High density lipoprotein and coronary artery disease risk factors in children with different lipoprotein profiles: Bogalusa Heart Study

Serum high density lipoprotein-cholesterol (HDL-C) and apoprotein A-1 (apo A-1) profiles were examined in subgroups of children (n = 338), initially aged 2-14 years, whose earlier beta-lipoprotein cholesterol (beta-LPC) and pre-beta-lipoprotein cholesterol (pre-beta-LPC) measurements were in extreme percentiles of values from a biracial community. Relationships of HDL-C and apo A-1 to serum lipoprotein lipids, apoprotein B (apo B), subscapular skinfold thickness, fasting and 1/2 hr postglucose plasma insulin, and fasting and 1 hr postglucose plasma glucose and free fatty acids were examined. Clustering of several coronary artery disease risk factors in these children was observed. HDL-C levels tended to be low in children having high pre-beta-LPC levels and apo A-1 levels were low in boys having high pre-beta-LPC levels. Within beta- and pre-beta-LPC strata, differences were also observed with respect to race, but not sex, in the mean levels of both HDL-C and apo A-1. HDL-C and apo A.1 were related inversely to subscapular skinfold thickness and plasma insulin levels in all children except those with low levels of both beta-LPC and pre-beta-LPC. Ratios of low density lipoprotein-cholesterol/HDL-C and of apo B/apo A-1 were related positively with other coronary artery disease risk factors except in children having low levels of both beta-LPC and pre-beta-LPC. The magnitude of these associations was greater in whites than in blacks. These observations may help to identify, at an early age, children at high risk of developing coronary artery disease in adulthood.     

Fasting plasma glucose and insulin levels and their relationship to cardiovascular risk factors in children: Bogalusa Heart Study

Plasma glucose and insulin levels were determined in a total biracial community of 3313 children, ages 5-17 years. Black children have significantly higher insulin and lower glucose levels than white children of comparable age and sex. Children of diabetic parents have elevated levels of age- and weight-adjusted fasting cholesterol. Moderate tracking (r = 0.31) of glucose levels over a 3-year period was seen. Insulin levels, however, track well (r = 0.36) only in older children (ages 9-14 years at initial examination). Fasting insulin levels are positively related to measures of obesity, systolic and diastolic blood pressure, triglyceride, beta-lipoprotein cholesterol and pre-beta-lipoprotein cholesterol levels. In addition, insulin levels are negatively related to alpha-lipoprotein cholesterol levels. Fasting glucose levels are positively related to systolic and diastolic blood pressure, triglycerides, pre-beta-lipoprotein cholesterol, and obesity levels. The relationship of plasma glucose and insulin levels to the traditional cardiovascular risk factors in children emphasizes the importance of subtle abnormalities in carbohydrate metabolism in the early natural history of cardiovascular disease.     

Relationship of carbohydrate intolerance to serum lipoprotein profiles in childhood. The Bogalusa Heart Study

Three hundred-eighty-eight children were selected from a total community and biracial (black-white) population for a special in-depth study related to serum lipoproteins and carbohydrate metabolism. Based on two previous serum lipoprotein determinations of high and/or low beta and pre-beta-lipoprotein cholesterol, they were stratified into four groups. A glucose tolerance test was performed for fasting, 30-minute, and one-hour glucose, insulin, free fatty acids, calcium, and magnesium. Observations of height, weight, and triceps skinfold were also obtained on the children. Children in the high beta-lipoprotein cholesterol groups tended to have higher glucose levels and were more obese than the other groups, while children in the high pre-beta-lipoprotein cholesterol group tended to have high insulin levels following the glucose load. Fasting blood levels were not appreciably different in the various groups, but after the glucose load an unusually high insulin secretory response occurred in black children, especially black girls. Black girls also demonstrated somewhat lower blood sugars than the other race-sex groups. The insulin/glucose ratios were dramatically different in the black children, especially black girls. These differences were particularly noted in the groups with the high pre-beta-lipoprotein. Black children also tended to have higher insulin/free fatty acid ratios during the glucose tolerance test. These differences persisted even after adjusting for obesity. Although not significant, calcium levels consistently decreased in all groups following a glucose load. The observation of racial contrasts in glucose and insulin responses are interesting. While black girls appear to show low glucose and high insulin responses to a glucose load, low and delayed insulin response along with high glucose response occur in whites, especially white girls. Since white children have greater body fat content, these observations suggest more insulin resistance in white children. Even at low levels of obesity, subtle carbohydrate lipid metabolic aberrations are found in children having high levels of serum lipoproteins. A persistence of these conditions could contribute to accelerated atherosclerosis and subsequent coronary artery disease.     

