Factors Influencing the Low Density Lipoprotein Profile in Type 2 Diabetic Patients

The lipoprotein distribution profile was examined in Type 2 (non-insulin-dependent) diabetic patients (n = 52), with particular emphasis on factors influencing low density lipoproteins (LDL). Triglycerides were negatively correlated with LDL-2 (r = 0.34, p < 0.05) and positively correlated with smaller, denser LDL-3 (r = 0.57, p < 0.001). This yielded a highly significant, negative correlation between triglycerides and the LDL-2/LDL-3 mass ratio (r = -0.59, p < 0.001) which is an indication of the presence of smaller LDL particles. Parameters of glycaemic control, in the form of fasting blood sugar and glycated haemoglobin (HbA_1c), were also negatively correlated with the LDL-2/LDL-3 mass ratio in univariate analyses; both remained significantly correlated with the mass ratio when corrected for triglycerides. Stepwise multiple regression analysis identified a three-parameter model comprising triglycerides, HbA_1c, and high density lipoprotein cholesterol as best defining the variations in the LDL-2/LDL-3 mass ratio (adjusted r² = 0.52). These observations are consistent with an independent impact of diabetes on the LDL distribution profile and the possibility that the latter may be subjected to multiple pathological influences in diabetic patients.     

Continuous and intermittent walking alters HDL(2)-C and LCATa

Purpose

The purpose of this study was to determine if exercise, whether continuous (CE: completed all in one session) or intermittent (completed in either two (IE 2) or three (IE 3) exercise sessions) expending the same number of calories alters reverse cholesterol transport or low density lipoprotein (LDL) particle size.

Methods

Sixteen healthy (22 ± 2.1 year old) men (VO₂ max = 37.0 ± 3.3 mL/kg/min) randomly completed three exercise trials, CE, IE 2 and IE 3, expending 450 calories. Blood samples were drawn immediately post-exercise (IPE) and 24 and 48 h following exercise and analyzed for total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) and subfractions (HDL₂-C, HDL₃-C). Samples were also analyzed to determine LDL-C particle size, lecithin cholesterol acyl transferase activity (LCATa) and cholesterol ester transfer protein activity (CETPa).

Results

HDL₂-C increased significantly 48 h post-exercise in the CE and IE 2 groups. Additionally, the IE 3 group had significant increases in HDL₂-C at 24 (39%) and 48 h post-exercise by 66%. This change in HDL₂-C was significantly and positively correlated (r = 0.62; p < 0.05) to the changes in LCATa which increased compared to baseline at 48 h post-exercise in the CE and IE 3 groups. No significant changes in LDL particle size or alterations in CETPa were seen.

Conclusions

The results of this study indicate that whether the exercise is continuous or intermittent, keeping calorie expenditure the same, causes significant changes in the HDL₂-C subfraction, which was augmented by an increase in LCATa.     

Resistance training improves the metabolic profile in individuals with type 2 diabetes

Aerobic endurance exercise has traditionally been advocated in the treatment of type 2 diabetes, while the potential role of resistance training has often been overlooked. The aim of the present study was to determine the effect of circuit-type resistance training on blood pressure, lipids and long-term glycaemic control (HbA_1c) in type 2 diabetic subjects. Thirty-eight type 2 diabetic subjects were enrolled in the study; 18 participated in a 5-month individualized progressive resistance training programme (moderate intensity, high volume) twice a week, while the remaining 20 served as controls. The exercise group showed improvements in total cholesterol (6.0±.3 vs 5.3±.3 mM; P<0.01), low density lipoprotein (LDL)-cholesterol (3.90±.22 vs 3.35±.21 mM; P<0.01) and triglycerides (1.91±.25 vs 1.53±.22 mM; P<0.01). Also, the difference in the change in HbA_1c between the groups (0.5%) achieved statistical significance (P<0.01). Circuit-type resistance training seems to be feasible in moderately obese, sedentary type 2 diabetic subjects and the inclusion of circuit-type resistance training in exercise training programmes for type 2 diabetic subjects seems appropriate. Received: 14 April 1997 / Accepted in revised form: 25 July 1997     

Plasma adiponectin is associated with less atherogenic lipoprotein phenotype

Background and aims

This study examined the relationships between plasma levels of adiponectin and the features of the atherogenic lipoprotein phenotype (ALP), including HDL subclasses.

