Serum lipids and lipoproteins in newly diagnosed non-insulin-dependent (type II) diabetic patients, with special reference to factors influencing HDL-cholesterol and triglyceride levels.

Serum and lipoprotein lipids were examined in 133 newly diagnosed (type II) diabetic patients (70 men, 63 women), aged 45-64 yr, and in 144 randomly selected nondiabetic control subjects of similar age (62 men, 82 women). The serum total cholesterol levels in diabetic and nondiabetic subjects were similar, but the HDL-cholesterol levels were lower and the serum total triglyceride levels higher in the diabetic than in nondiabetic subjects. No significant differences were found in apoprotein A-I and A-II levels between the diabetic and nondiabetic subjects. After adjustment for age, alcohol intake, obesity, 2-h postglucose serum insulin, and serum triglycerides, male diabetic subjects still had lower HDL-cholesterol levels than corresponding nondiabetic subjects. On the other hand, female diabetic subjects had higher serum triglycerides than their nondiabetic counterparts, even after adjustment for age, alcohol intake, 2-h postglucose serum insulin, and obesity.

Effects of bezafibrate on insulin sensitivity and glucose tolerance in subjects with combined hyperlipidemia.

To investigate whether the lowering of triglyceride levels has beneficial effects on glucose metabolism, we studied 13 nondiabetic men with combined hyperlipidemia (phenotype IIB) before and after 2 months of treatment with a slow-release formulation of bezafibrate (400 mg daily). The rates of whole body glucose disposal were quantitated by the euglycemic hyperinsulinemic clamp technique (insulin infusion rate of 80 mU/m2/min). In an oral glucose tolerance test, fasting glucose level decreased slightly (5.0 +/- 0.2 versus 4.8 +/- 0.2 mmol/L; p < 0.05) during bezafibrate treatment. Glucose and insulin levels after an oral glucose load remained unchanged. Rates of whole body glucose disposal did not change during bezafibrate treatment (39.5 +/- 3.3 mumol/kg/min before treatment versus 40.6 +/- 2.7 mumol/kg/min after treatment; difference not significant). Basal hepatic glucose output also remained unchanged (8.2 +/- 0.2 mumol/kg/min before treatment versus 8.3 +/- 0.2 mumol/kg/min after treatment; difference not significant). Our findings show that bezafibrate has a triglyceride-lowering effect without any significant influence on insulin sensitivity.

Lack of effect of hepatic enzyme induction on metabolic control in patients with type 2 (non-insulin-dependent) diabetes.

A placebo-controlled, double-blind crossover study was carried out in 11 non-insulin-dependent (type 2) diabetic patients to find out the effects of a hepatic enzyme inducer (phenobarbital, 100 mg/day for 2 months) on the metabolic control, plasma C-peptide, insulin, serum, and lipoprotein lipid levels. Phenobarbital induced a significant increase in hepatic antipyrine metabolizing activity, but no significant changes were found in fasting or postload blood glucose, plasma C-peptide, or insulin levels during the study. There was a significant increase in serum total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, as well as in serum total and very low-density lipoprotein triglycerides, during phenobarbital treatment as compared with placebo.

Effects of guar gum in male subjects with hypercholesterolemia.

Fourteen male subjects with hypercholesterolemia received daily supplementation with granulated guar gum or placebo, 15 g/day, during 12 wk in a double-blind, cross-over trial. A statistically significant reduction in serum total cholesterol (7.27 +/- 0.24 versus 8.23 +/- 0.26 mmol/l, mean +/- SEM, p less than 0.01) which was mainly due to a reduction in low-density lipoprotein cholesterol concentration (4.70 +/- 0.19 versus 5.32 +/- 0.23 mmol/l, p less than 0.05) was observed after 6 wk on guar gum as compared with placebo. Between 6 and 12 wk on guar gum the serum cholesterol and low-density lipoprotein cholesterol levels increased in most subjects, and after 12 wk the difference from placebo was no longer statistically significant. Serum high-density lipoprotein cholesterol levels were unaffected by guar gum. Serum and lipoprotein triglycerides showed no significant changes during the study, and the body weight of the subjects remained unchanged. Serum calcium, magnesium, phosphate, and iron levels, and urinary calcium excretion were not affected by guar gum supplementation. No severe side effects were observed, necessitating reduction of the dose or stopping the treatment. It is concluded that the hypocholesterolemic effect of guar gum seems to decrease during prolonged dietary supplementation. Further controlled studies are needed before the dose response and the long-term effects of guar gum in hypercholesterolemia can be evaluated.

