Diets high in glycemic index and glycemic load are associated with an increased risk of metabolic syndrome among Korean women

Background and aimsAccurate estimation of the glycemic index (GI) and glycemic load (GL) of diets is essential when assessing health implications of dietary GI and GL. The present study aimed to estimate dietary GI and GL utilizing the updated GI tables with a large number of new, reliable GI values and assess their associations with metabolic syndrome among Korean adults.Methods and resultsWe analyzed data from 3317 men and 6191 women for this cross-sectional study. Dietary intake was assessed with a validated food frequency questionnaire. Metabolic syndrome and its components were defined based on the harmonized criteria with Korean-specific cutoffs for waist circumference. Multivariate logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Compared with women in the lowest quintiles of energy-adjusted dietary GI and GL, women in the highest quintiles had significantly greater risks of metabolic syndrome (GI, OR = 1.56, 95% CI = 1.18–2.06; GL, OR = 1.80, 95% CI = 1.27–2.57), elevated blood pressure, reduced high-density lipoprotein cholesterol (HDL-C, both GI and GL), elevated triglycerides (GI only), elevated waist circumference, and elevated fasting glucose (GL only). Among men, no significant association was noted except for a higher risk of reduced HDL-C (OR = 1.59, 95% CI = 1.01–2.29) in the highest quintile of energy-adjusted dietary GI than in the lowest quintile.ConclusionOur findings suggest that dietary GI and GL are positively associated with metabolic syndrome risk among women, but not men, in Korea.     

Carbohydrate nutrition, glycaemic load, and plasma lipids: the Insulin Resistance Atherosclerosis Study.

AIMS: We evaluated the relationship of carbohydrate nutrition and selected food groups with lipids using data from the Insulin Resistance Atherosclerosis Study (IRAS Exam I, 1992-1994). METHODS AND RESULTS: A total of 1026 middle-aged adults with normal or impaired glucose tolerance had complete data on fasting lipids and usual dietary intake from an interviewer-administered, validated food frequency questionnaire. Published glycaemic index (GI) values were assigned to food items and average dietary GI and glycaemic load (GL) were calculated per participant. Intake of carbohydrates differed by gender, men consuming more absolute digestible carbohydrates with higher GI and GL than women. In multivariate models adjusting for energy intake, in men, GL and carbohydrates were associated positively with total and LDL cholesterol, and inversely with HDL. In women, associations were limited to triglycerides. We estimated that a 100 g higher intake in GL or carbohydrates was associated with a 7-8 mg/dL higher total or LDL cholesterol level in men, and a 13-17 mg/dL higher triglyceride level in women. In the combined sample, GL and carbohydrates were consistently associated with all lipid levels and GI was inversely associated with HDL cholesterol. CONCLUSION: Our findings underscore the importance of carbohydrate nutrition for plasma lipids.     

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

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

Dietary glycemic index and risk of type 2 diabetes mellitus in middle-aged Japanese men

This cohort study investigated the association between dietary glycemic index (GI), glycemic load (GL), and the incidence of type 2 diabetes mellitus in middle-aged Japanese men, and the effect of insulin resistance and pancreatic B-cell function on the association. Participants were 1995 male employees of a metal products factory in Japan. Dietary GI and GL were assessed using a self-administered diet history questionnaire. The incidence of diabetes was detected in annual medical examinations over a 6-year period. The association between GI, GL, and the incidence of diabetes was evaluated using Cox proportional hazards models. During the study, 133 participants developed diabetes. Age- and body mass index-adjusted hazard ratios across the GI quintiles were 1.00 (reference), 1.62, 1.50, 1.68, and 1.80; and those of GL were 1.00 (reference), 1.07, 1.48, 0.95, and 0.98. The hazard ratio for the highest GI quintile was significantly greater than that for the lowest quintile. The influence of GI was more pronounced in the lowest insulin resistance subgroups. GI and pancreatic B-cell function were independently associated with the incidence of type 2 diabetes mellitus; participants with low B-cell function and the highest tertile of GI had the highest risk of diabetes. Dietary GI is associated with the incidence of diabetes in middle-aged Japanese men. GI and B-cell function were independently associated with incidence of diabetes.     