Relationship between lipoprotein levels and in vivo insulin action in normal young white men

In epidemiologic studies, hyperinsulinemia has been found to be an independent risk factor for coronary heart disease (CHD). However, the mechanisms responsible for its role in atherogenesis remain unclear. We studied the relationship of in vivo insulin action and plasma lipids and lipoproteins in 44 normotriglyceridemic white men (aged 18 to 34 years). The euglycemic, hyperinsulinemic glucose clamp technique was used to quantitate insulin-mediated glucose disposal (M/I value) at a plasma insulin concentration of approximately 100 microU/mL. The M/I value correlated negatively with plasma triglycerides (r = -0.553, P less than .0001), as well as with fasting plasma insulin levels (r = -0.483, P less than .001), independent of age, body mass index, and fasting plasma glucose levels. A negative correlation of the M/I value was also observed with very low density lipoprotein (VLDL)-cholesterol (r = -0.347, P less than .05), VLDL-triglycerides (r = -0.474, P less than 0.005), and total cholesterol/high density lipoprotein (HDL)-cholesterol ratio (r = -0.431, P less than .01). The relationship between the M/I value and the total cholesterol/HDL-cholesterol ratio was independent of VLDL-cholesterol and VLDL-triglycerides, however, not independent of plasma triglycerides. No relationship was observed between insulin-mediated glucose uptake and total cholesterol, low density lipoprotein (LDL)-cholesterol, and HDL-cholesterol values. Individual differences in plasma triglycerides, fasting insulin concentration, and the total cholesterol/HDL-cholesterol ratio accounted for about half the variance observed in the M/I value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of plasma free fatty acids on lipoprotein synthesis and diabetic dyslipidemia.

The regulation of hepatic VLDL secretion mainly depends on apolipoprotein (apo) B synthesis, on microsomal triglyceride transfer protein, insulin and the availability of triglycerides, free fatty acids (FFA) and cholesteryl ester. Four sources of fatty acids are used for lipoprotein synthesis: de-novo lipogenesis, cytoplasmic triglyceride stores, fatty acids derived from lipoproteins taken up directly by the liver and plasma FFA. Quantitatively, de-novo lipogenesis plays a minor role in regulating VLDL synthesis, but evidently it is elevated under conditions of high carbohydrate feeding. Cytoplasmic triglyceride stores appear to essentially contribute to VLDL triglycerides. Plasma FFA enter the hepatocytes and are either oxidized or esterified. The relationship between oxidation and esterification appears to be important in regulating the VLDL synthesis. An enhanced esterification is accompanied by increased VLDL secretion. The addition of oleic acid to hepatocytes has been shown to stimulate production of VLDL triglyceride and apoB. In human beings, an acute experimental elevation of plasma FFA stimulates VLDL production. In healthy men strong positive relations were found between the late increases in large triglyceride-rich lipoproteins and plasma FFA concentrations after 6 h following a mixed meal. In contrast, n-3 fatty acids impair VLDL assembly and secretion. Chronic hyperinsulinemia seems to stimulate VLDL production. On the other hand, the short-term addition of insulin has been shown to inhibit VLDL-triglyceride and apoB production in vitro. There is in vivo evidence that acute hyperinsulinemia suppresses VLDL-apoB and VLDL-triglyceride production in insulin-sensitive humans. Part of this action is due to suppression of plasma FFA. In patients with impaired glucose tolerance (IGT), VLDL production was increased when compared with subjects with normal glucose (NGT). When infusing a lipid emulsion, VLDL production could not be further stimulated in IGT patients in contrast to NGT persons. Hypertriglyceridemia in type 2 diabetes mellitus is usually the consequence of a VLDL overproduction. In type 2 diabetic patients, in contrast to normal men, insulin failed to suppress VLDL1 particle release. In normal men, an elevation of blood glucose led to a decrease in fatty acid oxidation and an increase in hepatic triglyceride secretion. Under these conditions, approximately 30% of total VLDL triglycerides coming out of the liver did not originate from plasma FFA. In conclusion, plasma FFA seem to play an important role in stimulating hepatic VLDL production. Other factors such as chronic hyperinsulinemia or nutrition modify this effect.     

