Objective

To investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 levels) to the risk of developing Alzheimer disease (AD) and all-cause dementia.

Design

Prospective cohort study.

Setting

Dementia-free Framingham Heart Study participants had sera measured for these biomarkers at the 19th biennial examination (1985–1988) and were followed up prospectively for the development of AD and all-cause dementia.

Participants

Eight hundred forty (541 women, median age of 76 years) subjects participated in the study.

Main Outcome Measures

We used sex-pooled and sex-specific multivariable Cox proportional hazards models adjusted for age, education, body mass index, recent change in weight, APOE ε4 allele status, and plasma docosahexaenoic acid levels to determine association of these biomarkers with the development of all-cause dementia and AD.

Results

Over a mean follow-up period of 13 years, 159 persons developed dementia (including 125 with AD). After adjustment for other risk factors, only adiponectin in women was associated with an increased risk of all-cause dementia (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.00–1.66; P=.054) and AD (HR, 1.33; 95% CI, 1.00–1.76; P=.050) per 1-SD increase in adiponectin level. Women with baseline adiponectin values more than the median had a higher risk of all-cause dementia (HR, 1.63; 95% CI, 1.03–2.56; P=.04) and AD (HR, 1.87; 95% CI, 1.13–3.10; P=.01) as compared with those with values less than the median.

Conclusion

In women, increased plasma adiponectin levels are an independent risk factor for the development of both all-cause dementia and AD.

Background

Information is scarce regarding the effect of dietary protein type, with specific focus on the lysine to arginine (Lys:Arg) ratio, on cardiovascular risk factors and vascular reactivity in humans.

Objective

Determine effect of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults.

Design

Randomized cross-over design of two 35-day diet phases; thirty adults (21 females and 9 males, ≥50 y, LDL cholesterol ≥120 mg/dL). Diets had 20% energy (E) protein, 30%E fat, 50%E carbohydrate and were designed to have low (0.7) or high (1.4) Lys:Arg ratio. Measures included fasting and postprandial lipid, lipoprotein, apolipoprotein concentrations; fasting high sensitivity C-reactive protein (hsCRP), small dense LDL (sdLDL)-cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities; cholesterol fractional synthesis rate (FSR); and flow mediated dilation (FMD) and peripheral artery tonometry (PAT).

Results

No differences were observed in fasting and/or postprandial total, LDL, HDL and sdLDL cholesterol, RemLC, Lp(a) or apo B concentrations, LCAT and CETP activities, FSR, glycated albumin, immunoreactive insulin, FMD or PAT. The low, relative to the high, Lys:Arg ratio diet resulted in lower postprandial VLDL cholesterol (−24%, P=0.001) and triglycerides (−23%, P=0.001), and small but significant differences in fasting (−3%, P=0.003) and postprandial (−3%, P=0.018) apo AI, and fasting adiponectin concentrations (+7%, P=0.035). Fasting and postprandial hsCRP concentrations were 23% lower after the low Lys:Arg ratio diet (P=0.020 for both).

Conclusions

Diets differing in Lys:Arg ratios had no or small effects on cardiovascular risk factors and vascular reactivity.

Objectives

Familial combined hyperlipidemia (FCH) is a common familial lipid disorder characterized by increases in plasma total cholesterol, triglyceride and apolipoprotein B-100 levels. In light of prior metabolic and genetic research, our purpose was to ascertain whether FCH cases had significant abnormalities of plasma markers of cholesterol synthesis and absorption as compared to unaffected kindred members.

Methods and Results

Plasma levels of squalene, desmosterol and lathosterol (cholesterol synthesis markers) and campesterol, sitosterol and cholestanol (cholesterol absorption markers) were measured by gas-liquid chromatography in 103 FCH patients and 240 normolipidemic relatives (NLR). Squalene, desmosterol, and lathosterol levels were 6% (0.078), 31%, (p<0.001) and 51% (p<0.001) higher in FCH as compared to NLR, and these differences were especially pronounced in women. An interaction with obesity was also noted for a subset of these markers. We did not observe any apparent differences for the cholesterol absorption markers among FCH patients and NLR.

