Does conventional early life academic excellence predict later life scientific discovery? An assessment of the lives of great medical innovators.

BACKGROUND: Perhaps, as never before, we need innovators. With our growing population numbers, and with increasing pressures on our education systems, are we in danger of becoming more rigid and formulaic and increasingly inhibiting innovation? When young can we predict who will become the great innovators? For example, in medicine, who will change clinical practice? AIMS: We therefore determined to assess whether the current academic excellence approach to medical school entrance would have captured previous great innovators in medicine, assuming that they should all have well fulfilled current entrance requirements. METHODS: The authors assembled a list of 100 great medical innovators which was then approved, rejected or added to by a jury of 12 MD fellows of the Royal Society of Canada. Two reviewers, who had taken both the past and present Medical College Admission Test as part of North American medical school entrance requirements, independently assessed each innovator's early life educational history in order to predict the innovator's likely success at medical school entry, assuming excellence in all entrance requirements. RESULTS: Thirty-one percent of the great medical innovators possessed no medical degree and 24% would likely be denied entry to medical school by today's standards (e.g. had a history of poor performance, failure, dropout or expulsion) with only 24% being guaranteed entry. Even if excellence in only one topic was required, the figure would only rise to 41% certain of medical school entry. CONCLUSION: These data show that today's medical school entry standards would have barred many great innovators and raise questions about whether we are losing medical innovators as a consequence. Our findings have important implications for promoting flexibility and innovation for medical education, and for promoting an environment for innovation in general.

Risk Differences Between Prediabetes And Diabetes According To Breast Cancer Molecular Subtypes.

Hyperglycemia and hyperinsulinemia may play a role in breast carcinogenesis and prediabetes and diabetes have been associated with increased breast cancer (BC) risk. However, whether BC molecular subtypes may modify these associations is less clear. We therefore investigated these associations in all cases and by BC molecular subtypes among women living in Southern Italy. Cases were 557 patients with non-metastatic incident BC and controls were 592 outpatients enrolled during the same period as cases and in the same hospital for skin-related non-malignant conditions. Adjusted multivariate logistic regression models were built to assess the risks of developing BC in the presence of prediabetes or diabetes. The analyses were repeated by strata of BC molecular subtypes: Luminal A, Luminal B, HER2+, and Triple Negative (TN). Prediabetes and diabetes were significantly associated with higher BC incidence after controlling for known risk factors (OR = 1.94, 95% CI 1.32-2.87 and OR = 2.46, 95% CI 1.38-4.37, respectively). Similar results were seen in Luminal A and B while in the TN subtype only prediabetes was associated with BC (OR = 2.43, 95% CI 1.11-5.32). Among HER2+ patients, only diabetes was significantly associated with BC risk (OR = 3.04, 95% CI 1.24-7.47). Furthermore, when postmenopausal HER2+ was split into hormone receptor positive versus negative, the association with diabetes remained significant only in the former (OR = 5.13, 95% CI 1.53-17.22). These results suggest that prediabetes and diabetes are strongly associated with BC incidence and that these metabolic conditions may be more relevant in the presence of breast cancer molecular subtypes with positive hormone receptors. J. Cell. Physiol. 232: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc.

The effect of a dietary portfolio compared to a DASH-type diet on blood pressure.

BACKGROUND AND AIM: Compared to a DASH-type diet, an intensively applied dietary portfolio reduced diastolic blood pressure at 24 weeks as a secondary outcome in a previous study. Due to the importance of strategies to reduce blood pressure, we performed an exploratory analysis pooling data from intensively and routinely applied portfolio treatments from the same study to assess the effect over time on systolic, diastolic and mean arterial pressure (MAP), and the relation to sodium (Na(+)), potassium (K(+)), and portfolio components. METHODS AND RESULTS: 241 participants with hyperlipidemia, from four academic centers across Canada were randomized and completed either a DASH-type diet (control n = 82) or a dietary portfolio that included, soy protein, viscous fibers and nuts (n = 159) for 24 weeks. Fasting measures and 7-day food records were obtained at weeks 0, 12 and 24, with 24-h urines at weeks 0 and 24. The dietary portfolio reduced systolic, diastolic and mean arterial blood pressure compared to the control by 2.1 mm Hg (95% CI, 4.2 to -0.1 mm Hg) (p = 0.056), 1.8 mm Hg (CI, 3.2 to 0.4 mm Hg) (p = 0.013) and 1.9 mm Hg (CI, 3.4 to 0.4 mm Hg) (p = 0.015), respectively. Blood pressure reductions were small at 12 weeks and only reached significance at 24 weeks. Nuts, soy and viscous fiber all related negatively to change in mean arterial pressure (ρ = -0.15 to -0.17, p ≤ 0.016) as did urinary potassium (ρ = -0.25, p = 0.001), while the Na(+)/K(+) ratio was positively associated (ρ = 0.20, p = 0.010). CONCLUSIONS: Consumption of a cholesterol-lowering dietary portfolio also decreased blood pressure by comparison with a healthy DASH-type diet. CLINICAL TRIAL REG. NO.: NCT00438425, clinicaltrials.gov.

