Brian Fish

Effects of Insulin Resistance and Obesity on Lipoproteins and Sensitivity to Egg Feeding

Objective—This study was undertaken to determine if insulin resistance without and with obesity influences LDL response to dietary cholesterol and saturated fat. Methods and Results—We fed 0, 2, and 4 egg yolks per day to 197 healthy subjects in a 4-week, double-blind, randomized, crossover design. Subjects were dichotomized on body mass index (<27.5 and ≥27.5 kg/m2) and insulin sensitivity (insulin-sensitivity index ≥4.2×1.0−4 and <4.2×1.0−4 min−1 &mgr;U/mL), yielding insulin-sensitive (IS, n=65), insulin-resistant (IR, n=75), and obese insulin-resistant (OIR, n=58) subjects. Mean fasting baseline LDL cholesterol (LDL-C) levels were higher in IR and OIR subjects (3.44±0.67 and 3.32±0.80 mol/L) than in IS subjects (2.84±0.75 mmol/L) (P <0.001). Progressive triglyceride elevations and HDL-C decreases were seen across the 3 groups. Ingesting 4 eggs daily yielded significant LDL-C increases of 7.8±13.7% (IS) and 3.3±13.2% (IR) (both P <0.05) compared with 2.4±12.6% for OIR (NS). HDL-C increases were 8.8±10.4%, 5.2±10.4%, and 3.6±9.4% in IS, IR, and OIR, respectively (all P <0.01). Conclusions—Insulin resistance without and with obesity is associated with elevated LDL-C as well as elevated triglyceride and low HDL-C. The elevated LDL-C cannot be explained by dietary sensitivity, because the LDL-C rise with egg feeding is less in IR persons regardless of obesity status, probably attributable to diminished cholesterol absorption. The results suggest that dietary management of insulin resistance and obesity can focus more on restricting calories and less on restricting dietary fat.

The relationship between diet and breast cancer in men (United States)

Objectives: The purpose of this paper was to investigate the relationship between food and beverage consumption and the development of breast cancer in men.Methods: Possible relationships of dietary factors to risk of breast cancer in men were assessed in a case-control study conducted between 1983 and 1986. Cases (N=220) were ascertained from ten population-based cancer registries. Controls (N=291) were selected by random-digit dialing (<age 65) and from Health Care Financing Administration Medicare beneficiary lists (≥age 65).Results: No trends in risk were observed with increasing intakes of specific foods, except for an increase in risk with citrus fruits. No increase in risk with increasing amounts of specific fats, vitamins, or minerals or with amounts of protein, fiber, carbohydrate, starches, nitrites, or alcohol consumed was observed, except for an increase in risk with dietary vitamin C consumption. A decreasing trend in risk with dietary niacin and with coffee and an increasing trend in risk with tea consumption were observed. No associations were found with use of any dietary supplements, including vitamin C.Conclusions: The observed associations are not consistent with findings from studies of breast cancer in women and probably do not represent causal relationships. Dietary factors are unlikely to be strong determinants of breast cancer in men.

Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity

BACKGROUND The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. OBJECTIVE We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. DESIGN Plasma sterols were measured by gas chromatography-mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (S(I)) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. RESULTS The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol-cholesterol ratios were as follows: LIS > OIR (P < 0.001), LIS > LIR (P < 0.001), and LIR > OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS < OIR (P < 0.001), LIS < LIR (P = 0.03), and LIR < OIR (P = 0.002). Total sterol concentrations were positively associated with S(I) and negatively associated with obesity, whereas lathosterol correlations were the opposite. CONCLUSIONS Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I) and to decrease cholesterol overproduction in LIR and OIR persons.

Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease

INTRODUCTION Identification of factors associated with progression of cognitive symptoms in Parkinsons disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease. METHODS Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD. RESULTS Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males. CONCLUSIONS This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD.