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On Vitamin D und Diabetes basis of evidence from animal and human studies, vitamin D has emerged as a potential risk modifier for type 1 and type 2 diabetes type 1 diabetes and type 2 diabetes. Vitamin D is thought to have both direct through activation of the vitamin D receptor and indirect via regulation of calcium homeostasis effects on various mechanisms related to the pathophysiology of both types of diabetes, including pancreatic beta cell dysfunction, impaired insulin action and systemic inflammation.
Observational case-control Vitamin D und Diabetes have shown that vitamin D supplementation in pregnancy or early childhood is associated with reduced risk of incident type 1 diabetes. There are no trials on the effect of vitamin D ergocalciferol or cholecalciferol on Vitamin D und Diabetes 1 diabetes. An association between vitamin D insufficiency and incident type 2 diabetes has been reported in longitudinal observational studies, but the association is not consistent.
Results from small underpowered trials and post-hoc analyses of data from larger trials designed for bone-specific outcomes show no effect of vitamin D supplementation on glycemia in healthy adults but vitamin D may retard the progression to diabetes in adults with glucose intolerance. Because vitamin D is an excellent marker of general health status, the positive results reported in some observational studies might reflect unmeasured and unaccounted confounding.
Therefore, the hypothesis that vitamin D may modify diabetes risk needs to be confirmed in trials specifically designed for that purpose. Diabetes, a chronic condition associated with serious morbidity, increased mortality and accelerated health care costs, is rapidly becoming a global epidemic. The total number of people with diabetes world-wide is expected to rise from million in to million by [ 1 ].
Although the majority of new cases are due to type 2 diabetes, the incidence of type 1 diabetes has been increasing as well. The growing incidence and prevalence of diabetes highlights the need for innovative approaches for the management and prevention of the disease. Epidemiologic data suggest that 9 out of 10 cases of type 2 diabetes could be attributed to modifiable habits and lifestyle [ 2 ]; however lifestyle changes are Vitamin D und Diabetes to achieve and maintain long term.
Much less is known about modifiable risk factors for type 1 diabetes. Therefore, identification of modifiable risk factors for prevention of both types of diabetes is needed. Recently, there has been increasing evidence from animal and human studies, to suggest that vitamin D may play a role in modifying risk of diabetes [ 3 ]. Type 1 diabetes is due to autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency.
For type 2 diabetes Vitamin D und Diabetes develop, impaired pancreatic beta-cell function, insulin resistance and systemic inflammation are often present. There are several lines of evidence to support that vitamin D influences all these pathways [ 3 ].
A role for vitamin D Vitamin D und Diabetes pancreatic beta-cell function might be mediated by the binding of circulating 1,dihydroxyvitamin D to the beta-cell vitamin D receptor. Alternatively, vitamin D could function through activation of hydroxyvitamin D 25OHD by 1-alpha-hydroxylase, which is expressed in beta cells. Vitamin D may also affect insulin secretion and sensitivity indirectly via its Vitamin D und Diabetes in regulating extracellular calcium concentration and flux through cell membranes in the beta cell and peripheral insulin-target tissues.
Finally, the well-recognized immunomodulatory properties of vitamin D in relation to T-cell activity [ 4 ] would influence a number of steps in the autoimmune process leading to type 1 diabetes. Vitamin D insufficiency has long been suspected to be Vitamin D und Diabetes risk factor for type 1 diabetes. Indirect evidence comes from studies that have reported higher incidence and prevalence of type 1 diabetes in countries at higher latitude compared to counties at lower latitude [ 5 ].
There is also seasonal variation in the birth date of patients who subsequently develop 1 diabetes, with risk increasing Vitamin D und Diabetes births in the spring-summer months, which suggest an effect of lower sunshine in utero [ 6 ].
Type 1 diabetes is also more commonly diagnosed in the winter [ 78 ]. These ecological studies use latitude and season as proxies for limited sunshine, which is associated with lower vitamin D status; however, this is only a hypothesis as other factors may be responsible for the association e.
