Blood rheology and cardiovascular risk factors in type 1 diabetes: relationship with microalbuminuria.

Whole blood and plasma viscosity, erythrocyte aggregation and deformability, plasma fibrinogen, lipids, lipoproteins, apolipoproteins, and measures of blood glucose control were compared between 21 Type 1 diabetic patients with microalbuminuria (overnight albumin excretion rate 30-200 micrograms min-1) and 21 patients with albumin excretion below this range matched for age, sex, and duration of diabetes. Patients with microalbuminuria had significantly higher glycosylated haemoglobin (9.4 +/- 1.6 (+/- SD) vs 7.9 +/- 1.8% (normal range 5.0 to 7.6%)), total-cholesterol (5.6 +/- 1.1 vs 4.6 +/- 1.3 mmol l-1), apolipoprotein B (0.82 +/- 0.21 vs 0.66 +/- 0.14 g l-1), and apolipoprotein B:A1 ratio (0.58 +/- 0.18 vs 0.50 +/- 0.15) than those without microalbuminuria (all p less than 0.05). HDL-cholesterol was also raised (1.71 +/- 0.46 vs 1.43 +/- 0.37 mmol l-1, p less than 0.05). Lipoprotein(a) concentration was possibly higher in the microalbuminuric group (median (95% Cl) 105 (82-140) vs 72 (52-114) mg l-1, p = 0.06). No differences were seen in any of the rheological measurements. These results confirm the presence of potentially atherogenic lipoprotein changes in Type 1 diabetic patients with microalbuminuria, but suggest that altered blood rheology does not predate the development of nephropathy.     

The influence of regional adiposity on atherogenic risk factors in men and women with type 2 diabetes.

To determine firstly whether body fat distribution could predict the presence of atherogenic risk factors better than overall adiposity in Type 2 diabetes, and secondly whether sex differences in these risk factors could be explained by sex differences in fat distribution, waist-to-hip girth ratio (WHR), serum lipids, lipoproteins, apolipoproteins, plasma lipolytic activity, and blood pressure were assessed in 47 patients with Type 2 diabetes, 21 women matched for age, body mass index (BMI) and blood glucose control with 26 men. The men had higher WHR (0.95 (range 0.83-1.07) vs 0.82 (0.74-0.94), p less than 0.001), lower HDL-cholesterol (1.03 +/- 0.05 vs 1.38 +/- 0.06 mmol l-1, p less than 0.001) and apolipoprotein A1 (1.40 +/- 0.06 vs 1.76 +/- 0.06 gl-1, p less than 0.001) concentrations, and higher hepatic lipase activities (16.2 (6.4-38.0) vs 8.6 (2.3-23.1) mmol h-1 l-1, p less than 0.01). In both men and women, BMI and WHR were positively related to serum triglyceride, insulin and C-peptide concentrations. In women, HDL-cholesterol was negatively related to BMI (r = -0.45, p less than 0.05) but only possibly related to WHR (r = -0.33, NS). In men, by contrast, WHR was related negatively to HDL-cholesterol (r = -0.60, p less than 0.005), HDL2-cholesterol (r = -0.43, p less than 0.05), and apolipoprotein A1 (r = -0.70, p less than 0.001) and positively to hepatic lipase activity (r = 0.65, p less than 0.001), whereas the same relationships with BMI were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of low glycaemic index foods improves metabolic control of diabetic patients over five weeks.

The aim of the present study was to determine whether any benefit might occur from lowering the glycaemic index of diet in the medium term in diabetic patients. Eighteen well-controlled diabetic patients (12 Type 1 and 6 Type 2 non-insulin-treated), were assigned to either a high mean glycaemic index or low mean glycaemic index diet for 5 weeks each in a random order using a cross-over design. The two diets were equivalent in terms of nutrient content and total and soluble fibre content. The glycaemic indices were 64 +/- 2 (mean +/- SD) % and 38 +/- 5% for the two diets. The high glycaemic index diet was enriched in bread and potato and the low glycaemic index diet in pasta, rice, and legumes. At the end of the study periods, the following variables were improved on the low compared to the high glycaemic index diet: fructosamine (3.9 +/- 0.9 vs 3.4 +/- 0.4 mmol l-1, p less than 0.05); fasting blood glucose (10.8 +/- 2.8 vs 9.6 +/- 2.7 mmol l-1, p less than 0.02); 2-h postprandial blood glucose (11.6 +/- 2.9 vs 10.3 +/- 2.5 mmol l-1, p less than 0.02); mean daily blood glucose (12.0 +/- 2.5 vs 10.4 +/- 2.7 mmol l-1, p less than 0.02); serum triglycerides (1.5 +/- 0.9 vs 1.2 +/- 0.6 mmol l-1, p less than 0.05). No significant differences were found in body weight, HbA1C, insulin binding to erythrocytes, insulin and drug requirements, and other circulating lipids (cholesterol, HDL-cholesterol, phospholipids, Apolipoprotein A1, Apolipoprotein B). Thus the inclusion of low glycaemic index foods in the diet of diabetic patients may be an additional measure which slightly but favourably influences carbohydrate and lipid metabolism, requires only small changes in nutritional habits and has no known deleterious effects.     