The metabolic effects of lopinavir/ritonavir in HIV-negative men

BACKGROUND: Therapy with HIV protease inhibitors (PI) has been shown to worsen glucose and lipid metabolism, but whether these changes are caused by direct drug effects, changes in disease status, or body composition is unclear. Therefore, we tested the effects of the PI combination lopinavir and ritonavir on glucose and lipid metabolism in HIV-negative subjects. METHODS: A dose of 400 mg lopinavir/100 mg ritonavir was given twice a day to 10 HIV-negative men. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance, insulin sensitivity by euglycemic hyperinsulinemic clamp, and body composition were determined before and after lopinavir/ritonavir treatment for 4 weeks. RESULTS: On lopinavir/ritonavir, there was an increase in fasting triglyceride (0.89 +/- 0.15 versus 1.63 +/- 0.36 mmol/l; P = 0.007), free fatty acid (FFA; 0.33 +/- 0.04 versus 0.43 +/- 0.06 mmol/l; P = 0.001), and VLDL cholesterol (15.1 +/- 2.6 versus 20 +/- 3.3 mg/dl; P = 0.05) levels. There were no changes in fasting LDL, HDL, IDL, lipoprotein (a), or total cholesterol levels. Fasting glucose, insulin, and insulin-mediated glucose disposal were unchanged, but on a 2 h oral glucose tolerance test glucose and insulin increased. There were no changes in weight, body fat, or abdominal adipose tissue by computed tomography. CONCLUSION: Treatment with 4 weeks of lopinavir/ritonavir in HIV-negative men causes an increase in triglyceride levels, VLDL cholesterol, and FFA levels. Lopinavir/ritonavir leads to a deterioration in glucose tolerance at 2 h, but there is no significant change in insulin-mediated glucose disposal rate by euglycemic hyperinsulinemic clamp.     

Triglyceride, total cholesterol and lipoprotein fraction cholesterol levels in the blood plasma of elderly and long-lived persons in the Abkhazian SSSR]

The results of examination of 21 males and 30 females of the category of elderly and long-lived persons (81--106 years old) indicate the low content in the blood plasma of total cholesterol (173 mg/100 ml), beta-lipoprotein cholesterol (106 mg/100 ml), pre-beta-lipoprotein cholesterol (18 mg/100 ml), and triglycerides (91 mg/100 ml). The average content of these lipid complexes was lower in males than in females. The low concentration of beta- and pre-beta-lipoprotein cholesterol and the large portion of alpha-lipoprotein cholesterol content in relation to the content of total cholesterol in blood plasma are evidence of a favourable proportion of atherogenous and non-atherogenous classes of lipoproteins in blood plasma of elderly and long-lived persons, which is evidently one of the causes of the lower incidence of ischemic heart disease among them and their high longevity.     

