Author Archives: momsbrain

Still Some Unsettled Issues in Gestational Diabetes, But One Thing’s For Sure: Follow-up With Moms is Vital

An estimated 6 or 7 percent of pregnant women in the United States will develop gestational diabetes during pregnancy. That might not sound like much, but with 4 million births each year, that means about 250,000 annual cases of gestational diabetes – and these women have a seven-fold risk for developing Type 2 diabetes within a decade of delivery.

And yet, controversy still clouds gestational diabetes and how best to manage it, said Mark Landon, chair of the Department of Obstetrics and Gynecology at Ohio State University Wexner Medical Center.

Two large clinical trials, including one on which Landon was first author, have suggested that treating women with gestational diabetes – using dietary lifestyle interventions designed to keep blood sugar at normal levels for the vast majority of patients – significantly reduced the frequency of preeclampsia when compared to no treatment. Preeclampsia is a condition characterized by high blood pressure and protein in the urine after the 20th week of pregnancy. The only cure is delivery of the baby, but mild cases can be managed to delay delivery.

In spite of that, a meta-analysis published in 2010 stated that only modest evidence existed to show that treatment of gestational diabetes resulted in a benefit – but this analysis did not take preeclampsia into consideration.

Because gestational diabetes typically leads to larger babies, birth injuries also are a major concern – especially the possibility that a baby’s shoulder can get stuck in the birth canal, slowing delivery and creating conditions that could lead to shoulder nerve damage that lasts a lifetime.

Keeping the baby’s size in mind, practitioners must strike a balance between allowing a baby to develop safely to full term without letting it get so large that vaginal delivery becomes a dangerous prospect for mother and child. Waiting too long can lead to cesarean section, which carries its own complications.

A major analysis of 10 years of births appeared to suggest that 39 weeks gestation functioned as a good cutoff point to reduce risk of stillbirth or injury to the baby in mothers with gestational diabetes, though Landon said that seasoned physicians who have treated thousands of women with mild cases of gestational diabetes may not buy the argument that delivery is needed as early as 39 weeks.

Perhaps more useful to determine the optimal delivery time in the name of safety to mom and baby is estimating the baby’s weight. One national recommendation warned against prophylactic C-section in gestational diabetes pregnancies until a baby reached 4,500 grams, or just shy of 10 pounds, while a study suggested 4,250 grams, or 9.4 pounds, might be a more appropriate cutoff.

“Our approach continues to be for women who have never given birth vaginally is that we need to evaluate each woman carefully and individually … and consider a C-section even at a cutoff of 4,000 grams (8.8 pounds). This may seem like an aggressive approach, but given the flaws in the literature, it’s reasonable in clinical practice to do so,” Landon said.

Care for women with gestational diabetes does not stop in the delivery room, he noted, because of the elevated risk these women have of developing Type 2 diabetes and the need to plan these patients’ future pregnancies.

“We don’t do very well in this mission, and it is primarily a mission of those who provide obstetric care,” Landon noted, adding there are additional unknowns: “No one really knows what the appropriate time interval is for follow-up testing in women who screen normal for glucose in the immediate postpartum period but have a previous history of gestational diabetes.”

Landon co-authored a publication earlier this year calling on obstetricians to better promote women’s health after a diagnosis of gestational diabetes, including employing strategies that might reduce the frequency of diabetes and improve their overall general health.

Given the likelihood that children of women with gestational diabetes in some ethnic populations have increased risk for childhood obesity and metabolic syndrome, obstetricians have an opportunity to help break the cycle of diabetes, Landon suggested.

“Our responsibility doesn’t end in the delivery room. It extends to ensure the future health of that mother and her baby.”

-Emily Caldwell

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What Can WHI Tell Us About Diabetes in Postmenopausal Women?

Diabetes was not a focus of the Women’s Health Initiative, but the massive amounts of data collected on 161,000 postmenopausal participants will probably be answering questions about women’s health for years to come.

WHI consisted of randomized trials to test the effects of hormone therapy, low-fat diet and calcium + vitamin D on heart disease, cancer and fractures, as well as an observational study examining the relationship between lifestyle, health and risk factors and specific disease outcomes. Participants ranged in age from 50 to 79 years.

This being the largest, most comprehensive examination of women’s health ever in the United States, researchers did gather information on diabetes diagnoses in the participants, providing data that could be examined in later analyses.

