vitamin D does not prevent type 2 diabetes in people at high risk – Study finds

Taking a daily vitamin D supplement does not prevent type 2 diabetes in adults at high risk, according to results from a study funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. 

Observational studies have reported an association between low levels of vitamin D and increased risk for type 2 diabetes

The Vitamin D and Type 2 Diabetes (D2d) study enrolled 2,423 adults and was conducted at 22 sites across the United States. These findings were published in the New England Journal of Medicine and presented at the 79th Scientific Sessions of the American Diabetes Association in San Francisco.

D2d(link is external) is the largest study to directly examine if daily vitamin D supplementation helps keep people at high risk for type 2 diabetes from developing the disease. The study included adults aged 30 or older and assigned participants randomly to either take 4,000 International Units (IU) of the D3 (cholecalciferol) form of vitamin D or a placebo pill daily. All study participants had their vitamin D levels measured at the start of the study. At that time, about 80% of participants had vitamin D levels considered sufficient by U.S. nutritional standards.

“Observational studies have reported an association between low levels of vitamin D and increased risk for type 2 diabetes,” said Myrlene Staten, M.D., D2d project scientist at NIDDK. “Additionally, smaller studies found that vitamin D could improve the function of beta cells, which produce insulin. However, whether vitamin D supplementation may help prevent or delay type 2 diabetes was not known.”

The study screened participants every three to six months for an average of 2.5 years to determine if diabetes had developed. Researchers then compared the number of people in each of the two study groups that had progressed to type 2 diabetes. At the end of the study, 293 out of 1211 participants (24.2%) in the vitamin D group developed diabetes compared to 323 out of 1212 (26.7%) in the placebo group – a difference that did not reach statistical significance. The study was designed to detect a risk reduction of 25% or more.

D2d enrolled a diverse group of participants with a range of physical characteristics, including sex, age, and body mass index, as well as racial and ethnic diversity. This representation helps ensure that the study findings could be widely applicable to people at high risk for developing type 2 diabetes.

“In addition to the study’s size, one of its major strengths is the diversity of its participants, which enabled us to examine the effect of vitamin D across a large variety of people,” said lead author Anastassios G. Pittas, M.D., principal investigator from Tufts Medical Center, Boston. “When the study ended, we found no meaningful difference between the two groups regardless of age, sex, race or ethnicity.”

More than 50% of adults in the United States take nutritional supplements and use of vitamin D has increased substantially over the last 20 years. Because of these trends, the study also evaluated the safety of taking 4,000 units of vitamin D daily — greater than the average daily recommended dose of 600-800 IUs a day, but within limits deemed appropriate for clinical research by the Institute of Medicine. The researchers saw no difference in the number and frequency of predicted side effects such as high blood calcium levels and kidney stones when they compared the vitamin D and placebo groups. 

“As we learned from the NIDDK-funded Diabetes Prevention Program (DPP), type 2 diabetes is not a foregone conclusion, even for those at high risk for the disease,” said NIDDK Director Griffin P. Rodgers, M.D. “While we continue to search for new ways to prevent the disease, we know that lifestyle change or the drug metformin remain effective methods to prevent type 2 diabetes. We encourage the 84 million U.S. adults at high risk for developing type 2 diabetes to explore options like the CDC’s National DPP, available to communities throughout the country.”

NIAID-Funded Researchers Predict TB Relapse Risk

Each year, tuberculosis (TB) kills more people than any other single infectious disease. Although tuberculosis can often be treated through a long and grueling course of antibiotics, not everyone is completely cured.

A scanning electron micrograph of Mycobacterium tuberculosis bacteria. Credit: NIAID

Even among patients who are infected with Mycobacterium tuberculosis (Mtb) strains that are considered to be susceptible to the standard treatment regimen, 5 percent of patients relapse within six months of completing standard treatment. Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and through NIAID’s Tuberculosis Research Units Network (TBRU-N), found that a more refined analysis of TB strains collected from volunteers before treatment could accurately predict whether those volunteers would be likely to relapse after standard treatment was completed.

The consequences of TB relapse can reach beyond an individual patient, as any bacteria that remain in the patient after treatment has ended are more likely to be resistant to antibiotics. Multidrug-resistant tuberculosis is often much more difficult to treat, and its spread is a serious concern.

If health professionals could know whether a patient might relapse after standard treatment, they could decide to prescribe a different, or longer, treatment regimen. However, predicting whether a patient will relapse can be difficult. Research published in the New England Journal of Medicine in August sought to determine if identifying the level of drug required to kill the Mtb strains in a new patient’s sputum, a viscous mucus, could predict whether the patient would relapse later, once treatment was complete.