Correlates of plasma very-low-density lipoprotein concentration and composition in premenopausal women

Potential correlates of plasma very-low-density lipoprotein (VLDL) concentration and composition were studied in a sample of 75 premenopausal women. Fasting plasma free fatty acid (FFA) levels, as well as plasma glucose and insulin levels in the fasting state and during an oral glucose tolerance test, displayed significant positive correlations with plasma triglyceride (TG) and VLDL-TG levels (P less than .005). Plasma post-heparin lipoprotein lipase (LPL) activity, measured in a subsample of 31 women from the original sample, was negatively correlated with plasma TG, VLDL-cholesterol (CHOL), VLDL-TG, and VLDL-apolipoprotein (apo) B concentrations (.005 greater than P less than .05). Multivariate analyses showed that, after LPL was considered, the insulin area was the only other metabolic variable studied that was significantly correlated with VLDL-apo B concentration, whereas fasting FFA levels were significantly correlated with plasma TG and VLDL-TG levels. ANOVA revealed that plasma VLDL-CHOL, VLDL-TG, and VLDL-apo B levels were not associated with the glucose area, but were significantly associated with the insulin area (P less than .005). When the effect of insulin area was controlled for, the plasma FFA levels did not contribute significantly to the variance in VLDL-CHOL and VLDL-apo B, but showed an independent effect on VLDL-TG levels (P less than .05). Finally, stepwise multiple regression analyses indicated that once the variance explained by plasma LPL activity and by the insulin area was considered, no other metabolic variable could account for the variation in VLDL-CHOL and VLDL-apo B levels, whereas fasting FFA levels explained a further 5% of the VLDL-TG variance and one third of the variance observed in the VLDL-TG/apo B ratio.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic physiologic hyperinsulinemia impairs suppression of plasma free fatty acids and increases de novo lipogenesis but does not cause dyslipidemia in conscious normal rats

Type 2 diabetes mellitus and obesity are characterized by fasting hyperinsulinemia, insulin resistance with respect to glucose metabolism, elevated plasma free fatty acid (FFA) levels, hypertriglyceridemia, and decreased high-density lipoprotein (HDL) cholesterol. An association between hyperinsulinemia and dyslipidemia has been suggested, but the causality of the relationship remains uncertain. Therefore, we infused eight 12-week-old male catheterized conscious normal rats with insulin (1 mU/min) for 7 days while maintaining euglycemia using a modification of the glucose clamp technique. Control rats (n = 8) received vehicle infusion. Baseline FFAs were 1.07+/-0.13 mmol/L, decreased to 0.57+/-0.10 (P < .05) upon initiation of the insulin infusion, and gradually increased to 0.95+/-0.12 by day 7 (P = NS vbaseline). On day 7 after a 6-hour fast, plasma insulin, glucose, and FFA levels in control and chronically hyperinsulinemic rats were 32+/-5 versus 116+/-21 mU/L (P < .005), 122+/-4 versus 129+/-8 mg/dL (P = NS), and 1.13+/-0.18 versus 0.95+/-0.12 mmol/L (P = NS); total plasma triglyceride and cholesterol levels were 78+/-7 versus 66+/-9 mg/dL (P = NS) and 50+/-3 versus 47+/-2 mg/dL (P = NS), respectively. Very-low-density lipoprotein (VLDL) + intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and HDL2 and HDL3 subfractions of plasma triglyceride and cholesterol were similar in control and hyperinsulinemic rats. Plasma FFA correlated positively with total (r = .61, P < .005) triglycerides. On day 7 after an 8-hour fast, hyperinsulinemic-euglycemic clamps with 3-3H-glucose infusion were performed in all rats. Chronically hyperinsulinemic rats showed peripheral insulin resistance (glucose uptake, 15.8+/-0.8 v 19.3+/-1.4 mg/kg x min, P < .02) but normal suppression of hepatic glucose production (HGP) compared with control rats (4.3+/-1.0 v 5.6+/-1.4 mg/kg x min, P = NS). De novo tissue lipogenesis (3-3H-glucose incorporation into lipids) was increased in chronically hyperinsulinemic versus control rats (0.90+/-0.10 v 0.44+/-0.08 mg/kg x min, P < .005). In conclusion, chronic physiologic hyperinsulinemia (1) causes insulin resistance with regard to the suppression of plasma FFA levels and increases lipogenesis; (2) induces peripheral but not hepatic insulin resistance with respect to glucose metabolism; and (3) does not cause an elevation in VLDL-triglyceride or a reduction in HDL-cholesterol.     