Pharmacologic therapy of lipid disorders in the elderly

Older men and women with coronary artery disease, prior stroke, peripheral arterial disease, and extracranial carotid arterial disease with a serum low-density lipoprotein (LDL) cholesterol >125 mg/dL despite diet should be treated with lipid-lowering drug therapy, preferably with statins, to reduce the serum LDL cholesterol to <100 mg/dL. If statin drug therapy does not lower the serum LDL cholesterol to <100 mg/dL in older persons with coronary artery disease, a bile acid binding resin, such as cholestyramine, should be added, since this drug does not increase the incidence of myositis in persons taking statins. The physician should use statins to treat older persons without atherosclerotic cardiovascular disease with a serum LDL cholesterol=160 mg/dL plus one major risk factor, or a serum LDL cholesterol=130 mg/dL plus a serum high-density lipoprotein (HDL) cholesterol <50 mg/dL. Gemfibrozil may be useful in reducing the incidence of coronary events in persons with coronary artery disease whose primary lipid abnormality is a low serum HDL cholesterol level. There are no good data supporting treatment of hypertriglyceridemia unassociated with increased LDL cholesterol or decreased HDL cholesterol for prevention of cardiovascular disease.     

Cardiovascular risk profile of asymptomatic healthy young adults with increased femoral artery intima-media thickness: The Bogalusa Heart Study

BACKGROUND: Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. This study examined the cardiovascular disease risk profile of asymptomatic young adults with increased femoral artery IMT. METHODS: Femoral artery IMT was measured by B-mode ultrasonography in 1080 black and white subjects (aged 24-43 years; 71% white, 43% male) enrolled in the Bogalusa Heart Study. Individuals in the top (n=54) versus bottom fifth (n=54) percentiles distribution of femoral IMT were compared for traditional cardiovascular risk factors profile. Univariate analysis compared the two groups, t-tests and chi tests were performed. RESULTS: The top and bottom fifth percentiles of IMT differed with respect to age (P<0.001), systolic blood pressure (P<0.05), diastolic blood pressure (P<0.05), total cholesterol (P<0.01), low-density lipoprotein (LDL) cholesterol (P<0.001), non-high-density lipoprotein (HDL) cholesterol (P<0.01) and smoking status (P<0.01). In terms of prevalence of clinically defined traditional risk factors, individuals at the top versus bottom fifth percentile of IMT distribution had significantly higher prevalence of high LDL cholesterol (>OR=130 mg/dL), non-HDL cholesterol (>OR=160 mg/dL), and cigarette smoking. The odds ratio for individuals with three or more risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (P=0.01). CONCLUSION: The observed adverse effect of cardiovascular risk factors on IMT of femoral artery, a surrogate measure of coronary and peripheral atherosclerosis, in asymptomatic young individuals underscores the need for risk factors profiling in early life. These observations have important implications in preventive medicine.     

Effects of antirheumatic therapy on serum lipid levels in patients with rheumatoid arthritis: a prospective study

BACKGROUND: Patients with newly diagnosed rheumatoid arthritis have adverse serum lipid profiles. We sought to determine the effects of treating rheumatoid arthritis with antirheumatic drugs on these abnormal lipid levels. SUBJECTS AND METHODS: We studied 42 patients with newly diagnosed rheumatoid arthritis who had not been treated with corticosteroids or disease-modifying antirheumatic drugs. We measured serum lipid profiles at baseline and 1 year later, and determined whether there were differences in the changes in lipid levels between patients who met the American College of Rheumatology criteria for a 20% improvement in rheumatoid arthritis and those who did not. RESULTS: Of the 42 patients, 27 (64%) met the criteria for a 20% improvement in rheumatoid arthritis during the 12-month study. In these patients, mean high-density lipoprotein (HDL) cholesterol levels increased by 21% (P <0.001), apolipoprotein A-I levels increased by 23% (P <0.001), and the ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol level decreased by 13% (P = 0.10). There were significant between-group differences (responders-nonresponders) in the mean 12-month changes in HDL cholesterol levels (8.0 mg/dL; 95% confidence interval [CI]: 3 to 13 mg/dL; P = 0.002), apolipoprotein A-I levels (21 mg/dL; 95% CI: 8 to 33 mg/dL; P = 0.003), and the LDL cholesterol to HDL cholesterol ratio (-0.6; 95% CI: -0.1 to -1.0; P = 0.03), but not in LDL cholesterol, apolipoprotein B-100, or lipoprotein(a) levels. CONCLUSION: Active rheumatoid arthritis is associated with an adverse lipid profile that improves substantially following effective treatment of rheumatoid arthritis. This improvement may reduce the risk of cardiovascular disease.     