Among the diabetes-related findings:

Looking at diabetes prevalence and incidence by ethnicity, WHI measures were similar to those seen in the broader adult population – lowest in whites and a tad higher in Asians, even higher in Hispanics and most prevalent among African Americans.

Researchers found a somewhat lower rate of diabetes among women who took estrogen plus progestin hormone therapy compared to placebo. In the estrogen-alone trial, there was also a decrease in diabetes, but it was not statistically significant.

“No one would tell you to take hormones or prescribe them to prevent diabetes because this minimal effect is far overshadowed by adverse effects,” said Barbara Howard, senior scientist at the MedStar Health Research Institute and professor of medicine at Georgetown University School of Medicine. “But this gives us clues … and could lead to research on viable approaches to preventing diabetes.”

About those adverse effects: The WHI was famous for its findings that combination hormone therapy was associated with increased risk of heart attack, stroke, blood clots and breast cancer as well as reduced risk of colorectal cancer and fewer fractures compared to placebo. Estrogen-only therapy, meanwhile, was associated with increased risk of stroke and blood clots, uncertain effects on breast cancer and no effect on colorectal cancer risk, and reduced risk of fracture.

Among the 49,000 women randomized to a low-fat diet or comparison group and followed for about eight years, there was no impact found on the diabetes rate. At the time of the study design, the aim was to reduce all kinds of fat to 20 percent of the diet to test effects of this diet on cancer prevention. The intervention led to more weight loss than did the control condition. “Our conclusion was that low-fat dietary patterns can be a useful approach for weight loss in lifestyle programs designed to prevent diabetes,” Howard said.

The calcium and vitamin D trial provided no hints that vitamin D, even measured in blood samples, had any effect on the incidence of diabetes.

In looking at relationships between diabetes risk and physical activity and body mass index, researchers found that in all women, no matter their race, higher BMI and lower physical activity were strong predictors of risk for diabetes, and the combination was an especially strong predictor. And the evidence suggested that in this area, different racial groups will respond roughly the same to lifestyle interventions emphasizing more physical activity and lower weight.

When scientists adjusted the data, they saw a 28 percent increase in risk for developing diabetes in current smokers compared to never smokers. New quitters retained a relatively high risk, primarily because they tended to gain weight. Once the cessation period passed, the risk lowered dramatically.

Howard’s take on this: It’s never too late to obtain health benefits from quitting smoking.

-Emily Caldwell

Future of Diabetes Diagnosis, with Help from Pharmacogenetics: Dozens of Type 2 Subtypes

Personalized health care in the context of diabetes, and especially Type 2, someday is likely to involve the diagnosis of patients with one of multiple diabetes subtypes based on an individual’s biological symptoms, physical characteristics and genetic profile, according to Ewan Pearson, a clinical senior lecturer at the University of Dundee in Scotland.

Speaking at a plenary session of the 2012 Global Diabetes Summit hosted by Ohio State’s Diabetes Research Center at Wexner Medical Center, Pearson outlined how stratifying diabetes patients by the origins of their disease and genetic predispositions that influence their response to drugs could dramatically change how patients are treated.

This practice could be a long way off, he said, or, “Who knows? This might not be too far away.”

Pearson, also honorary consultant in diabetes & endocrinology at Ninewells Hospital and Medical School, said the current approach to diabetes diagnosis is oversimplified, with the vast majority of cases defined as Type 2 diabetes. Only a tiny percentage are diagnosed as MODY – maturity onset diabetes of the young.

Detailing a number of case studies that make it abundantly clear how different Type 2 diabetes patients can be in terms of biological symptoms and sensitivity to drugs, Pearson suggested that MODY is not considered frequently enough as an alternative diagnosis to Type 2.

Personalized drug treatment could be much more effective in these stratified patients because their genes would offer clues about which medications, and at which doses, will work best for them. For example, studies have already uncovered gene variants that can affect how statins work at different doses – and roughly 90 percent of diabetes patients take these drugs to control cholesterol.

Similar pharmacogenetic research into genetic variants that influence sensitivity to blood sugar-lowering drugs are in their earliest stages. Pearson and colleagues have identified a likely target gene on chromosome 11 that influences the effects of metformin, an enormously popular drug for lowering blood sugar in Type 2 diabetes, but much more work is required to fully understand that gene’s role. Scientists also have some hints about variants that influence response to another class of glucose-control agents as well.

