol). Blood samples were collected to measure: blood glucose and HbA1c levels; haemolysate levels of enzymatic antioxidants and non-enzymatic antioxidants and malondialdehyde (MDA); and serum total cholesterol, triglyceride and high-density lipoprotein (HDL)-cholesterol levels. Correlations between blood HbA1c values and all parameters were sought.

Results

Significantly lower mean activities/levels of antioxidant parameters and significantly higher mean levels of MDA were noted in haemolysate samples from patients with diabetes than in those from control individuals. Significantly higher mean serum concentrations of total cholesterol and triglycerides and significantly lower mean concentrations of HDL-cholesterol were noted in patients with diabetes than in control individuals. Further, moderate to strong correlations were observed between values of antioxidants, MDA and lipid profile parameters and blood concentrations of HbA1c.

Conclusion

These results suggest that HbA1c values may be potentially useful not only to indicate long-term glycemic control to indicate onset of complications at a clinically detectable level and molecular level.     

The effect of dietary intervention on serum lipid levels in type 2 diabetes mellitus

Dietary therapy is the cornerstone of lipid management in patients with type 2 diabetes mellitus. The key strategies are the reduction of intake of saturated fat, trans unsaturated fat and cholesterol, and the reduction of energy intake to promote weight loss. This approach will produce significant improvements in the serum levels of low-density lipoprotein (LDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol. According to both the American Diabetes Association and the National Cholesterol Education Program (NCEP), the primary target of therapy is the serum LDL cholesterol level, with the secondary targets being non-HDL cholesterol, triglycerides, and HDL cholesterol. The recently updated guidelines of the NCEP place new emphasis on increasing soluble fiber intake to 10 to 25 g/d and adding foods fortified with plant stanols/sterols (2 g/d) as options to enhance the LDL cholesterol-lowering effect of diet.     

Nuclear magnetic resonance-determined lipoprotein abnormalities in nonhuman primates with the metabolic syndrome and type 2 diabetes mellitus

The lipid profile in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) is commonly characterized by increased levels of triglycerides and decreased levels of high-density lipoprotein (HDL) cholesterol. However, within each lipoprotein class, the changes are more complex. The present study defined the characteristics of dyslipidemia among nonhuman primates, using nuclear magnetic resonance (NMR) spectroscopy as well as the classic beta-quantification method, and examined the pattern of multiple lipoprotein fractions in relation to the main factors identified with the MetS. Seventy-three rhesus monkeys were classified into 3 groups: healthy monkeys, monkeys with MetS, and monkeys with T2DM. Characteristics of dyslipidemia in the MetS and T2DM groups included increased levels of triglyceride-rich very low-density lipoprotein, intermediate-density lipoprotein, and small, dense, low-density lipoprotein (LDL) particles. Reduced concentrations of large LDL and large HDL particles together with reduction of LDL and HDL particle sizes were also observed. Correlation analysis revealed that poor glycemic and lipid profiles, glucose intolerance, and insulin resistance were associated with an atherogenic NMR profile. Compared with the conventional lipid panel, the NMR lipoprotein profile presented in greater detail distinctive differences between the dyslipidemia of the MetS and that of diabetes and demonstrated significant and divergent shifts in both particle size and number within lipoprotein classes between those 2 groups. Detailed lipoprotein profiling may provide additional indicators for more timely intervention. Rhesus monkeys are likely to provide an excellent model for novel drug testing designed to address the specific differences in lipoprotein fraction profile across these 3 groups that reflect the progression of pathophysiology from normal to overt diabetes.