Methods and results

Blood lipids and apolipoproteins were measured in 293 healthy individuals. LDL particle size and HDL subspecies (HDL₂, HDL₃) were measured using gradient gel electrophoresis. Plasma adiponectin levels were negatively correlated with levels of apoB (r = −0.199, p < 0.001), TG (r = −0.262, p < 0.001), and HOMA-IR (r = −0.323, p < 0.001) and positively correlated with levels of apoAI (r = 0.173, p = 0.006), HDL-cholesterol (r = 0.287, p < 0.001), and LDL particle size (r = 0.289, p < 0.001). Multiple linear regression analysis revealed the relationship between plasma adiponectin and LDL particle size (p < 0.05) was no longer significant after adjusting for plasma TG levels. However, adiponectin (p < 0.005) together with apoAI and TG were independent factors for HDL-cholesterol. With regard to HDL subclasses, plasma adiponectin levels were positively correlated with HDL_2b (r = 0.204, p < 0.001), HDL_2a (r = 0.132, p < 0.05) and negatively with HDL_3a (r = −0.128, p < 0.05), HDL_3b (r = −0.203, p < 0.001), and HDL_3c (r = −0.159, p < 0.01). The relationship between circulating adiponectin and HDL₂ (HDL_2b + HDL_2a) was independent of apoB and TG levels (p < 0.05), but not of apoAI and HOMA-IR.

Conclusions

Our results show that circulating adiponectin is associated with reduced manifestations of ALP.     

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     

Electronegative low density lipoprotein subform is increased in patients with short-duration IDDM and is closely related to glycaemic control

Summary We evaluated the effect of improving glycaemic control with intensive insulin therapy on LDL susceptibility to oxidation, electronegative LDL proportion, and LDL subfraction phenotype in a group of 25 patients with short-duration insulin-dependent diabetes mellitus (IDDM); 25 matched healthy control subjects were also studied. LDL susceptibility to oxidation was measured by continuous monitoring of conjugated diene formation. Electronegative LDL was isolated by anion exchange chromatography, and quantified as percentage of total LDL. Six LDL subfractions were isolated by density gradient ultracentrifugation and phenotype A or B classified as the quotient (LDL1-LDL3)/(LDL4-LDL6). Compared to the control group, IDDM subjects with poor glycaemic control showed higher electronegative LDL (19.03 ± 10.09 vs 9.59 ± 2.98 %, p < 0.001), similar LDL subfraction phenotype and lower susceptibility to oxidation (lag phase 45.6 ± 8.8 vs 41.2 ± 4.7 min, p < 0.05). After three months of intensive insulin therapy, HbA_{1 c} decreased from 10.88 ± 2.43 to 5.69 ± 1.54 % (p < 0.001), and electronegative LDL to 13.84 ± 5.15 % (p < 0.05). No changes in LDL susceptibility to oxidation or LDL subfraction phenotype were observed. Electronegative LDL appeared significantly correlated to HbA_{1 c} and fructosamine (p < 0.01 and p < 0.001) only in poorly controlled IDDM patients. These findings suggest that high electronegative LDL in IDDM subjects is related to the degree of glycaemic control, and could therefore be due to LDL glycation rather than to LDL oxidation or changes in LDL subfraction phenotype. [Diabetologia (1996) 39: 1469–1476] Received: 20 December 1995 and in final revised form: 19 June 1996     

Effect of plasma metformin concentrations on serum lipid levels in type II diabetic patients

Summary In this study we evaluated the relationships between plasma metformin levels, measured by reversed-phase high-performance liquid chromatography, and serum lipid levels in 20 metformintreated, type II diabetic patients. Mean fasting plasma metformin concentration was 490 ± 188 ng/ml. No correlation was found between daily dose of drug and lipid parameters. A significant correlation emerged between circulating metformin concentration and serum triglycerides (r=−0.574, p<0.01), HDL-cholesterol (r=0.583, p<0.01) and HDL₂-cholesterol (r=0.670, p<0.05). Multiple linear regression analysis showed that the correlation between plasma metformin concentration and serum triglycerides still remained significant after correction for other clinical and metabolic parameters. Total cholesterol and HDL₃-cholesterol were not correlated with metformin concentrations. These results demonstrate the clinical usefulness of measuring plasma metforminc concentrations and indicate that some effects of metformin on lipid metabolism depend on the drug plasma levels.     

