Osteoporosis is a common chronic disease characterized by a decrease in bone mineral density, impaired bone strength, and an increased risk of fragility fractures. Fragility fractures are associated ...with significant morbidity, mortality and disability and are a major public health problem worldwide. The influence of nutritional factors on the development and progression of this disease can be significant and is not yet well established. Calcium intake and vitamin D status are considered to be essential for bone metabolism homeostasis. However, some recent studies have questioned the usefulness of calcium and vitamin D supplements in decreasing the risk of fractures. The adequate intake of protein, vegetables and other nutrients is also of interest, and recommendations have been established by expert consensus and clinical practice guidelines. It is important to understand the influence of nutrients not only in isolation but also in the context of a dietary pattern, which is a complex mixture of nutrients. In this review, we evaluate the available scientific evidence for the effects of the main dietary patterns on bone health. Although some dietary patterns seem to have beneficial effects, more studies are needed to fully elucidate the true influence of diet on bone fragility.
The relationship between vitamin D status, calcium intake and the risk of developing type 2 diabetes (T2D) is a topic of growing interest. One of the most interesting non-skeletal functions of ...vitamin D is its potential role in glucose homeostasis. This possible association is related to the secretion of insulin by pancreatic beta cells, insulin resistance in different tissues and its influence on systemic inflammation. However, despite multiple observational studies and several meta-analyses that have shown a positive association between circulating 25-hydroxyvitamin D concentrations and the risk of T2D, no randomized clinical trials supplementing with different doses of vitamin D have confirmed this hypothesis definitively. An important question is the identification of what 25-hydroxyvitamin D levels are necessary to influence glycemic homeostasis and the risk of developing T2D. These values of vitamin D can be significantly higher than vitamin D levels required for bone health, but the currently available data do not allow us to answer this question adequately. Furthermore, a large number of observational studies show that dairy consumption is linked to a lower risk of T2D, but the components responsible for this relationship are not well established. Therefore, the importance of calcium intake in the risk of developing T2D has not yet been established. Although there is a biological plausibility linking the status of vitamin D and calcium intake with the risk of T2D, well-designed randomized clinical trials are necessary to answer this important question.
Obesity and Bone Health: A Complex Relationship Piñar-Gutierrez, Ana; García-Fontana, Cristina; García-Fontana, Beatriz ...
International journal of molecular sciences,
08/2022, Letnik:
23, Številka:
15
Journal Article
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Recent scientific evidence has shown an increased risk of fractures in patients with obesity, especially in those with a higher visceral adipose tissue content. This contradicts the old paradigm that ...obese patients were more protected than those with normal weight. Specifically, in older subjects in whom there is a redistribution of fat from subcutaneous adipose tissue to visceral adipose tissue and an infiltration of other tissues such as muscle with the consequent sarcopenia, obesity can accentuate the changes characteristic of this age group that predisposes to a greater risk of falls and fractures. Other factors that determine a greater risk in older subjects with obesity are chronic proinflammatory status, altered adipokine secretion, vitamin D deficiency, insulin resistance and reduced mobility. On the other hand, diagnostic tests may be influenced by obesity and its comorbidities as well as by body composition, and risk scales may underestimate the risk of fractures in these patients. Weight loss with physical activity programs and cessation of high-fat diets may reduce the risk. Finally, more research is needed on the efficacy of anti-osteoporotic treatments in obese patients.
Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extra-skeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, ...cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association.
Abstract Objective Moderate‐to‐vigorous physical activity (MVPA) improves glucose levels; however, whether its timing affects daily glycemic control remains unclear. This study aims to investigate ...the impact of lifestyle MVPA timing on daily glycemic control in sedentary adults with overweight/obesity and metabolic impairments. Methods A total of 186 adults (50% women; age, 46.8 SD 6.2 years) with overweight/obesity (BMI, 32.9 SD 3.5 kg/m 2 ) and at least one metabolic impairment participated in this cross‐sectional study. MVPA and glucose patterns were simultaneously monitored over a 14‐day period using a triaxial accelerometer worn on the nondominant wrist and a continuous glucose‐monitoring device, respectively. Each day was classified as “inactive” if no MVPA was accumulated; as “morning,” “afternoon,” or “evening” if >50% of the MVPA minutes for that day were accumulated between 0600 and 1200, 1200 and 1800, or 1800 and 0000 hours, respectively; or as “mixed” if none of the defined time windows accounted for >50% of the MVPA for that day. Results Accumulating >50% of total MVPA during the evening was associated with lower 24‐h (mean difference 95% CI, −1.26 mg/dL 95% CI: −2.2 to −0.4), diurnal (−1.10 mg/dL 95% CI: −2.0 to −0.2), and nocturnal mean glucose levels (−2.16 mg/dL 95% CI: −3.5 to −0.8) compared with being inactive. This association was stronger in those participants with impaired glucose regulation. The pattern of these associations was similar in both men and women. Conclusions These findings suggest that timing of lifestyle MVPA is significant. Specifically, accumulating more MVPA during the evening appears to have a beneficial effect on glucose homeostasis in sedentary adults with overweight/obesity and metabolic impairments.