Conclusions

Our data indicate that both men and women with FCH have alterations in the cholesterol synthesis pathway, resulting in 51% higher levels of lathosterol (and additionally desmosterol in women). Plasma levels of the cholesterol precursor sterol squalene were only slightly increased (6%), suggesting enhanced conversion of squalene to lathosterol in this disorder.

Objective

Compared to vegetable oils in their unmodified state, partially-hydrogenated fat is associated with less favorable effects on cardiovascular disease (CVD) risk factors. Acceptable alternatives must be adjudicated. Our objective was to assess the effect of a recent commercial fat substitution, corn oil for partially-hydrogenated soybean oil.

Methods

Using a double-blind cross-over design, 30 postmenopausal women ≥50 y with LDL-cholesterol concentrations ≥120 mg/dL were randomly assigned to each of two 35-day phases; all food and beverage was provided to maintain body weight. Corn or partially-hydrogenated soybean oil was incorporated throughout the diet and contributed two-thirds of fat. Primary outcomes included fasting and non-fasting lipid, lipoprotein, apolipoprotein, and fasting high sensitivity C-reactive protein (hsCRP) concentrations; secondary outcomes included fasting small dense LDL (sdLDL)-cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, and endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities.

Results

Relative to the partially-hydrogenated soybean oil-enriched diet, the corn oil enriched diet resulted in lower fasting total cholesterol (7%; P<0.0001), LDL-cholesterol (10%; P<0.0001), VLDL-cholesterol (7%; P=0.052), apo B (9%; P<0.0001), Lp(a) (5%; P=0.024), sdLDL-cholesterol (17%; P=0.001), and RemLC (20%; P=0.007) concentrations, and no significant effect on the other outcomes. Changes in postprandial (4-h post-meal) lipid, lipoprotein and apolipoprotein concentrations were similar to the fasting state.

Conclusion

The replacement of partially-hydrogenated soybean oil with corn oil favorably affects a range of CVD risk factors and is an appropriate option to decrease cardiovascular disease risk factors in moderately hypercholesterolemic individuals.

Objectives

Extended-release niacin effectively lowers plasma TG levels and raises plasma HDL cholesterol levels, but the mechanisms responsible for these effects are unclear.

Methods and Results

We examined the effects of extended-release niacin (2 g/d) and extended-release niacin (2 g/d) plus lovastatin (40 mg/d), relative to placebo, on the kinetics of apolipoprotein (apo) A-I and apoA-II in HDL, apoB-100 in TG-rich lipoproteins (TRL), intermediate-density lipoproteins (IDL) and LDL, and apoB-48 in TRL in five men with combined hyperlipidemia. Niacin significantly increased HDL cholesterol and apoA-I concentrations, associated with a significant increase in apoA-I production rate (PR) and no change in fractional catabolic rate (FCR). Plasma TRL apoB-100 levels were significantly lowered by niacin, accompanied by a trend toward an increase in FCR and no change in PR. Niacin treatment significantly increased TRL apoB-48 FCR but had no effect on apoB-48 PR. No effects of niacin on concentrations or kinetic parameters of IDL and LDL apoB-100 and HDL apoA-II were noted. The addition of lovastatin to niacin promoted a lowering in LDL apoB-100 due to increased LDL apoB-100 FCR.

Conclusion

Niacin treatment was associated with significant increases in HDL apoA-I concentrations and production, as well as enhanced clearance of TRL apoB-100 and apoB-48.

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.

We investigated the significance of endogenous reactive oxygen species (ROS) produced by fungi treated with miconazole. ROS production in Candida albicans was measured by a real-time fluorogenic assay. The level of ROS production was increased by miconazole at the MIC (0.125 μg/ml) and was enhanced further in a dose-dependent manner, with a fourfold increase detected when miconazole was used at 12.5 μg/ml. This increase in the level of ROS production was completely inhibited by pyrrolidinedithiocarbamate (PDTC), an antioxidant, at 10 μM. In a colony formation assay, the decrease in cell viability associated with miconazole treatment was significantly prevented by addition of PDTC. Moreover, the level of ROS production by 10 clinical isolates of Candida species was inversely correlated with the miconazole MIC (r = −0.8818; P < 0.01). These results indicate that ROS production is important to the antifungal activity of miconazole.