The effects of a low-carbohydrate regimen on glycemic control and serum lipids in diabetes mellitus

The Diabetes Complications and Control Trial (DCCT) established that diabetic complications could be reduced by improvement in glycemic control. The ideal diabetes treatment protocol would maintain blood glucose levels in normal ranges without resulting in frequent hypoglycemia. Because several studies suggest an inverse relationship between carbohydrate consumption and the level of glycemic control, the effects of an intensive treatment program, which included dietary carbohydrate restriction, are examined in this paper. A chart review was performed of 30 patients who self-reported the consumption of 30 g of carbohydrate daily, followed a strict insulin regimen, monitored blood glucose levels at least four times daily, and had follow-up clinical visits or phone calls with their physician. For both type I and type II diabetics, there were significant improvements in glycemic control and mean fasting lipid profiles at follow-up. The mean hemoglobin A1c decreased by 27.8% from 7.9 to 5.7 (p < 0.001). The LDL cholesterol decreased by 16.5%, from 155.4 to 129.7 mg/dL (p = 0.004). The triglycerides decreased by 31.1%, from 106.8 to 73.6 mg/dL (p = 0.005). The HDL cholesterol increased by 43.3%, from 50.4 to 72.2 mg/dL (p < 0.001). The cholesterol/HDL ratio decreased by 31.5%, from 4.99 to 3.42 (p < 0.001). A carbohydrate-restricted regimen improved glycemic control and lipid profiles in selected motivated patients. Therefore, further investigation of the effects of this protocol on treating diabetes mellitus should be considered. Additionally, the reduction of insulin afforded by this diet could theoretically lead to a reduction in hypoglycemic events.     

Cholesterol 2001. Rationale for lipid-lowering in older patients with or without CAD

Statin treatment of men and women age > or = 50 with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, and intermittent claudication. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg/dL in older patients with CAD, prior stroke, peripheral arterial disease, or extracranial carotid arterial disease and serum LDL cholesterol > 125 mg/dL despite diet therapy. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia but without cardiovascular disease. Consider using statins in patients age 50 to 80 without cardiovascular disease, serum LDL cholesterol > 130 mg/dL, and serum high-density lipoprotein (HDL) cholesterol < 50 mg/dL.     

Effects of the glycemic index of foods on serum concentrations of high-density lipoprotein cholesterol and triglycerides

The role of carbohydrates in cardiovascular disease prevention has garnered increasing attention due to accumulating evidence showing deleterious effects of low-fat, high-carbohydrate diets on serum triglycerides and high-density lipoprotein (HDL) cholesterol. Researchers argue that classifying carbohydrates based on their capacity for increasing blood glucose (termed the glycemic index [GI]) is a useful tool for elucidating the effects of carbohydrate-rich foods on glucose and lipid metabolism. Several epidemiologic reports show that lower dietary GI is associated with lower serum triglycerides and higher HDL cholesterol. Results from intervention studies show that substituting low-GI for high-GI foods in a low-fat, high-carbohydrate diet lowers serum triglycerides by 15% to 25%. The available evidence to date suggests that the glycemic index of foods will be an important factor in future dietary prevention research.     

Effects of phytosterol ester-enriched margarine on plasma lipoproteins in mild to moderate hypercholesterolemia are related to basal cholesterol and fat intake