The researchers used data and samples from volunteers who had participated in a prior study run by the Tuberculosis Trial Consortium(link is external) of the Centers for Disease Control and Prevention. Roughly 1,000 adult volunteers from the United States and Canada, all of whom tested positive to drug-susceptible TB, enrolled in the study between April 1995 and February 2001. Before the study began, volunteers gave samples of sputum, which were stored for later testing. Volunteers then underwent both eight weeks of standard antibiotic therapy and an additional 16 weeks of either once-per-week rifapentine and isoniazid treatments, or twice-weekly rifampicin and isoniazid treatments. For two years after treatment completion, researchers followed the volunteers, noting who relapsed.

In this current study, researchers analyzed the TB strains in the volunteers’ stored sputum. They studied Mtb strains collected from all 57 volunteers who relapsed after completion of treatment and whose sputum bacteria could be cultured, and from 68 randomly selected volunteers who were cured as controls. The researchers cultured the bacteria isolated from the sputum of the 125 volunteers before they started TB treatment and tested for the bacteria’s susceptibility to isoniazid and rifampicin at different concentrations. The researchers found that strains collected from volunteers who relapsed required higher concentrations of isoniazid and rifampicin to halt their growth, on average, as compared to strains collected from patients who were cured. Based on these results, researchers developed a model to predict how likely a patient with drug-susceptible TB will relapse.

The researchers then conducted a follow-up study to validate their model using a group of volunteers enrolled in a different study led by NIAID’s Division of Microbiology and Infectious Diseases at sites in Brazil, the Philippines, and Uganda. These volunteers, who had also been diagnosed with drug-susceptible TB, also provided sputum samples prior to undergoing standard treatment with isoniazid, rifampin, ethambutol, and pyrazinamide, followed by two months of isoniazid and rifampin. Some volunteers were randomly assigned to an additional two months of isoniazid and rifampin. Using the model developed in the first study, researchers demonstrated that bacteria in pre-treatment sputum samples from 11 volunteers who experienced a relapse required higher concentrations of drugs to be killed in culture, as compared to bacteria cultured from pre-treatment sputum from 14 volunteers who did not relapse.

The results of this study provide a first step in identifying which patients are likely to relapse after completion of TB standard therapy. This has the potential to improve TB treatment success rates and decrease the development of drug-resistant Mtb.

ARTICLE:

Colangeli, R. et al. Bacterial Factors that Predict Relapse after Anti-Tuberculosis Therapy(link is external). The New England Journal of Medicine. DOI: 0.1056/NEJMoa1715849(link is external) (2018).

Induced labor at 39 weeks may reduce likelihood of C-section, NIH study suggests

Elective induction at 39 weeks also linked to lower risk of maternal high blood pressure disorders.

Healthy first-time mothers whose labor was induced in the 39th week of pregnancy were less likely to deliver by cesarean section, compared to those who waited for labor to begin naturally, according to a study funded by the National Institutes of Health.

Researchers also found that infants born to women induced at 39 weeks were no more likely to experience stillbirth, newborn death or other severe complications, compared to infants born to uninduced women. The study results, which were presented earlier in brief form(link is external), now appear in detail in the New England Journal of Medicine.

“Prior to this study, there was concern that induction of labor would increase the chance of cesarean delivery,” said study author Uma M. Reddy, M.D., of the Pregnancy and Perinatology Branch of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “Our analysis suggests that elective induction at 39 weeks is associated with a lower rate of cesarean delivery and does not increase the risk of major complications for newborns.”

Although cesarean delivery is safe for mother and baby, it is major surgery and does carry risks. It takes longer to recover from a C-section, compared to vaginal birth, and the surgery may increase the risk of problems with vaginal birth in future pregnancies.

Elective induction — labor induced when there is no medical need to do so — before 39 weeks(link is external) is known to pose health risks for newborns. However, elective induction at 39 weeks, or one week before the due date, has become more common in recent years, said Dr. Reddy. NICHD funded the current study to determine the potential risks and benefits of elective induction at 39 weeks, compared to expectant management, or waiting for labor to begin naturally, with health care practitioners intervening if problems occur.

The study enrolled more than 6,000 pregnant women at 41 hospitals participating in the NICHD-supported Maternal-Fetal Medicine Units Network. Roughly half of the women were assigned at random to have their labor induced in the 39^th week of pregnancy; the remaining women received expectant management.

The researchers compared births between the two groups in terms of a primary outcome, a composite measure that included death of the baby during or after birth; the newborn’s need for respiratory support; seizure, infection, birth trauma (injury) or hemorrhage; and other birth complications.

The primary outcome occurred in 4.3 percent of the induced labor group and 5.4 percent of the expectant management group, a difference that was not statistically significant. However, the proportion of cesarean delivery was significantly lower for the induced group (18.6 percent), compared to the other group (22.2 percent). Similarly, the rate of blood pressure disorders of pregnancy was significantly lower in women who were induced (9.1 percent), compared to the other group (14.1 percent).

The researchers estimate that one cesarean delivery could be avoided for every 28 low-risk, first-time mothers undergoing elective induction at 39 weeks.

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD conducts and supports research in the United States and throughout the world on fetal, infant and child development; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.