Glycemic index, glycemic load and glycemic response: An International Scientific Consensus Summit from the International Carbohydrate Quality Consortium (ICQC).

BACKGROUND AND AIMS: The positive and negative health effects of dietary carbohydrates are of interest to both researchers and consumers. METHODS: International experts on carbohydrate research held a scientific summit in Stresa, Italy, in June 2013 to discuss controversies surrounding the utility of the glycemic index (GI), glycemic load (GL) and glycemic response (GR). RESULTS: The outcome was a scientific consensus statement which recognized the importance of postprandial glycemia in overall health, and the GI as a valid and reproducible method of classifying carbohydrate foods for this purpose. There was consensus that diets low in GI and GL were relevant to the prevention and management of diabetes and coronary heart disease, and probably obesity. Moderate to weak associations were observed for selected cancers. The group affirmed that diets low in GI and GL should always be considered in the context of diets otherwise understood as healthy, complementing additional ways of characterizing carbohydrate foods, such as fiber and whole grain content. Diets of low GI and GL were considered particularly important in individuals with insulin resistance. CONCLUSIONS: Given the high prevalence of diabetes and pre-diabetes worldwide and the consistency of the scientific evidence reviewed, the expert panel confirmed an urgent need to communicate information on GI and GL to the general public and health professionals, through channels such as national dietary guidelines, food composition tables and food labels.

Dietary fiber effects in chronic kidney disease: a systematic review and meta-analysis of controlled feeding trials.

BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) is a major health concern associated with increased risk of cardiovascular disease, morbidity and mortality. Current CKD practice guidelines overlook dietary fiber, which is chronically low in the renal diet. However, increasing dietary fiber has been proposed to ameliorate the progress of CKD. We therefore conducted a systematic review and meta-analysis on the effect of dietary fiber intake on serum urea and creatinine as classical markers of renal health in individuals with CKD. SUBJECTS/METHODS: We searched MEDLINE, EMBASE, CINHAL and the Cochrane Library for relevant clinical trials with a follow-up ⩾7 days. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean difference (MD) with 95% confidence intervals (95% CIs). Heterogeneity was assessed by the Cochran Q statistic and quantified by I(2). RESULTS: A total of 14 trials involving 143 participants met the eligibility criteria. Dietary fiber supplementation significantly reduced serum urea and creatinine levels in the primary pooled analyses (MD, -1.76 mmol/l (95% CI, -3.00, -0.51), P<0.01 and MD, -22.83 mmol/l (95% CI, -42.63, -3.02), P=0.02, respectively) with significant evidence of interstudy heterogeneity only in the analysis of serum urea. CONCLUSIONS: This is the first study to summarize the potential beneficial effects of dietary fiber in the CKD population demonstrating a reduction in serum urea and creatinine, as well as highlighting the lack of clinical trials on harder end points. Larger, longer, higher-quality clinical trials measuring a greater variety of uremic toxins in CKD are required (NCT01844882).

Nut consumption, serum fatty acid profile and estimated coronary heart disease risk in type 2 diabetes.