Effects of transdermal 17β-oestradiol combined with oral progestogen on lipids and lipoproteins in hypercholesterolaemic postmenopausal women

Abstract. Objectives. The purpose of the study was to evaluate the effect of transdermal 17β-oestradiol with oral progestogen on the plasma levels of lipids, lipoproteins and apolipoproteins in hypercholesterolaemic postmenopausal women. Design. During 6 months of replacement therapy with transdermal 17β-oestradiol combined with oral progestogen, plasma lipids, lipoproteins and apolipoproteins after 3 and 6 months were measured and compared with pretreatment values by Student's t-test. Setting. From January 1992 until September 1992 patients were diagnosed and treated in an outpatient clinic of the Department of Endocrinology Medical Centre for Postgraduate Education, Warsaw. Subjects. The patients studied were 11 non-obese postmenopausal women with hypercholesterolaemia based on the World Health Organization criteria. Interventions. Venous blood samples were obtained before and 3 and 6 months after the beginning of cyclic replacement therapy with transdermal 17β-oestradiol (E2 100 μg day^?1 combined with oral chlormadinone acetate (2 mg day^?1 for 7 days in each cycle). Main outcome measures. The antiatherogenic effect of transdermal oestrogen replacement therapy exerted by increased levels of high-density lipoprotein sub-fraction 2 cholesterol (HDL₂-C) leading to the decrease of the total cholesterol level was anticipated. Results. After 6 months of the treatment the concentrations of HDL₂ cholesterol (HDL₂-C) increased from 0.45 ± 0.07 mmol l^?1 to 0.73 ± 0.03 mol l^?1 (P < 0.05) but the levels of HDL₃ cholesterol (HDL₃-C) decreased from 1.15 ± 0.06 mmol l^?1 to 0.89 ± 0.07 mmol l^?1 (P < 0.05). The concentrations of total cholesterol decreased from 6.9 ± 0.13 mmol l^?1 to 6.2 ± 0.2 mmol l^?1 (P < 0.05). No changes were observed in the plasma levels of total triglycerides, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, apolipoproteins A-I and B. Conclusions. In hypercholesterolaemic postmenopausal women, transdermally administered 17β-oestradiol 100 μg daily in combination with oral chlormadinone acetate has a beneficial effect through raising the level of the antiatherogenic HDL₂-C subfraction and decreasing the level of total cholesterol.     

The postprandial state does not impair endothelial function in women with Type 2 diabetes irrespective of glycaemic control

Aims/hypothesis The postprandial state has been shown to be associated with endothelial dysfunction, a predictor of cardiovascular morbidity. In Type 2 diabetes, postprandial metabolic excursions are prolonged and exaggerated, but less pronounced if glycaemic control is optimised. We investigated the impact of improved glycaemic control on endothelial function in the postprandial state.Methods We studied 19 postmenopausal women with Type 2 diabetes and ten non-diabetic subjects. Participants with diabetes were re-studied 3 months after intensive glucose regulation. We measured forearm blood flow by strain gauge plethysmography during rest, during acetylcholine infusion and post ischaemia in the fasting state, and again 3 hours after a mixed meal (660 kcal, 55% fat).Results Endothelium-dependent vasodilation was impaired in the diabetic group (p<0.005) and improved following an HbA₁c reduction of 0.96% (p<0.05 for high-dose acetylcholine infusion). Postprandial metabolic excursions were higher in the diabetic group (p<0.001, p<0.01 and p<0.05 for glucose, insulin and triglycerides respectively). Resting forearm blood flow increased in all groups after the meal (p<0.005). There was no difference in fasting and postprandial endothelium-dependent vasodilation before and after improved glucose regulation in either group.Conclusions/interpretation The postprandial state does not impair endothelial function in non-diabetic women and does not make pre-existing endothelial dysfunction worse in women with Type 2 diabetes, irrespective of glycaemic control.     