Urinary excretion of albumin and lipid abnormalities in hypertensive insulin-dependent diabetics

Patients with insulin dependent diabetes mellitus (IDDM) often suffer from cardiovascular diseases as renal failure occurs. Elevated albumin excretion rate (AER) is a predictive value of this event. Relations between AER, blood pressure, serum lipids and apoproteins concentrations in 100 patients with IDDM have been surveyed. Twenty one hypertensive patients (HT group) were compared to 21 patients without hypertension (n HT group), matched for sex, age, diabetes duration, and metabolic control, assessed by glycosylated haemoglobin. Comparison of both groups showed HT group had elevated systolic blood pressure (137 +/- 12 vs 126 +/- 20 mmHg; p less than .05), elevated diastolic blood pressure (80 +/- 7 vs 71 +/- 8 mmHg; p less than .001), increase in AER (27 range 3-4023 vs 6 range 2-51 mg/day; p less than .001), slightly elevated serum creatinine (95 +/- 32 vs 78 +/- 15 mumol/l; p less than .05). In HT group, serum lipid composition showed: raise in total cholesterol (251 +/- 43 vs 221 +/- 41 mg/dl; p less than 0.5), elevated apoprotein B (130 +/- 30 vs 99 +/- 21 mg/dl; p less than .001) elevated apoprotein B/apoprotein A1 ratio (.91 +/- .32 vs .66 +/- .27; p less than .001), elevated triglycerides (157 +/- 53 vs 98 +/- 43 mg/dl; p less than .005) and elevated LDL-cholesterol (170 +/- 42 vs 143 +/- 33 mg/dl; p less than .05). Levels of apoprotein A1 and HDL-cholesterol were not significantly different. Body mass index, daily insulin requirement and tobacco usage were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of enprostil on glucose and lipid metabolism in type 2 diabetes

Enprostil, a dehydro-prostaglandin E2 analogue, has been tested as treatment for peptic ulcer. Its effect on blood glucose and lipid metabolism in Type 2 diabetes was assessed in a randomized, double-blind trial. Fifteen patients on sulphonylurea therapy received, in addition, enprostil 35 micrograms or placebo thrice daily for two weeks, with a 2-week wash-out before crossover. Data from 12 patients were analysed. After a 530 Cal test breakfast at the end of active treatment, plasma glucose rose from a fasting concentration similar to that after the last placebo dose (10.5 +/- 0.8 (+/- SE) and 10.6 +/- 1.1 mmol l-1 respectively) to 1, 2 and 3 h concentrations which were 1.5 to 2.1 mmol l-1 lower than on placebo (2 h concentration 14.6 +/- 0.9 vs 16.4 +/- 1.3 mmol l-1, p less than 0.05). Serum fructosamine concentrations at the end of active treatment and placebo were 3.66 +/- 0.22 and 3.78 +/- 0.24 respectively (p = 0.051). No changes in fasting or post-prandial insulin concentrations were observed. After 2 weeks of enprostil, fasting serum triglyceride (1.76 +/- 0.18 mmol l-1) and total cholesterol (6.27 +/- 0.29 mmol l-1) concentrations were lower than after placebo (2.14 +/- 0.25 and 7.35 +/- 0.46 mmol l-1, p = 0.031 and p = 0.002, respectively), the latter effect being primarily due to reduced LDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Placebo-controlled trial of the effects of guar gum and metformin on fasting blood glucose and serum lipids in obese, type 2 diabetic patients