Insulin sensitivity indices of glucose and free fatty acid metabolism in obese children and adolescents in relation to serum lipids

OBJECTIVE: Most studies concerning the association between insulin resistance and the features of metabolic syndrome in obese children are based on measurement of insulin sensitivity indices (ISI) of glucose metabolism and not of fat metabolism. METHODS: We studied fasting low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, insulin, free fatty acids (FFA), blood glucose, ISI of glucose (homeostasis model assessment [HOMA] %S), and FFA metabolism (ISI-FFA) in 124 obese children aged 6 to 16 years. ISI-FFA was calculated based on the formula 2/(insulin x FFA + 1). Stepwise forward regression analyses were performed with triglycerides, HDL-C and LDL-C as dependent variables and age, sex, stage of puberty, body mass index, insulin, FFA, and blood glucose as independent variables. Direct multiple regression analyses were conducted with the dependent variables triglycerides, HDL-C, and LDL-C including age, sex, stage of puberty, body mass index, HOMA %S, and ISI-FFA as independent variables. Furthermore, ISI-FFA was measured in 13 normal-weight children aged 6 to 16 years. RESULTS: ISI-FFA (median 0.30) was significantly (P < .05) reduced in obese children compared with normal-weight children (median ISI-FFA 0.64). In stepwise regression analyses, triglycerides were significantly correlated with insulin and FFA (P < .05), LDL-C levels were significantly correlated with FFA (P < .05), and HDL-C was related to stage of puberty (P < .05), whereas all other variables demonstrated no significant associations with triglycerides, LDL-C, and HDL-C levels. In contrast to HOMA %S, ISI-FFA was significantly (P < .05) related to triglycerides and LDL-C in direct multiple regression analysis. CONCLUSIONS: Insulin resistance in respect to FFA metabolism is already detectable in childhood. Insulin sensitivity index of FFA metabolism seems to be a better tool for describing insulin resistance in lipid metabolism than ISI of glucose metabolism, because FFA and partially insulin but not glucose were related to triglycerides and LDL-C.     

The effects of thiazide diuretics upon plasma lipoproteins

In a double-blind, placebo-controlled, crossover study in 16 hypertensives, 4 weeks of 50 mg hydrochlorothiazide twice daily, caused significant elevations in total plasma cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, very low density lipoprotein (VLDL)-cholesterol and triglycerides. Significant elevations in fasting plasma glucose and in plasma insulin were observed, but no correlation between individual lipid elevations and either glucose or insulin elevations was apparent. The metabolic effects developed within 2 weeks, and dissipated within 4 weeks. Changes induced within 4 weeks of treatment with hydrochlorothiazide were unaltered at 6 months. Hydrochlorothiazide induces elevation of all lipoprotein cholesterol fractions and VLDL-triglyceride. However, as the important ratio between LDL- and HDL-cholesterol is unchanged, coronary risk may be unchanged.     

Acarbose lowers serum triglyceride and postprandial chylomicron levels in type 2 diabetes

AIM: This study was designed to examine the therapeutic effect of acarbose on serum triglyceride (TG), free fatty acid (FFA), very low-density lipoprotein (VLDL) and chylomicron (CM) in the meal tolerance test (MTT) before and after acarbose treatment in type 2 diabetes mellitus (DM2). METHODS: Effects of acarbose on postprandial lipid metabolism were examined in DM2 patients. The subjects with normotriglyceridaemia (TG > or = 1.7 mmol/l, n = 60) were divided to three groups (A, B and C), and DM2 patients with hypertriglyceridaemia (TG > 1.7 mmol/l, n = 20) were designated group D. Group A was a control, and group B was designed to examine the one-dose effect of acarbose (100 mg) on lipid levels in MTT using the balanced food of 400 kcal. In groups C and D, acarbose 300 mg/day was administered for 8 weeks, and MTT with the one-dose acarbose administration was performed. We determined the levels of fasting and postprandial levels of glucose, insulin, FFA and TG-rich lipoproteins such as CM and VLDL. RESULTS: Acarbose treatment lowered plasma glucose levels and insulin secretion. In comparison among study groups A, B and C, acarbose significantly lowered serum TG levels in postprandial state. In group D, after the 8-week acarbose administration, fasting or postprandial FFA, TG and VLDL levels were also lowered. Interestingly, postprandial increase in CM was suppressed by acarbose administration in group B, C or D. CONCLUSIONS: Acarbose lowers postprandial TG and CM levels in DM2 with either normotriglyceridaemia or hypertriglyceridaemia. Improvement of insulin resistance with acarbose may also reduce fasting TG levels in DM2 with hypertriglyceridaemia. Acarbose is a beneficial therapeutic agent to reduce TG levels in DM2 patients, thereby leading to suppression of cardiovascular events.     

