ROCKVILLE, Md. -- Against the background of the growing incidence of type 2 diabetes and obesity in the United States came news this year about the first new insulin delivery system in 80 years, as well as new categories of drugs for type 2 disease.
ROCKVILLE, Md., Dec. 22 -- Against the background of the growing incidence of type 2 diabetes and obesity in the United States came news this year about the first new insulin delivery system in 80 years, as well as new categories of drugs for type 2 disease.
Other researchers focused on diabetes risk factors, prevention, and cutting edge therapies, such as islet-cell transplants.
The following summary reviews some of the highlights of the year in diabetes research, treatment, and prevention. For fuller accounts, links to the individual articles published during the year in MedPage Today have been provided.
The FDA in January approved Exubera, the first new insulin delivery system since the discovery and isolation of the hormone by Frederick Banting and associates in 1921.
Exubera is an inhaled insulin. It was approved nearly five months after the powder form of the Pfizer recombinant human inhalation insulin won an endorsement by the FDA's Endocrinologic and Metabolic Drugs Advisory Committee, by a seven-to-two vote.
"Until today, patients with diabetes who need insulin to manage their disease had only one way to treat their condition," said Steven Galson, M.d., director of the FDA's Center for Drug Evaluation and Research. "It is our hope that the availability of inhaled insulin will offer patients more options to better control their blood sugars."
Although clinical trials had demonstrated Exubera to have efficacy similar to that of short-acting insulins, but without the needle stick, a host of concerns had cropped up, including worries about pulmonary toxicities, and questions about Exubera's ability to achieve a reduction in glycosylated hemoglobin (HbA1c) levels to below 7%, the accepted gold standard.
In its approval statement, the FDA noted that the safety and efficacy of Exubera have been studied in approximately 2,500 adult patients with type 1 and type 2 diabetes. In clinical studies, said the FDA, peak insulin levels were achieved at 49 minutes (range 30 to 90 minutes) with Exubera inhaled insulin, compared with 105 minutes (range 60 to 240 minutes) for short-acting insulin.
In October, the FDA smiled on Januvia (sitagliptin), the first dipetidyl peptidase-4 (DDP-4) inhibitor, as an oral agent for type 2 diabetes.
The agent was approved as monotherapy or in combination with Glucophage (metformin) or a peroxisome proliferator-activated receptor (PPAR) agonist, such as Actos (pioglitazone).or Avandia (rosiglitazone).
Januvia was evaluated in a total of 2,719 patients with type 2 diabetes, in studies lasting from 12 weeks to more than a year, according to the FDA. These studies demonstrated improved blood sugar control when Januvia was used alone or in patients not satisfactorily managed with metformin or a PPAR agonist.
The most common side effects in clinical studies were upper respiratory tract infection, sore throat, and diarrhea.
Avandia Prevents Onset in High-Risk Patients
Avandia (rosiglitazone) prevents the onset of type 2 diabetes in a large proportion of high-risk patients, Canadian researchers reported in The Lancet and at the European Association for the Study of Diabetes meeting.
The drug also restored normal blood glucose concentrations in about half of treated patients, according to Hertzel Gerstein, M.D., of McMaster University in Hamilton, Ontario.
In the DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trial, 306 of the 2,365 patients given Avandia (11.6%) and 686 of the 2,634 given placebo (26.0%) developed the composite primary outcome of incident diabetes or death. The hazard ratio was 0.40 (95% confidence interval 0.35 to 0.46, P
Drug Lowers HbA1c, Increases Insulin Secretion
Liraglutide, an investigational injectable drug for type 2 diabetes, has produced significant decreases in HbA1c levels, as well as significant and sustained weight loss, according to phase II studies.
Patients on the highest dose of liraglutide had a mean reduction in HbA1c of 1.7%, and lost about 3 kg (6.6 pounds) during a 14 week study, reported Tina Vilsboll, M.D., of Gentofte Hospital in Vedbaekm, Denmark, and colleagues, at the American Diabetes Association meeting.
In addition, the drug appears to significantly increase insulin secretion by beta cells, especially during the first phase insulin response, the investigators reported. Liraglutide is an analog of glucagons-like peptide-1 (GLP-1), a naturally occurring hormone that is released from the gastrointestinal tract on ingestion of food. But GLP-1 is normally degraded rapidly by the enzyme dipetidyl peptidase-4 (DPP-4), the enzyme targeted by Januvia.
Statin therapy may have an anti-inflammatory benefit for patients with metabolic syndrome, researchers at the University of California at Davis reported.
In a double-blind, randomized, placebo-controlled study, statin therapy reduced two biomarkers of inflammation-C-reactive protein (CRP) and interleukin-6 (IL6)-according to a study reported in the Sept. 12 issue of the Journal of Clinical Endocrinology and Metabolism.
Lifestyle intervention in type 2 diabetes showed staying power, researchers in Finland reported. Even three years after cessation of active counseling, beneficial lifestyle changes were maintained, found Jaana Lindstrm, M.Sc., of the University of Helsinki, and colleagues. As a result, the relative risk of diabetes versus controls decreased 36% during this period.
