Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes.

OBJECTIVE: Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding. RESEARCH DESIGN AND METHODS: This double-blinded and placebo (PL)-controlled study included 22 patients with T2DM patients (11 male, 11 female; age 57.1±12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of WP was compared with PL in parallel-armed acute challenge studies. Next, in a crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5 days each week. Identical diets were provided by the study during both CGM periods. During the first CGM, one serving of either WP or PL was consumed before breakfast and another before dinner. During the second CGM, participants switched to the alternate supplement. Order of the supplements was randomized. RESULTS: During acute challenge studies, WP stimulated insulin and glucagon-like peptide (GLP)-1 secretion; suppressed ghrelin (all p<0.05), while PL had no effect. During CGM, glucose response to WP varied depending on the baseline characteristics of the patients. When evaluated using linear regression, the most predictive baseline variables were body mass index (BMI) (p=0.0006), triglycerides (p=8.3×10-5) and GLP-1 (p=0.006). Lower BMI, triglyceride and GLP-1 predicted decreased glucose levels on WP. Obesity, hypertriglyceridemia and high fasting GLP-1 concentrations predicted increased glucose levels. CONCLUSIONS: Effects of WP supplementation on glycemia in T2DM depend on the baseline characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high baseline GLP-1 predict increased glucose response.

Lignan content of the flaxseed influences its biological effects in healthy men and women.

OBJECTIVE: The omega-3 polyunsaturated fatty acid (n-3 PUFA) as well as lignan components of flaxseed (FLX) can have beneficial effects. In this 6-week-long, randomized, double-blinded, placebo-controlled study, we investigated the effects of FLX lignans on cardiovascular risk factors. METHODS: Thirty-seven subjects (13 men and 24 women, age: 54±7 years, body mass index [BMI]: 29.7±1 kg/m2) consumed nutrition bars with similar macronutrient contents. The fatty acid composition and the lignan contents of the bars differed significantly. Two FLX bars both contained 3.0 g of alpha linolenic acid (ALA: 18:3 n-3) but different amount of lignans (0.15 g vs. 0.41 g). RESULTS: High-lignan FLX decreased total cholesterol (C) by 12% (p=0.044), LDL-C by 15% (p=0.022), and oxidized (Ox)-LDL by 25% (p=0.035). Regular FLX tended to increase Ox-LDL by 13% (p=0.051). The difference between the effects of high-lignan vs. regular lignan FLX on Ox-LDL was highly significant (p=0.004). CONCLUSION: High-lignan FLX has the unique property of decreasing Ox-LDL, which is an independent risk factor for cardiovascular disease.

Lean mass and insulin resistance in women with polycystic ovary syndrome.

Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Muscle is the major tissue utilizing glucose while excess adipose tissue relates to insulin resistance. Thus, body composition is likely to be an important regulator of insulin sensitivity. Thirty-nine PCOS patients (age: 29.9±1.0 years; BMI: 33.8±1.2 kg/m(2)) participated in a cross sectional study. Body composition was measured by dual energy x-ray absorptiometry (DEXA). Insulin resistance and secretion were assessed using oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FS-IVGTT). In contrast with the conventional expectations, lean mass correlated directly (P<.05) with the insulin resistance measure HOMA (r=0.440); and inversely with the insulin sensitivity index QUICKI (r=-0.522) independent of fat mass. In 11 pairs of subjects matched for fat mass (35.6±2.2 and 35.6±2.4 kg) but with discordant lean mass (52.8±1.8 vs 44.4±1.6 kg), those with higher lean mass had a higher glucose response during OGTT (AUC(Glucose); P=.034). In contrast, 17 pairs matched for lean mass (48.7±1.7 and 48.9±1.6 kg) but discordant for fat mass (43.3±2.6 vs 30.3±8.9 kg) showed no differences in insulin resistance parameters. These novel findings indicate that lean mass relates directly to insulin resistance in PCOS.

Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome.

The objective of the study was to compare the effects of essential vs long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) in polycystic ovary syndrome. In this 6-week, prospective, double-blinded, placebo (soybean oil)-controlled study, 51 completers received 3.5 g n-3 PUFA per day (essential PUFA from flaxseed oil or long-chain PUFA from fish oil). Anthropometric variables, cardiovascular risk factors, and androgens were measured; oral glucose tolerance test (OGTT) and frequently sampled intravenous GTT (IVGTT) were conducted at baseline and 6 weeks. Between-group comparisons showed significant differences in serum triglyceride response (P = .0368), whereas the changes in disposition index also tended to differ (P = .0621). When within-group changes (after vs before intervention) were considered, fish oil and flaxseed oil lowered serum triglyceride (P = .0154 and P = .0176, respectively). Fish oil increased glucose at 120 minutes of OGTT (P = .0355), decreased the Matsuda index (P = .0378), and tended to decrease acute insulin response during IVGTT (P = .0871). Soybean oil increased glucose at 30 (P = .0030) and 60 minutes (P = .0121) and AUC for glucose (P = .0122) during OGTT, tended to decrease acute insulin response during IVGTT (P = .0848), reduced testosterone (P = .0216), and tended to reduce sex hormone-binding globulin (P = .0858). Fasting glucose, insulin, adiponectin, leptin, or high-sensitivity C-reactive protein did not change with any intervention. Long-chain vs essential n-3 PUFA-rich oils have distinct metabolic and endocrine effects in polycystic ovary syndrome; and therefore, they should not be used interchangeably.