Nineteen obese patients with Type 2 diabetes mellitus were treated for periods of 3 months with placebo, guar gum (5 g three times daily) and metformin (500 mg three times daily) in a randomized double-blind, double-placebo, cross-over study. Both active agents decreased fasting blood glucose from 11.4 +/- 3.7 mmol l-1 (mean +/- SD) to 8.6 +/- 2.8 mmol l-1 on metformin (p less than 0.001) and to 9.5 +/- 3.9 mmol l-1 on guar gum (p less than 0.01). Metformin significantly reduced the very low density lipoprotein (VLDL) cholesterol concentration from 0.62 (+0.73, -0.34) mmol l-1 (geometric mean (+SD, -SD)) to 0.43 (+0.58, -0.25) mmol l-1, (p less than 0.02), but unless hyperlipidaemia was present there were no changes in other serum lipid or lipoprotein levels. In patients with serum cholesterol greater than 6.5 mmol l-1 decreases in serum triglycerides from 3.29 (+3.27, -1.64) to 2.46 (+2.55, -1.25) mmol l-1 (p less than 0.02) occurred with metformin. In these patients guar gum produced a reduction in serum cholesterol (from 7.70 +/- 0.90 to 6.41 +/- 1.11 mmol l-1, p less than 0.01) due to an effect on low density lipoproteins. These differential effects may be important in planning therapy when hyperlipidaemia accompanies Type 2 diabetes.     

The comparative treatment with lovastatin and bezafibrate of primary hypercholesterolemia. A randomized and double-blind trial

The efficacy and tolerability of lovostatin (L) and bezafibrate (B) were compared in a total of 39 patients, 24 males and 15 females, 59 +/- 9 years old. Showing a total serum cholesterol superior to 250 mg/dl and total serum triglycerides inferior to 350 mg/dl, after 1 month on a low cholesterol diet and another on placebo, were eligible for participation. After randomization 19 treated with L started with 20 or 40 mg at night according to baseline cholesterol under or above 300 respectively and 20 with B received 200 mg tid. If after 6 weeks of therapy cholesterol remained above 200, the doses of L or matching placebo in those with B was double while dose of B or matching placebo remained constant. Cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol were determined using an enzymatic analytical method. Apolipoproteins were obtained by radial immunodiffusion. Routine hematological analysis and blood chemistry safety tests were performed at baseline and every 6 weeks during active treatment. The average most important results, after 12 weeks of treatment, comparing L vs B were: 1) cholesterol was reduced 26 vs 10% (p less than 0.001); 2) LDL-cholesterol decreased 35 vs 15% (p less than 0.001); 3) HDL-cholesterol increased 5 vs 19% (p = NS); 4) triglycerides diminished 15 vs 18% (p = NS). Three patients in L and 1 in B showed adverse events and two of them, one each group, were drop-out. In summary: a) L was more effective lowering total cholesterol and LDL-cholesterol; b) B was more potent decreasing triglycerides and increasing HDL-cholesterol; c) both drugs showed good tolerability.     

The prevalence of hypercholesterolaemia and its relationship with albuminuria in insulin-dependent diabetic patients: an epidemiological study.

To assess the prevalence of hypercholesterolaemia and its relationship with metabolic control and urinary albumin excretion in Type 1 diabetic patients, all 1577 insulin-dependent patients attending the outpatient clinic at the Steno Memorial Hospital were studied. None had previously received lipid-lowering drugs. Hypercholesterolaemia, defined as plasma concentration of cholesterol above 6.4 mmol l-1 was found in 156 patients (10%) (95%) confidence intervals (CI) 8.4-11.5%) compared with 11% in the Danish background population. Compared with the normolipidaemic diabetic patients, the hyperlipidaemic patients were older (42 vs 37 years: p less than 0.001, 95% CI for difference in means 3-7 years), they had a higher glycosylated HbA1C (9.2 vs 8.6%, p less than 0.001, 95% CI for difference in means 0.4-1.3%) and their urinary albumin excretion was 32 vs 12 mg 24 h-1, p less than 0.001. Of the 1577 diabetic patients, 1084 patients (73%) had normal urinary albumin excretion (UAE less than 30 mg 24 h-1), 255 (17%) had microalbuminuria (UAE 30-300 mg 24 h-1) and 136 (9%) had overt clinical nephropathy (UAE greater than 300 mg 24 h-1). The plasma concentration of cholesterol rose significantly with increasing urinary albumin excretion; normoalbuminuric 4.78 mmol l-1 +/- 1.06 (mean +/- SD); microalbuminuric: 5.12 mmol l-1 +/- 1.23 and macroalbuminuric: 4.89 mmol l-1 +/- 1.38 (p less than 0.001). The influence of metabolic control on the plasma level of cholesterol was of only minor clinical importance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-density lipoprotein particle size, triglyceride-rich lipoproteins, and glucose tolerance in non-diabetic men with essential hypertension

