Low vitamin-D levels found in northern California residents with metabolic syndrome

ScienceDaily (Nov. 30, 2010) ? Researchers from the UC Davis Health System have found that compared with healthy controls, blood levels of vitamin D are significantly reduced in patients in the Sacramento area with metabolic syndrome, a constellation of disease risk factors that affects about one in three U.S. adults and predisposes them to diabetes, heart disease and stroke.

The study is the first to examine vitamin-D status in patients with metabolic syndrome living in Northern California, where the many hours of sunshine make the vitamin-D deficiency finding surprising. The study was published online November 30 and will appear in the January 2011 issue of the journal Hormone and Metabolic Research.

"In spite of our great sun exposure in Northern California, 30 percent of patients with metabolic syndrome have vitamin-D deficiency, and even many subjects in the control group had inadequate levels," said Ishwarlal Jialal, the study's principal investigator and professor of pathology and laboratory medicine at the UC Davis Health System. "Considering our climate and healthy lifestyles here, these findings were unexpected."

The study measured serum vitamin D levels in 44 people with metabolic syndrome and compared them to 37 healthy controls matched for age and gender. They found that 30 percent of subjects with metabolic syndrome were deficient in vitamin D compared with eight percent of controls. The difference between the groups was statistically significant and could not be explained by differences in sun exposure or other factors that are known to alter vitamin-D levels, such as kidney disease and amount of body fat. Furthermore, the low levels correlated with risk of diabetes such as insulin resistance and plasma glucose levels.

Metabolic syndrome has become highly prevalent in the United States with the obesity epidemic. The syndrome is characterized by having at least three of the following risk factors: a large waistline, a high blood-triglyceride level, a low-blood level of high-density lipoprotein (HDL) cholesterol, high-blood pressure and high-fasting blood sugar. These factors indicate disturbances in the body's metabolism, conferring at least a five-fold increased risk of developing diabetes and doubling the risk for developing cardiovascular diseases, including heart attack and stroke.

Vitamin D is a nutrient that has come under increased scrutiny in recent years as more of its roles in the human body are discovered. It has long been known to be important for healthy bone growth and maintaining normal calcium levels in the blood. More recent studies have also linked low vitamin-D levels to an increased risk of diabetes and cardiovascular disease as well as many cancers. Reduced vitamin D levels are also associated with higher fasting blood sugar, more insulin resistance and increased body fat, components of the metabolic syndrome.

Vitamin D is obtained naturally through sun exposure as well as through certain foods, including fish, liver and eggs. It can also be taken through supplements, and many dairy products, margarines and cereals are fortified with it. Although most people in California are traditionally thought to receive adequate vitamin D through routine outdoor activity, this study indicates that this is not the case in Northern California. A similar study recently conducted in Southern California found no difference in vitamin-D levels between subjects with and without metabolic syndrome, and in Florida, even diabetics do not tend to have low vitamin-D levels. These results indicate that vitamin D levels are probably adequate for most people living in those sunny latitudes, and that metabolic syndrome and diabetes arise mostly because of other factors in those areas.

"That our results were so different from the study undertaken in Southern California was amazing to us," said Jialal, who also serves as director of the Laboratory for Atherosclerosis and Metabolic Research at UC Davis. "The difference in latitude is not that great, but apparently sun exposure in southern California is adequate and in northern California it is not."

Controversy exists surrounding optimum blood levels of vitamin D. Current government guidelines for sufficient blood levels of vitamin D as well as daily intake are based on those required for bone health and are much lower than what are now believed by many experts to help prevent cancer, diabetes and cardiovascular disease. National Institutes of Health guidelines recommend a minimum blood level of 15 ng/mL as adequate for bone and overall health. However, many experts now feel that 30 to 100 ng/mL should be the goal. Levels above 150 ng/mL are potentially toxic and can be life-threatening.

In this study, vitamin D levels averaged 23.1 ng/mL among people with metabolic syndrome and 27.8 ng/mL in healthy controls, a difference that was found to be significant. Vitamin D deficiency in this study was defined as less than 20 ng/mL, and was found in 30 percent of subjects with metabolic syndrome and 8 percent of healthy controls. "Insufficiency" was defined as less than 30 ng/mL: 84 percent of the metabolic syndrome group and 67 percent of controls were found to have insufficient levels.

Jialal's team intends to continue to investigate the connections between vitamin D and metabolic syndrome. They plan to study diets of subjects with and without metabolic syndrome to determine whether vitamin D intake is adequate. According to Jialal, it is possible that people with metabolic syndrome have higher than average needs for vitamin D. Because the vitamin is fat-soluble, it tends to get sequestered in fat, making it less likely to circulate in the blood and to be available to other tissues.