In polycystic ovary syndrome, adrenal steroids are regulated differently in the morning versus in response to nutrient intake.

OBJECTIVE: To investigate adrenal steroid regulation in polycystic ovary syndrome. DESIGN: Five-hour oral glucose tolerance test (OGTT) and frequently sampled-intravenous gluclose tolerance test. SETTING: University research center. PATIENT(S): Thirty patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Anthropometrics, leptin, cortisol, DHEAS, glucose, insulin. RESULT(S): Morning cortisol correlated with sensitivity index (SI, r = .540), DHEAS correlated inversely with age (r = -.6359), body mass index (BMI, r = -.6199), fat mass (r = -0.630), and leptin (r = -0.5676). Between the second and fourth hour of OGTT, cortisol changes (Delta) exhibited three patterns: I, responders (n = 9, Delta: 10.7 +/- 1.0 microg/dL); II, nonresponders (n = 10, Delta: -3.5 +/- 0.6 microg/dL); III, intermediates (n = 11, Delta: 4.3 +/- 1.0 microg/dL). Compared with nonresponders, responders were more obese (BMI: 37.0 +/- 1.6 vs. 31.7 +/- 1.8 kg/m(2)); had higher leptin (28.9 +/- 1.7 vs. 24.1 +/- 1.1 ng/mL), and lower DHEAS (133 +/- 12 vs. 236 +/- 32 ng/mL), higher glucose at 1 h of OGTT (195 +/- 13 vs. 131 +/- 12 mg/dL), higher area under the curve (AUC)(Glucose) (332 +/- 20 vs. 265 +/- 17 mg/dL), higher AUC(Insulin) (244 +/- 50 vs. 125 +/- 30 muU/mL), and lower nadir glucose (61 +/- 2 vs. 70 +/- 2 mg/dL). CONCLUSION(S): Obesity and insulin resistance are associated with lower morning cortisol and DHEAS but increased cortisol and DHEA responses after glucose ingestion. Morning steroid levels may not reflect the day-long exposure.

Serum fatty acid binding protein 4, free fatty acids, and metabolic risk markers.

Fatty acid binding protein (FABP) 4 chaperones free fatty acids (FFAs) in the adipocytes during lipolysis. Serum FFA relates to metabolic syndrome, and serum FABP4 is emerging as a novel risk marker. In 36 overweight/obese women, serum FABP4 and FFA were measured hourly during 5-hour oral glucose tolerance test. Insulin resistance was determined using frequently sampled intravenous glucose tolerance test. Serum lipids and inflammation markers were measured at fasting. During oral glucose tolerance test, serum FABP4 decreased by 40%, reaching its nadir at 3 hours (from 45.3 +/- 3.1 to 31.9 +/- 1.6 ng/mL), and stayed below the baseline at 5 hours (35.9 +/- 2.2 ng/mL) (P < .0001 for both, compared with the baseline). Serum FFA decreased by 10-fold, reaching a nadir at 2 hours (from 0.611 +/- 0.033 to 0.067 +/- 0.004 mmol/L), then rebounded to 0.816 +/- 0.035 mmol/L at 5 hours (P < .001 for both, compared with baseline). Both fasting FABP4 and nadir FABP4 correlated with obesity. Nadir FABP4 correlated also with insulin resistance parameters from frequently sampled intravenous glucose tolerance test and with inflammation. Nadir FFA, but not fasting FFA, correlated with the metabolic syndrome parameters. In conclusion, fasting FABP4 related to metabolic risk markers more strongly than fasting FFA. Nadir FABP4 and nadir FFA measured after glucose loading may provide better risk assessment than the fasting values.

Effects of protein versus simple sugar intake on weight loss in polycystic ovary syndrome (according to the National Institutes of Health criteria).