The aim of the study is to investigate serum lipoproteins abnormalities including low-density lipoprotein (LDL) particle size, and their relationship with other cardiovascular risk factors in men with essential hypertension. Plasma glucose and serum insulin levels during oral glucose tolerance test (OGTT), serum lipoprotein(a), apolipoprotein (apo) A-I. apo B. cholesterol and triglycerides in serum and in lipoproteins, and LDL particle diameter were measured in thirty-eight consecutive newly-diagnosed non-diabetic untreated hypertensive men and 38 healthy male controls. Plasma glucose at baseline, 60 and 120 min during OGTT was significantly higher in patients than controls whereas serum insulin levels did not differ between patients and controls. Serum apo B and triglycerides were significantly raised in patients compared with controls (1.08 +/- 0.17 g/L [mean +/- SD] vs 0.97 +/- 0.22 g/L. p < 0.05, and 1.56 +/- 0.90 mmol/L vs 1.15 +/- 0.57 mmol/L, p < 0.05, respectively). Very-low-density lipoprotein (VLDL) triglycerides and LDL-cholesterol were increased in patients compared with controls (0.89 +/- 0.79 mmol/L and 0.54 +/- 0.35 mmol/L, p < 0.05, and 4.08 +/- 0.85 mmol/L and 3.60 +/- 0.92 mmol/L, p < 0.05, respectively) whereas high-density lipoprotein (HDL) cholesterol was lower in patients compared with controls 0.95 +/- 0.22 mmol/L and 1.07 +/- 0.20 mmol/L, p < 0.05). Adjustment for body mass index, abdominal/hip perimeter ratio and area under the glucose curve did not attenuate the relationship between hypertension and VLDL-triglycerides. Six patients and two controls had a mean LDL diameter < or = 25.5 nm and in the former serum triglycerides ranged from 1.86 mmol/L to 2.37 mmol/L. Mean LDL particle diameter in both patients and controls showed an inverse relationship with log-transformed serum triglycerides (r = - 0.51, p < 0.001 and r = - 0.47, p < 0.005, respectively). Among patients, those with serum triglycerides > or = [corrected] 1.58 mmol/L had a lesser mean LDL diameter than those with triglycerides above this threshold (25.78 +/- 0.47 nm vs 26.30 +/- 0.35 nm, p < 0.001). Higher plasma glucose, serum apo B and LDL-cholesterol as well as the decrease in serum HDL-cholesterol in patients with hypertension are consistent with high coronary heart disease risk. Not only mild hypertriglyceridemia but also high-normal serum triglycerides in themselves or as a surrogate of a predominance of small dense LDL particles in plasma convey an additional risk for cardiovascular disease in hypertensive patients even though routine plasma lipids are within or near normal range.     

A nation-wide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood

Nation-wide screening for microalbuminuria in Denmark was performed in 22 paediatric departments treating children with Type 1 diabetes. Over a period of 6 months 1020 children (less than or equal to 12 years) and adolescents (greater than 12 to 19 years) were screened (81% of total). Of these, 957 (94%) performed at least two timed overnight urine collections. In 209 non-diabetic subjects the upper 95% limit for normal albumin excretion rate (AER) was 20 micrograms min-1. Mean overnight AER was significantly (p less than 0.001) elevated in diabetic (3.0 x/divided by 2.3 (SD tolerance factor) micrograms min-1) and in non-diabetic (2.5 x/divided by 2.2 micrograms min-1) adolescents compared with diabetic (1.7 x/divided by 2.1 micrograms min-1) and non-diabetic (1.3 x/divided by 2.2 micrograms min-1) children. In the diabetic patients AER was positively correlated with the body surface area and age. Among the patients with Type 1 diabetes, 4.3% (18 males and 23 females) had AER greater than 20 to 150 micrograms min-1 (persistent microalbuminuria). A further 7 adolescents (0.7%) had overt proteinuria (greater than 150 micrograms min-1). Clinical data for the 41 diabetic patients with AER greater than 20 to 150 micrograms min-1 were compared with those for 569 diabetic adolescents with AER less than or equal to 20 micrograms min-1 and duration of diabetes more than 2 years. The group with AER greater than 20 to 150 micrograms min-1 had significantly higher mean age (16.5 years) than the group with AER less than or equal to 20 micrograms min-1 (15.0 years; p less than 0.001). Females with AER greater than 20 to 150 micrograms min-1 had significantly higher mean HbA1c level (10.8 +/- 1.9%) than those with AER less than or equal to 20 micrograms min-1 (9.8 +/- 1.9%, p less than 0.003); they also had impaired linear growth (standard deviation score -0.25 vs + 0.16; p = 0.003). These associations were not found in males. Mean body mass index (BMI) was significantly increased in both females (22.2 +/- 2.9 kg m-2) and males (20.8 +/- 2.7 kg m-2) with AER greater than 20 to 150 micrograms min-1, compared with diabetic patients with AER less than or equal to 20 micrograms min-1 (females 20.8 +/- 3.0 kg m-2, p = 0.02; males 19.7 +/- 2.4 kg m-2, p less than 0.006).(ABSTRACT TRUNCATED AT 400 WORDS)     

