Popular Diabetes Treatment Could Trigger Pancreatitis, Pancreatic Cancer

A drug widely used to treat Type 2 diabetes may have unintended effects on the pancreas that could lead to a form of low-grade pancreatitis in some patients and a greater risk of pancreatic cancer in long-term users, UCLA researchers have found.

In a study published in the online edition of the journal Diabetes, researchers from the Larry L. Hillblom Islet Research Center at UCLA found that sitagliptin, sold in pill form as Januvia, caused abnormalities in the pancreas that are recognized as risk factors for pancreatitis and, with time, pancreatic cancer in humans. Januvia is marketed by Merck & Co. Inc. Sitagliptin is a member of a new class of drugs that enhance the actions of the gut hormone known as glucagon-like peptide 1 (GLP-1), which has been shown to be effective in lowering blood sugar in people with Type 2 diabetes. The study is available at http://diabetes.diabetesjournals.org/cgi/content/abstract/db09-0058v1. "Type 2 diabetes is a lifelong disease -- people often take the same drugs for many years, so any adverse effect that could over time increase the risk for pancreatic cancer would be a concern," said Dr. Peter Butler, director of the Hillblom Center and the study's lead investigator. "A concern here is that the unwanted effects of this drug on the pancreas would likely not be detected in humans unless the pancreas was removed and examined."

An observed connection between Byetta, a drug used to treat Type 2 diabetes that is related to Januvia in its intended actions, and pancreatitis has already been reported, prompting a Food and Drug Administration warning. Amylin Corp., which markets Byetta, has suggested that since there is no known mechanism linking the cases of pancreatitis with Byetta, the association might be chance. The UCLA study suggests that there may indeed be a link between drugs that enhance the actions of GLP-1 and pancreatitis -- by increasing the rate of formation of cells that line the pancreatic ducts.

In the study, researchers used human IAPP transgenic (HIP) rats to test both sitagliptin and metformin; metformin, a member of an older, different class of diabetes drugs in use since the 1950s, has recently been found to have anti-tumor properties. The researchers sought to determine how the drugs, both singly and in combination, affected islet disease progression in the pancreas -- particularly how they affected beta cells in the pancreas's Islets of Langerhans. Beta cells are responsible for releasing insulin in people with normal metabolism, but they don't produce insulin in sufficient amounts in diabetes patients. HIP rats approximate both the islets and metabolism of people with Type 2 diabetes. The drugs were tested in 40 rats for 12 weeks.

The researchers found that the two drugs in combination had a synergistic effect that helped preserve beta cells, improved their function and enhanced insulin sensitivity in the test rats. With the sitagliptin alone, however, the rats had abnormally high rates of cell production in their pancreatic ducts; a few developed an abnormality known as ductal metaplasia, and one developed pancreatitis.

But the metformin, trade name Glucophage, seems to counteract sitagliptin's adverse effect.

"The apparent protection against the unwanted actions of sitagliptin in the exocrine pancreas are intriguing and may offer a potential way of using the GLP-1 class of drugs safely," Butler said. "The protective effect may have been either by the actions of metformin to decrease blood glucose values or its recently appreciated properties as a tumor suppressive agent."

Butler noted that the present study was undertaken in rats and that it is possible the adverse effects observed would not occur in humans.

"Given these findings, it is probably sensible to use the GLP-1 class of drugs only with metformin until other data is forthcoming," he said.

The National Institutes of Health, the Larry Hillblom Foundation and the Merck Research Foundation funded this study.

In addition to Butler, researchers included Aleksey V. Matveyenko, Heather I. Cox, Artemis Moshtaghian, Tatyana Gurlo, Ryan Galasso and Alexandra E. Butler, all of the Hillblom Center, and Sarah Dry of the department of pathology and laboratory medicine at the David Geffen School of Medicine at UCLA.

The Larry L. Hillblom Islet Research Center at UCLA, established in 2004, is the first center dedicated to the study of the Islets of Langerhans, which include the insulin-producing cells in the pancreas. An understanding of the causes of islet cell destruction is key to finding a cure for diabetes. The center's faculty members, recruited from around the world, provide leadership in the worldwide fight against the disease. The center is funded by a grant from the Larry Hillblom Foundation, which supports medical research in the state of California.

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Obesity, Diabetes Interfere With Work Productivity

Obese workers with type 2 diabetes report less productivity on the job than their normal-weight co-workers, according to a new study of 7,338 working adults.

"We obtained information directly from individuals on how effective they were at the workplace to provide their perspective of the impact of diabetes and obesity on patients' lives," said study co-author Kathleen Fox, Ph.D. In a survey of adults with or at risk for diabetes, participants answered questions about missed work time, reduced on-the-job effectiveness and impairment in daily activities.

The analysis, which appears in the May/June issue of the American Journal of Health Promotion, found that being obese and having diabetes predicted on-the-job problems with productivity.