BACKGROUND AND AIMS: Nut consumption has been associated with decreased risk of coronary heart disease (CHD) and type 2 diabetes which has been largely attributed to their healthy fatty acid profile, yet this has not been ascertained. Therefore, we investigated the effect of nut consumption on serum fatty acid concentrations and how these relate to changes in markers of glycemic control and calculated CHD risk score in type 2 diabetes. METHODS AND RESULTS: 117 subjects with type 2 diabetes consumed one of three iso-energetic (mean 475 kcal/d) supplements for 12 weeks: 1. full-dose nuts (50-100 g/d); 2. half-dose nuts with half-dose muffins; and 3. full-dose muffins. In this secondary analysis, fatty acid concentrations in the phospholipid, triacylglycerol, free fatty acid, and cholesteryl ester fractions from fasting blood samples obtained at baseline and week 12 were analyzed using thin layer and gas chromatography. Full-dose nut supplementation significantly increased serum oleic acid (OA) and MUFAs compared to the control in the phospholipid fraction (OA: P = 0.036; MUFAs: P = 0.024). Inverse associations were found with changes in CHD risk versus changes in OA and MUFAs in the triacylglycerol (r = -0.256, P = 0.011; r = -0.228, P = 0.024, respectively) and phospholipid (r = -0.278, P = 0.006; r = -0.260, P = 0.010, respectively) fractions. In the cholesteryl ester fraction, change in MUFAs was inversely associated with markers of glycemic control (HbA1c: r = -0.250, P = 0.013; fasting blood glucose: r = -0.395, P < 0.0001). CONCLUSION: Nut consumption increased OA and MUFA content of the serum phospholipid fraction, which was inversely associated with CHD risk factors and 10-year CHD risk. CLINICAL TRIAL REG NO: NCT00410722, clinicaltrials.gov.

Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials.

BACKGROUND/OBJECTIVES: In the absence of consistent clinical evidence, there are concerns that fructose contributes to non-alcoholic fatty liver disease (NAFLD). To determine the effect of fructose on markers of NAFLD, we conducted a systematic review and meta-analysis of controlled feeding trials. SUBJECTS/METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library (through 3 September 2013). We included relevant trials that involved a follow-up of ≥ 7 days. Two reviewers independently extracted relevant data. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean difference (SMD) for intrahepatocellular lipids (IHCL) and mean difference (MD) for alanine aminotransferase (ALT). Inter-study heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). RESULTS: Eligibility criteria were met by eight reports containing 13 trials in 260 healthy participants: seven isocaloric trials, in which fructose was exchanged isocalorically for other carbohydrates, and six hypercaloric trials, in which the diet was supplemented with excess energy (+21-35% energy) from high-dose fructose (+104-220 g/day). Although there was no effect of fructose in isocaloric trials, fructose in hypercaloric trials increased both IHCL (SMD=0.45 (95% confidence interval (CI): 0.18, 0.72)) and ALT (MD=4.94 U/l (95% CI: 0.03, 9.85)). LIMITATIONS: Few trials were available for inclusion, most of which were small, short (≤ 4 weeks), and of poor quality. CONCLUSIONS: Isocaloric exchange of fructose for other carbohydrates does not induce NAFLD changes in healthy participants. Fructose providing excess energy at extreme doses, however, does raise IHCL and ALT, an effect that may be more attributable to excess energy than fructose. Larger, longer and higher-quality trials of the effect of fructose on histopathological NAFLD changes are required.

Associations of bread and pasta with the risk of cancer of the breast and colorectum.

BACKGROUND: Carbohydrate foods with high glycemic and insulinemic potential may influence cancer risk possibly through the insulin/growth-factor axis. Two staple carbohydrate foods of the Mediterranean diet, bread and pasta, have different glycemic and insulinemic responses and hence may affect cancer risk differently. MATERIALS AND METHODS: We studied the association of bread and pasta with breast and colorectal cancer risk using data from two Italian case-control studies. These studies included 2569 women with histologically confirmed breast cancer and 1953 men and women with colorectal cancer. Controls were 2588 and 4154, respectively, admitted to the same hospitals as cases for acute, non-neoplastic conditions. Multivariate odds ratios (ORs) were obtained after allowance for relevant confounding factors. RESULTS: The ORs of breast cancer for the highest versus the lowest quintile were 1.28 (95% confidence interval, CI: 1.03-1.58, P-trend = 0.0342) for bread and 1.07 (95% CI: 0.88-1.31, P-trend = 0.7072) for pasta. The association with bread remained virtually unchanged with postmenopause and overweight. The ORs of colorectal cancer in women for the highest versus the lowest quintile were 2.02 (95% CI: 1.46-2.80, P-trend = 0.0002) for bread and 1.37 (95% CI: 1.00-1.88, P-trend = 0.0164) for pasta. The associations remained significant only for bread in strata of menopausal status and in women with overweight. No significant associations were seen in men for either bread or pasta. CONCLUSIONS: Overall, these two cancer case-control studies showed stronger positive associations with bread than pasta in women, particularly if overweight, suggesting possible hormonal-related mechanisms.