The relationship between serum LDL-cholesterol, HDL-cholesterol and systolic blood pressure in patients with type 2 diabetes

BACKGROUND: The prevalence of hypertension and lipid disorders is increased in patients with diabetes. The relationship between cholesterol and blood pressure values has not yet been well established in this group of patients. AIM: To assess the correlation between lipid levels and blood pressure values in patients with type 2 diabetes. METHODS: The study group consisted of 122 patients (82 females, 40 males, mean age 63+/-10 years) with type 2 diabetes. The mean duration of diabetes was 7.4+/-5.8 years, and hypertension 3.2+/-4.6 years. In all patients glycosylated haemoglobin (HbA1c) and lipid serum concentrations were assessed. RESULTS: The mean serum LDL-cholesterol was 112+/-37 mg/dl (median: 112 mg/dl) and HDL-cholesterol - 47+/-18 mg/dl (median: 44 mg/dl). A significant inverse correlation between HDL-cholesterol and systolic blood pressure (r=-0.177, p=0.05) as well as a positive correlation between LDL-cholesterol and systolic blood pressure values (r=0.196, p=0.031) were found. CONCLUSION: In patients with type 2 diabetes there is a significant relationship between lipid levels and blood pressure values, which suggests an increased susceptibility to vascular disease associated with LDL-cholesterol in these patients.     

Effects of octreotide on lipoproteins and endothelial function of type 1 (insulin-dependent) diabetic patients

Hypersecretion of growth hormone (GH) is a characteristic feature of Type 1 diabetic patients. In healthy subjects growth hormone is able to induce an increase in endothelial cell proteins such as fibrinogen and von Willebrand factor. Plasma concentrations of such proteins, which are markers of cardiovascular risk, are elevated in diabetic patients with microalbuminuria, suggesting endothelial cell dysfunction. In a randomized prospective study we therefore evaluated the possible effects of 1 year's treatment with a somatostatin analogue, octreotide, on lipoproteins and on endothelial function in Type 1 diabetes mellitus. Seven patients were allocated to treatment with a continuous subcutaneous infusion of 400 micrograms octreotide per day. Seven patients served as a control group. During treatment a decrease in plasma LDL-cholesterol (2.62 (2.17-3.11) (median (range] vs 2.00 (1.89-2.96) mmol l-1, p less than 0.05) and serum apolipoprotein A-I (1.47 (1.25-1.60) vs 1.23 (1.13-1.90) g l-1, p less than 0.05) was observed in the treated group. Furthermore a probable reduction during treatment in plasma concentrations of von Willebrand factor (1.72 (0.84-3.04) vs 1.24 (0.94-1.82) U ml-1, p = 0.08) and fibrinogen (11.3 (7.3-25.3) vs 8.1 (7.5-11.8) mumol l-1, p = 0.06) was found, and after withdrawal of treatment an increase towards the initial levels was seen. The platelet count declined (326 (301-612) vs 217 (206-400) x 10(9) l-1, p less than 0.01) during octreotide treatment and remained depressed 2 months after withdrawal.     