Effect of inorganic chromium supplementation on glucose tolerance, insulin response, and serum lipids in noninsulin-dependent diabetics.

A placebo-controlled double-blind cross-over study was carried out to assess the effect of chromium supplementation (200 micrograms trivalent chromium daily for 6 wk) on glucose tolerance, insulin response, long-term diabetic control, and serum lipids in 10 noninsulin-dependent diabetics aged 37 to 68 yr. After chromium supplementation 24-h urinary chromium excretion showed a 9-fold increase indicating a positive chromium balance in the subjects. There was no significant difference between chromium supplementation and placebo periods in glucose tolerance and in fasting or 2-h postglucose serum insulin levels but the 1-h postglucose serum insulin level was slightly lower on chromium supplementation than on the placebo (55 +/- 9.0 versus 64 +/- 11; p less than 0.01, paired t test). Serum total cholesterol and triglycerides and their high-density, low-density, and very low-density lipoprotein subfractions showed no change after chromium supplementation as compared to the placebo period.

Familial aggregation of non-insulin dependent diabetes and coronary heart disease are accompanied by different effects on serum lipids, lipoproteins and apolipoproteins.

This study was designed to investigate whether the presence of non-insulin-dependent diabetes mellitus (NIDDM) or coronary heart disease (CHD) in probands have different effects on serum lipid, lipoprotein and apolipoprotein concentrations in the first-degree relatives. Altogether 161 probands (114 men, 47 women) and 788 first-degree relatives of these probands (174 brothers, 246 sisters, 180 sons, 188 daughters) were included in the analyses. The presence of NIDDM in the proband was associated with lowered total, LDL and HDL cholesterol and apolipoprotein A1 and elevated total triglyceride levels in the brothers (P less than 0.05) and elevated total and LDL cholesterol levels in the sisters (P less than 0.05). Total LDL and VLDL cholesterol and apolipoprotein B were higher (P less than 0.05) and HDL/total cholesterol ratio and apolipoprotein A1/B ratio lower (P less than 0.05) in the daughters of the nondiabetic and diabetic probands were pooled, CHD in the proband was associated particularly with low apolipoprotein A1/B ratio. In conclusion, (1) the presence of NIDDM in the proband appears to be associated in siblings with more profound lipid and lipoprotein changes (especially low HDL cholesterol and high total triglycerides) than a history of CHD in the proband, (2) a history of CHD in the proband is associated in children with apolipoprotein changes favouring atherosclerosis (low apolipoprotein A1, high apolipoprotein B, low apolipoprotein A1/B ratio). Different effects of a history of NIDDM and CHD in the proband on lipid, lipoprotein and apolipoprotein levels in the first-degree relatives warrants more population-based studies.

Serum lipoprotein lipid and apoprotein levels as indicators of the severity of angiographically assessed coronary artery disease.

Serum lipoprotein cholesterol and triglycerides and apoproteins A-I, A-II and B were determined in 71 consecutive male subjects undergoing coronary angiography because of severe angina pectoris. Among the factors studied, apoprotein B, apoprotein B/A-I ratio, VLDL- and LDL cholesterol showed the most consistent association with the severity of coronary artery disease as assessed by angiography whereas serum HDL cholesterol and apoproteins A-I and A-II showed no correlation. Subjects with stenosis of the left main coronary artery had higher serum HDL cholesterol and apoprotein A-I and B levels than the others. In this series which comprised males with severe angina pectoris, derived from a population with high prevalence of coronary heart disease, LDL was the best indicator of the severity of coronary artery disease.

Serum lipids and lipoproteins in middle-aged non-insulin-dependent diabetics.