Dietary phytosterols have been reported to lower total and low-density lipoprotein (LDL) cholesterol. However, less is known about the influence of cholesterol and fat intake on the cholesterol-lowering effect of esterified phytosterols in mild to moderate hypercholesterolemia. Sixty-three healthy subjects (38 women, 25 men, 42 +/- 11 years, LDL cholesterol > 130 mg/dL) were investigated in a randomized, double-blind, placebo-controlled, cross-over study. A total of 20 g/d of a phytosterol ester-enriched margarine (1.82 g/d of phytosterols) was compared with a control margarine (0.06 g/d of phytosterols). After 3 weeks of intake, participants crossed over to the other margarine. A 3-day dietary recall was performed at the beginning and at the end of the study to assess cholesterol, fat, and energy intake. Phytosterol ester-enriched margarine significantly changed total cholesterol (-3.4%, P <.005), LDL cholesterol (-5.4%, P <.001, 144 +/- 28 v 154 +/- 26 mg/dL), high-density lipoprotein (HDL) cholesterol (+3.4%, P <.05), apolipoprotein B (-4.0%, P <.005), and LDL/HDL cholesterol ratio (-7.8%, P <.001) compared with the control margarine. In the tertiles with the highest dietary intake of cholesterol, energy, total fat, and saturated fatty acids, and with the highest baseline proportion of campesterol to cholesterol, LDL cholesterol reduction was 11.6% (P <.001), 9.5% (P =.001), 9.4% (P =.001), 8.4% (P =.005), and 6.2% (P =.014), respectively. Triglycerides, plasma viscosity, and fibrinogen concentration did not change significantly. The improvements of LDL, HDL, total cholesterol, apolipoprotein B concentrations, and LDL/HDL cholesterol ratio during the daily consumption of a phytosterol ester-enriched margarine were most marked in those subjects with a high dietary intake of cholesterol, energy, total fat, and saturated fatty acids and with high baseline cholesterol absorption.     

A population-based, cross-sectional comparison of lipid-related indexes for symptoms of atherosclerotic disease

Current lipid guidelines recommend that therapy be targeted primarily at low-density lipoprotein (LDL) cholesterol, and that other lipid indexes may be used as secondary or supplementary targets. Emerging data have suggested that measures such as non-high-density lipoprotein (HDL) cholesterol, apolipoprotein-B, or the total/HDL cholesterol ratio may be more predictive of cardiovascular risk than LDL cholesterol. We conducted a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey to directly compare the strengths of the associations among various lipid-related indexes and clinical features consistent with atherosclerotic disease. From approximately 9,500 data sets in the overall analysis, the apolipoprotein-B/HDL cholesterol ratio emerged as the strongest correlate (odds ratio 1.177 per 1 mg/dl increment, 95% confidence interval 1.063 to 1.302, p <0.01), followed by the total or non-HDL cholesterol/HDL cholesterol ratio (odds ratio for each 1.070 per 1 mg/dl increment, 95% confidence interval 1.024 to 1.118, p <0.01), followed by the triglyceride/HDL cholesterol ratio (odds ratio 1.033 per 1 mg/dl increment, 95% confidence interval 1.011 to 1.056, p <0.01). Neither LDL cholesterol nor the LDL/HDL cholesterol ratio correlated significantly. Parallel analyses comparing tertile extremes and analyses in subgroups determined by gender, age, and body mass index revealed similar findings. The LDL/HDL cholesterol ratio was only significant for lean patients. In conclusion, these observations add to the published data suggesting that LDL cholesterol may not be the best target of lipid-lowering treatment strategies.     

HDL-C levels and revascularization procedures in coronary heart disease patients treated with statins to target LDL-C levels

Background:

A low level of high‐density lipoprotein cholesterol (HDL‐C) is a strong predictor for cardiovascular disease morbidity and mortality at all low‐density lipoprotein cholesterol (LDL‐C) concentrations.

Hypothesis:

We evaluated this association in routine clinical practice among statin‐treated coronary heart disease patients who achieved LDL‐C target levels. This association also exists in routine clinical practice.

Methods:

A retrospective dynamic cohort included all male coronary heart disease patients of the Sharon‐Shomron district, Clalit Health Services, Israel, with LDL‐C levels <100 mg/dL and who were receiving statins (≥6 purchases/y) from January 1998 to June 2008. Data were collected on demographic variables; coexistence of hypertension, diabetes mellitus, and peripheral vascular diseases; details of revascularization procedures; and lipid levels. The outcome variable was revascularization procedure, by either percutaneous intervention or coronary artery bypass graft.

Results:

The study group of 909 male patients was stratified into quintiles, based on mean HDL‐C levels: Q1 (n = 179): ≤26.4 mg/dL; Q2 (n = 190): 26.4–≤30.0 mg/dL; Q3 (n = 191): >30.0–≤34.0 mg/dL; Q4 (n = 186): >34.0–≤41.0 mg/dL; Q5 (n = 163): >41.0 mg/dL. During the study period, 307 (33.8%) of the cohort required ≥1 revascularization procedure. Those in the highest quintile underwent significantly fewer procedures (40.8% for Q1 vs 16.6% for Q5, P<0.001). This significant effect of the highest HDL‐C quintile was not influenced by any variable.

