Effects of potato resistant starch intake on insulin sensitivity, related metabolic markers and appetite ratings in men and women at risk for type 2 diabetes: a pilot cross-over randomised controlled trial.

BACKGROUND: The intake of certain types of resistant starch (RS) has been associated in some studies with increased whole-body insulin sensitivity. This randomised, cross-over pilot trial evaluated the effect of consuming cooked, then chilled potatoes, a source of RS, compared to isoenergetic, carbohydrate (CHO)-containing control foods, on insulin sensitivity and related markers. METHODS: Nineteen adults with body mass index 27.0-39.9 kg m-2 consumed 300 g day-1 RS-enriched potatoes (approximately two potatoes; ~18 g RS) or CHO-based control foods, as part of lunch, evening and snack meals, over a 24-h period. After an overnight fast, insulin sensitivity, CHO metabolism markers, free fatty acids, breath hydrogen levels and appetite were assessed for up to 5 h after the intake of a standard breakfast. The primary endpoint was insulin sensitivity, assessed with the Matsuda index. P < 0.05 (one-sided) was considered statistically significant. RESULTS: Insulin sensitivity was not significantly different between the potato and control conditions. The potato intervention resulted in higher postprandial breath hydrogen (P = 0.037), lower postprandial free fatty acid concentrations (P = 0.039) and lower fasting plasma glucose (P = 0.043) compared to the control condition. Fullness ratings were significantly lower after potato versus control (P = 0.002). No other significant effects were observed; however, there was a trend toward lower fasting insulin (P = 0.077) in the potato versus the control condition. CONCLUSIONS: The results of this pilot study suggest RS-enriched potatoes may have a favourable impact on carbohydrate metabolism and support the view that additional research in a larger study sample is warranted.

The Bile Acid Sequestrant Acceptability scale validation study.

AIMS: The primary objective of this study was to validate a novel Bile Acid Sequestrant Acceptability (BASA) Scale intended to assess the acceptability and/or tolerability of bile acid sequestrant (BAS) beverage preparations. A secondary objective was to assess the utility of weightings based on subjective clinical importance for the BASA scale individual components and its composite score. METHODS: This was a randomised, single-blind, single site, controlled study of oral administration of 4 g of orange-flavoured generic cholestyramine powder, 12 g of orange-flavoured generic cholestyramine powder and an orange-flavoured sweetened control drink powder, each mixed with water. RESULTS: The study sample included 42 subjects; 26 men and 16 women. Participants were non-Hispanic white (76.2%) or black/African American (23.8%), with a mean age of 51.4 years and body mass index of 30.1 kg/m(2). The components of the BASA scale were taste, texture, appearance and mixability; the possible total BASA scores ranged being 4-20; the higher the BASA scale score, the better the acceptability/tolerability. Composite BASA scale scores were significantly lower for the 4 g (mean BASA score = 10.3) and 12 g (mean BASA score = 9.4) cholestyramine compared with the control drink powder (mean BASA score = 16.7) (p < 0.001). BASA scale scores did not significantly differ between the 4 and 12 g of cholestyramine. (p = 0.215). Weighting of the components did not materially alter the results. Findings for the individual components of the BASA scale were similar to the composite values. CONCLUSION: The BASA scale effectively distinguished between an orange-flavoured BAS powder and a commercial orange-flavour control powder.

Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus.

This trial evaluated the effects of 16 weeks of consumption of 1000mg rebaudioside A (n=60) a steviol glycoside with potential use as a sweetener, compared to placebo (n=62) in men and women (33-75 years of age) with type 2 diabetes mellitus. Mean+/-standard error changes in glycosylated hemoglobin levels did not differ significantly between the rebaudioside A (0.11+/-0.06%) and placebo (0.09+/-0.05%; p=0.355) groups. Changes from baseline for rebaudioside A and placebo, respectively, in fasting glucose (7.5+/-3.7mg/dL and 11.2+/-4.5mg/dL), insulin (1.0+/-0.64microU/mL and 3.3+/-1.5microU/mL), and C-peptide (0.13+/-0.09ng/mL and 0.42+/-0.14ng/mL) did not differ significantly (p>0.05 for all). Assessments of changes in blood pressure, body weight, and fasting lipids indicated no differences by treatment. Rebaudioside A was well-tolerated, and records of hypoglycemic episodes showed no excess vs. placebo. These results suggest that chronic use of 1000mg rebaudioside A does not alter glucose homeostasis or blood pressure in individuals with type 2 diabetes mellitus.