Changes of lipolytic enzymes cluster with insulin resistance syndrome

Summary The activities of hepatic and lipoprotein lipase and the levels of lipo- and apoproteins were compared in two groups of normoglycaemic men representing the highest (n=18) and lowest (n=15) fasting insulin quintiles of first degree male relatives of non-insulin-dependent diabetic patients. The high insulin group representing insulin-resistant individuals had significantly lower post-heparin plasma lipoprotein lipase activity than the low insulin group (14.2±4.0 vs 20±5.8 mol NEFA·ml^–1·h^–1, p<0.001); hepatic lipase activity did not differ between the two groups (24.2±11 vs 18.0±5.3 mol NEFA·ml^–1·h^–1, NS). The lipoprotein lipase/hepatic lipase ratio in the high insulin group was decreased by 66% as compared to the low insulin group (0.75±0.57 vs 1.25±0.65, p<0.01). In the high insulin group both total and VLDL triglycerides were higher than in the low insulin group (1.61±0.57 vs 0.86±0.26 mmol/l, p< 0.001 and 1.00±0.47 vs 0.36±0.16 mmol/l, p<0.001, respectively) whereas HDL cholesterol and HDL₂ cholesterol were lower (1.20±0.30 vs 1.43±0.22 mmol/l, p<0.05 and 0.49±0.21 vs 0.71±0.17 mmol/l, p<0.05, respectively). Total cholesterol, LDL cholesterol or HDL₃ cholesterol did not differ between the two groups. The mean particle size of LDL was smaller in the high insulin group than in the low insulin group (258±7 vs 265±6 å, p<0.05). We propose that the changes of lipoprotein lipase and lipoprotein lipase/hepatic lipase ratio cluster with insulin resistance and provide a possible mechanism to explain the lowering of HDL cholesterol and elevation of triglyceride concentrations observed in insulin-resistant subjects.Abbreviations LPL Lipoprotein lipase - HL hepatic lipase - VLDL very low density lipoprotein - IDL intermediate density lipoprotein - LDL low density lipoprotein - HDL high density lipoprotein - chol cholesterol - TG triglycerides - NEFA non-esterified fatty acids     

A Study of Fluoxetine in Obese Elderly Patients with Type 2 Diabetes

In order to establish the safety and efficacy of fluoxetine in subjects over 60 years of age with Type 2 diabetes, a randomized, double-blind, parallel study of 30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily with placebo. Subjects were diet controlled with an HbA₁ < 14% (reference range 6–9%) and BMI > 29 kg m². Those taking fluoxetine had a median weight loss of 2.6 kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0–02), compared with weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months, respectively. Improved glycaemic control was also demonstrated in the fluoxetine group compared with placebo, initial HbA₁ levels of 8.0% vs 8.7% (NS) falling at 4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained improvement in fasting blood glucose levels was demonstrated. Reporting of adverse events was similar in both groups. Fluoxetine in the short term aids weight loss and improves glycaemic control without a significant increase in adverse events in elderly Type 2 diabetic subjects.     

Acute increase in lipoprotein lipase following prolonged exercise

We investigated the acute effects of prolonged exercise on lipoprotein metabolism. Serum lipid and lipoprotein concentrations and plasma postheparin lipolytic activity were measured in ten well-trained men (ages 21 to 39) the day before and after a 42 km foot race. LDL cholesterol decreased by 10% (113 ± 31 to 103 ± 32 mg/dL, P < 0.01) and total HDL-cholesterol levels increased by 9% (65 ± 18 to 71 ± 19 mg/dL, P < 0.01) the day after the race. No changes in the concentration of apolipoprotein A-I or A-II occurred. Triglyceride levels decreased by 39% (95 ± 38 to 58 ± 23 mg/dL, P < 0.001). Two days after the race, total HDL cholesterol (74 ± 21 mg/dL, P < 0.05) and the HDL₂ subfraction (37 ± 19 mg/dL, P < 0.05) remained significantly elevated compared to pre-race values. Most dramatically, the level of lipoprotein lipase activity measured in postheparin plasma nearly doubled after the race, demonstrating that vigorous exercise acutely increases this enzyme activity. The increase in lipoprotein lipase activity probably mediated the fall in serum triglycerides after exercise and may also account for the increase in HDL cholesterol.     

The Role of Plasma Non-esterified Fatty Acids During Exercise in Type 2 Diabetes Mellitus