Conclusions:

The protective effect of high HDL‐C levels, regardless of other risk factors, in preventing revascularization procedures was confirmed in the routine clinical practice among statin‐treated CHD patients who reached LDL‐C level <100 mg/dL. Possible additional benefits of using agents to raise HDL‐C levels should be investigated. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Dietary glycemic index,glycemic load and cancer: An overview of the literature

Aims

The aim of this paper is to provide an overview of the current evidence for associations between dietary glycemic index (GI) and dietary glycemic load (GL), and the risk of various types of cancer, and to summarize mechanisms proposed to explain the associations found.

Effect of acute myocardial infarction on cholesterol ratios

OBJECTIVE: In patients with acute myocardial infarctions (MIs), cholesterol levels are no longer valid after 24 h from presentation because acute MI causes a rapid decline in serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. The objective of this study was to evaluate the effect of acute MI on the total cholesterol/HDL cholesterol ratio and the LDL cholesterol/HDL cholesterol ratio. METHODS: The study consisted of 45 patients who were admitted to the hospital with acute MIs. Serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were determined on day 1 post-MI and day 4 post-MI. The total cholesterol/HDL cholesterol ratio and the LDL cholesterol/HDL cholesterol ratio were calculated. Serum lipid levels and cholesterol ratios were compared between day 1 post-MI and day 4 post-MI. RESULTS: From day 1 post-MI to day 4 post-MI, the mean (+/- SD) serum levels of total cholesterol (188.4 +/- 52.5 vs. 170.5 +/- 57.2 mg/dL, respectively; p = 0.01), LDL cholesterol (120.3 +/- 48.9 vs. 105.9 +/- 43.0 mg/dL, respectively; p = 0.009), and HDL cholesterol (45.0 +/- 18.5 vs 39.3 +/- 16.1 mg/dL, respectively; p < 0.001) decreased, but the mean serum level of triglycerides (119.2 +/- 81.2 vs 149.3 +/- 68.3 mg/dL, respectively; p = 0.006) increased. The cholesterol ratios, however, remained unchanged between day 1 post-MI and day 4 post-MI. The total cholesterol/HDL cholesterol ratio was 4.59 +/- 1.84 on day 1 post-MI and 4.67 +/- 1.77 on day 4 post-MI (change not significant). The LDL cholesterol/HDL cholesterol ratio was 2.96 +/- 1.58 on day 1 post-MI and 2.99 +/- 1.44 on day 4 post-MI (change not significant). CONCLUSION: Acute MI does not affect the cholesterol ratios. Therefore, when the absolute levels of serum cholesterol are no longer valid (beyond 24 h after an MI), the cholesterol ratios still could be useful for cholesterol risk assessment in patients with acute MIs.     

Familial aggregation of insulin resistance and cardiovascular risk factors in hypertension

The authors assessed the familial aggregation of cardiometabolic abnormalities (elevated homeostasis model assessment [HOMA], triglycerides [TG], and low-density lipoprotein [LDL] and reduced high-density lipoprotein [HDL]) among hypertensive siblings (N=287 from 138 families). Evidence for familial aggregation required sibling-pair concordance of outcome variables dichotomized according to predefined values (concordance for highest-quartile HOMA [>3.3], TG [>170 mg/dL], and LDL [>138 mg/dL] and lowest-quartile HOMA for HDL [<32 mg/dL]). Hypertensive individuals with insulin resistance (high-quartile HOMA) had higher TG and lower HDL and LDL levels compared with insulin-sensitive hypertensives. High-quartile HOMA, TG, and LDL aggregated in hypertensive families, and TG plus HOMA coaggregated. HDL did not show aggregation. In a multivariate logistic regression, the only significant predictor of an individual's HOMA status was a sibling's HOMA status in a model including age, sex, race, and body mass index (odds ratio=9.12; 95% confidence interval, 3.64-23.14; P<.001). Cardiometabolic variables demonstrate heritability in hypertensive families. Further exploration of common genetic susceptibility loci in hypertension involving these factors is warranted.     

Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant

Acromegaly is associated with premature cardiovascular mortality. GH replacement therapy decreases inflammatory markers of cardiovascular risk, but little is known about these markers in patients with acromegaly. The GH receptor antagonist, pegvisomant, reduces IGF-I levels in 98% of patients treated. We investigated the effects of GH receptor blockade on inflammatory and other cardiovascular risk markers in active acromegaly. Forty-eight patients with acromegaly and 47 age- and body mass index-matched controls were included. The study consisted of 3 parts: a cross-sectional study, a prospective randomized 12-wk placebo-controlled study, and a longitudinal open-label study of up to 18 months of pegvisomant treatment. After baseline evaluation, patients with acromegaly were randomized to placebo (n = 14), 10 mg (n = 12), 15 mg (n = 10), or 20 mg (n = 12) daily pegvisomant for 12 wk. Subsequently, all patients received at least 10 mg pegvisomant daily for up to 18 months, with dose adjustments to achieve a normal IGF-I level. Anthropometry, GH, IGF-I, and pegvisomant levels were measured monthly. C-reactive protein (CRP), IL-6, homocysteine, lipoprotein(a), glucose, insulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were determined at baseline, 4 and 12 wk in the placebo-controlled study and at 3-month intervals (during which IGF-I levels were normal) in the longitudinal study. In the cross-sectional study, patients had lower CRP than did controls [median, 0.3 (range, 0.2-0.8) vs. 2.0 (0.6-3.7) mg/liter; P < 0.0001] and had higher insulin [78.6 (55.8-130.2) vs. 54.5 (36.6-77.5) pM, P = 0.0051]. IL-6, homocysteine, triglycerides, lipoprotein(a), LDL cholesterol and HDL cholesterol were not different between groups. In the placebo-controlled study, CRP increased in patients treated with 20 mg pegvisomant, compared with placebo (mean +/- SEM, 13.7 +/- 3.6 vs. 0.5 +/- 3.3 mg/liter; P = 0.010). There were no significant differences in IL-6, homocysteine, glucose, insulin, triglyceride, total cholesterol, LDL cholesterol and HDL cholesterol levels. In the longitudinal open-label study (median duration, 15.6 months), CRP increased by 2.0 +/- 0.5 mg/liter (P = 0.0002). Total cholesterol and triglycerides increased (0.22 +/- 0.11 mM, P = 0.050; and 0.25 +/- 0.09 mM, P = 0.007, respectively), whereas lipoprotein(a) decreased (-70 +/- 33 mg/liter, P = 0.039). Glucose, insulin, homocysteine, HDL cholesterol, and IL-6 did not change. We conclude that patients with active acromegaly have lower CRP and higher insulin levels than healthy controls. Administration of pegvisomant increases CRP levels. We propose that GH secretory status is an important determinant of serum CRP levels, although additional studies are needed to determine the mechanism and significance of this finding.     

Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women.

The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, total cholesterol, very-low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-I and B levels and LDL particle size were assessed in 20 postmenopausal women with a previous hysterectomy and various forms of dyslipidemia (LDL cholesterol > or = 4.14 mmol/L [160 mg/dL] and/or HDL cholesterol < or = 1.03 mmol/L [40 mg/dL]). All subjects were studied while on a standard cholesterol-lowering diet, and were sampled in the fasting state before beginning estrogen therapy and after a mean of 13 weeks of estrogen therapy. Lipids were measured by standardized enzymatic techniques, apos were measured by enzyme-linked immunoassays, and LDL particle size was measured by gradient gel electrophoresis. Mean values for plasma lipid parameters (mmol/L) at baseline and during estrogen replacement were as follows: triglyceride, 2.11 and 2.75 (30% increase); total cholesterol, 7.45 and 6.52 (13% decrease); VLDL cholesterol, 1.09 and 1.22 (12% increase); LDL cholesterol, 5.09 and 3.70 (27% decrease); and HDL cholesterol, 1.27 and 1.58 (24% increase). Mean values for apo A-I were 163 and 254 mg/dL (56% increase), and for apo B they were 170 and 148 mg/dL (13% decrease). The LDL particle score was 4.09 and 4.52 (11% smaller). Changes in all parameters were statistically significant (P = .05) except for VLDL cholesterol. These data indicate that estrogen replacement is effective in decreasing LDL cholesterol and apo B concentrations and increasing HDL cholesterol and apo A-I concentrations in dyslipidemic postmenopausal women, but it should not be used in patients with baseline fasting triglyceride levels higher than 2.82 mmol/L (250 mg/dL) unless it is accompanied by a progestin. Our data indicate that this form of estrogen replacement could lower the risk of coronary artery disease (CAD) by more than 50% in these women, based on favorable alterations in plasma lipoproteins.     

Effects of continuous insulin infusion therapy on lipoprotein surface and core lipid composition in insulin-dependent diabetes mellitus

To determine whether intensive insulin therapy has the same beneficial effects on lipoprotein composition that it has been shown to have in insulin-dependent diabetes mellitus (IDDM) on the routinely measured plasma lipids, we studied 10 patients after 6 months of conventional therapy (CIT) and again after 6 months of therapy with continuous subcutaneous insulin infusion (CSII). While the mean of home blood glucose levels (8.1 +/- 0.5 v 7.9 +/- 0.5 mmol/L) decreased no further, plasma triglycerides (TG) (CIT, 102.7 +/- 25.0; CSII, 89.6 +/- 27.1 mg/dL; P less than .001) decreased after CSII, and high-density lipoprotein cholesterol (HDL-C) increased significantly, primarily as a consequence of an increase in HDL2 (CIT, 12.2 +/- 6.0; CSII, 18.1 +/- 6.3 mg/dL; P less than .02). Low-density lipoprotein cholesterol (LDL-C) was unchanged (CIT, 82.2 +/- 32; CSII, 84.0 +/- 27.8 mg/dL). After CIT, two indices of lipoprotein surface composition were altered: (1) the free cholesterol (FC) to lecithin ratio, which is a new cardiovascular risk factor, was abnormally increased in plasma, very-low-density lipoprotein (VLDL) + LDL, and HDL, and (2) the sphingomyelin to lecithin ratio, an index of the surface rigidity of lipoproteins, was increased in the HDL subfractions. While CSII treatment resulted in favorable changes in whole plasma lipids, it failed to correct these disturbances in composition. Since the participation of lipoproteins in certain steps in reverse cholesterol transport appears to be impaired when their surface constituents are altered, persistence of these disturbances may sustain the increased cardiovascular risk of IDDM patients, even when their clinical control is very good and their plasma lipids are normal.     

Hyperbetalipoproteinemia with small low-density lipoprotein, a characteristic disorder of lipoprotein in essential hypertension

The purpose of the present study was to elucidate the characteristic lipoprotein disorder in essential hypertension. Twenty-six patients with essential hypertension (HT) but without diabetes mellitus or obesity and 24 healthy subjects (control) were recruited into this study. Lipoproteins of HT and controls were separated by ultracentrifugation to very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low-density liproprotein (LDL), and (HDL) fractions. Cholesterol and triglycerides were determined with enzyme assay, and apoB were determined by highly sensitive latex agglutination (Kyowa-hakko Co. LD). There was no difference in age (mean ± SE; HT, 63 ± 2 versus control, 60 ± 2 years) or body-mass index (22.7 ± 0.4 versus 21.7 ± 0.5 kg/m²) between HT and controls. Blood pressure in HT and controls was 158 ± 2/87 ± 12 mm Hg and 123 ± 3/72 ± 2 mm Hg, respectively. Cholesterol did not change significantly in plasma (192.1 ± 7.0 versus 176.4 ± 4.2 mg/dL), VLDL (15.2 ± 2.4 versus 11.8 ± 1.7 mg/dL), IDL (14.8 ± 2.4 versus 10.7 ± 1.6 mg/dL), LDL (93.7 ± 4.6 versus 83.1 ± 3.9 mg/dL), nor in HDL (51.9 ± 2.7 versus 58.1 ± 3.2 mg/dL). Triglycerides (TG) increased in plasma (120.0 ± 10.0 versus 87.5 ± 9.3 mg/dL, p < 0.05), although TG did not change in all subfractions. ApoB increased in plasma (105.5 ± 5.1 versus 85.6 ± 3.6 mg/dL, p < 0.01), IDL (9.0 ± 1.3 versus 5.4 ± 0.6 mg/dL, p < 0.05), and LDL (76.3 ± 4.3 versus 59.4 ± 3.7 mg/dL, p < 0.01) in HT compared with controls. The ratio of cholesterol to apoB in LDL decreased (1.27 ± 0.06 versus 1.48 ± 0.08, p < 0.05). In essential HT, number of apoB containing lipoproteins (IDL, LDL) increased. Low ratio of cholesterol to apoB was noted in LDL, indicating the presence of small, dense LDL. As cholesterol in LDL was normal, hyperbetalipoproteinemia is also a characteristic disorder of essential HT.