Lipoprotein fractions, lipoprotein lipase and hepatic triglyceride lipase during short-term and long-term uptake of ethanol in healthy subjects

In short-term experiments, healthy fasting persons were given a basic dose of 0.5 g of ethanol/kg body weight, followed by hourly maintenance doses of 0.15 g of ethanol/kg body weight. After 10 h there was a significant increase of triglycerides in the VLDL, LDL, and HDL, the main rise (from 42 to 92 mg/dl) being found in the VLDL triglycerides. Other subjects, who received nourishment isocaloric with ethanol, likewise showed a significant rise of triglycerides in all lipoprotein fractions. Chylomicron triglycerides increased from 9.3 to 35.5 mg/dl. There was no significant change in postheparin HTGL, but postheparin LPL activity decreased after 10 h from 17.9 to 12.2 mmol FFA/ml/h in the fasting subjects, and from 28.5 to 10.2 mmol/FFA/ml/h in the persons receiving food. In long-term experiments after 4 weeks of 70 - 80 g of ethanol and isocaloric food daily, triglycerides increased, especially in the VLDL (from 50 to 82 mg/dl). The increase in the HDL, however, was also significant. After 4 weeks of ethanol, the chylomicron triglycerides in the plasma of the fasting subjects reached a value of 29.3 mg/100 ml, LDL cholesterol decreased, and HDL cholesterol increased. After 4 weeks of ethanol there was an increase in the lipoprotein lipase of the adipose tissue.     

Influence of endogenous hyperinsulinism on high density lipoprotein2 level in type 2 (non-insulin-dependent) diabetes mellitus and impaired glucose tolerance

We determined the insulin response to an oral glucose ingestion and levels of serum lipoproteins in 25 untreated patients with type 2 diabetes mellitus, in 26 subjects with impaired glucose tolerance (IGT), and in 35 non-diabetic control subjects. The three groups had similar compositions with respect to age and sex distribution. The levels of VLDL triglycende in the subjects with type 2 diabetes or IGT were higher than those in controls. Serum HDL- and HDL₂ cholesterol were significantly decreased in type 2 diabetics, and the subjects with IGT showed a similar tendency. Serum apolipoprotein A-II levels were lower in the male subjects with type 2 diabetes or IGT than in controls. Insulin reponse, i.e., sum of immunoreactive insulin (IRI) levels at basal, 30, 60, 90 and 120 min after a 75-g oral glucose load, negatively correlated to HDL and HDL₂ cholesterol levels (r = −0.396, P < 0.05; r = −0.482, P < 0.001, respectively), and positively correlated to VLDL triglyceride values (r = 0.485, P < 0.001) in the male subjects with type 2 diabetes or IGT. In the female subjects, fasting plasma IRI values significantly correlated to HDL cholesterol (r = −0.496, P < 0.05). There was a significant negative correlation between the concentrations of HDL₂ cholesterol and VLDL trgglyceride. These data show that lipoprotein metabolism, not only in type 2 diabetics, but also in IGT tends to show changes such as decreased HDL₂ cholesterol and increased VLDL triglyceride levels, and which might be related to the hypersecretion of endogenous insulin.     

Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals

Summary We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male (n = 120) and female subjects (n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40–70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, proinsulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A_{1 c}, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia. [Diabetologia (1998) 41: 706–712] Received: 21 August 1997 and in final revised form: 3 February 1998     

Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes

In order to compare the effects of intraperitoneal (IP) versus subcutaneous (SC) insulin delivery on plasma lipoproteins, lipoprotein cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) metabolism were compared in five type I diabetic patients while they were receiving continuous IP insulin (CIPII) or continuous subcutaneous insulin infusion (CSII). Each therapy regimen was of at least 1 month duration, and patients were treated in random order. Mean daily plasma insulin was lower on CIPII compared with CSII. CIPII was associated with lower VLDL triglycerides and VLDL apolipoprotein (apo) B, and higher high-density lipoprotein (HDL) and HDL3 cholesterol. The decreased VLDL on CIPII appeared to be the result of both decreased production and increased clearance of VLDL apo B. The results suggest that the more physiologic route of insulin therapy (CIPII) is associated with lipoprotein profiles of lower atherogenic potential.     

Achievement of glycaemic control is associated with improvements in lipid profile with iGlarLixi versus iGlar: A post hoc analysis of the LixiLan-L trial

Diabetic dyslipidaemia is a major risk factor for accelerated atherosclerosis. Glycaemic treatments that improve dyslipidaemia may help reduce the burden of atherosclerosis. This analysis investigated the effect of iGlarLixi [insulin glargine U100 (iGlar) and lixisenatide] versus iGlar on lipid profiles in patients with type 2 diabetes uncontrolled on basal insulin. Data from LixiLan-L were used to estimate changes in fasting lipid levels from baseline to week 30, overall and in patients stratified by achievement of glycaemic targets {2-hour postprandial glucose [≤10, >10 mmoL/L], fasting plasma glucose [≤6.1, >6.1 mmoL/L], HbA1c [≤7, >7% (≤53, >53 mmol/mol)]}. At week 30, median percentage change in triglycerides remained nearly unchanged (0.3% increase) with iGlarLixi versus a 6.5% increase with iGlar (P = 0.035; overall); similarly, trends towards better total and LDL cholesterol levels were observed with iGlarLixi versus iGlar. In patient subgroups achieving glycaemic targets, all lipid variables except for HDL cholesterol improved with iGlarLixi but not with iGlar. In summary, patients with type 2 diabetes uncontrolled on basal insulin showed improved fasting lipid profiles with iGlarLixi compared with iGlar, particularly when achieving glycaemic targets.     

Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride

Increased plasma insulin and triglycerides and decreased high density lipoprotein concentrations are primary risk factors in the development of coronary artery disease. The aim of the present study was to verify whether there was an independent relationship between plasma insulin levels and both HDL cholesterol and triglyceride in a worker population of 607 subjects, 389 men and 218 women, aged 23-73 years. An oral glucose tolerance test (75 g) was performed. Plasma glucose, insulin, triglyceride and HDL cholesterol were measured at fasting, plasma glucose and insulin were determined also 1 h and 2 h after glucose load. The results, examined separately in men and women documented a significant negative relationship between plasma insulin and HDL cholesterol level, as well as pointing out that both HDL cholesterol and insulin are significantly correlated to degree of hypertriglyceridemia, degree of obesity and level of glucose tolerance. The partial correlation coefficients between HDL cholesterol and plasma insulin levels at fasting in men and post-glucose load in women, demonstrated an independent relationship between increased plasma insulin and decreased plasma HDL concentration. However, the strongest relationship, revealed by partial correlation coefficient analysis, was between the degree of hyperinsulinemia and hypertriglyceridemia.     

Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables

OBJECTIVE Although often associated with insulin resistance and glucose intolerance, various lipoprotein abnormalities have been found in polycystic ovary syndrome (PCOS) but not Invariably so when the degree of obesity is taken into account. We have therefore Investigated the serum lipid profile in a group of women with polycystic ovary syndrome with and without obesity. DESIGN Cross-sectional study of serum lipoprotein lipids and plasma free fatty acids in relation to anthropometric, metabolic and hormonal variables in women with PCOS and weight-matched controls. PATIENTS Twenty-four obese (Pob, mean BMI ± SD 30·6±3·3kg/m²) and 25 non-obese (Pnob, 22·2 ±2·3kg/m²) women with PCOS. Twenty obese (Cob, 30·2 ± 3·5 kg/m²) and 20 non-obese (Cnob, 21·4 ± 1·5 kg/m²) controls. MEASUREMENTS Fasting concentrations of plasma free fatty acids, serum cholesterol and triglycerides in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) In relation to insulin sensitivity index (M/I; assessed with the euglycaemic insulin clamp), glucose tolerance (k-value; intravenous glucose tolerance test), basal serum hormone concentrations, and body fat distribution (skinfolds and waist hip ratio). RESULTS Plasma concentrations of free fatty acids were markedly higher in Pob than in the other groups (all P < 0 001). The lipoprotein lipids did not differ between Pob and Cob, or between the non-obese groups, whereas both obese groups had higher serum concentrations of triglycerides, totally and in VLDL, and lower HDL-cholesterol than their non-obese counterparts. Pob also had higher serum levels of total and LDL-cholesterol than Pnob. Pob had a more pronounced subcutaneous truncal-abdominal adiposity, higher fasting insulin levels and lower M/I than the other groups, and a lower k-value than Cob. Cob had higher levels of fasting insulin than Cnob. Free fatty acid levels correlated with the k-value (inversely) in both women with PCOS and controls, and with M/I (inversely), age and testosterone levels in PCOS. Step-wise regression analysis for the total population, comparing endocrine, anthropometric and metabolic explanatory variables, showed that the serum levels of HDL-cholesterol and triglycerides were mainly correlated with body fat distribution (both) and fasting insulin levels (triglycerides), and levels of total and LDL-cholesterol with BMI and age. CONCLUSIONS Plasma free fatty acid correlations were markedly increased In obese women with PCOS, closely associated with the lower insulin sensitivity and lower glucose tolerance in these women. In spite of these profound metabolic aberrations, the lipoprotein lipid profile was not significantly more abnormal in obese women with PCOS than in their weight-matched controls.     

Varied effects of dietary sucrose and cholesterol on serum lipids, lipoproteins and apolipoproteins in rhesus monkeys.

Serum lipid, lipoproteins, apolipoproteins and plasma insulin and glucose were studied in rhesus monkeys (Macaca mulatta) fed high sucrose diets (69%, w/w), with and without added cholesterol. When compared to basal diet, a high sucrose diet with no added cholesterol fed for 6 weeks increased serum total cholesterol and triglycerides by factors of 1.2 and 2.8, respectively. Cholesterol supplementation of sucrose diets increased the serum total cholesterol levels by a factor of 2.2 and decreased the serum triglycerides by 0.47. The serum cholesterol response to experimental diets was reflected predominantly in beta-lipoprotein and to a lesser extent in alpha-lipoprotein. Sucrose diets without cholesterol enriched the beta- and pre-beta-lipoproteins with triglycerides and protein at the expense of cholesterol. On the same diet, the protein content of alpha-lipoprotein increased at the expense of cholesterol and triglycerides. In contrast, dietary cholesterol decreased the triglyceride content and increased the cholesterol content of all the lipoprotein classes. Sucrose feeding seems to increase ApoB more than non-ApoB proteins. The proportion of ApoC-II relative to ApcoC-III increased in each animal on a sucrose diet; exogenous cholesterol further increased this trend. While sucrose diet decreased ApoA-I/ApoA-II ratios, cholesterol supplementation reversed this trend. Dietary sucrose increased the plasma glucose, insulin, and insulin-glucose ratios. The addition of cholesterol also tended to decrease plasma glucose and insulin levels. These observations indicate varied responses of serum lipoproteins and apoproteins to dietary sucrose with and without cholesterol supplementation.