The glycemic effect of nut-enriched meals in healthy and diabetic subjects.

BACKGROUND AND AIMS: The intake of nuts has been linked to a reduced risk of cardiovascular disease (CVD) and diabetes in large cohort studies. One potential contributing mechanism may be the ability of nuts to improve post-meal glycemic response. We, therefore, examined the effect of nuts alone and in combination with white bread on postprandial glycemia. METHODS AND RESULTS: 30, 60 and 90 g (approximately 1, 2 and 3 ounces) of mixed nuts were consumed with and without 50 g available carbohydrate from white bread by 10-14 normoglycemic and 5-10 type 2 diabetic subjects. Glycemic response (GR) was assessed by calculating the incremental area under the 2 h blood glucose curve. All three doses of mixed nuts, when fed alone, significantly reduced the glycemic response in both normoglycemic and diabetic patients. Furthermore, in the normoglycemic subjects, adding nuts to white bread progressively reduced the GR of the meal by 11.2 ± 11.6%, 29.7 ± 12.2% and 53.5 ± 8.5% for the 30, 60, and 90 g doses (P = 0.354, P = 0.031 and P < 0.001, respectively), while in subjects with type 2 diabetes, the effect was half of that seen in the non-diabetic subjects (P = 0.474, P = 0.113 and P = 0.015, respectively). CONCLUSION: Nuts alone have little effect on post-meal blood glucose response. Furthermore, when taken with bread, nuts progressively reduce the glycemic response in a dose-dependent manner. While these findings support a short-term benefit for nuts in postprandial glucose response, more studies are required to determine whether these acute benefits result in long-term improvements in glycemic control.

The impact of pistachio intake alone or in combination with high-carbohydrate foods on post-prandial glycemia.

BACKGROUND/OBJECTIVES: Dietary strategies that reduce post-prandial glycemia are important in the prevention and treatment of diabetes and coronary heart disease (CHD). This may be achieved by addition of high-quality protein and fat contained in pistachio nuts, to carbohydrate-containing foods or meals. SUBJECTS/METHODS: A total of 10 healthy volunteers (3 males, 7 females); aged 48.3±6.4 years; Body mass index (BMI) 28.0±4.8 kg/m(2) participated in two studies. Study 1 assessed the dose-response effect of 28, 56 and 84 g pistachios consumed alone or co-ingested with white bread (50 g available carbohydrate); Study 2 assessed the effective dose (56 g) of pistachios on post-prandial glycemia consumed with different commonly consumed carbohydrate foods (50 g available carbohydrate). Relative glycemic responses (RGRs) of study meals compared with white bread, were assessed over the 2 h post-prandial period. RESULTS: The RGRs of pistachios consumed alone expressed as a percentage of white bread (100%) were: 28 g (5.7±1.8%); 56 g (3.8±1.8%); 84 g (9.3±3.2%), P<0.001. Adding pistachios to white bread resulted in a dose-dependent reduction in the RGR of the composite meal; 28 g (89.1±6.0, P=0.100); 56 g (67.3±9.8, P=0.009); 84 g (51.5±7.5, P<0.001). Addition of 56 g pistachios to carbohydrate foods significantly reduced the RGR: parboiled rice (72.5±6.0) versus rice and pistachios (58.7±5.1) (P=0.031); pasta (94.8±11.4) versus pasta and pistachios (56.4±5.0) (P=0.025); whereas for mashed potatoes (109.0±6.6) versus potatoes and pistachios, (87.4±8.0) (P=0.063) the results approached significance. CONCLUSIONS: Pistachios consumed alone had a minimal effect on post-prandial glycemia and when taken with a carbohydrate meal attenuated the RGR. The beneficial effects of pistachios on post-prandial glycemia could, therefore, be part of the mechanism by which nuts reduce the risk of diabetes and CHD.