They also plan to undertake a study on vitamin D supplementation for people with metabolic syndrome to see if it lowers fasting blood sugars and increases insulin sensitivity, trends that would lower the risk of developing diabetes.

"We have the potential to significantly delay or prevent the emergence of diabetes, heart attacks and strokes in people with metabolic syndrome through vitamin D supplementation," said Dr. Jialal. "This may offer a very simple yet powerful weapon to combat this burgeoning health problem in our society."

The other UC Davis study authors include Professor Sridevi Devaraj, student volunteer Ganesh Jialal and technologist Teri Cook measured the vitamin-D levels. David Siegel assisted in the study design and manuscript preparation. This study was supported by grants from the National Institutes of Health and American Diabetes Association.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of California - Davis Health System, via EurekAlert!, a service of AAAS.

Journal Reference:

Ishwarlal Jialal et al. Low vitamin D levels in North American adults with the metabolic syndrome. Hormone and Metabolic Research, November 30, 2010

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Language delays found in siblings of children with autism

ScienceDaily (Oct. 1, 2010) ? Siblings of children with autism have more frequent language delays and other subtle characteristics of the disorder than previously understood. Girls also may be mildly affected more often than recognized in the past.

A new study, led by researchers at Washington University School of Medicine in St. Louis, found mild traits, not strong enough to provoke a diagnosis of autism, seem to be present in the siblings of affected children at significantly higher rates than seen in the general population. The findings appear online and will be published in the November issue of The American Journal of Psychiatry.

"Mild symptoms, called quantitative traits, may be confounding studies that compare children with autism to their siblings," says first author John N. Constantino, MD. "Researchers presume one child is affected, and the other is not, but our findings suggest that although one child may have autism while the other does not, it's very possible both children are affected to some degree by genes that contribute to autism."

Genetic factors exert their influence in different ways. Some families have only a single child with autism and no other affected children. But in other families, more than one child may be affected, or other siblings may have a number of autism characteristics.

The study found that approximately one in five siblings thought to be unaffected experienced language delays or speech problems early in life. The researchers also noticed many female siblings had subtle traits, but few had full-blown autism spectrum disorders. Boys are thought to be affected four times more often than girls. But when the researchers used standardized methods to account for the presence of quantitative traits, the rate looked more like three affected boys for every two affected girls.

"The gender difference may not be as pronounced as we once thought it was," Constantino says. "If we rely only on a professional diagnosis of autism to determine who is affected, then boys vastly outnumber girls. But it may be that many girls are being missed."

The data comes from almost 3,000 U.S. children in 1,235 families who are part of the Interactive Autism Network, a national online research registry. Developed by study co-author Paul Law, MD, director of medical informatics at Kennedy Krieger Institute in Baltimore, the network has more than 35,000 participants who share information to help advance autism research.

For this study, parents provided information about their children using the Social Responsiveness Scale, a survey developed at Washington University that identifies traits associated with autism and autism spectrum disorders such as Asperger Syndrome and Pervasive Developmental Disorder.

About 10 percent of children with autism have genetic mutations believed to directly lead to the disorder. In others, common gene variations create small increases in susceptibility. When a child has an accumulation of quantitative traits, that child will be diagnosed with autism or a related disorder, but siblings can have subtle quantitative traits without reaching the threshold for a diagnosis.

"It's not an all-or-nothing condition," Constantino says. "When we look only at the full syndrome for inherited traits, we miss a lot of individuals who may have genetic susceptibility and subtle aspects of autism. In other words, many siblings of children on the spectrum have significant, subclinical traits of autism, but, for whatever reason, they never actually develop the disorder."

Constantino, the Blanche F. Ittleson Professor of Psychiatry and Pediatrics and director of the William Greenleaf Eliot Division of Child and Adolescent Psychiatry at Washington University, compares it to the difference between insulin resistance and diabetes. Not all people with insulin resistance are diabetic, and some never develop diabetes, but they are at a much higher risk for the disease. The same thing is true for autism, he says.

One striking finding was that among siblings, 20 percent had received a diagnosis of language delay or speech problems early in life. And half of them had particular qualities of speech that are autistic in nature. So the investigators believe that what is aggregating in these families is more than just the full syndrome of autism. In about 11 percent of families, more than one sibling has autism, and in many others, these subtle, quantitative signs and symptoms indicate many undiagnosed children are affected as well.

That's important, Constantino says, because in studies involving DNA tests, brain imaging or biological comparisons between affected children and their unaffected siblings, researchers traditionally assume undiagnosed children are unaffected. But this study would suggest that's not necessarily the case.