The hemodynamic effects of rebaudioside A in healthy adults with normal and low-normal blood pressure.

Rebaudioside A and stevioside are steviol glycosides extracted from the plant Stevia rebaudiana Bertoni and are used in several countries as food and beverage sweeteners. This randomized, double-blind trial evaluated the hemodynamic effects of 4weeks consumption of 1000mg/day rebaudioside A vs. placebo in 100 individuals with normal and low-normal systolic blood pressure (SBP) and diastolic blood pressure (DBP). Subjects were predominantly female (76%, rebaudioside A and 82%, placebo) with a mean age of approximately 41 (range 18-73) years. At baseline, mean resting, seated SBP/DBP was 110.0/70.3mmHg and 110.7/71.2mmHg for the rebaudioside A and placebo groups, respectively. Compared with placebo, rebaudioside A did not significantly alter resting, seated SBP, DBP, mean arterial pressure (MAP), heart rate (HR) or 24-h ambulatory blood pressures responses. These results indicate that consumption of as much as 1000mg/day of rebaudioside A produced no clinically important changes in blood pressure in healthy adults with normal and low-normal blood pressure.

Effects of consuming foods containing oat beta-glucan on blood pressure, carbohydrate metabolism and biomarkers of oxidative stress in men and women with elevated blood pressure.

OBJECTIVE: To assess the effects of consuming foods containing oat beta-glucan on blood pressure, carbohydrate homeostasis and biomarkers of oxidative stress. DESIGN: A randomized, double-blind, controlled clinical trial. SETTING: The trial was conducted at two clinics. SUBJECTS AND INTERVENTIONS: Ninety-seven men and women with resting systolic blood pressure 130-179 mm Hg and/or diastolic blood pressure 85-109 mm Hg were randomly assigned to consume foods containing oat beta-glucan or control foods for 12 weeks. Resting blood pressures, insulin and glucose values before and after standard breakfast meals, and four biomarkers of oxidative stress were measured before and at the end of the treatment period. RESULTS: Changes from baseline to week 12 in mean peak insulin and incremental area under the insulin curve differed significantly between groups (P=0.037 and 0.034, respectively), with the beta-glucan group showing declines and the control group remaining essentially unchanged. Blood pressure responses were not significantly different between groups overall. However, in subjects with body mass index above the median (31.5 kg/m(2)), both systolic (8.3 mm Hg, P=0.008) and diastolic (3.9 mm Hg, P=0.018) blood pressures were lowered in the beta-glucan group compared to controls. No significant differences in biomarkers of oxidative stress were observed between treatments. CONCLUSIONS: The results of the present trial suggest beneficial effects of foods containing beta-glucan from oats on carbohydrate metabolism, and on blood pressure in obese subjects.

Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil.

BACKGROUND: Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels. OBJECTIVES: The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women. SUBJECTS/METHODS: As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation. RESULTS: Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL1+2-C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6 versus 0.7 mg/dl, respectively, P=0.016). CONCLUSIONS: CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.

A comparison of Canadian and American guidelines for lipid management using data from the National Cholesterol Education Program Evaluation ProjecT Utilizing Novel E-technology (NEPTUNE) II survey.