Serum lipids and lipoproteins were measured in 277 non-insulin-dependent diabetics (NIDDs) and in 124 non-diabetic control subjects (65 males, 59 females), aged 45-64 years. Altogether 88 of the diabetics were treated with diet (48 males, 40 females), 134 with oral drugs (56 males and 49 females treated with sulphonylureas, 14 males and 15 females treated with a combination therapy of sulphonylurea drug and metformin) and 55 with insulin (17 males, 38 females). The postglucagon C-peptide concentration in insulin-treated diabetics exceeded 0.60 nmol/l. The diabetics had lower levels of HDL and HDL2 cholesterol and higher levels of total and VLDL triglycerides than non-diabetic control subjects irrespective of the mode of treatment. The HDL2 subfraction seemed to be alone responsible for the decrease of HDL cholesterol. In the whole group of diabetics body mass index had a significant negative correlation to HDL cholesterol and a positive correlation to total triglyceride concentration in both sexes but plasma glucose failed to show any consistent association to HDL cholesterol concentration. The difference in HDL cholesterol between diabetics and non-diabetics persisted after adjustment for age, physical activity, alcohol intake and body mass index. In conclusion, the dyslipoproteinaemia in non-insulin-dependent diabetes is principally characterized by decreased HDL and HDL2 cholesterol concentrations and by increased total and VLDL triglycerides. These manifestations of dyslipoproteinaemia are little influenced by the degree of glycaemia and obesity.

Inverse relationship of serum HDL and HDL2 cholesterol to C-peptide level in middle-aged insulin-treated diabetics.

Serum lipids and lipoproteins were measured in 170 insulin-treated diabetics (90 females, 80 males) and in 124 nondiabetic control subjects (59 females, 65 males) aged 45 to 64 years. Plasma C-peptide response to intravenous (IV) glucagon was measured in order to classify the patients according to their capacity of endogenous insulin secretion. In both sexes, HDL and HDL2 cholesterol were higher in diabetics with no C-peptide response than in controls, whereas diabetics with high C-peptide response (postglucagon C-peptide level greater than 0.60 nmol/L) showed lower levels of HDL and HDL2 than nondiabetic controls. When adjustment for age, alcohol consumption, physical activity, body mass index, and insulin dose was made by analysis of covariance, the highly significant difference in HDL and HDL2 cholesterol level between diabetics with no C-peptide response and diabetics with high C-peptide response still remained in both sexes. This study gives support to the hypothesis that elevated HDL and HDL2 cholesterol levels in insulin-treated diabetics are not explained by effects of treatment with exogenous insulin, but rather are associated with the type of diabetes characterized by deficient endogenous insulin secretion.

Measuring social class differences in cancer patient survival: is it necessary to control for social class differences in general population mortality? A Finnish population-based study.

STUDY OBJECTIVES: Estimation of cancer patient survival by social class has been performed using observed, corrected (cause specific), and relative (with expected survival based on the national population) survival rates. Each of these measures are potentially biased and the optimal method is to calculate relative survival rates using social class specific death rates to estimate expected survival. This study determined the degree to which the choice of survival measure affects the estimation of social class differences in cancer patient survival. SETTING AND PARTICIPANTS: All Finnish residents diagnosed with at least one of 10 common malignant neoplasms during the period 1977-1985 were identified from the Finnish Cancer Registry and followed up for deaths to the end of 1992. DESIGN: Survival rates were calculated by site, sex, and age at 5, 10, and 15 years subsequent to diagnosis for each of three measures of survival; relative survival, corrected (cause specific) survival, and relative survival adjusted for social class differences in general mortality. Regression models were fitted to each set of rates for the first five years of follow up. MAIN RESULTS: The degree of variation in relative survival resulting from social class decreased, although did not disappear, after controlling for social class differences in general mortality. The results obtained using corrected survival were close to those obtained using relative survival with a social class correction. The differences between the three measures were largest when the proportion of deaths from other causes was large, for example, in cancers with high survival, among older patients, and for longer follow up times. CONCLUSIONS: Although each of the three measures gave comparable results, it is recommended that relative survival rates are used with expected survival adjusted for social class when studying social class variation in cancer patient survival. If this is not an available option, it is recommended that corrected survival rates are used. Relative survival rates without the social class correction overestimate social class differences and should be used with caution.