In cases where variants have been identified that affect patient response to drugs, however, the effects are too limited or affect too few people to justify incorporating genomic analysis into clinical care at this point, he noted.

Pearson asserted that pharmacogenetics will continue to advance discoveries that will have clear implications and lead to “good clinical medicine” that will avoid oversimplification.

“I do think this is the future of diabetes and I’m optimistic that we’ll start identifying some subtypes over the course of the next 5 years,” he said.

-Emily Caldwell

Initial Combination Therapy for Type 2 Diabetes: Is It Ready for Prime Time?

Cancer, HIV, tuberculosis and asthma are complex diseases that are routinely, and immediately upon diagnosis, treated with medication cocktails. Diabetes is complex, too, so clinicians should strongly consider a combination therapy approach for this disease, according to Bernard Zinman, a clinician-scientist at Mount Sinai Hospital in Toronto, Ontario, Canada.

Zinman borrowed from a point made in a journal article about how cellular pathways operate more like webs than like superhighways – meaning there are multiple routes that could be activated in response to inhibition of one pathway.

“If you get blocked one way going to Cleveland from Columbus, there are other ways to get there. The same is true in cellular pathways,” Zinman told attendees at the 2012 Global Diabetes Summit hosted by Ohio State’s Diabetes Research Center at Wexner Medical Center.

That article was pointing to the need for combination therapies for tumors and infectious diseases. “I believe the same principles apply to metabolic pathways and the use of pharmacological interventions,” he said, adding that there are a lot of pathways that lead to excess blood glucose and that the disease is progressive, getting worse over time as beta cells disappear.

This being the case, he said, why wait? Why “treat to failure,” as is the current standard of care for new diabetes cases?

Zinman published a 2011 article in the American Journal of Medicine detailing his rationale for the cocktail approach. His reasoning is that starting with combination therapy could: more rapidly lower hemoglobin A1c, a measure of blood glucose levels in the previous two to three months; avoid clinical inertia associated with the current stepwise approach to therapy; potentially improve beta cell function; set off multiple mechanisms of action that work well together; and allow for less than maximal doses, which could reduce side effects.

“We should start with combination therapy right from the get-go,” he said, also acknowledging, “It’s a major paradigm shift.”

Studies of combination therapies for diabetes have produced mixed results, and often show quick improvements in health measures that disappear over time. Acknowledging that the best evidence doesn’t yet exist to support his argument in favor of early combination treatments, Zinman said the most effective study would be a randomized clinical trial of monotherapy with the existing stepwise approach compared to initial combination therapy.

Current guidelines tend to recommend this stepwise approach, meaning that they recommend clinicians begin treatment with lifestyle interventions and a single drug to combat hyperglycemia. The addition of new therapies is typically recommended when A1c levels reach 9 – though the normal A1c level is 5.6 and 7 or above triggers a diabetes diagnosis. That A1c threshold is too high in Zinman’s estimation.

“Combination therapies with complementary mechanisms of action should be used early in the disease process. The earlier we achieve the target, the better off patients will be,” he concluded.

-Emily Caldwell

It’s ‘All Hands on Deck’ or Bust in National Diabetes Prevention Effort

The staggering numbers associated with Type 2 diabetes in the United States are enough to get any health professional down: 26 million currently diagnosed, 79 million with high enough blood sugar to be at highest risk for the disease.

If the trajectory of new diagnoses doesn’t change, says Ann Albright, director of the Division of Diabetes Translation for the Centers for Disease Control and Prevention (and Ohio State alumna), experts predict that one in three Americans will have diabetes by 2050.

“That is not sustainable,” Albright told attendees at the 2012 Global Diabetes Summit hosted by Ohio State’s Diabetes Research Center at Wexner Medical Center. “If we think prevention is difficult now, we ain’t seen nothing yet if we don’t get it together.”

But one intervention does not fit all at risk for diabetes, she noted, referring repeatedly to a “risk continuum.” People at low or moderate risk for diabetes cannot be cast aside in prevention efforts, but they are not the focus of the most ambitious prevention effort that the CDC is responsible for implementing.

The Diabetes Prevention Program (DPP) trial was an important milestone in national prevention efforts.

“It was vital for us to know whether or not we can say that you can prevent Type 2 diabetes in high-risk people,” Albright said. The trial showed that a lifestyle intervention aimed at dietary changes and increased physical activity was more effective than medicine at delaying or preventing high-risk individuals from developing diabetes.