Obese people with type 2 diabetes experienced the most work impairment, losing 11 percent to 15 percent of work time -- about 5.9 hours per week -- because of health problems that affected productivity on the job, said Fox, president of Strategic Healthcare Solutions, LLC.

In comparison, normal-weight participants at low risk for diabetes reported losing only 9 percent of work time -- about 3.6 hours per week -- due to health problems.

Obese workers with type 2 diabetes also experienced the most problems off the job, reporting impairment during 20 percent to 34 percent of their daily activities, like shopping, exercising and childcare.

The study supports previously published research that "the heavier people are, the more lost productivity at work," said Anne Wolf, an instructor at the University of Virginia School of Medicine who specializes in researching the economic impact of obesity.

What differed was that researchers found an independent effect of diabetes on productivity, Wolf said.

"From an employer's perspective, this study provides evidence that workplace wellness programs that include weight loss and weight management would be beneficial for obese employees with or at risk for diabetes," Fox said.

"Employers who spend money in a lifestyle intervention will find their investment returned to them in the form of increased productivity and reduced absenteeism," Wolf agreed.

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Diabetes Self-Care Might Not Mean Lower Blood Sugar

Proactive people with diabetes might take good care of themselves and believe they have the condition under control, but that doesn't necessarily mean they have good blood sugar.  Other believe that whatever they do, they have no control over their diabetes. According to a study in Health Services Research, these and other factors effect how people manage their diabetes risk. 

"People are not always adherent in managing their diabetes care, which affects overall health and the risk of diabetic complications," said lead study author Frank Sloan, Ph.D.

From the article:

People with diabetes who feel they have better control over life events are more likely to take good care of themselves and to believe they have the condition under control, but these factors do not translate to improved blood sugar levels, according to a new study of 1,034 adults.

Participants' responses to survey items on their risk tolerance, concern about their future and beliefs about their longevity had no correlation to clinical measures of their hemoglobin A1c levels, which reflect average blood glucose (or blood sugar) during the previous two to three months. The study, which appears online in the journal Health Services Research, also found no differences by race or Hispanic ethnicity in how people took charge of their self-care.

People are not always adherent in managing their diabetes care, which affects overall health and the risk of diabetic complications, said lead study author Frank Sloan, Ph.D.

"What we are able to do here is bring some new measures to bear," said Sloan, a professor of health policy and management at the Center for Health Policy at Duke University.

Some people believe that whatever they do, they have no control over their diabetes; others are very tolerant of the risks of diabetes; and, some have a philosophy that they will live for today and not care about the future, Sloan said. "One result that comes through is that people who have self-control over life in general are more likely to adhere," he said.

"This area of study is valuable as we attempt to better understand the relationship between how people from all ethnic and cultural backgrounds perceive their destinies with diabetes," said Sue McLaughlin, a registered dietitian and president of health care and education with the American Diabetes Association.

"This study illustrates the insidious nature of hyperglycemia: it is a silent and deadly killer," added Miller, who had no affiliation with the study. Many people with diabetes assume they are in good health because they do not feel bad, she said.

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Top Story: Ethnic Background Matters for Type 2 Diabetes

It makes sense that people with similar weight, diet, and body mass index (BMI) numbers should have similar risks for Diabetes, right? Actually, diabetes prevalence is at least twice as high in some ethnic groups as it is in whites.

In a recent study, diabetes prevalence was 16.1% in Native Hawaiians, 15.8% in Latinos, 15% in African-Americans, 10.2% in Japanese-Americans, and 6.3% in whites. Overall diabetes prevalence in the study was 11.6%

"Clearly, genes are involved in allowing type 2 diabetes to happen," said Matt Petersen, an American Diabetes Association spokesperson. "Genes allow you to put on the weight, and a lot of different genes can contribute."

From the article:

The prevalence of diabetes is at least twice as high in some ethnic groups as it is in whites, even among people with similar body mass index (BMI) numbers, a large new study finds.

Many studies have shown an association between excess body weight and physical inactivity in the development of type 2 diabetes. However, in this study, the researchers found that the effects of body weight and diet appear to differ depending on an individual's ethnic background. Moreover, differences in prevalence among different ethnic groups persisted in normal-weight and underweight participants. The researchers analyzed data from more than 187,000 people who came from five ethnic groups. They found that overall, those who reported having diabetes made up 11.6 percent of the total. However, when adjusting for age, diabetes prevalence was 16.1 percent in Native Hawaiians, 15.8 percent in Latinos, 15 percent in African-Americans, 10.2 percent in Japanese-Americans, and 6.3 percent in whites.

"It is very difficult for us to understand, but there are different ways for being at high risk for diabetes," said lead study author Gertraud Maskarinec, M.D., of the Cancer Research Center of Hawaii in Honolulu. "Everyone who is really overweight has a high risk for developing diabetes," she said.