Relationship of branched-chain alpha-keto-acids and lipids in sera of hypertriglyceridemic subjects.

According to the present study, in hyperlipidemias where triglyceride values in serum are raised, the triglyceride values are associated with increased amounts of branched-chain alpha-keto-acids (BCKA) in the serum. In particular, the concentration of alpha-ketoisocaproic acid (KICA), which in the control sera was 34.4 mumol/l, was in type IIB hyperlipidemia 40.4% and in type IV 49.4% higher than in controls with normal serum lipid values. In type IV hyperlipidemia, values for alpha-ketoisovaleric acid (KIVA) and alpha-keto-beta-methyl-n-valeric acid (KMVA) were also high when compared to the corresponding mean values of the controls, 7.1 and 18.8 mumol/l. The respective differences were 57.7 and 44.1 per cent. In type IIB hyperlipidemia, KIVA was significantly and KMVA insignificantly increased compared to the control group. In type IIA hyperlipidemia with normal triglyceride values, none of the three BCKA differed significantly from the controls. These results also indicate that the increased amounts of individual BCKA somehow depend on the concentration of triglycerides in serum, while no relationship was found between BCKA values and cholesterol concentration.

Body mass index and physical fitness as determinants of serum lipoprotein levels in middle-aged men.

The aim of the present study was to analyse to what extent serum lipoproteins are determined by overweight and physical fitness. Fifty-eight middle-aged males were divided into lean, overweight and obese subgroups according to their body mass indices, which characterization was also well in accordance with two skinfold thicknesses. Maximal oxygen consumption per body weight was lowest in the obese. HDL cholesterol was decreased in the obese compared to the lean. HDL cholesterol correlated separately significantly with maximal oxygen consumption and body mass index when all the three groups were combined. Physical fitness was a less dominant determinant of HDL cholesterol than body mass index. The importance of physical fitness as a determinant of HDL cholesterol was less marked in the obese than in the lean and overweight suggesting a need for certain level of physical activity before it can influence serum lipoprotein levels.

Association of low HDL and HDL2 cholesterol with coronary heart disease in noninsulin-dependent diabetics.

Lipids and lipoproteins were measured in 139 men and 145 women who were noninsulin-dependent diabetics (NIDDs) aged 45 to 64 years. Of these, 27 men and 16 women had had a previous definite myocardial infarction (MI). The NIDDs with MI (MI+) showed lower values of HDL and HDL2 cholesterol concentrations than NIDDs without previous MI (MI-) or NIDDS without any symptoms or electrocardiographic signs of coronary heart disease (CHD-). The inverse relationship between HDL, HDL2, and CHD was evident in both sexes, but it was particularly strong among male NIDDs. The difference in HDL and HDL2 cholesterol concentrations between the MI+ and MI- groups or between the MI+ and CHD- groups persisted after adjustment by analysis of covariance for the effect of physical activity, alcohol intake, obesity, duration of diabetes, and glycemic control. It is concluded that in a cross-sectional study, even among NIDDs with generally low HDL and HDL2 cholesterol concentrations, the presence of CHD is associated with a further depression of HDL and HDL2 cholesterol levels. Prospective studies are needed, however, to confirm that the association is predictive and not a consequence of CHD.

Plasma insulin and serum lipids and lipoproteins in middle-aged non-insulin-dependent diabetic and non-diabetic subjects.