A randomized cross-over study of the effects of proinsulin on lipid metabolism in type 2 diabetes

The effects of human proinsulin and insulin on lipid metabolism in Type 2 diabetes were examined in a randomized cross-over study in 15 patients. Blood glucose control was indistinguishable at the end of the two treatment periods, but fasting levels of triglycerides appeared somewhat lower after proinsulin (1.17(SE 0.16) vs 1.39(0.21) mmol I-1; p less than 0.07), and the maximal postprandial triglyceride response (2.19 (0.25) vs 2.87(0.28) mmol I-1, p less than 0.001) and triglyceride area under the curve (p less than 0.01) were significantly reduced. In five hyperlipidaemic patients postprandial triglyceridaemia was reduced with proinsulin (2.89(0.60) vs 3.68(0.56); p less than 0.001), but in addition fasting serum triglycerides (1.20(0.30) vs 1.96(0.30) mmol I-1, p less than 0.04) and possibly VLDL-cholesterol (0.49(0.15) vs 0.60(0.20) mmol I-1; p less than 0.10) were lower and fasting LDL-cholesterol levels higher (4.82(0.42) vs 3.92(0.57) mmol I-1, p less than 0.03) after proinsulin therapy. Proinsulin appears to preferentially suppress the production of triglyceride-rich lipoproteins in Type 2 diabetes, particularly postprandially, and may enhance their clearance and conversion to LDL, especially in hyperlipidaemic Type 2 diabetes.     

Lipoprotein lipids and apolipoproteins (AI, AII, B, CII, CIII) in type 1 and type 2 diabetes mellitus in young Kuwaiti women.

Plasma lipid and apolipoprotein levels of Type 1 and Type 2 young Kuwaiti diabetic women on insulin therapy were investigated to elucidate the relationship between coronary artery disease risk factors and lipid levels. Forty Type 1 and 52 Type 2 diabetic women and 45 and 62 corresponding control subjects (matched for age and body mass index) were investigated. In comparison with control subjects, both groups of diabetic patients showed marked increases in total-cholesterol, LDL-cholesterol, triglycerides, very low density triglycerides, apolipoprotein B, glucose, fructosamine, and glycosylated haemoglobin HbA1c (all p less than 0.001). However, apolipoprotein CIII was significantly elevated in Type 2 diabetic patients (p less than 0.001) but not in Type 1 patients. Concentrations of apolipoproteins CII and AII in both diabetic groups were not significantly different from those in control subjects. Levels of HDL-, HDL2- and HDL3-cholesterol and plasma apolipoprotein AI were markedly decreased in both the diabetic groups compared with their control groups (all p less than 0.001 except HDL3-cholesterol in Type 1 diabetic vs control, p less than 0.05). In Type 2 diabetic patients, HbA1c correlated positively with triglycerides (r = 0.70, p less than 0.001), cholesterol (r = 0.60, p less than 0.001), apolipoprotein B (r = 0.77, p less than 0.001), and apolipoprotein CIII (r = 0.55, p less than 0.001) and negatively with apolipoprotein AI (r = -0.49, p less than 0.001). In Type 1 diabetic patients HbA1c correlated positively only with apolipoprotein CIII (r = 0.50, p less than 0.001).     

Microalbuminuria and risk factors in type 1 and type 2 diabetic patients

A prospective study of normoalbuminuric diabetic patients was performed between 1997 and 2002 on 4097 type 1 and 6513 type 2 diabetic patients from the Swedish National Diabetes Register (NDR); mean study period, 4.6 years. The strongest independent baseline risk factors for the development of microalbuminuria (20-200 microg/min) were elevated HbA(1c) and diabetes duration in both types 1 and 2 diabetic patients. Other risk factors were high BMI, elevated systolic and diastolic BP in type 2 patients, and antihypertensive therapy in type 1 patients. A subsequent larger cross-sectional study in 2002 showed that established microalbuminuria was independently associated with HbA(1c), diabetes duration, systolic BP, BMI, smoking and triglycerides in types 1 and 2 diabetic patients, and also with HDL-cholesterol in type 2 patients. Relatively few types 1 and 2 patients with microalbuminuria achieved treatment targets of HbA(1c) < 6.5% (21-48%), BP < 130/85 mmHg (33-13%), cholesterol < 5 mmol/l (48-46%), triglycerides < 1.7 mmol/l (83-48%) and BMI < 25 kg/m(2) (50-18%), respectively. In conclusion, high HbA(1c), BP and BMI were independent risk factors for the development of microalbuminuria in types 1 and 2 diabetic patients. These risk factors as well as triglycerides, HDL-cholesterol and smoking were independently associated with established microalbuminuria. Treatment targets were achieved by a relatively few patients with microalbuminuria.     

