Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

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.

Body weight and risk of molecular breast cancer subtypes among postmenopausal Mediterranean women.

Breast cancer (BC) is the most common malignant tumor in women, obesity is associated with increased BC incidence and mortality and high levels of circulating insulin may negatively impact on cancer incidence. In the present study, we investigated whether the strength of several anthropometric and metabolic parameters varies between BC molecular subtypes. Eligible cases were 991 non-metastatic BC patients recruited between January 2009 and December 2013. Anthropometric, clinical and immunohistochemical features were measured. Multivariate logistic regression models were built to assess HER2 positive BC risk, comparing (a) triple positive (TP) with luminal A, luminal B and triple negative (TN) and (b) HER2-enriched group with luminal A, luminal B and TN. We stratified patients in pre- and post-menopause: significant differences emerged for luminal A in relation to age: they were more likely to be older compared to other groups. Among postmenopausal patients, the adjusted multivariate analysis showed that high BMI and high waist circumference were inversely correlated to TP subtype when compared to luminal B (OR=0.48 and OR=0.49, respectively). Conversely, HOMA-IR was a risk factor for TP when compared to luminal A and TN (OR=2.47 and OR=3.15, respectively). Our findings suggest a potential role of higher abdominal fat in the development of specific BC molecular subtypes in postmenopausal women. Moreover, they support a potential role of insulin resistance in the development of HER2 positive BC, although this role appears to be stronger when hormone receptors are co-expressed, suggesting a difference in the etiology of these two BC subtypes.

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.

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.

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.

Relationship between a wide range of alcohol consumptions, components of the insulin-like growth factor system and adiponectin.

OBJECTIVE: To explore the relation between a wide range of alcohol consumptions and levels of the components of insulin-like growth factor system (IGFs) and adiponectin in humans. DESIGN: A cross-sectional study using controls from a case-control study on ovarian and endometrial cancer. SETTINGS: The study included women hospitalized between 1999 and 2002 in Pordenone, Italy. SUBJECTS: One hundred and eight cancer-free (controls) with a median age of 61 years (range 29-79 years), admitted for acute conditions unrelated to gynecologic, hormonal or metabolic disorders or diseases leading to dietary modifications. INTERVENTIONS: Levels of IGF-I (total and free), total IGF-II, IGF-binding protein 1 (IGFBP-1), IGFBP-3 and adiponectin were individually measured, and their distributions across strata of alcohol consumption were tested by the Kruskal-Wallis statistic. RESULTS: Median concentrations of total IGF-I were higher (P<0.01) in women reporting low (151 ng/ml) or no alcohol consumption (134 ng/ml) compared to drinkers of 12-23 g/day (103 ng/ml) or >or=24 g/day (118 ng/ml). Median concentrations were higher (P=0.05) for IGFBP-3 in non-drinkers (2333 ng/ml) and in light drinkers (2647 ng/ml) compared to drinkers of >or=24 g/day (2090 ng/ml). No statistically significant difference emerged for other IGFs across levels of alcohol intakes. Adiponectin was slightly lower for non-drinkers, compared to all drinkers categories. CONCLUSIONS: Our study suggests that alcohol consumption is related to circulating levels of components of the IGF system and adiponectin. These results may have a potential impact on the prevention of several chronic diseases. SPONSORSHIP: Italian Association for Research on Cancer, Milan, Italy, and Italian League against Tumours, Milan, Italy.

Glycemic index, glycemic load and risk of gastric cancer.

BACKGROUND: Dietary carbohydrates have been directly associated with gastric cancer risk and have been considered general indicators of a poor diet. However, elevated levels of glucose and insulin elicited by consumption of high amounts of refined carbohydrates may stimulate mitogenic and cancer-promoting insulin-like growth factors (IGF). Glycemic index (GI) and glycemic load (GL), which represent indirect measures of dietary insulin demand, were analysed to understand further the association between carbohydrates and gastric cancer. PATIENTS AND METHODS: Data were derived from a hospital-based case-control study on gastric cancer, conducted in Italy between 1985 and 1997, including 769 cases with incident, histologically confirmed gastric cancer and 2081 controls admitted to the same hospital network as cases for acute, non-neoplastic diseases. All subjects were interviewed using a reproducible food frequency questionnaire. RESULTS: The multivariate odds ratios (OR) for subsequent quartiles of dietary GL were 1.44 [95% confidence interval (CI) 1.11-1.87], 1.62 (95% CI 1.24-2.12) and 1.94 (95% CI 1.47-2.55). No consistent pattern of risk was seen with GI. The associations were consistent in different strata of age, education and body mass index, and were stronger in women. CONCLUSIONS: This study supports the hypothesis of a direct association between GL and gastric cancer risk, thus providing an innovative interpretation, linked to excess circulating insulin and related IGFs, for the association between carbohydrates and risk of gastric cancer.

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.