BACKGROUND: The United States' National Cholesterol Education Program (NCEP) Adult Treatment Panel III and the Canadian Working Group on Hypercholesterolemia and Other Dyslipidemias (CWG) have each issued guidelines for the treatment of dyslipidemia. OBJECTIVE: The present analysis compared the percentage of patients reaching target lipid levels according to NCEP and CWG guidelines among participants of the NCEP Evaluation ProjecT Utilizing Novel E-technology (NEPTUNE) II, a survey performed in the United States. METHODS: American physicians who were high prescribers of lipid-modifying medications (n=376) each enrolled 10 to 20 consecutive patients from February to September 2003. Medical information, laboratory measurements and treatment plans associated with a single office visit were entered into a personal digital assistant and uploaded to a central database via the Internet. RESULTS: Under both sets of guidelines, treatment success was strongly related to risk category (P<0.001). Treatment goal achievement in the low-risk (zero or one risk factor) and moderate-risk (two or more risk factors) categories was not substantially different between NCEP and CWG guidelines; however, in the high-risk category (coronary artery disease [CAD] and risk equivalents [RE]), CWG treatment goals were met less frequently than NCEP goals. NCEP combined low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals were met by 39% of hypertriglyceridemic patients (27% in the CAD + CAD RE category). CWG combined low-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio treatment goals were met by 38% of hypertriglyceridemic patients (19% in the CAD + CAD RE category). CONCLUSIONS: These data indicate substantial underachievement of treatment goals by patients at high risk under both the CWG and NCEP guidelines. The lower frequency of treatment success in high-risk patients according to the CWG definition indicates that more aggressive treatment is needed to reach CWG goals.

A comparison of estrogen replacement, pravastatin, and combined treatment for the management of hypercholesterolemia in postmenopausal women.

OBJECTIVES: To evaluate and compare the lipid-altering effects of conjugated estrogens and pravastatin, alone and in combination, in postmenopausal women with hypercholesterolemia. METHODS: This was a double-blind, randomized, placebo-controlled clinical trial with 4 parallel groups. Participants (N = 76) were randomly assigned to receive conjugated estrogens, 0.625 mg/d; pravastatin sodium, 20 mg/d; conjugated estrogens plus pravastatin; or a placebo for 16 weeks. RESULTS: Primary end points were changes in serum lipid parameters. Among participants treated with conjugated estrogens, levels of non-high density lipoprotein cholesterol (non-HDL-C) (13.0%) and calculated low density lipoprotein cholesterol (LDL-C) (13.5%) decreased, while levels of HDL-C (22.5%) and triglycerides (4.2%) increased. Participants in the pravastatin group achieved reductions of 23.7% and 25.4% in non-HDL-C and calculated LDL-C levels, respectively. Levels of HDL-C increased slightly (3.7%) and triglycerides decreased by 12.1%. Among participants treated with a combination of conjugated estrogens plus pravastatin, the non-HDL-C (-25.2%) and calculated LDL-C (-28.7%) responses were similar to those of the pravastatin group, and the HDL-C response (21.2%) was similar to that observed in the conjugated estrogens group. Triglyceride levels remained similar to baseline (-0.9%) in the combined treatment group. CONCLUSIONS: Administration of conjugated estrogens resulted in potentially antiatherogenic changes in levels of non-HDL-C, HDL-C, and calculated LDL-C. The HDL-C response to combined treatment was similar to that observed in women taking conjugated estrogens alone, while the non-HDL-C and LDL-C responses to combined treatment were similar to those produced by pravastatin therapy alone. These findings support the position of the National Cholesterol Education Program that estrogen replacement, with a progestin where indicated, should be given consideration as a therapeutic option for the management of hypercholesterolemia in postmenopausal women.

Comparison of the effects of lean red meat vs lean white meat on serum lipid levels among free-living persons with hypercholesterolemia: a long-term, randomized clinical trial.

BACKGROUND: Patients with hypercholesterolemia are often counseled to limit or eliminate intake of red meats, despite evidence that lean red meats (LRMs) are not hypercholesterolemic in comparison with lean white meats (LWMs). The objective of this study was to evaluate the long-term effects on serum lipids of incorporating LRM (beef, veal, and pork) vs LWM (poultry and fish) into a National Cholesterol Education Program (NCEP) Step I diet in free-living individuals with hypercholesterolemia. METHODS: Subjects included 191 men and women with a serum low-density lipoprotein cholesterol level of 3.37 to 4.92 mmol/L (130-190 mg/dL) and triglyceride level less than 3.96 mmol/L (350 mg/dL). After a 4-week baseline phase, subjects were counseled to follow an NCEP Step I diet including 170 g (6 oz) of lean meat per day, 5 to 7 days per week. Based on random assignment, subjects were instructed to consume at least 80% of their meat in the form of LRM or LWM. Fasting serum lipid levels were assessed 4, 12, 20, 28, and 36 weeks after randomization. RESULTS: After randomization, mean concentrations of total cholesterol (6.09 mmol/L [235.7 mg/dL] vs 6.08 mmol/L [235.2 mg/dL]) and low-density lipoprotein cholesterol (3.99 mmol/L [154.1 mg/dL] vs4.01 mmol/L [154.7 mg/dL]) were nearly identical in the LRM and LWM groups (1%-3% below baseline) during treatment. Mean triglyceride levels remained similar to baseline values and high-density lipoprotein cholesterol concentrations increased by approximately 2% in both groups. CONCLUSIONS: The NCEP Step I diets containing primarily LRM or LWM produced similar reductions in low-density lipoprotein cholesterol and elevations in high-density lipoprotein cholesterol levels, which were maintained throughout 36 weeks of treatment.