Elevated fasting plasma non-esterified fatty acid (NEFA) levels have been reported in Type 2 diabetes. We examined whether such changes persist during low-grade exercise and influence carbohydrate metabolism. Eight Type 2 diabetic patients with moderate glycaemic control and eight healthy controls received the anti-lipolytic agent, acipimox, or placebo on separate occasions before exercising for 45 min at 35 % pre-determined V_o2max. Fasting plasma NEFA levels were similar (0.40 ± 0.06 (SEM) and 0.45 ± 0.05 mmol l^?1; healthy and Type 2 diabetic subjects) following placebo, and increased to comparable levels with exercise (0.73 ± 0.07 and 0.73 ± 0.10 mmol l^?1). Acipimox lowered basal NEFA levels (0.14 ± 0.03 and 0.28 ± 0.04 mmol I^?1; both p < 0.05 vs placebo), and prevented the rise with exercise. Blood glucose (p < 0.001) and serum insulin (p < 0.01) levels were higher in the Type 2 diabetic patients (vs controls) for both treatments. Whole body lipid oxidation increased from baseline to a comparable degree with exercise following placebo (3.2 ± 0.3 and 2.8 ± 0.3 mg kg^?1 min^?1; healthy and Type 2 diabetic subjects, both p < 0.02). Although less marked, the same was also observed following acipimox (2.0 ± 0.4 and 2.1 ± 0.5 mg kg^?1 min^?1; both p < 0.05). Carbohydrate oxidation increased with exercise in both subject groups, but with no significant difference between the treatments. Thus, the metabolic response to low-grade exercise was normal in Type 2 diabetic patients with moderate glycaemic control, but occurred against a background of hyperinsulinaemia. Plasma NEFA do not exert a major regulatory effect on carbohydrate metabolism during low-grade exercise.     

Glycaemic control and cardiovascular risk factors in Type 2 diabetes: a population-based study

The objective of this study was to estimate the prevalence of poor glycaemic control and cardiovascular risk factors in an Italian population-based cohort of subjects with Type 2 diabetes mellitus (DM). Out of a cohort of 1967 subjects (estimated completeness of ascertainment 80 %), 1574 (80 %) were investigated, and adherence to targets for control of the European NIDDM Policy Group assessed. Prevalence of poor glycemic control (HbA_1c > = 8) was 47.7 %. Obesity was present in 23.4 % of the cohort, hypertension in 83.4 %, hypertriglyceridaemia (>2.26 mM) in 19.3 %, hypercholesterolaemia (>6.46 mM) in 25.5 %, and low HDL-cholesterol (<0.90 mM in men and <1.03 mM in women) in 13.7 %. Only 153 (9.7 %) subjects were free from other disorders. Subjects were treated as follows: 26.2 % exclusively by general practitioners; 13.3 %, 69.9 %, 10.9 %, and 5.9 % with diet, oral hypoglycaemic drugs, insulin, and both, respectively. Multiple linear regression analysis showed associations between HbA_1c and fibrinogen (p < 0.001), total cholesterol (p = 0.006), and triglycerides (p = 0.04), independent of age, sex, duration of diabetes, and antidiabetic treatment. Neither BMI nor blood pressure were associated with HbA_1c. In conclusion, this Italian population-based cohort of subjects with Type 2 DM showed a high prevalence of poor glycaemic control, high consumption of oral hypoglycaemic drugs, and an independent association between glycaemic control and cardiovascular risk factors (fibrinogen, total cholesterol, and triglycerides). The presence of obesity or hypertension was not significantly associated with glycaemic control. © 1998 John Wiley & Sons, Ltd.     

Comparison of Bezafibrate and Simvastatin in the Treatment of Dyslipidaemia in Patients with NIDDM

Fibrates and HMG CoA reductase inhibitors are commonly used in the treatment of diabetic dyslipidaemia. However, these two groups of drugs have not been compared in diabetic patients in a randomized controlled trial. Therefore, a multicentre study was performed in 73 subjects with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and combined hyperlipidaemia (serum cholesterol 6.2–10.0 mmol l⁻¹, serum triglycerides 2.3–10.0 mmol l⁻¹), comparing the efficacy of 400 mg bezafibrate with 10 mg simvastatin in a double-blind fashion. Treatment with bezafibrate during 12 weeks reduced serum triglycerides significantly more than simvastatin (−41 % vs −22 %, p < 0.001) and increased HDL cholesterol more (bezafibrate: + 17 % vs simvastatin: + 9 %, p < 0.05). LDL cholesterol levels decreased by 14 % (p < 0.001) during simvastatin and increased by 21 % (p < 0.01) during bezafibrate. This increase in LDL cholesterol was positively correlated with fasting serum triglycerides (p < 0.001) and was associated with a reduction of the serum apolipoprotein B concentration, suggesting an increase in LDL particle size. Metabolic control of diabetes (fasting glycaemia; HbA_1c) and insulin secretion (C-peptide levels) were unaffected by both treatments. The incidence of side-effects during treatment was similar for both drugs. Thus, 400 mg bezafibrate mainly increases HDL cholesterol and lowers serum triglycerides but at the expense of an increase in LDL cholesterol; 10 mg simvastatin lowers LDL cholesterin more effectively but has a smaller effect on HDL cholesterol and triglycerides. © 1997 John Wiley & Sons, Ltd.     