Plasma lipids and urinary albumin excretion rate in Type 1 diabetes mellitus: the EURODIAB IDDM Complications Study.

AIMS: To examine the relationship between increased urinary albumin excretion rate and fasting plasma lipids among male and female respondents to the EURODIAB IDDM Complications Study, and attempt to explain inconsistencies in previous reports. METHODS: A cross-sectional study of 3250 randomly selected Type 1 diabetic patients from 31 diabetes clinics in 16 European countries was carried out between 1989 and 1990. Plasma lipids and urinary albumin were measured centrally. The present analysis was confined to the subgroup of 2205 patients attending after a 10-12 h overnight fast. Mean age was 33 years (SD 10) and mean duration of Type 1 diabetes mellitus was 15 years (SD 9). RESULTS: The prevalence of microalbuminuria (24-h urinary albumin excretion rate 20-200 microg/min) was 21.7% (95% confidence interval 19.9-23.5) and macroalbuminuria (24-h urinary albumin excretion rate > 200 microg/min) 7.8% (6.6-9.0). In comparison to patients with normal urinary albumin excretion rate (< 20 microg/min), and after controlling for age, sex, glycaemic control, duration of diabetes and current smoking, macroalbuminuria was associated with significantly (P<0.01) increased fasting plasma triglycerides, cholesterol, LDL-cholesterol, cholesterol:HDL-cholesterol ratio and, in women, reduced HDL-cholesterol. In men and women with microalbuminuria, the only significant association was with increased plasma triglycerides. CONCLUSIONS: These data confirm that there is an association between fasting plasma lipids and increasing urinary albumin excretion rate in European Type 1 diabetic patients. In microalbuminuric patients, however, the association was weaker than previously reported and partly explained by confounding factors.     

Hormonal replacement therapy and lipid metabolism in women on hemodialysis with secondary to uremia estrogen deficiency

It has been reported that postmenopausal women taking hormonal replacement therapy (HRT) are at reduced risk for cardiovascular disease mainly because of favorable changes in serum LDL- and HDL-cholesterol. However, the therapy is also known to increase hepatic triglyceride production. Cardiovascular events are the leading cause of death in patients on dialysis and lipid abnormalities are common. The aim of the study was to evaluate the influence of HRT on lipid metabolism in premenopausal women undergoing hemodialysis with premature oestrogen withdrawal. 25 hemodialyzed women, aged 37 +/- 9 years (19-44 years) with serum 17 beta-estradiol < 30 pg/ml were divided into: group I (n = 13) treated with transdermal HRT (estradiol with cyclic norethisterone acetate--Estracomb TTS 50/0.25; Novartis), and control group II (n = 12). Before the treatment serum LDL-cholesterol concentrations were increased in 24% and serum triglycerides in 40% of patients, whereas HDL-cholesterol was decreased in 72% of patients. During one year, in group I a noticeable, 15% increase in serum HDL-cholesterol was observed from 0.90 +/- 0.23 to 1.04 +/- 0.19 mmol/l (34.8 +/- 8.8 to 39.8 +/- 7.4 mg/100 ml; p < 0.01). It was parallel to the increase in serum 17 beta-estradiol concentrations (from 20.5 +/- 8.91 to 50.3 +/- 17.20 pg/ml; p < 0.01). Serum LDL-cholesterol and triglycerides did not change significantly. In the control group all those values remained unchanged. CONCLUSIONS: In hemodialysis women with premature estrogen deficiency the transdermal cyclic HRT leads to the clinically important increase in serum HDL-cholesterol without significant changes in serum triglyceride concentrations and could be beneficial in reducing cardiovascular risk in this population.     

Changes in carbohydrate metabolism in association with glipizide treatment of type 2 diabetes

Nineteen patients with Type 2 diabetes were treated with glipizide for 2.5-6 months, and measurements made of metabolic variables before and after glipizide treatment. For purposes of analysis, the glipizide associated decrease in fasting plasma glucose concentration was used to divide patients into 'good' responders (decrease of 4.0 mmol l-1 or more, n = 9) or 'fair' responders (decrease of 3.0 mmol l-1 or less, n = 10). Good responders had a significantly greater fall in their mean (+/- SE) hourly plasma glucose (6.3 +/- 0.6 vs 2.7 +/- 0.3 mmol l-1, p less than 0.001) and NEFA (164 +/- 40 vs 60 +/- 37 mumol l-1, p less than 0.05) concentrations from 0800 to 1600 h in response to meals (0800 and 1200 h) than did the fair responders. However, the increase in hourly plasma insulin concentration following glipizide treatment was the same in the good (323 +/- 103 to 413 +/- 124 pmol l-1) and fair (276 +/- 42 to 345 +/- 43 pmol l-1) responders.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of simvastatin on LDL-subtypes in patients with heterozygous familial hypercholesterolemia and in patients with diabetes mellitus and mixed hyperlipoproteinemia.

This study evaluates the influence of simvastatin on lipid concentrations and on LDL-subtype distribution in patients with heterozygous familial hypercholesterolemia and in patients with type 2 diabetes and mixed hyperlipoproteinemia. Nine patients with familial hypercholesterolemia (LDL-cholesterol: 7.1 +/- 1.1 mmol/L, triglycerides: 1.3 +/- 0.4 mmol/L) and 8 patients with type 2 diabetes mellitus and mixed hyperlipoproteinemia (HbA1c 6.8 +/- 1.1%, LDL-cholesterol: 4.8 +/- 0.7 mmol/L, triglycerides: 2.5 +/- 1.1 mmol/L) were examined. Cholesterol concentration was determined in 7 LDL-subfractions isolated by density gradient ultracentrifugation before and during simvastatin treatment (10-20 mg/d, 4 weeks). Simvastatin decreased LDL-cholesterol (-34%/-30%, all p < 0.05) and triglycerides (-2%, n.s./-25%, p < 0.05), but had little effect on HDL-cholesterol (+7%/+2%, n.s.) in patients with familial hypercholesterolemia and diabetes mellitus, respectively. In both groups a significant reduction of cholesterol in each LDL-subfraction was observed. Large-buoyant (LDL-1, LDL-2) and intermediate-dense (LDL-3, LDL-4) LDL were reduced more than small-dense (LDL-5-LDL-7) LDL-subtypes (-36%/-38%/-23%, respectively) in patients with familial hypercholesterolemia, while in diabetic patients cholesterol reduction was uniform in all LDL-subtypes (-29%/-27%/-31%, respectively). Simvastatin decreases cholesterol concentration in all LDL-subfractions in patients with familial hypercholesterolemia and in patients with diabetes mellitus with mixed hyperlipoproteinemia. However, the relative reduction of individual LDL-subtypes differed between both groups. This suggests that the effect of simvastatin on LDL-subtype distribution depends on the type of underlying hyperlipoproteinemia.     

Can Life-styles of Subjects With Impaired Glucose Tolerance Be Changed? A Feasibility Study

Thirty-one subjects with impaired glucose tolerance were randomly allocated to a group receiving advice to improve their diet and physical activity levels over 6 months (n = 23) or to a control group (n = 8). At 6 months, 18 of the 23 subjects receiving 'healthy living' advice were re-examined (five subjects had withdrawn). Fourteen of the 18 subjects showed an alteration in diet or an increase in exercise. The 18 subjects re-evaluated showed a reduction in systolic blood pressure (118 +/- 15 vs 124 +/- 15 mmHg, p less than 0.05) and decrease in total plasma cholesterol (4.5 +/- 1 vs 5.2 +/- 1 mmol l-1, p less than 0.01) and LDL-cholesterol levels (2.8 +/- 0.9 vs 3.2 +/- 0.9 mmol l-1, p less than 0.05). Plasma glucose levels were unchanged. One subject withdrew from the control group. At 6 months, the seven control subjects examined showed no significant change in metabolic parameters, with little measurable change in diet or exercise. At 2 years, 17 of the 23 'healthy living' subjects were reassessed. Nine of the subjects had continued to exercise or maintained a decreased weight compared to baseline. Fasting plasma glucose levels had increased (6.0 +/- 1.2 vs 5.5 +/- 0.6 mmol l-1, p less than 0.05), with the only continued improvement being a reduced LDL level (2.8 +/- 0.7 vs 3.1 +/- 0.9 mmol l-1, p less than 0.05). At 2 years, a similar proportion of the control group were taking regular exercise compared with the 'healthy living' group.(ABSTRACT TRUNCATED AT 250 WORDS)