Effects of continuous estrogen and estrogen-progestin replacement regimens on cardiovascular risk markers in postmenopausal women.

OBJECTIVE: To evaluate the influence of 2 continuous combined estrogen-progestin replacement products, compared with unopposed estrogen and placebo, on cardiovascular risk markers in postmenopausal women in a randomized, double-blind, placebo-controlled trial. METHODS: Two hundred seventy healthy postmenopausal women were randomly assigned to 1 of 4 treatment groups: placebo, unopposed 17-beta estradiol (1 mg), 1 mg of 17-beta estradiol with 0.25 mg of norethindrone acetate, or 1 mg of 17-beta estradiol with 0.5 mg of norethindrone acetate. The primary outcome variable was change from baseline in low-density lipoprotein cholesterol concentration. Additional outcome variables included changes in other serum lipid levels, hemostatic variables, and indicators of carbohydrate metabolism. RESULTS: The low-density lipoprotein cholesterol level was reduced to a similar degree in all groups receiving active treatment (10%-14% from baseline; P =.001 for 17-beta estradiol with 0.5 mg of norethindrone acetate, P =.004 for 17-beta estradiol with 0.25 mg of norethindrone acetate, and P =. 001 for 1 mg of 17-beta estradiol vs placebo). Compared with unopposed 17-beta estradiol, 17-beta estradiol with 0.5 mg of norethindrone acetate enhanced the reductions in total cholesterol and apolipoprotein B levels (P<.01 vs 17-beta estradiol). 17-beta Estradiol plus norethindrone blunted or reversed the increases in levels of high-density lipoprotein cholesterol, apolipoprotein A-I, and triglycerides produced by 17-beta estradiol alone. Effects of 17-beta estradiol plus norethindrone on hemostatic variables were similar to those of 17-beta estradiol except for factor VII activity, which was significantly reduced with 17-beta estradiol combined with 0.25 mg (P<.01) and 0.5 mg (P<.05) of norethindrone acetate. 17-beta Estradiol plus norethindrone appeared to blunt reductions in C-peptide and insulin levels produced by unopposed 17-beta estradiol but did not elevate these values compared with placebo. CONCLUSIONS: 17-beta Estradiol plus norethindrone produced favorable changes in most cardiovascular risk markers evaluated and has a profile distinct from that of unopposed 17-beta estradiol. The impact of these differences on cardiovascular events warrants investigation. Arch Intern Med. 2000;160:3315-3325.

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols.

This randomized, double-blind, placebo-controlled multi-center trial investigated the lipid-altering effects of a medical food (PDL-0101) providing 1.8 g/d eicosapentaenoic acid; 12 mg/d astaxanthin, a marine algae-derived carotenoid; and 100 mg/d tocopherol-free gamma/delta tocotrienols enriched with geranylgeraniol, extracted from annatto, on triacylglycerols (TAG), other lipoprotein lipids, and oxidized low-density lipoprotein (LDL) in 102 subjects with TAG 150-499 mg/dL (1.69-5.63 mmol/L) and LDL cholesterol (LDL-C) ≥70 mg/dL (1.81 mmol/L). Compared to placebo, after eight weeks of treatment, PDL-0101 significantly reduced median TAG (-9.5% vs. 10.6%, p<0.001), while not significantly altering mean LDL-C (-3.0% vs. -8.0% for PDL-0101 and placebo, respectively, p=0.071), mean high-density lipoprotein cholesterol (~3% decrease in both groups, p=0.732), or median oxidized LDL concentrations (5% vs. -5% for PDL-0101 and placebo, respectively, p=0.112). These results demonstrate that PDL-0101 is an effective medical food for the management of elevated TAG.