Comparison of the effect of multiple short-duration with single long-duration exercise sessions on glucose homeostasis in type 2 diabetes mellitus

Aims/hypothesis We evaluated and compared the effects on glycaemic control of two different exercise protocols in elderly men with type 2 diabetes mellitus. Methods Eighteen patients with type 2 diabetes mellitus carried out home-based bicycle training for 5 weeks. Patients were randomly assigned to one of two training programmes at 60% of maximal oxygen uptake: three 10 min sessions per day (3 × 10) or one 30 min session per day (1 × 30). Plasma insulin, C-peptide and glucose concentrations were measured during a 3 h oral glucose tolerance test (OGTT). Insulin sensitivity index (ISI_composite), pre-hepatic insulin secretion rates (ISR) and change in insulin secretion per unit change in glucose concentrations (B_total) were calculated. Results Cardiorespiratory fitness increased in response to training in both groups. In group 3 × 10 (n = 9) fasting plasma glucose (p = 0.01), 120 min glucose OGTT (p = 0.04) and plasma glucose concentration areas under the curve at 120 min (p < 0.04) and 180 min (p = 0.07) decreased. These parameters remained unchanged in group 1 × 30 (n = 9). No significant changes were found in ISI_composite, ISR and B_total in either of the exercise groups. In a matched time-control group (n = 10), glycaemic control did not change. Conclusions/interpretation Moderate to high-intensity training performed at 3 × 10 min/day is preferable to 1 × 30 min/day with regard to effects on glycaemic control. This is in spite of the fact that cardiorespiratory fitness increased similarly in both exercise groups. A possible explanation is that the energy expenditure associated with multiple short daily sessions may be greater than that in a single daily session.     

Plasma lipoproteins and apolipoproteins in insulin-dependent and young non-insulin-dependent Arab women

Summary Plasma lipids, lipoproteins and apolipoproteins (apo) were analysed in 30 young Arab IDDM and 50 young insulin-requiring NIDDM women. The mean age of IDDM and NIDDM groups was 20.2 and 34.5 years, and mean duration of diabetes was 5.7 and 4.6 years, respectively. Two groups of 40 and 60 healthy women (matched for age and BMI) provided corresponding control groups. In comparison with control subjects, diabetics showed marked increases in the following parameters: total cholesterol (TC), low density lipoprotein (LDL) cholesterol, total triglycerides (TG), very low density lipoprotein (VLDL) triglycerides, phospholipids, apoB, LDL apoB, glucose and glycosylated hemoglobin (HbA_1c) as well as the ratios of total cholesterol/high density lipoprotein (HDL) cholesterol, LDL-cholesterol/HDL-cholesterol, LDL cholesterol/high density lipoprotein 2 (HDL₂) cholesterol and apoB/apoAI. Plasma LCAT activity, concentrations of HDL₃ apoAI and apoAII in plasma and lipoprotein fractions were normal in both the diabetic groups. Levels of C-peptide, HDL, HDL₂ and HDL₃ cholesterol, plasma apoAI, HDL apoAI and HDL₂ apoAI were markedly decreased in the diabetic groups as compared to their corresponding controls. There was no significant correlation between fasting glucose or HbA_1c and any of the above parameters. Despite insulin therapy in both the diabetic groups studied, abnormalities in lipids, apoB and apoAI still persisted. Our data suggest a possible higher risk of atherosclerosis in these patients.     

Effects of dietary cholesterol on plasma lipoproteins and their subclasses in IDDM patients