The risk reduction was related to the success in achieving the intervention goals of weight loss, reduced intake of total and saturated fat, increased intake of dietary fiber, and increased physical activity, the researchers said.
In a similar vein, Boston researchers found that two common genetic variants appear to contribute to the development of type 2 diabetes for some patients with impaired glucose tolerance, but lifestyle moves seem to be able to combat the enhanced risk.
The genetic finding helps to elucidate diabetes risk mechanisms, but it may not have an immediate therapeutic payoff, reported investigators with the Diabetes Prevention Program in the July 20 issue of the New England Journal of Medicine.
"Our data, combined with previous longitudinal studies and genetic findings, show that type 2 diabetes can be triggered by decreased insulin production and not just by insulin resistance," said Jose Florez, M.D., Ph.D., of Massachusetts General Hospital. "However, researchers need to learn more about this gene before they can even begin to translate the discovery into a drug treatment that benefits people with diabetes or those at risk."
Diabetes is a strong predictor of acute organ failure and early death for obese or non-obese patients alike, eclipsing even obesity without diabetes, according to researchers from the University of Kentucky in Lexington, and Emory University in Atlanta.
In the absence of diabetes, a patient's body mass index (BMI) did not foretell organ failure or in-hospital death, according to a prospective cohort study of 15,408 middle-age adults, they reported in the Sept. 25 issue of Critical Care.
By contrast, diabetic patients had a threefold higher rate of organ failure over three years from baseline versus non-diabetics, said David Mannino, M.D., of the University of Kentucky, and colleagues. Within three years, 5.4% of those with diabetes died, compared with 1.6% of those without diabetes.
The Physicians Committee for Responsible Medicine, a crusading group that has long ranked vegetarianism high on its agenda, made a compelling case for a low-fat vegan diet to improve glycemic control in the August issue of Diabetes Care.
Both a low-fat vegan diet and a diet following American Diabetes Association guidelines improved glycemic control and cardiovascular risk factors in patients with type 2 diabetes, found a 22-week study partially funded by NIH.
But the vegan diet was better, reported Neal D. Barnard, M.D., an adjunct associate professor of medicine at George Washington University, who is president of the Physicians Committee for Responsible Medicine, and colleagues.
Diabetes Plays the Race Card
Blacks with diabetes have worse control of blood sugar than whites, a factor that may help explain the disease's disparity between African Americans and Caucasians in morbidity and mortality, according to researchers at Wake Forest University,
A meta-analysis of 11 studies that compared HbA1c levels between blacks and whites showed blacks averaged 0.65% higher than whites, reported Julienne Kirk, Pharm.D.., and colleagues, in the September issue of Diabetes Care.
"The difference corresponds to about a 14% reduction in risk of any diabetic complication for whites compared to blacks. This lower level of control may partly explain why blacks have disproportionately higher rates of death and complications from diabetes," Dr. Kirk said.
Part of that difference could be compliance, however. African-Americans with type 2 diabetes appear to be less likely than whites to take prescribed medications, reported Rahul A. Shenolikar, M.S., of Ohio State University, and colleagues, in a July issue of the Journal of the National Medical Association.
In a retrospective study comparing medication compliance among Medicaid-insured patients who were given first-time prescriptions for oral antidiabetic agents, African Americans had a 12% lower adherence rate than whites, they found.
"That's an unacceptable difference, particularly because African Americans tend to have higher rates of diabetes and disease-related complications," said Rajesh Balkrishnan, Ph.D., a professor of pharmacy, a co-author.
"Adherence rates for these types of medications should be better than 90% regardless of who takes them," he added. "Such low rates of adherence may be related to lower socioeconomic status and to lower levels of education."
High levels of retinol binding protein 4 (RBP4), which transports vitamin A as its main job, may be an early warning sign for insulin resistance and type 2 diabetes, according to researchers at Beth Israel Deaconess Hospital and Harvard Medical School in Boston.
Serum levels of retinol binding protein 4 are correlated with insulin resistance in a range of patients at risk for diabetes, found Barbara Kahn, M.D., of Beth Israel Deaconess Medical Center and Harvard Medical School, and colleagues.
What's more, therapeutic interventions that lowered insulin resistance also lowered serum RBP4 levels, Dr. Kahn and colleagues reported in the June 15 issue of the New England Journal of Medicine.
Java Junkies Rejoice
Lastly, University of Minnesota researchers reported that coffee drinking can cut down on the risk of type 2 diabetes, especially when the brew is decaf.
Postmenopausal women who reported drinking more than six cups of java daily - presumably without extra cream or laden with sugar - had a 22% lower risk for type 2 diabetes, reported Mark A. Pereira, Ph.D., and colleagues, of the University of Minnesota School of Public Health.
The more coffee the women drank, the lower their risk for diabetes over an 11-year observation period, the authors wrote in the June 26 issue of Archives of Internal Medicine.
"Although the first line of prevention for diabetes is exercise and diet, in light of the popularity of coffee consumption and high rates of type 2 diabetes mellitus in older adults, these findings may carry high public health significance," they wrote.