Circulating levels of insulin-like growth factor (IGF) binding protein-1 and -3 in aging men: relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures.

Reduced secretion of GH and production of insulin-like growth factor I (IGF-I) contribute to altered body composition in human aging. IGF-binding proteins (IGFBPs) are important modulators of IGF action, yet little is known regarding their role and regulation in aging. Accordingly, we measured levels of IGFBP-1, an important short term modulator of IGF bioavailability that is suppressed by insulin, and levels of IGFBP-3, the major circulating IGF carrier protein, and examined their relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures in old (63-89 yr) and young (23-39 yr) men. Serum levels of IGFBP-1 were increased 3-fold in old vs. young men despite high insulin levels in elders. Nevertheless, IGFBP-1 and insulin levels correlated in old and young men (r = - 0.49; P < 0.002 and r = -0.42; P < 0.025), suggesting that insulin continues to play an important role in the regulation of IGFBP-1 in aging. Glucose levels also were significantly inversely related to IGFBP-1 in old and young men (r = 0.37; P = 0.02 and r = -0.49; P < 0.01), and this relationship was not accounted for by the effect of insulin. IGF-I levels were reduced by 33% in elders (P < 0.001) and correlated with IGFBP-1 levels among old (r = -0.40; P < 0.01), but not young, men, indicating that low GH secretion and/or IGF-I production may contribute to the elevation of IGFBP-1 levels in aging. IGFBP-3 levels were reduced among elders, but not to the same extent as IGF-I, resulting in a relative excess of IGFBP-3 in elders (IGFBP-3/IGF-I ratio, 20.1 +/- 0.9 vs. 15.4 +/- 1.0; P < 0.001). The IGFBP-3/IGF-I ratio correlated with IGF-I levels in young and old men (r = -0.79; P < 0.001 and r = -0.82; P < 0.001), indicating that diminished GH secretion also may contribute to a relative excess of IGFBP-3 among elders. Dehydroepiandrosterone sulfate levels were low in elders, but did not correlate with IGF, IGFBP, insulin, or glucose levels in either age group. Serum levels of IGFBP-1 (but not IGF-I or -II or IGFBP-3) correlated with body mass index and upper arm fat and muscle areas in elders. These relationships were accounted for by the effects of insulin, suggesting that regulation of IGFBP-1 by insulin may play a role in determining body composition in aging. We conclude that insulin remains an important determinant of IGFBP-1 levels in elders, that the fasting glucose level is also a significant determinant of IGFBP-1 in both old and young subjects, and that reduced secretion of GH may contribute to impaired anabolism in aging through multiple mechanisms, including reduced production of IGF-I and alterations in circulating levels of both IGFBP-1 and -3. These findings are consistent with the concept that alterations in IGFBP levels may contribute to changes in IGF bioavailability and body composition in aging.

Long-term effects of consuming foods containing psyllium seed husk on serum lipids in subjects with hypercholesterolemia.

The effects of consuming foods containing 0 (control), 3.4, 6.8, or 10.2 g psyllium seed husk (PSH)/d for 24 wk on the serum lipid profile were assessed in this randomized, double-blind controlled study. Men and women (n = 286) with LDL-cholesterol concentrations between 3.36 and 5.68 mmol/L (130 and 220 mg/dL) were randomly assigned to one of four treatment groups after following a low-fat diet for > or = 8 wk. At week 24, LDL cholesterol was 3% above baseline in the control group. In the group consuming 10.2 g PSH/d, LDL cholesterol remained below baseline during treatment, with a value 5.3% below that of the control group at week 24 (P < 0.05 compared with the control group). No significant differences were observed in HDL cholesterol or triacylglycerol. Although modest, the effect of 10.2 g PSH/d on LDL cholesterol (relative to the control) persisted throughout the 24-wk treatment period, indicating potential for long-term benefit.

Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet.

BACKGROUND: Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet. OBJECTIVE: This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia. DESIGN: Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group). RESULTS: Subjects in the low- and high-sterol groups who consumed > or = 80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control). CONCLUSION: A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia.