The study also found quantitative traits of autism tended to occur more frequently in children from families with more than one fully affected child. In families with only one child with autism, it was much more common for that child's siblings not to have any evidence of quantitative traits. And the study also found that it was less common for siblings to be affected with those traits than for non-identical twins -- a finding suggested by pooling the results of this study with a recent twin study from Law and his colleagues at Kennedy Krieger Institute that used exactly the same methods and the same family registry.

Law and Constantino say their findings provide insight into the inheritance patterns of autism and its associated traits. Although those severely affected with autism spectrum disorders seldom have their own children, those who are affected with quantitative traits of autism usually grow up to be parents themselves, and understanding how best to predict patterns of transmission in families and identifying the specific genetic and environmental factors underlying those patterns could offer hope for new, more effective interventions that could be used early in the lives of affected children, Constantino says.

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Washington University School of Medicine.

Journal Reference:

Constantino JN, Zhang Y, Frazier T, Abbacchi AM, Law P. Sibling recurrence and the genetic epidemiology of autism. The American Journal of Psychiatry, Vol. 167 (11), published online Oct. 1, 2010 DOI: 10.1176/appi.ajp.2010.09101470

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Strong link between diabetes and air pollution found in national U.S. study

ScienceDaily (Sep. 30, 2010) ? A national epidemiologic study finds a strong, consistent correlation between adult diabetes and particulate air pollution that persists after adjustment for other risk factors like obesity and ethnicity, report researchers from Children's Hospital Boston. The relationship was seen even at exposure levels below the current EPA safety limit.

The report, published in the October issue of Diabetes Care, is among the first large-scale population-based studies to link diabetes prevalence with air pollution. It is consistent with prior laboratory studies finding an increase in insulin resistance, a precursor to diabetes, in obese mice exposed to particulates, and an increase in markers of inflammation (which may contribute to insulin resistance) in both the mice and obese diabetic patients after particulate exposure.

Like the laboratory studies, the current study focused on fine particulates of 0.1-2.5 nanometers in size (known as PM2.5), a main component of haze, smoke and motor vehicle exhaust. The investigators, led by John Pearson and John Brownstein, PhD, of the Children's Hospital Informatics Program, obtained county-by-county data on PM2.5 pollution from the Environmental Protection Agency (EPA), covering every county in the contiguous United States for 2004 and 2005.

They then combined the EPA data with data from the Centers for Disease Control (CDC) and the U.S. Census to ascertain the prevalence of adult diabetes and to adjust for known diabetes risk factors, including obesity, exercise, geographic latitude, ethnicity and population density (a measure of urbanization).

"We wanted to do everything possible to reduce confounding and ensure the validity of our findings," says Pearson, the study's first author.

In all analyses, there was a strong and consistent association between diabetes prevalence and PM2.5 concentrations. For every 10 μg/m3 increase in PM2.5 exposure, there was a 1 percent increase in diabetes prevalence. This finding was seen in both 2004 and 2005, and remained consistent and significant when differing estimates of PM2.5 exposure were used.

"We didn't have data on individual exposure, so we can't prove causality, and we can't know exactly the mechanism of these peoples' diabetes," acknowledges Brownstein. "But pollution came across as a significant predictor in all our models."

Even among counties falling within EPA limits for exposure, those with highest versus the lowest levels of PM2.5 pollution had a more than 20 percent increase in diabetes prevalence, which remained after controlling for diabetes risk factors.

"From a policy perspective, the findings suggest that the current EPA limits on exposure may not be adequate to prevent negative public health outcomes from particulate matter exposure," Brownstein says.

"Many environmental factors may contribute to the epidemic of diabetes in the United States and worldwide," notes Allison Goldfine, MD, head of clinical research at the Joslin Diabetes Center and a coauthor on the study. "While a lot of attention has correctly been attributed to caloric excess and sedentary behaviors, additional factors may provide novel approaches to diabetes prevention."

Based on their findings, the researchers call for more study of environmental factors in diabetes, including basic research on the inflammatory mechanisms in diabetes and the role of PM2.5.

"We would like to access better individual-level data on diabetes and exposure," adds Brownstein. "We also have an interest in investigating this finding internationally where standards may be less stringent."

The study was funded by the National Center for Biomedical Computing of the National Institutes of Health.

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Children's Hospital Boston.

Journal Reference:

J. F. Pearson, C. Bachireddy, S. Shyamprasad, A. B. Goldfine, J. S. Brownstein. Association Between Fine Particulate Matter and Diabetes Prevalence in the U.S.. Diabetes Care, 2010; 33 (10): 2196 DOI: 10.2337/dc10-0698

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