Association between serum ferritin and osteocalcin as a potential mechanism explaining the iron-induced insulin resistance

Background: Increased iron stores are associated with increased risk of type 2 diabetes, however, the mechanisms underlying these associations are poorly understood. Because a reduction of circulating osteocalcin levels after iron overload have been demonstrated in cell cultures, and osteocalcin is related to glucose and insulin metabolism, the ironinduced osteocalcin reductions could contribute to explain the role of iron metabolism in the development of type 2 diabetes mellitus. Objective: To analyzed the associations between serum total and uncarboxylated osteocalcin and adiponectin concentrations with serum ferritin and soluble transferrin receptor (sTfR) in elderly subjects. Design: We evaluated a total of 423 subjects from the PREDIMED cohort in a population-based cross-sectional analysis. Extensive clinical, nutritional and laboratory measurements, including total and uncarboxylated osteocalcin, adiponectin, ferritin and sTfR were recorded. Results: Serum ferritin was positively correlated with increased glucose and insulin circulating levels but also with HOMA-IR, and was inversely associated with total osteocalcin and adiponectin. A regression analysis revealed that serum ferritin and transferrin receptor levels were significantly associated with a decrease in total and uncarboxylated osteocalcin. Serum sTfR levels were associated with lower uncarboxylated osteocalcin levels in the whole-study subjects and remained significant only in the IFG (impaired fasting glucose) individuals. Conclusions: We described, for the first time, an inverse association between serum ferritin and sTfR with osteocalcin and extend previous results on adiponectin, thus supporting that factors related to iron metabolism could contribute to the insulin resistance and the development of type 2 diabetes mellitus. Trial Registration: Controlled-Trials.com ISRCTN35739639 ,http://www.controlled-trials.com/ISRCTN35739639.

Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk

BACKGROUND: Vitamin K has been related to glucose metabolism, insulin sensitivity and diabetes. Because inflammation underlies all these metabolic conditions, it is plausible that the potential role of vitamin K in glucose metabolism occurs through the modulation of cytokines and related molecules. The purpose of the study was to assess the associations between dietary intake of vitamin K and peripheral adipokines and other metabolic risk markers related to insulin resistance and type 2 diabetes mellitus. METHODS: Cross-sectional and longitudinal assessments of these associations in 510 elderly participants recruited in the PREDIMED centers of Reus and Barcelona (Spain). We determined 1-year changes in dietary phylloquinone intake estimated by food frequency questionnaires, serum inflammatory cytokines and other metabolic risk markers. RESULTS: In the cross-sectional analysis at baseline no significant associations were found between dietary phylloquinone intake and the rest of metabolic risk markers evaluated, with exception of a negative association with plasminogen activator inhibitor-1. After 1-year of follow-up, subjects in the upper tertile of changes in dietary phylloquinone intake showed a greater reduction in ghrelin (-15.0%), glucose-dependent insulinotropic peptide (-12.9%), glucagon-like peptide-1 (-17.6%), IL-6 (-27.9%), leptin (-10.3%), TNF (-26.9%) and visfatin (-24.9%) plasma concentrations than those in the lowest tertile (all p<0.05). CONCLUSION: These results show that dietary phylloquinone intake is associated with an improvement of cytokines and other markers related to insulin resistance and diabetes, thus extending the potential protection by dietary phylloquinone on chronic inflammatory diseases. TRIAL REGISTRATION: http://www.controlled-trials.com as ISRCTN35739639

Dietary intake of phylloquinone is related to a reduced risk of all-cause mortality: the predimed study

Resumen del trabajo presentado en el 20th International Congress of Nutrition, celebrado en Granada (España) del 15 al 20 de septiembre de 2013.[Background and objectives]: Vitamin K has been associated with a reduced risk of CHD and fatal cancer. Dietary menaquinones intake has been associated with cancer mortality. However, the association between the dietary intake of vitamin K and all-cause mortality has not been evaluated in a Mediterranean population at high cardiovascular risk.[Methods]: A prospective analysis was conducted in 7216 participants in the framework of the PREDIMED cohort (median follow-up: 4.8y). Energy and nutrient intakes were evaluated using a previously validated 137-item food frequency questionnaire. Dietary phylloquinone and menaquinone intake was calculated using the USDA database and previous published Abstracts Ann Nutr Metab 2013;63(suppl 1):1– 1960 921 data, respectively. All-cause mortality was verified by medical records and consultation of National Death Index. Cox proportional hazard models were fitted to assess the relative risk of all-cause mortality.[Results]: At baseline, energy-adjusted dietary phylloquinone intake was associated with a significantly reduced risk of all-cause mortality after controlling for potential confounders (HR: 0.64; 95% CI: 0.43, 0.96). No significant associations were found between quartiles of energy adjusted dietary menaquinones intake and risk of all-cause mortality. In a longitudinal manner, subjects who increase their consumption of vitamin K, phylloquinone or menaquinone, had a lower risk of allcause mortality (HR: 0.58; 95% CI: 0.45, 0.74 and HR: 0.59; 95% CI: 0.45, 0.78, respectively) compared with subjects who decrease their consumption.[Conclusions]: The results showed that an increase of dietary intake of vitamin K is related with a reduced risk of all-cause mortality in a Mediterranean population at high cardiovascular risk

Dietary glycemic index and glycemic load are positively associated with risk of developing metabolic syndrome in middle-aged and elderly adults

© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society. Objectives To evaluate how glycemic index (GI) and glycemic load (GL) are associated with the metabolic syndrome (MetS) and its features in middle-aged and elderly adults at high cardiovascular risk. Design Prospective, longitudinal, population-based cohort. Setting PREvenciõn con DIeta MEDiterránea study. Participants Men and women (N = 6,606) divided into three age groups (<65, 65-74, ≥75). Measurements Energy and nutrient intake was evaluated using a validated 137-item food frequency questionnaire. MetS and its features were defined in accordance with the criteria of the American Heart Association and National Heart, Lung, and Blood Institute. Results A positive association was observed between GI and MetS prevalence in the youngest and middle age groups for participants without diabetes mellitus, but no relationship was found for those with diabetes mellitus. During the median follow-up of 4.8 years, higher GI and GL were related to greater risk of MetS in the middle age group, independent of the presence of diabetes mellitus. Changes in dietary GI were associated with risk of developing the high fasting glucose component of the MetS in the oldest age category, and changes in dietary GL were associated with risk of developing abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and high blood pressure in the youngest age category. Conclusion Dietary GI and GL have a potential role in the development of MetS and associated clinical features, with particular age-dependent considerations.Funded by: Centro Nacional de Investigaciones Cardiovasculares. Grant Number: 06/2007; Instituto de Salud Carlos III; Fondo de Investigación Sanitaria PI. Grant Number: 07/0473; Ministerio de Ciencia e Innovación. Grant Numbers: AGL-2009–13906-C02, AGL2010–22319-C03; Ministerio de Sanidad-Plan Nacional de Drogas. Grant Number: 2010/087; Fondo de Investigaciones Sanitarias. Grant Number: PI1002658 Fundación Mapfre 2010 Government of the Basque Country. Grant Number: IT386–10 University of the Basque Country. Grant Number: UFI 11/32 Catalan government Miguel Servet. Grant Number: 06/00100Peer Reviewe

Association between serum ferritin and osteocalcin as a potential mechanism explaining the iron-induced insulin resistance

Background: Increased iron stores are associated with increased risk of type 2 diabetes, however, the mechanisms underlying these associations are poorly understood. Because a reduction of circulating osteocalcin levels after iron overload have been demonstrated in cell cultures, and osteocalcin is related to glucose and insulin metabolism, the ironinduced osteocalcin reductions could contribute to explain the role of iron metabolism in the development of type 2 diabetes mellitus. Objective: To analyzed the associations between serum total and uncarboxylated osteocalcin and adiponectin concentrations with serum ferritin and soluble transferrin receptor (sTfR) in elderly subjects. Design: We evaluated a total of 423 subjects from the PREDIMED cohort in a population-based cross-sectional analysis. Extensive clinical, nutritional and laboratory measurements, including total and uncarboxylated osteocalcin, adiponectin, ferritin and sTfR were recorded. Results: Serum ferritin was positively correlated with increased glucose and insulin circulating levels but also with HOMA-IR, and was inversely associated with total osteocalcin and adiponectin. A regression analysis revealed that serum ferritin and transferrin receptor levels were significantly associated with a decrease in total and uncarboxylated osteocalcin. Serum sTfR levels were associated with lower uncarboxylated osteocalcin levels in the whole-study subjects and remained significant only in the IFG (impaired fasting glucose) individuals. Conclusions: We described, for the first time, an inverse association between serum ferritin and sTfR with osteocalcin and extend previous results on adiponectin, thus supporting that factors related to iron metabolism could contribute to the insulin resistance and the development of type 2 diabetes mellitus. Trial Registration: Controlled-Trials.com ISRCTN35739639 ,http://www.controlled-trials.com/ISRCTN35739639.

Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk

BACKGROUND: Vitamin K has been related to glucose metabolism, insulin sensitivity and diabetes. Because inflammation underlies all these metabolic conditions, it is plausible that the potential role of vitamin K in glucose metabolism occurs through the modulation of cytokines and related molecules. The purpose of the study was to assess the associations between dietary intake of vitamin K and peripheral adipokines and other metabolic risk markers related to insulin resistance and type 2 diabetes mellitus. METHODS: Cross-sectional and longitudinal assessments of these associations in 510 elderly participants recruited in the PREDIMED centers of Reus and Barcelona (Spain). We determined 1-year changes in dietary phylloquinone intake estimated by food frequency questionnaires, serum inflammatory cytokines and other metabolic risk markers. RESULTS: In the cross-sectional analysis at baseline no significant associations were found between dietary phylloquinone intake and the rest of metabolic risk markers evaluated, with exception of a negative association with plasminogen activator inhibitor-1. After 1-year of follow-up, subjects in the upper tertile of changes in dietary phylloquinone intake showed a greater reduction in ghrelin (-15.0%), glucose-dependent insulinotropic peptide (-12.9%), glucagon-like peptide-1 (-17.6%), IL-6 (-27.9%), leptin (-10.3%), TNF (-26.9%) and visfatin (-24.9%) plasma concentrations than those in the lowest tertile (all p<0.05). CONCLUSION: These results show that dietary phylloquinone intake is associated with an improvement of cytokines and other markers related to insulin resistance and diabetes, thus extending the potential protection by dietary phylloquinone on chronic inflammatory diseases. TRIAL REGISTRATION: http://www.controlled-trials.com as ISRCTN35739639