Separate and joint effects of marine oil and simvastatin in patients with combined hyperlipidemia.

Marine oil plus simvastatin is an effective therapy for improving serum triglycerides, non-high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with combined hyperlipidemia. Concurrent administration does not attenuate the individual effects of either marine oil or simvastatin on the serum lipid profile.

Association between elevated plasma fibrinogen and the small, dense low-density lipoprotein phenotype among postmenopausal women.

A predominance of small, dense low-density lipoprotein (LDL) particles (subclass pattern B) has been associated with a 2- to threefold increase in coronary heart disease risk. Recently, it has been reported that LDL subclass pattern B is associated with hyperfibrinogenemia, which is also a coronary heart disease risk factor. The present study examined the relation between hyperfibrinogenemia and LDL subclass pattern in 258 postmenopausal women. A significant univariate correlation was observed between the concentration of cholesterol carried in small, dense LDL particles and plasma fibrinogen concentration (r = 0.17, p = 0.01). The prevalence of LDL subclass pattern B was 41.9% in the highest fibrinogen tertile, compared with 27.9% and 24.4% in the first and second tertiles, respectively (global chi-square 6.8, p = 0.03). The crude odds ratio (OR) for LDL subclass pattern B among women in the highest fibrinogen tertile, compared with the lower tertiles, was 2.03 (95% confidence interval [CI] 1.18 to 3.51, p = 0.01). After adjustment for age and plasma lipids (log(e) triglycerides, LDL cholesterol, and high-density lipoprotein cholesterol), the OR was 2.14 (95% CI 1.17 to 3.96, p = 0.01). Further adjustment for hematocrit, indicators of carbohydrate homeostasis, body mass index, waist circumference, and several variables related to lifestyle did not attenuate this association (OR 2.56, 95% CI 1.27 to 5.27, p = 0.01). These data suggest that hyperfibrinogenemia and LDL subclass pattern B may be 2 components of a common syndrome and suggest that hyperfibrinogenemia may contribute to the increased coronary heart disease risk associated with LDL subclass pattern B.

Cholesterol lowering with high-viscosity hydroxypropylmethylcellulose.

Hydroxypropylmethylcellulose (HPMC) is a food gum having several structural and functional properties in common with hypocholesterolemic soluble fibers. The safety and cholestero-lowering efficacy of HPMC, incorporated into a National Cholesterol Education Program Step I diet, was compared with placebo in patients with mild to moderate hypercholesterolemia. After an 8-week National Cholesterol Education Program Step I dietary lead-in phase, 160 patients with low-density lipoprotein (LDL) cholesterol between 130 and 200 mg/dl and triglycerides <300 mg/dl were randomized to placebo, 2.5, 5.0, or 7.5 g/day of HPMC for a 6-week treatment period. Patients returned to the clinic every 2 weeks for lipid measurements and safety assessments. HPMC significantly lowered total, LDL, and non-high-density lipoprotein (HDL) cholesterol. LDL cholesterol concentrations (average of weeks 4 and 6) decreased by 3.0% (4.9 mg/dl), 5.9% (10.3 mg/dl), 12.1% (20.4 mg/dl), and 11.7% (20.3 mg/dl) from baseline levels in the placebo and 2.5, 5.0, and 7.5 g/day HPMC treatment groups, respectively. Statistically significant (p<0.05) reductions in LDL cholesterol were observed in the 5.0 and 7.5 g/day HPMC groups compared with placebo and 2.5 g/day HPMC treatment groups. Total and non-HDL cholesterol responses paralleled those of LDL cholesterol. There were no significant differences between the treatment groups in HDL cholesterol or triglyceride responses, incidence of adverse experiences, or gastrointestinal-related adverse experiences. These results suggest that HPMC is a well-tolerated and effective adjunct to diet for lowering LDL cholesterol in patients with mild to moderate hypercholesterolemia.

Colesevelam hydrochloride: a non-absorbed, polymeric cholesterol-lowering agent.