However, BMI alone does not tell the whole story. The BMI calculation, which relies on weight and height only, does not account for fat distribution or the percentage of an individual's body that is lean muscle mass: two factors that may have more influence on the development of diabetes.

The study, published in the winter issue of the journal Ethnicity & Disease, used data from the Multiethnic Cohort survey of people from Hawaii and California. Participants answered basic demographic questions, as well as questions about body size and shape, and medical, lifestyle and food consumption behaviors.

"Clearly, genes are involved in allowing type 2 diabetes to happen," said Matt Petersen, an American Diabetes Association spokesperson. "Genes allow you to put on the weight, and a lot of different genes can contribute."

For example, both Maskarinec and Petersen said that Japanese-Americans are more likely to have problems with the beta cells of the pancreas, responsible for insulin production. "They have more weight distributed to the abdomen and have a higher body fat proportion, even though their BMIs are often not over 25," Maskarinec said. "Yet they still are at high risk of diabetes and, in the pancreas, the beta cells seem to exhaust themselves faster."

Regardless of ethnic group, avoiding obesity and staying physically active can help stave off type 2 diabetes, but with humans' natural drive to consume calories, that is easier said than done for most. Petersen said we should be careful not to blame people who develop diabetes: "Weight loss is a nearly constant struggle for most people."

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Depression Can Hamper Glucose Control in People With Diabetes

Newswise — Depression can cause diabetes patients to suffer from higher glucose levels over time compared to those who are not depressed, finds a study of older veterans with the disease.

“Our study shows that depression is a major and important comorbidity in people with type 2 diabetes,” said study co-author Leonard Egede, M.D., from the Center for Health Disparities Research at the Medical University of South Carolina.

Through a combination of diet, exercise and medication, people with type 2 diabetes work to keep their blood glucose levels within a certain range. Past research has shown that those who are also depressed have a tougher time doing so. About 30 percent of adults with diabetes have depression and the combination is linked to poor glucose control, higher complication rates, decreased quality of life and increased risk of death.

The current study appears in the November/December issue of the journal General Hospital Psychiatry.

Egede and his colleagues analyzed data from 11,525 veterans (98 percent men) with type 2 diabetes who received medical care at a Veterans Administration facility in the Southeast. The participants’ average age was 66 years and 48 percent were white, 27 percent were African-American and 25 percent were of other races.

Researchers evaluated each participant at three-month intervals from 1997 to 2006, with 36 intervals. At each 3-month interval, clinicians checked their HbA1c level, a blood test that measures long-term glucose control. Experts recommend a target level of less than 7 percent.

Six percent of the participants had depression, researchers determined.

They found that over the four-year period, the HbA1c values in the veterans who were depressed averaged 0.13 percent higher than the veterans who were not depressed. Egede said the difference is quite significant — enough to raise people with diabetes above the desirable range for glucose control, putting them at higher risk.

“The fact that the difference persisted over time and that the depressed group had higher mean HbA1c at all 36 time points was surprising,” Egede said.

The researchers also found that the change in HbA1c among the depressed participants did not differ based on race or age.

Evette Joy Ludman, Ph.D., senior research associate at the Group Health Center for Health Studies in Seattle, said that although the link between depression and diabetes complications might seem daunting, it is possible for adults to follow treatment orders for their depression while also managing their diabetes.

“I think it is a reasonable expectation that health care teams can help patients who have both depression and diabetes manage both conditions,” she said. “I don’t think patients see themselves as a collection of different illnesses and if we take a more proactive, integrated approach to caring for them, it is likely they can benefit. Research currently in the field is addressing that exact question.”

General Hospital Psychiatry is a peer-reviewed research journal published bimonthly by Elsevier Science. For information about the journal, contact Wayne Katon, M.D., at (206) 543-7177.

Richardson LK, et al. Longitudinal effects of depression on glycemic control in veterans with type 2 diabetes. General Hosp Psychiatry, 30(6), 2008.

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Childhood Diabetes Verging on Epidemic

Concerns about children’s health in America is growing along with their waistlines, and medical experts fear that the childhood obesity epidemic could lead to large numbers of younger adults developing type 2 diabetes, causing serious and lasting health complications for future generations of Americans.

In an article in the July issue of the Archives of Pediatric & Adolescent Medicine, University of Michigan C.S. Mott Children’s Hospital pediatric endocrinologist Joyce Lee, M.D., M.P.H, warns that the most damaging effects of childhood obesity have yet to surface, and will likely result in an epidemic of type 2 diabetes among young adults, leading to a greater number of diabetes complications, and ultimately, lower life expectancy.

“The full impact of the childhood obesity epidemic has yet to be seen because it can take up to 10 years or longer for obese individuals to develop type 2 diabetes,” says Lee, a member of the Child Health Evaluation and Research (CHEAR) Unit at Mott. “Children who are obese today are more likely to develop type 2 diabetes as young adults.”

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