The relationship between fasting plasma insulin and serum lipid and lipoprotein levels was studied in 1982-1983 in Kuopio, East Finland in 225 patients with non-insulin-dependent diabetes mellitus (119 men and 106 women) and 124 non-diabetic controls (65 men and 59 women). Compared to the non-diabetic controls, diabetic subjects showed significantly lower levels of high density lipoprotein (HDL) cholesterol and high density lipoprotein2 (HDL2) cholesterol and higher levels of total triglycerides and very low density lipoprotein (VLDL) triglycerides. Fasting plasma insulin correlated significantly with total triglycerides and VLDL triglycerides and negatively with HDL cholesterol and HDL2 cholesterol in both male and female diabetic subjects and non-diabetic control subjects. The correlation between fasting plasma insulin and HDL cholesterol remained statistically significant in non-insulin-dependent diabetic subjects and in female non-diabetic control subjects after adjustment for body mass index, alcohol intake, physical activity, smoking, and fasting plasma glucose. The correlation between fasting plasma insulin and total triglycerides remained significant after adjustment for these variables only in females. By multiple stepwise linear regression analysis, fasting plasma insulin had an independent association with HDL cholesterol in female non-diabetic control subjects and in male diabetic subjects and with triglycerides in female non-diabetic control subjects and in female diabetic subjects. The results show that hyperinsulinemia is related to low HDL cholesterol and HDL2 cholesterol and high total triglycerides and VLDL triglycerides in both non-insulin-dependent diabetic subjects and non-diabetic control subjects. This effect of hyperinsulinemia on lipid and lipoprotein patterns may be one explanation why high plasma insulin can promote accelerated atherosclerosis, particularly in patients with non-insulin-dependent diabetes mellitus.

Lipid and lipoprotein abnormalities associated with coronary heart disease in patients with insulin-dependent diabetes mellitus.

We measured serum lipid and lipoprotein levels in 63 insulin-dependent diabetic (IDD) patients (32 men, 31 women) and in 63 nondiabetic control subjects (32 men, 31 women) without coronary heart disease (CHD) and in 19 IDD patients (11 men, 8 women) and in 18 nondiabetic subjects (8 men, 10 women) with CHD. All diabetic patients had postglucagon C-peptide levels of less than 0.60 mmol/liter and none had signs of renal failure. Male IDD patients with CHD had higher levels of total cholesterol, low density lipoprotein (LDL) cholesterol, total triglycerides, very low density lipoprotein (VLDL) triglycerides and lower level of high density lipoprotein (HDL) cholesterol than male IDD patients without CHD. In female IDD patients, similar lipid and lipoprotein abnormalities were observed between the groups of diabetics with and without CHD except for total cholesterol, which was the same in both groups. A comparison between IDD patients without CHD and nondiabetic control subjects without CHD showed no difference in lipid and lipoprotein levels in males; female IDD patients without CHD showed even higher levels of HDL and HDL2 cholesterol and lower levels of VLDL triglycerides than nondiabetic controls. Our results indicate that in IDD patients without nephropathy and CHD, the lipid and lipoprotein levels do not differ from nondiabetic controls, but in IDD patients with CHD the lipid and lipoprotein pattern is similar to that known to be characteristic for nondiabetic patients with CHD.

Physical training of middle-aged men with borderline hypertension.

The aim of the study was to clarify the feasibility of physical training for middle-aged borderline-hypertensive males. Blood pressure of 59 subjects was followed for nine months, whereafter 25 persons were classified as borderline-hypertensive and 34 persons as normotensive. Both groups were randomly allocated into training and control groups. Training lasted for four months, of which the first two included supervised bicycle ergometer exercise. During the last two months training was unsupervised. After training estimated maximal oxygen consumption increased significantly both in borderline-hypertensive and normotensive men. After training resting diastolic blood pressure decreased significantly both in training and control groups. This finding supports the importance of sufficiently long follow-up of blood pressure before eventual drug therapy when blood pressure is mildly elevated. Diastolic blood pressure during 50-minute ergometer exercise was decreased after four months of training in borderline-hypertensives and did not any longer differ from that of normotensives. Individually prescribed physical training is worth regarding as one treatment modality for middle-aged borderline-hypertensive patients.

Comparison of different analytical and precipitation methods for direct estimation of serum high-density lipoprotein cholesterol.