The relation of low glycaemic index fruit consumption to glycaemic control and risk factors for coronary heart disease in type 2 diabetes.

AIMS/HYPOTHESIS: Sugar has been suggested to promote obesity, diabetes and coronary heart disease (CHD), yet fruit, despite containing sugars, may also have a low glycaemic index (GI) and all fruits are generally recommended for good health. We therefore assessed the effect of fruit with special emphasis on low GI fruit intake in type 2 diabetes. METHODS: This secondary analysis involved 152 type 2 diabetic participants treated with glucose-lowering agents who completed either 6 months of high fibre or low GI dietary advice, including fruit advice, in a parallel design. RESULTS: Change in low GI fruit intake ranged from -3.1 to 2.7 servings/day. The increase in low GI fruit intake significantly predicted reductions in HbA(1c) (r = -0.206, p =0.011), systolic blood pressure (r = -0.183, p = 0.024) and CHD risk (r = -0.213, p = 0.008). Change in total fruit intake ranged from -3.7 to 3.2 servings/day and was not related to study outcomes. In a regression analysis including the eight major carbohydrate foods or classes of foods emphasised in the low GI diet, only low GI fruit and bread contributed independently and significantly to predicting change in HbA(1c). Furthermore, comparing the highest with the lowest quartile of low GI fruit intake, the percentage change in HbA(1c) was reduced by -0.5% HbA(1c) units (95% CI 0.2-0.8 HbA(1c) units, p < 0.001). CONCLUSIONS/INTERPRETATION: Low GI fruit consumption as part of a low GI diet was associated with lower HbA(1c), blood pressure and CHD risk and supports a role for low GI fruit consumption in the management of type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00438698.

Effect of non-oil-seed pulses on glycaemic control: a systematic review and meta-analysis of randomised controlled experimental trials in people with and without diabetes.

AIMS/HYPOTHESIS: Dietary non-oil-seed pulses (chickpeas, beans, peas, lentils, etc.) are a good source of slowly digestible carbohydrate, fibre and vegetable protein and a valuable means of lowering the glycaemic-index (GI) of the diet. To assess the evidence that dietary pulses may benefit glycaemic control, we conducted a systematic review and meta-analysis of randomised controlled experimental trials investigating the effect of pulses, alone or as part of low-GI or high-fibre diets, on markers of glycaemic control in people with and without diabetes. METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant controlled trials of >or=7 days. Two independent reviewers (A. Esfahani and J. M. W. Wong) extracted information on study design, participants, treatments and outcomes. Data were pooled using the generic inverse variance method and expressed as standardised mean differences (SMD) with 95% CIs. Heterogeneity was assessed by chi (2) and quantified by I (2). Meta-regression models identified independent predictors of effects. RESULTS: A total of 41 trials (39 reports) were included. Pulses alone (11 trials) lowered fasting blood glucose (FBG) (-0.82, 95% CI -1.36 to -0.27) and insulin (-0.49, 95% CI -0.93 to -0.04). Pulses in low-GI diets (19 trials) lowered glycosylated blood proteins (GP), measured as HbA(1c) or fructosamine (-0.28, 95% CI -0.42 to -0.14). Finally, pulses in high-fibre diets (11 trials) lowered FBG (-0.32, 95% CI -0.49 to -0.15) and GP (-0.27, 95% CI -0.45 to -0.09). Inter-study heterogeneity was high and unexplained for most outcomes, with benefits modified or predicted by diabetes status, pulse type, dose, physical form, duration of follow-up, study quality, macronutrient profile of background diets, feeding control and design. CONCLUSIONS/INTERPRETATION: Pooled analyses demonstrated that pulses, alone or in low-GI or high-fibre diets, improve markers of longer term glycaemic control in humans, with the extent of the improvements subject to significant inter-study heterogeneity. There is a need for further large, well-designed trials.

Long-term effects of a plant-based dietary portfolio of cholesterol-lowering foods on blood pressure.

OBJECTIVE: To determine the effect on blood pressure of dietary advice to consume a combination of plant-based cholesterol-lowering foods (dietary portfolio). METHODS: For 1 year, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (22.5 g/1000 kcal). There was no control group. Seven-day diet record, blood pressure and body weight were monitored initially monthly and later at 2-monthly intervals throughout the study. RESULTS: Fifty subjects completed the 1-year study. When the last observation was carried forward for non-completers (n=9) or those who changed their blood pressure medications (n=7), a small mean reduction was seen in body weight 0.7+/-0.3 kg (P=0.036). The corresponding reductions from baseline in systolic and diastolic blood pressure at 1 year (n=66 subjects) were -4.2+/-1.3 mm Hg (P=0.002) and -2.3+/-0.7 mm Hg (P=0.001), respectively. Blood pressure reductions occurred within the first 2 weeks, with stable blood pressures 6 weeks before and 4 weeks after starting the diet. Diastolic blood pressure reduction was significantly related to weight change (r=0.30, n=50, P=0.036). Only compliance with almond intake advice related to blood pressure reduction (systolic: r=-0.34, n=50, P=0.017; diastolic: r=-0.29, n=50, P=0.041). CONCLUSIONS: A dietary portfolio of plant-based cholesterol-lowering foods reduced blood pressure significantly, related to almond intake. The dietary portfolio approach of combining a range of cholesterol-lowering plant foods may benefit cardiovascular disease risk both by reducing serum lipids and also blood pressure.

Effect on hematologic risk factors for coronary heart disease of a cholesterol reducing diet.

BACKGROUND: A dietary portfolio of cholesterol-lowering ingredients has proved effective in reducing serum cholesterol. However, it is not known whether this dietary combination will also affect hematologic risk factors for coronary heart disease (CHD). Reductions in hematocrit and polymorphonuclear leukocytes have been reported to improve cardiovascular risk. We, therefore, report changes in hematological indices, which have been linked to cardiovascular health, in a 1-year assessment of subjects taking an effective dietary combination (portfolio) of cholesterol-lowering foods. METHODS: For 12 months, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (23 g/1000 kcal). Fifty-five subjects completed the study. RESULTS: Over the 1 year, data on completers indicated small but significant reductions in hemoglobin (-1.5+/-0.6 g/l, P=0.013), hematocrit (-0.007+/-0.002 l/l, P<0.001), red cell number (-0.07+/-0.02 10(9)/l, P<0.001) and neutrophils (-0.34+/-0.13 10(9)/l, P=0.014). Mean platelet volume was also increased (0.16+/-0.07 fl, P=0.033). The increase in red cell osmotic fragility (0.05+/-0.03 g/l, P=0.107) did not reach significance. CONCLUSIONS: These small changes in hematological indices after a cholesterol-lowering diet are in the direction, which would be predicted to reduce CHD risk. Further research is needed to clarify whether the changes observed will contribute directly or indirectly to cardiovascular benefits beyond those expected from reductions previously seen in serum lipids and blood pressure.

Better cognitive performance following a low-glycaemic-index compared with a high-glycaemic-index carbohydrate meal in adults with type 2 diabetes.

AIMS/HYPOTHESIS: Transient hyperglycaemia, consistent with that observed with normal meal ingestion, may be detrimental to cognitive performance in adults with type 2 diabetes. This study determined whether minimising the postprandial increase in blood glucose through the ingestion of low- rather than high-glycaemic-index (GI) carbohydrate meals differentially affected cognitive performance in the postprandial period. SUBJECTS AND METHODS: Using a within-individual design, 21 free-living subjects (65+/-7.29 years) with type 2 diabetes consumed 50 g carbohydrate as a meal with either a low GI (pasta) or a high GI (white bread), or water on three separate mornings following an overnight fast. Neuropsychological tests were administered and plasma glucose concentrations measured. RESULTS: Higher postprandial blood glucose AUC (gAUC) was associated with poorer verbal memory (paragraph recall, p=0.01; word list recall, p=0.012). Both the GI of the carbohydrate meal and individual differences in response to meal ingestion contributed to the variation in gAUC and consequent memory recall. Bread consumption, relative to pasta, resulted in both a higher gAUC (p<0.05) and worse delayed verbal memory performance (paragraph recall, p=0.042; wordlist recall, p=0.035). Additionally, performance following bread consumption was poorer than that following pasta on measures of working memory, executive function and auditory selective attention, while sustained attention showed no sensitivity to type of carbohydrate food consumed. CONCLUSIONS/INTERPRETATION: Consuming 50 g of a low-GI carbohydrate meal, relative to a high-GI carbohydrate meal, generally results in better cognitive performance in the postprandial period in adults with type 2 diabetes, particularly in those individuals who experience the greatest food-induced elevations in blood glucose levels.

Effect of soy protein-rich diet on renal function in young adults with insulin-dependent diabetes mellitus.

BACKGROUND: Diabetic nephropathy is the most frequent cause of end-stage renal disease in the Western world. Dietary intake, including protein amount and type, seems to affect the progression of renal disease. This pilot study tested the hypothesis that substituting soy protein for animal protein in the diets of diabetics would help correct glomerular hyperfiltration. METHODS: Twelve young adults (aged 29.9 +/- 2.4 years) with type 1 diabetes mellitus (duration of diabetes 15.1 +/- 2.3 years) and hyperfiltration (glomerular filtration rate, GFR > 120 ml/min/1.73 m2) completed a crossover, dietary intervention trial. After a four-week assessment of baseline characteristics and dietary habits, subjects were assigned to either a control or soy diet for eight weeks after which each subject was crossed over to the alternative diet for another eight-week period. RESULTS: Mean GFR was significantly reduced (p < 0.02) after eight weeks on the soy diet (143 +/- 7.4 ml/min/1.73 m2) compared with baseline (159 +/- 7.7 ml/min/ 1.73 m2) and control diets (161 +/- 10.0 ml/min/1.73 m2). Urinary excretion of the soy isoflavones was significantly higher (p < 0.01) at the end of the soy diet (genistein 1,014.6 +/- 274.1 nmol/h, daidzein 2,645.1 +/- 989.6 nmol/h) compared with baseline (genistein 53.7 +/- 31.1 nmol/h, daidzein 151.1 +/- 74.1 nmol/h) and control diets (genistein 41.1 +/- 13.3 nmol/h, daidzein 127.5 +/- 54.0 nmol/h). The soy diet significantly reduced total and LDL cholesterol by 7% and 9%, respectively. CONCLUSIONS: Implementation of a soy-based diet appears to reduce the GFR and total and LDL cholesterol of young adults with type 1 diabetes and glomerular hyperfiltration, thus affecting positively their clinical profile.

Direct comparison of dietary portfolio vs statin on C-reactive protein.

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) markedly reduce serum cholesterol and have anti-inflammatory effects. The effect of cholesterol-lowering diets on inflammatory biomarkers is less well known. OBJECTIVE: To compare the efficacy of a dietary combination (portfolio) of cholesterol-lowering foods vs a statin in reducing C-reactive protein (CRP) as a biomarker of inflammation linked to increased cardiovascular disease risk. METHODS: In all, 34 hyperlipidemic subjects completed three 1-month treatments as outpatients in random order: a very low-saturated fat diet (control); the same diet with 20 mg lovastatin (statin); and a diet high in plant sterols (1.0 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000 kcal), and almonds (14 g/1000 kcal) (portfolio). Fasting blood samples were obtained at weeks 0, 2, and 4. RESULTS: Using the complete data, no treatment reduced serum CRP. However, when subjects with CRP levels above the 75th percentile for previously reported studies (> 3.5 mg/l) were excluded, CRP was reduced similarly on both statin, -16.3 +/- 6.7% (n = 23, P = 0.013) and dietary portfolio, -23.8 +/- 6.9% (n = 25, P = 0.001) but not the control, 15.3 +/- 13.6% (n = 28, P = 0.907). The percentage CRP change from baseline on the portfolio treatment (n = 25) was greater than the control (n = 28, P = 0.004) but similar to statin treatment (n = 23, P = 0.349). Both statin and portfolio treatments were similar in reducing CRP and numerically more effective than control but only the change in portfolio was significant after the Bonferroni adjustment. CONCLUSIONS: A combination of cholesterol-lowering foods reduced C-reactive protein to a similar extent as the starting dose of a first-generation statin.

Carbohydrates, dietary glycaemic load and glycaemic index, and risk of acute myocardial infarction.

OBJECTIVES: To assess the relation between selected carbohydrate foods, dietary glycaemic load and glycaemic index, and the risk of non-fatal acute myocardial infarction in a population with a high intake of refined carbohydrates. DESIGN AND SETTING: Hospital based case-control study conducted in Milan, Italy, between 1995 and 1999. PATIENTS: 433 non-diabetic subjects with a first episode of non-fatal acute myocardial infarction, and 448 controls admitted to hospital for a wide spectrum of acute conditions unrelated to known or potential risk factors for acute myocardial infarction. METHODS: Information was collected by interviewer administered questionnaires. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained by multiple logistic regression models. RESULTS: Compared with patients in the lowest tertile of intake, the multivariate OR for those in the highest tertile was 1.00 for bread, 1.27 for pasta and rice, 1.38 for soups, 0.78 for potatoes, 0.97 for desserts, and 1.00 for sugar. The OR for the highest tertile of score was 1.08 for glycaemic load and 1.38 for glycaemic index. None of the estimates was significant. A significant association with acute myocardial infarction risk was found for glycaemic index in patients aged > or = 60 years (OR 1.81, 95% CI 1.07 to 3.07 for the highest tertile of score compared with the lowest) and in those with a body mass index > or = 25 kg/m2 (OR 2.02, 95% CI 1.21 to 3.34). CONCLUSIONS: In this Italian population high glycaemic load and glycaemic index were not strongly associated with acute myocardial infarction risk, but slightly increased odds ratios were observed for glycaemic index in elderly people and in association with overweight.

Effect of high vegetable protein diets on urinary calcium loss in middle-aged men and women.

OBJECTIVE: To determine the effect of high-protein diets, which have recently been promoted for their health benefits, on urinary calcium losses and bone turnover in older subjects. DESIGN: Randomized controlled cross-over study. SETTING: Teaching hospital and university. SUBJECTS: Twenty hyperlipidemic men and postmenopausal women (age 56+/-2 y) completed the study. INTERVENTION: One-month test and control phases during which subjects consumed equi-energy metabolic diets high in calcium (1578 and 1593 mg/day, respectively). On the test diet 11% of total dietary energy from starch in the control bread was replaced by protein (wheat gluten), resulting in 27% of energy from protein on the test diet vs 16% on the control diet. MAIN OUTCOME MEASURE: Urinary calcium excretion. RESULTS: Compared with the control diet, at week 4, the test diet increased mean (+/-s.e.m.) 24 h urinary output of calcium (139+/-15 vs 227+/-21 mg, P=0.004). The treatment difference in urinary calcium loss correlated with the serum anion gap as a marker of metabolic acid production (r=0.57, P=0.011). Serum calcium levels were marginally lower 2.41+/-0.02 vs 2.38+/-0.02 mmol/l (P=0.075), but there was no significant treatment difference in calcium balance, possibly related to the high background calcium intake on both diets. CONCLUSION: In the presence of high dietary calcium intakes the vegetable protein gluten does not appear to have a negative effect on calcium balance despite increased urinary calcium loss.

Dietary glycemic index, glycemic load and ovarian cancer risk: a case-control study in Italy.

BACKGROUND: Dietary carbohydrates vary in their ability to raise blood glucose and insulin levels, which, in turn, influence levels of sex hormones and insulin-like growth factors. We analyzed the effect of type and amount of carbohydrates on ovarian cancer risk, using the glycemic index (GI) and the glycemic load (GL) measurement in a large case-control study conducted in Italy. MATERIALS AND METHODS: Cases included 1031 women with incident, histologically confirmed epithelial ovarian cancer, from four Italian regions. Controls included 2411 women admitted to the same hospital networks for acute, non-neoplastic conditions. Average daily GI and GL were calculated from a validated food frequency questionnaire. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were computed using multiple logistic regression. RESULTS: Ovarian cancer was directly associated with dietary GI (OR for highest versus lowest quartile = 1.7, 95% CI 1.3-2.1) and GL (OR = 1.7, 95% CI 1.3-2.1). The associations were observed in pre- and postmenopausal women, and they remained consistent across strata of major covariates identified. CONCLUSIONS: This study supports the hypothesis of a direct association between GI and GL and ovarian cancer risk and, consequently, of a possible role of hyperinsulinemia/insulin resistance in ovarian cancer development.