As experts work to translate the program to communities in which high-risk people live, they note that one element of the DPP cannot practically be scaled to a national level: the one-on-one counseling each participant experienced.

Instead, the intervention now is offered in group settings, and an analysis of 28 studies of the effectiveness of group counseling suggested that average weight loss among participants was 4 percent – a bit shy of the goal of 5-7 percent weight loss.

An interesting finding: The weight loss was similar no matter which kind of leader hosted the counseling – a health professional or a lay educator. And this is why it’s an “all-hands-on-deck” situation, Albright said.

“If we build this on the backs of health professionals, we’ll never get where we need to go.”

The Affordable Care Act of 2010 authorized the CDC to lead a national DPP, “but this is not a CDC program. This belongs to the US and around the world,” she said. CDC is responsible for providing organizing infrastructure so a national DPP can be implemented in the United States.

Elements of that infrastructure include training to increase the work force; assuring quality; delivering the program at identified intervention sites; and marketing to increase referrals so the program is put to use on the scale required.

Participant engagement is vital, and the culture needs to shift so that community-based programs are “the thing to do, the place to be for diabetes prevention,” she said.

So far, the national program has served or is serving 9,000 people and is being run by more than 1,000 lifestyle coaches serving citizens in this country. Early data suggest weight loss achievement is about 4.9 percent, and that goes up to 5.1 percent among programs that have been running the longest. Retention is best after participants get through the first four sessions.

Planners are heartened by the results, but Albright warned that health gains being made in people currently diagnosed with diabetes are being overtaken by new cases, driving home now critical prevention of diabetes will be to the country’s economic and public health future.

“If we don’t do this,” she said, “one in three, one in three, one in three.”

-Emily Caldwell

National Research Battling Diabetes On Multiple Fronts

Federally funding basic and clinical research isn’t enough to stem the tide of Type 2 diabetes, says Griffin Rodgers, director of the National Institute of Diabetes and Digestive and Kidney Diseases. The federal government also must – and does – support efforts to get the results into public hands.

Speaking at the 2012 Global Diabetes Summit hosted by the Ohio State’s Diabetes Research Center at Wexner Medical Center, Rodgers outlined the research efforts of the federal agency responsible for diabetes as well as numerous related conditions, including kidney disease and obesity.

Because of those multiple areas of research, Rodgers said the agency’s approach is integrated, recognizing that in the United States, Type 2 diabetes is the leading cause of kidney disease, which can have an amplifying effect on cardiovascular complications.

“These diseases are common, costly and consequential,” he said.

Prevention of diabetes is a significant national effort. While about 26 million Americans have diabetes, 79 million have prediabetes – meaning their blood sugar is higher than normal but not high enough to trigger the diabetes diagnosis. They are considered at highest risk for developing diabetes.

The decade-old Diabetes Prevention trial showed that a lifestyle intervention emphasizing dietary changes and 150 minutes of physical activity per week was highly effective at delaying or preventing the onset of diabetes in high-risk individuals compared to a drug, metformin, or no intervention at all. The lifestyle intervention showed a 58 percent reduction in diabetes onset, compared to a 31 percent reduction for those on metformin. A follow-up showed that the results can be sustained in the long term. Among participants who were 65 or older, the reduction was 71 percent.

Women who develop gestational diabetes during pregnancy are also considered a high-risk group under study for the most effective interventions. Research suggests that children born to these women are at higher risk, as well, for developing Type 2 diabetes.

In addition, children are being watched closely as experts grow increasingly concerned about weight issues in youths. Researchers are seeing an increase in the prevalence of Type 2 diabetes in the pediatric population, Rodgers noted, which indicates that the need for prevention interventions must start earlier in life. A middle-school-based program helped children lower weight, but not any more than could be attributed to chance.

“Not only does one have to intervene in schools, but also in other settings,” Rodgers said.

Perhaps the biggest challenge is engaging potential intervention participants – which is why sharing information about research results is so vital.

“Fundamentally, if one is funding studies that develop the acquisition of knowledge and subsequently transformation of that data into knowledge that can affect patients, if one doesn’t also invest in dissemination, one is in a sense leaving at the table discoveries as well as efficiencies,” he said. “Not only is it important to fund clinical research, but also the dissemination of information to individuals so that we might make a substantial public health impact.”

-Emily Caldwell