In this study two commercial enzymatic methods for the determination of serum cholesterol have been adapted for a continuous-flow analyser and a discrete multichannel analyser. The selective precipitation methods for lipoproteins using either dextran sulphate/MgCl2, heparin/MnCl2, phosphotungstate/MgCl2 or polyethylene glycol (mol. wt 6000) were compared with each other and with ultracentrifugal analysis as well as with agarose gel electrophoresis for lipoproteins. The results indicated that the dextran sulphate/MgCl2 precipitation procedure was the method of choice for the determination of HDL-cholesterol from clear and hyperlipemic sera. HDL-cholesterol values for 391 apparently health women (X +/- SD) were 1.58 +/- 0.34 mmol/l and for 432 men 1.27 +/- 0.29 mmol/L. The corresponding HDL-cholesterol/cholesterol ratios for women were 0.292 +/- 0.068 and for men 0.229 +/- 0.069. The HDL-cholesterol in serum was slightly age dependent in women, while the HDL-cholesterol/cholesterol ratio showed highly significant negative correlation with the age in both women and men.

Obese men with type IIB hyperlipidemia are insulin resistant.

By using the euglycemic clamp technique and indirect calorimetry, we determined the degree of insulin resistance in 12 obese (body mass index > 27.0 kg/m2), normotensive patients with type IIB hyperlipidemia (HLIIB) (total cholesterol > or = 6.5 mmol/L and total triglycerides > or = 2.0 mmol/L) and 17 control subjects (total cholesterol < or = 6.1 mmol/L and total triglycerides < 1.8 mmol/L) who were carefully matched for sex, age, and obesity. Fasting plasma insulin was higher in HLIIB patients than in control subjects (18.4 +/- 4.6 versus 8.9 +/- 1.2 mU/L, respectively; P = .010). The rates of whole-body glucose uptake were significantly lower in HLIIB patients than in control subjects during the last hour of the clamp (42.2 +/- 3.9 versus 54.6 +/- 2.8 mumol/kg per minute, respectively; P = .013). Glucose oxidation during the last 30 minutes of the euglycemic clamp was lower in HLIIB patients than in control subjects (14.6 +/- 0.9 versus 19.0 +/- 1.3 mumol/kg per minute, respectively; P = .017). Nonoxidative glucose disposal during the last 30 minutes of the euglycemic clamp was also lower in HLIIB patients than in control subjects, but the difference was not statistically significant (27.6 +/- 3.3 versus 35.8 +/- 2.8 mumol/kg per minute, respectively; P = .069). Lipid oxidation during the clamp was completely suppressed in control subjects (-0.24 +/- 0.44 mumol/kg per minute) but was significantly less suppressed in the HLIIB patients (0.94 +/- 0.29 mumol/kg per minute, P = .024).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance in familial and nonfamilial hypercholesterolemia.

High levels of very low density lipoprotein triglycerides and low levels of high density lipoprotein cholesterol have been found to be associated with insulin resistance measured by the euglycemic clamp technique. In contrast, the association of isolated hypercholesterolemia with insulin resistance has not been systematically studied. Therefore, we performed two separate studies designed to investigate the degree of insulin resistance in familial hypercholesterolemia (FH) (study 1) and nonfamilial hypercholesterolemia (non-FH) (study 2). Study 1 included eight young adults with FH and 13 corresponding control subjects. Fasting blood glucose, insulin, and C-peptide levels were similar in FH patients and control subjects during an oral glucose tolerance test. During the euglycemic hyperinsulinemic (1,200-1,300 pmol/l) clamp studies, FH patients and control subjects had similar rates of whole-body glucose uptake (73 +/- 6 versus 70 +/- 3 mumol/kg per minute, respectively; p = NS). Glucose oxidation, glucose nonoxidation, lipid oxidation, suppression of free fatty acid levels, and potassium disposal were similar in both groups. Study 2 included 25 middle-aged non-FH patients and 18 corresponding control subjects. Glucose, insulin, and C-peptide responses in an oral glucose tolerance test were similar in both groups. During the euglycemic hyperglycemic clamp studies, non-FH patients and control subjects had similar rates of whole-body glucose uptake (61 +/- 3 versus 58 +/- 3 mumol/kg per minute, p = NS). In addition, glucose oxidation, glucose nonoxidation, lipid oxidation, and suppression of free fatty acid levels as well as potassium disposal were similar in non-FH patients and control subjects. We conclude that FH and non-FH are not insulin-resistant states.