Summary To compare the effects of dietary cholesterol supplementation in insulin-dependent diabetic (IDDM) patients and normal subjects, 10 male IDDM patients in good glycaemic control (HbA_{1 c} 7.3 ± 0.9 %) (mean ± SD) and normal plasma lipid levels, and 11 control male subjects of similar age, body mass index and lipid plasma levels underwent a double blind, cross-over, sequential study. Cholesterol supplementation of 800 mg/day or placebo were given for consecutive periods of 3 weeks. The concentration of plasma total cholesterol increased significantly with the dietary cholesterol supplementation compared to placebo in IDDM patients by 6 % (p < 0.05) and in control subjects by 9 % (p < 0.05). No changes were observed in the concentration of plasma triglycerides in either group. The LDL cholesterol level increased by 12 % (p < 0.01) in patients and by 7 % (p < 0.05) in control subjects. In patients plasma HDL cholesterol concentration remained the same, while in control subjects it tended to increase after cholesterol supplementation (from 1.14 ± 0.26 to 1.23 ± 0.27 mmol/l, p = 0.06). During the cholesterol intake period the mean concentration of LDL1, LDL2 and LDL3 subclasses in patients showed a significant increase by 21.0 (p < 0.05), 20.4 (p < 0.001) and 11.1 % (p < 0.05), respectively, resulting in an 18.0 % increase in mean total LDL mass (p < 0.001) without major changes in LDL composition. In the control subjects the changes in the concentrations of LDL subclasses during cholesterol intake were less and not significant. In the IDDM patients the cholesterol intake did not affect the concentration or composition of HDL subclasses or total HDL mass. In contrast, in control subjects cholesterol intake increased the mean concentration of HDL2 a by 12.2.% (p < 0.05) and this increase was significantly different if compared to changes obtained in the patients. In conclusion, compared to normal subjects, in IDDM patients, dietary cholesterol intake increased the LDL particle mass significantly and had no positive effect on HDL. [Diabetologia (1998) 41: 193–200] Received: 4 July 1997 and in revised form: 12 September 1997     

Alterations in serum lipids and apolipoproteins in male Type 1 (insulin-dependent) diabetic patients with microalbuminuria

Summary The relationships between serum lipid, apolipoprotein levels and urinary albumin excretion were investigated in 20 male Type 1 (insulin-dependent) diabetic patients with microalbuminuria (overnight urinary albumin excretion between 10 and 200 g/min), in 18 male Type 1 diabetic patients without microalbuminuria and in 18 male control subjects. In the microalbuminuric patients low density lipoprotein cholesterol was higher than in the control subjects (p<0.05); the high density lipoprotein/low density lipoprotein cholesterol ratio was lower than in the normoalbuminuric diabetic patients (p<0.05), and in the control subjects (p<0.01); apolipoprotein B was higher than in the normoalbuminuric patients (p<0.05); the apolipoprotein A₁/B ratio was lower than in the normoalbuminuric diabetic patients (p<0.05). Serum triglyceride was higher in the microalbuminuric diabetic patients and in the control subjects than in the normoalbuminuric diabetic patients (p<0.05, for both), but was not different between the microalbuminuric diabetic patients and the control subjects. No significant differences between the 3 groups were present with respect to serum cholesterol, high density lipoprotein cholesterol and apolipoprotein A₁. In the 2 combined Type 1 diabetic groups there were significant correlations between urinary albumin excretion and the high density lipoprotein/low density lipoprotein cholesterol ratio (R -0.40, p<0.02), apolipoprotein B (R0.35, p<0.05) and the apolipoprotein A₁/B ratio (R -0.44, p<0.01). These results indicate microalbuminuria related differences in lipid and apolipoprotein levels in male Type 1 diabetic patients, which may contribute to an increased risk of cardiovascular disease.     

Increased postprandial lipemia in patients with normolipemic peripheral arterial disease

Methods We evaluated the postprandial lipid metabolism in patients with normolipemic peripheral arterial disease (PAD) after the administration of an oral fat load. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL₂ and HDL₃ subfractions, triglycerides (TGs), lipoprotein(a), and LDL size were determined at baseline and for 8 hours after the meal. Results In patients with PAD, TGs increased significantly at the 4th, 6th, and 8th hours postprandially; in control subjects, TGs increased at the 4th and 6th hours. HDL decreased significantly at the 4th, 6th, and 8th hours in patients with PAD and at the 6th hour in control subjects. The magnitude of postprandial lipemia, expressed as “the area under the incremental curve for TGs,” was higher in patients with PAD than in control subjects (770 ± 476 vs 391 ± 195 mg/dL at 8 hours, P < .05). Multiple-regression analysis showed that baseline TGs were positively related to the magnitude of postprandial lipemia (P = .01) and that LDL size was negatively related (P = .05). Conclusions This is the first documentation of postprandial behavior in patients with normolipemic PAD, suggesting the relevance of postprandial lipoprotein metabolism in the pathogenesis of peripheral atherosclerosis. (Am Heart J 2002;143:733-8.)