Hypophosphatasia: A Unique Disorder of Bone Mineralization Villa-Suárez, Juan Miguel; García-Fontana, Cristina; Andújar-Vera, Francisco ...
International journal of molecular sciences,
04/2021, Letnik:
22, Številka:
9
Journal Article
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Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the
gene, which is abundantly ...expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the
gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5'-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the
gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the
gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients.
This article reviews the role of fibroblast growth factor 23 (FGF23) protein in phosphate metabolism, highlighting its regulation of vitamin D, parathyroid hormone, and bone metabolism. Although it ...was traditionally thought that phosphate-calcium homeostasis was controlled exclusively by parathyroid hormone (PTH) and calcitriol, pathophysiological studies revealed the influence of FGF23. This protein, expressed mainly in bone, inhibits the renal reabsorption of phosphate and calcitriol formation, mediated by the α-klotho co-receptor. In addition to its role in phosphate metabolism, FGF23 exhibits pleiotropic effects in non-renal systems such as the cardiovascular, immune, and metabolic systems, including the regulation of gene expression and cardiac fibrosis. Although it has been proposed as a biomarker and therapeutic target, the inhibition of FGF23 poses challenges due to its potential side effects. However, the approval of drugs such as burosumab represents a milestone in the treatment of FGF23-related diseases.
Summary Background Basal insulin therapy does not stop loss of β-cell function, which is the hallmark of type 2 diabetes mellitus, and thus diabetes control inevitably deteriorates. Insulin degludec ...is a new, ultra-longacting basal insulin. We aimed to assess efficacy and safety of insulin degludec compared with insulin glargine in patients with type 2 diabetes mellitus. Methods In this 52 week, phase 3, open-label, treat-to-target, non-inferiority trial, undertaken at 123 sites in 12 countries, we enrolled adults (aged ≥18 years) with type 2 diabetes mellitus and a glycated haemoglobin (HbA1c ) of 7·0–10·0% after 3 months or more of any insulin regimen (with or without oral antidiabetic drugs). We randomly allocated eligible participants in a 3:1 ratio to receive once-daily subcutaneous insulin degludec or glargine, stratified by previous insulin regimen, via a central interactive response system. Basal insulin was titrated to a target plasma glucose concentration of 3·9–<5·0 mmol/L self-measured before breakfast. The primary outcome was non-inferiority of degludec to glargine measured by change in HbA1c from baseline to week 52 (non-inferiority limit of 0·4%) by ANOVA in the full analysis set. We assessed rates of hypoglycaemia in all treated patients. This study is registered with ClinicalTrials.gov , number NCT00972283. Findings 744 (99%) of 755 participants randomly allocated degludec and 248 (99%) of 251 allocated glargine were included in the full analysis set (mean age 58·9 years SD 9·3, diabetes duration 13·5 years 7·3, HbA1c 8·3% 0·8, and fasting plasma glucose 9·2 mmol/L 3·1); 618 (82%) and 211 (84%) participants completed the trial. After 1 year, HbA1c decreased by 1·1% in the degludec group and 1·2% in the glargine group (estimated treatment difference degludec–glargine 0·08%, 95% CI −0·05 to 0·21), confirming non-inferiority. Rates of overall confirmed hypoglycaemia (plasma glucose <3·1 mmol/L or severe episodes requiring assistance) were lower with degludec than glargine (11·1 vs 13·6 episodes per patient-year of exposure; estimated rate ratio 0·82, 95% CI 0·69 to 0·99; p=0·0359), as were rates of nocturnal confirmed hypoglycaemia (1·4 vs 1·8 episodes per patient-year of exposure; 0·75, 0·58 to 0·99; p=0·0399). Rates of severe hypoglycaemia seemed similar (0·06 vs 0·05 episodes per patient-year of exposure for degludec and glargine) but were too low for assessment of differences. Rates of other adverse events did not differ between groups. Interpretation A policy of suboptimum diabetes control to reduce the risk of hypoglycaemia and its consequences in advanced type 2 diabetes mellitus might be unwarranted with newer basal insulins such as degludec, which are associated with lower risks of hypoglycaemia than insulin glargine. Funding Novo Nordisk.
Influence of the Mediterranean Diet on Healthy Aging Andreo-López, Maria Carmen; Contreras-Bolívar, Victoria; Muñoz-Torres, Manuel ...
International journal of molecular sciences,
02/2023, Letnik:
24, Številka:
5
Journal Article
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The life expectancy of the global population has increased. Aging is a natural physiological process that poses major challenges in an increasingly long-lived and frail population. Several molecular ...mechanisms are involved in aging. Likewise, the gut microbiota, which is influenced by environmental factors such as diet, plays a crucial role in the modulation of these mechanisms. The Mediterranean diet, as well as the components present in it, offer some proof of this. Achieving healthy aging should be focused on the promotion of healthy lifestyle habits that reduce the development of pathologies that are associated with aging, in order to increase the quality of life of the aging population. In this review we analyze the influence of the Mediterranean diet on the molecular pathways and the microbiota associated with more favorable aging patterns, as well as its possible role as an anti-aging treatment.
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