There are four case—control studies retrospective and one longitudinal prospective, Table 1 cohort study all from Europe reporting an association between vitamin D status in the pregnant mother or the infant and incident type 1 diabetes [ 9 ]. These studies have reported an inverse association between intake of vitamin D supplements during lactation [ 10 ] or infancy [ 11 ], or intake Vitamin D und Diabetes cod liver oil a major source of vitamin D in certain countries during pregnancy or infancy [ 12 ] and incident type 1 diabetes.
A recent meta-analysis of these studies reported a lower risk for developing type 1 diabetes with self-reported vitamin D supplementation in early childhood odds ratio 0. Other studies have found that increased vitamin D intake during pregnancy [ 13 ] Vitamin D und Diabetes during infancy [ 14 Vitamin D und Diabetes is associated with reduced diabetes-related autoimmunity, providing indirect evidence for a beneficial role of vitamin D on the pathophysiology of type 1 diabetes.
However, the association between vitamin D intake during pregnancy or in early life and type 1 diabetes risk is not consistent [ 1214 ]. Prospective longitudinal observational cohort Vitamin D und Diabetes of vitamin D status and diabetes. Only studies where the predictor vitamin D status was assessed prior to the outcome type 1 or type 2 diabetes are included. There are no trials that have reported the effect of vitamin D 2 ergocalciferol or D 3 cholecalciferol supplementation on prevention or treatment of type 1 diabetes.
In a Vitamin D und Diabetes, open-label trial in 70 children, mean age of 14 years, with recent-onset type 1 diabetes, calcitriol had a modest favorable effect on residual pancreatic beta-cell function; however, the reduction in hemoglobin A1c concentration after 1 year was not statistically significant [ 15 ]. Several cross sectional studies have examined the association between vitamin D status and prevalence of glucose intolerance or type 2 diabetes. Although most have reported an inverse association between vitamin D status and glucose intolerance, others failed to show such an association studies reviewed by Pittas Vitamin D und Diabetes al [ 3 ].
Vitamin D und Diabetes longitudinal cohort studies from the US and one study from Finland which analyzed 2 separate cohorts have reported an association between vitamin D status and risk of incident type 2 diabetes [ 16 - 18 ] Table 1.
However, this analysis did not adjust for any covariates other than age. In a subgroup analysis from the Nurses Health Study, there was a statistically significant association with lower risk of type 2 diabetes among women who reported the highest intake of both vitamin D and calcium RR 0.
A statistically significant association between higher vitamin D status and lower risk of incident type 2 diabetes was also reported among men in the Mini-Finland Health Survey cohort RR 0. Three analyses two in women [ 1718 ] and one in men [ 18 ] suggested a lower, but statistically non-significant, risk of type 2 diabetes among participants in the highest versus the lowest vitamin D status category, while one analysis in men reported a non-statistically significant increase in risk with higher vitamin D status.
There are seven controlled trials that have examined the effect of supplementation with a variety of formulations of vitamin D on type 2 diabetes related parameters fasting plasma glucose, hemoglobin A1c or incident type 2 diabetes Vitamin D und Diabetes 2 [ 19 - 25 ].
In five studies that provided vitamin D supplementation without concomitant calcium, there was no effect on glycemic measures [ 192023 - 25 ].
There are two trials that have reported the effect of combined vitamin D 3 and calcium supplementation on type 2 diabetes, in post-hoc analyses. In the WHI, there was also no significant effect of treatment on fasting glycemia Vitamin D und Diabetes simple indices of insulin resistance.
Summary of randomized controlled trials of vitamin D supplementation ergocalciferol [D 2 ] or cholecalciferol [D 3 ] on diabetes outcomes. Although cross-sectional studies have reported relatively consistent associations between low vitamin D status and prevalent type 1 or type 2 diabetes [ 326 ], the evidence from longitudinal observational studies is sparse and inconclusive and, therefore, definite conclusions cannot be drawn for a variety of reasons: recall Vitamin D und Diabetes in the case-control studies in type 1 diabetes when the predictor vitamin D status was ascertained by recall years after the diagnosis of diabetes, Vitamin D und Diabetes variability among the various cohorts, lack of adjustment for important confounders and, importantly, residual confounding given that vitamin D status is an excellent marker of overall health.
It is also difficult to draw definitive conclusions from trials, because there is only a small underpowered trial in relation to type 1 diabetes that used the active form of vitamin D while trials in relation to type 2 diabetes were post-hoc analyses.