OBJECTIVE: To compare the effects of protein vs. simple sugars on weight loss, body composition, and metabolic and endocrine parameters in polycystic ovary syndrome (PCOS). DESIGN: A 2-month, free-living, randomized, single-blinded study. SETTING: University PCOS clinic. PATIENT(S): Thirty-three patients with PCOS. INTERVENTION(S): To achieve a final energy reduction of 450 kcal/day, first the daily energy intake was reduced by 700 kcal; then a 240-kcal supplement containing either whey protein or simple sugars was added. MAIN OUTCOME MEASURE(S): Changes in weight, fat mass, fasting glucose and insulin, plasma lipoproteins, and sex steroids. RESULT(S): Twenty-four subjects (13 in the simple sugars group and 11 in the protein group) completed the study. The protein group lost more weight (-3.3 +/- 0.8 kg vs. -1.1 +/- 0.6 kg) and more fat mass (-3.1 +/- 0.9 kg vs. -0.5 +/- 0.6 kg) and had larger decreases in serum cholesterol (-33.0 +/- 8.4 mg/dL vs. -2.3 +/- 6.8 mg/dL), high-density lipoprotein cholesterol (-4.5 +/- 1.3 mg/dL vs. -0.4 +/- 1.3 mg/dL), and apoprotein B (-20 +/- 5 mg/dL vs. 3 +/- 5 mg/dL). CONCLUSION(S): In patients with PCOS, a hypocaloric diet supplemented with protein reduced body weight, fat mass, serum cholesterol, and apoprotein B more than the diet supplemented with simple sugars.

Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome.

Effects of a polyunsaturated fatty acid (PUFA)-rich diet were investigated in 17 polycystic ovary syndrome (PCOS) patients. After a 3-month habitual diet period, dietary fats were partly replaced with PUFAs for another 3 months. The PUFA-rich diet increased plasma linoleic acid from 28.36 +/- 1.00% to 33.76 +/- 1.08% (P < 0.002) and alpha-linolenic acid from 0.52 +/- 0.03% to 1.06 +/- 0.10% (P < 0.0001). Fasting glucose increased from 76 +/- 3 to 95 +/- 3 mg/dl (4.2 +/- 0.2 to 5.30.2 mmol/liter; P < 0.0001), and the area under the curve for glucose during oral glucose tolerance test increased from 421 +/- 34 to 503 +/- 31 mg/dl (23.4 +/- 1.9 to 27.9 +/- 1.7 mmol/liter; P < 0.001). Plasma insulin did not change either at fasting or during oral glucose tolerance test. Fasting plasma free fatty acids decreased from 0.596 +/- 0.048 to 0.445 +/- 0.058 mg/dl (P = 0.037), and ketone bodies decreased from 9.14 +/- 1.57 to 3.63 +/- 0.62 mg/dl (895 +/- 154 to 356 +/- 61 micromol/liter; P < 0.003). Plasma 15-deoxyprostaglandin J(2) tended to decrease (from 239 +/- 65 to 171 +/- 60 ng/ml; P = 0.053). Plasma testosterone, free testosterone, SHBG, dehydroepiandrosterone sulfate, LH, FSH, and urinary estrogen conjugates did not change. Urinary pregnanediol 3-glucuronide increased from 18.6 +/- 2.2 to 31.0 +/- 5.7 micro g/mg creatinine (P = 0.038). In conclusion, increased dietary PUFA intake can exert significant metabolic and endocrine effects in women with PCOS.

Effects of prune consumption on the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone.

BACKGROUND: A higher urinary ratio of the biologically inactive estrogen metabolite, 2-hydroxyestrone (2OHE1), to the biologically active metabolite, 16alpha-hydroxyestrone (16alphaOHE1), may be associated with a lower risk of breast cancer. High fiber intake is also associated with decreased breast cancer risk. OBJECTIVE: We investigated the effects of prunes, which are naturally rich in both soluble and insoluble fiber, on the concentrations of 2OHE1 and 16alphaOHE1 and on the ratio of 2OHE1 to 16alphaOHE1. DESIGN: Nineteen healthy premenopausal women consumed their habitual diets for 3 menstrual cycles and then consumed 100 g prunes/d for the next 3 cycles. Concentrations of urinary 2OHE1 and 16alphaOHE1 were determined during the follicular and luteal phases. RESULTS: Prune supplementation increased total and soluble fiber intakes by 4 and 2 g/d, respectively (P < 0.001). Mean (+/- SEM) luteal 2OHE1 excretion decreased from 3.92 +/- 0.79 to 2.20 +/- 0.40 nmol/mmol creatinine during the third cycle (P = 0.017). Luteal 16alphaOHE1 excretion decreased from 1.38 +/- 0.24 to 0.87 +/- 0.10 and 0.87 +/- 0.15 nmol/mmol creatinine during the first and third cycles, respectively (P = 0.018 for both values). Follicular 16alphaOHE1 excretion decreased significantly only during the first cycle (from 0.82 +/- 0.12 to 0.45 +/- 0.09 nmol/mmol creatinine; P = 0.005). The 2OHE1-16alphaOHE1 ratio did not change significantly after prune supplementation. CONCLUSIONS: Prune supplementation significantly decreased the excretion of 16alphaOHE1 during the follicular phase of the first menstrual cycle and during the luteal phases of both the first and third menstrual cycles. The 2OHE1-16alphaOHE1 ratio did not change significantly. The potential significance of the decrease in 16alphaOHE1 excretion, without a change in the 2OHE1-16alphaOHE1 ratio, on the prevention of estrogen-dependent cancers remains to be determined.