Colesevelam hydrochloride (formerly known as Cholestagel((R)) and re-named WelCholtrade mark, GelTex Pharmaceuticals, Inc. and Sankyo Parke-Davis) is a new, polymeric, high potency, water-absorbing hydrogel. It has been shown to be a safe and effective cholesterol-lowering agent with a non-systemic mechanism of action, good tolerability and minimal side effects. To date, the lipid-lowering activity of colesevelam has been evaluated in approximately 1400 subjects. Colesevelam reduces low density lipoprotein (LDL)-cholesterol levels, in a dose-dependent manner, by as much as 20% (median) in patients with hypercholesterolaemia. Dosing regimen evaluations indicate that colesevelam is effective at both once per day and twice daily dosing and that concurrent administration of colesevelam with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), specifically lovastatin, does not alter the absorption of the statin. Combination therapy with HMG-CoA reductase inhibitors, including lovastatin, simvastatin and atorvastatin, produces an additional reduction (8 - 16%) in LDL-cholesterol levels above that seen with the statin alone. The overall incidence of adverse effects with colesevelam alone and in combination with statins is comparable with that seen with placebo. Colesevelam lacks the constipating effect seen with typical bile acid sequestrants, a trait that would be expected to improve compliance with lipid-lowering therapy. Colesevelam, recently approved by the US FDA, represents a valuable non-absorbed alternative in the armamentarium against hypercholesterolaemia, both for monotherapy and combination therapy, as an adjunct to diet and exercise.

Effects of oral albuterol on serum lipids and carbohydrate metabolism in healthy men.

beta(2)-Selective adrenergic agonists are used in the management of bronchial asthma and preterm labor. Due to their ability to increase muscle strength and size in animal models, new applications for these agents are also being explored for neuromuscular disorders and in rehabilitation. However, the effects of long-term beta(2)-agonist administration on lipoprotein and carbohydrate metabolism are incompletely understood. This investigation evaluated the effects of a beta(2)-agonist, albuterol, on serum lipids and carbohydrate homeostasis in eight healthy nonsmoking men aged 24 to 61 years. Collection of fasting blood samples was completed in duplicate on separate days at baseline, during 14 days of oral albuterol administration (Proventil Repetabs, 8 mg twice daily; Schering Pharmaceuticals, Kenilworth, NJ) and during a 7-day washout period. Carbohydrate homeostasis was evaluated using the minimal model technique at the end of the baseline and albuterol periods. Fasting glucose and insulin, intravenous glucose tolerance, acute insulin response to intravenous glucose (AIRg), insulin sensitivity (Si), and glucose effectiveness (Sg) were not significantly changed during albuterol administration. Significant alterations (P < or = .02) were observed in total cholesterol ([TC] -9.1% +/- 2.5%), low-density lipoprotein cholesterol ([LDL-C] -15.0% +/- 2.9%), and high-density lipoprotein cholesterol ([HDL-C] +10.4% +/- 3.2%) concentrations, as well as the TC/HDL-C (-17.4% +/- 2.6%) and LDL-C/HDL-C (-22.9% +/- 2.4%) ratios. During washout, TC and LDL-C returned to baseline levels, whereas HDL-C remained elevated by 5.8% +/- 2.4% (P < .05). Thus, albuterol administration was associated with favorable changes in the serum lipid profile without marked impairment of glucose tolerance or its physiologic determinants.

Simultaneous monitoring of heart rate and motion to assess energy expenditure.

Measurement of energy expenditure in free-living individuals represents a methodologic challenge in epidemiologic research. Heart rate monitors, while closely tied to energy expenditure at high levels of energy output, provide much less predictive power at low levels; however, measurement of motion may improve the predictive ability. This study was undertaken to determine the usefulness of simultaneously monitoring heart rate and motion for the estimation of energy expenditure. Ten subjects were studied during simulated activities of daily living (ADLC) and submaximal treadmill tests. Compared to direct measurement, the motion sensor predicted oxygen consumption poorly (r2 = 0.53) for both tests. Heart rate measured simultaneously yielded an r2 of 0.81 for ADLC and 0.90 for the treadmill. Addition of motion data increased the r2 value for the ADLC for all but one individual and increased the group mean from 0.81 to 0.86. This improvement was not observed for the treadmill, confirming the hypothesis that the principle value of monitoring motion occurs at lower heart rates.