The optimal vitamin D intake and 25OHD concentration is currently hotly debated and there is growing consensus Vitamin D und Diabetes vitamin D intakes above the current recommendations may be associated with better health outcomes. Based on the available studies reviewed here, it is difficult to draw definitive conclusion for the optimal 25OHD level in relation to diabetes.
An inverse association between vitamin D status and both types of diabetes is suggested by observational studies. However, the lack of large prospective observational Vitamin D und Diabetes that have measured 25 OH D as the exposure variable prior to ascertainment of the outcome and the lack of randomized trials specifically designed to test the effects of Vitamin D und Diabetes D on diabetes limits drawing any definitive conclusions.
To better define the clinical role of vitamin D as a potential intervention for prevention and management of diabetes, high quality observational studies that measure 25 OH D as the exposure variable and randomized controlled trials specifically designed to test such an hypothesis are needed.
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J Steroid Biochem Mol Biol. Author manuscript; available in PMC Jul 1. Author information Copyright and License information Disclaimer. Pittas, M. Copyright notice. See other articles in PMC that cite the Vitamin D und Diabetes article. Abstract On the basis of evidence from animal and human studies, vitamin D has emerged as Vitamin D und Diabetes potential risk modifier for type 1 and type 2 diabetes type 1 diabetes and type 2 diabetes.
Keywords: Vitamin D, diabetes mellitus. Introduction Diabetes, a chronic condition associated with serious morbidity, increased mortality and accelerated health care costs, is rapidly becoming Vitamin D und Diabetes global epidemic. Potential mechanisms of action of vitamin D on glucose metabolism Type 1 diabetes is due to autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency.
Evidence from human studies linking vitamin D and type 1 diabetes 4. Observational studies for type Vitamin D und Diabetes diabetes Vitamin D insufficiency has long been suspected to be a risk factor for type 1 diabetes. Table 1 Prospective longitudinal observational cohort studies of vitamin D status and diabetes. Open in a separate window. Evidence from human studies linking vitamin D and type 2 diabetes 5. Table 2 Summary of randomized controlled trials of vitamin D supplementation ergocalciferol [D 2 ] or cholecalciferol [D 3 ] on diabetes outcomes.
Summary of evidence from the human studies on type 1 and 2 Diabetes Although cross-sectional studies have reported relatively consistent associations between low vitamin D status and prevalent type 1 or type 2 diabetes [ 326 ], the evidence Vitamin D und Diabetes longitudinal observational studies is sparse and inconclusive and, therefore, definite conclusions cannot be drawn for a variety of reasons: recall bias in the case-control studies in type 1 diabetes when the predictor vitamin D Vitamin D und Diabetes was ascertained by recall years after the diagnosis of diabetes, considerable variability among the various cohorts, lack of adjustment for important confounders and, importantly, residual confounding given that vitamin D status is an excellent marker of overall health.
Vitamin D und Diabetes intake of vitamin D in relation to diabetes The optimal vitamin D intake and 25OHD concentration is currently hotly debated and there is growing consensus that vitamin D intakes above the current recommendations may be associated with better health outcomes.
Conclusions and future directions An inverse association between vitamin D status and both Vitamin D und Diabetes of diabetes is suggested by observational studies.
Footnotes Publisher's Disclaimer: This is a Vitamin D und Diabetes file of an unedited manuscript that has been accepted for publication. Global prevalence of diabetes: estimates for the year and projections for Diabetes Care.
Diet, lifestyle, and the risk of Vitamin D und Diabetes 2 diabetes mellitus in women. N Engl J Med. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. Immunoregulation by 1,dihydroxyvitamin D3: basic concepts. The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Seasonality of birth in children and young adults years with type 1 diabetes in Ukraine.
Incidence, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus in Denmark. The Pittsburgh insulin-dependent diabetes mellitus registry: seasonal incidence. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis.
Archives of disease in childhood. Major childhood infectious diseases and other determinants associated with type 1 diabetes: a case-control study. Acta diabetologica. Intake of Vitamin D und Diabetes D and risk of type 1 diabetes: a birth-cohort study.
Vitamin D und Diabetes LC, Joner G.