Diabetes Continues to Rise

(HealthDay News) — News from the diabetes front seems to grow more discouraging by the day.

Rates of the disease, fueled by obesity and sedentary lifestyles, have risen unchecked in the United States, with diabetes now affecting about 7 percent of the population. That’s an estimated 20.8 million adults and children, according to the American Diabetes Association.

Federal projections estimate that by 2050, some 48 million Americans will have type 2 diabetes. And the disease will bring with it complications such as blindness, hearing loss, kidney disease, nervous system disorders and amputations of extremities.

“Studies have suggested that for the first time in history, the generation of people born in 2000 is probably going to have shorter life expectancy than their parents,” said Dr. Sue Kirkman, vice president of clinical affairs for the American Diabetes Association. “That’s attributable to obesity, diabetes and heart disease. Is that what we want for our children?”

What’s worse, one of the most promising medicines for treating type 2 diabetes — Avandia — now appears to increase a person’s risk of heart attack and heart failure, according to recent studies.

Still, medical experts say the fight against diabetes can be won — if everyone decides to do what’s best for themselves and their families.

That fight will get its yearly boost on Tuesday when the American Diabetes Association will “sound the alert” about diabetes on the 20th annual American Diabetes Alert Day. It’s a one-day “call to action” to encourage those at risk for developing type 2 diabetes or those with loved ones at risk to take the Diabetes Risk Test and, if they score high, to schedule an appointment to see their health-care provider. The Diabetes Risk Test is available in English and Spanish by calling the association at 1-800-DIABETES (1-800-342-2383) or online at www.diabetes.org/alert.

But the finding on Avandia calls into question the safety of the entire class of drugs known as thiazolidinediones. For now, Avandia — and other thiazolidinediones such as Actos — remains on the market. But last year, the U.S. Food and Drug Administration mandated stricter labeling, including “black box” warnings, for the medications.

Medical experts recommend that each person discuss with their physician the risks and rewards of using Avandia.

“Every patient is different,” said Kirkman. “Every patient has different risk factors. Every patient has reasons why one medicine might be better for them than another.”

But medicines are only part of the solution. A better response would be drastic changes to American lifestyles, starting with improved diets and more exercise, to avoid type 2 diabetes in the first place.

“The statistics are pretty gloomy, but we also know people who are at risk for diabetes can do a lot to prevent it from coming on,” Kirkman said. “There’s a lot people can do to try and control their fate.”

Diabetes comes in two types.

The most common form, type 2, or what used to be called adult-onset diabetes, occurs when either the body does not produce enough of the hormone insulin or the cells ignore the insulin. The body needs insulin to transport sugar in the blood to cells for energy. Being overweight, an unhealthy diet, and lack of exercise are common contributors to this form of the disease.

Type 1 diabetes, usually diagnosed in children and young adults, occurs when the body isn’t capable of producing insulin.

Researchers reviewing data from the National Health Interview Survey found that from 1990 to 2005, cases of diabetes increased 4.6 percent each year. They rose from 26.4 cases per 1,000 people to 54.5 per 1,000 people in the most recent year available.

The diabetes epidemic has grave implications for America, said Martha Funnell, a clinical nurse specialist for the University of Michigan and a past president of the American Diabetes Association. Health care costs are expected to soar as more people with diabetes complications fill doctors’ offices and emergency rooms.

Even the U.S. economy will be affected as potentially healthy people find themselves unable to work. “You’re losing folks in the prime of their years, and that has an impact on society and our economy,” Funnell said.

Fortunately, there are steps that can be taken, both large and small, to help fight diabetes.

On the large-scale side, Kirkman said, governments should spend more money on physical education in schools and on public transportation, instead of new road construction.

“We know people who take public transportation are more physically active,” she said. “Do we choose to encourage that?”

On a more personal level, people can make healthy lifestyle choices and help pass those choices along to their children, Funnell said.

But is anyone listening and willing to try?

“The messages are those same old ‘eat healthy and exercise,’ and we hear those to the point where we think, ‘Yeah, yeah, yeah, everybody knows we need to do these things,’ ” Funnell said.

However, even small measures — standing more often during the day or walking during a lunch break or eating an apple instead of ice cream — can help make a difference.

“Maybe it would seem to outsiders as a small step, but it’s just taking that one step and the next step and the next,” Funnell said. “Like global warming, it’s saying, ‘What can I do for myself and my family this week, this month, this year, that will make a difference?’ “

Those Most At Risk, Referred Less for Colonoscopies

This is not surprising based on the research that demonstrated that if you do not have insurance, you are not tested for certain serious conditions until it may be too late. I posted the article earlier, click here to read it.

(HealthDay News) — Even when there is a family history of colon cancer, blacks are much less likely to get colonoscopies than their white counterparts are, a new study finds.

While blacks who have an increased chance of developing colon cancer continue to lag behind their white counterparts in colonoscopy rates, the lack of a doctor referral stood out as the primary reason why high-risk patients of either race had not been screened.

For people who have close relatives that have been diagnosed with colon cancer, the recommended screening is a colonoscopy every five years after the age of 40.

“People with a family history of colon cancer have a two to four times increased risk of developing the disease compared with people who don’t have such a history,” explained lead researcher Dr. Harvey J. Murff, an assistant professor of medicine at Vanderbilt University in Nashville, Tenn.

“When you look at people who have more than one close relative diagnosed with colon cancer, African-Americans were about half as likely to have reported undergoing the appropriately recommended screening as compared to whites,” Murff said.

The reasons for this disparity aren’t clear, Murff said. It could be that doctors don’t perceive blacks as having an increased risk for colon cancer, he speculated. It may also be that doctors are remiss in collecting a complete family medical history, he said.

“If providers aren’t aware of family history, they may be less likely to recommend the test,” Murff said. “There is a problem collecting family history and using it to risk-assess patients.”

Other conditions that limit access to care, such as not having health insurance or a usual care provider, may also play a role, Murff said.

The report was published in the March 24 issue of the Archives of Internal Medicine.

In the study, Murff’s group collected data on 41,830 people aged 40 to 79. Among these, 32,265 were black and 9,565 were white. The researchers specifically looked at how these patients were screened for colon cancer.

There were 538 blacks who reported having close relatives diagnosed with colon cancer, compared with 255 whites. Among blacks, 27.3 percent reported having a colonoscopy within the past five years, compared with 43.1 percent of whites.

The main reason for not having a colonoscopy among both blacks and whites was that their doctor had not recommended one. Among blacks, 59.3 percent said their doctor had not recommended a colonoscopy, compared with 51 percent of whites.

Doctors need to be sure that they get a complete family medical history, Murff said. “In addition, it is important for patients to know what your family history is, and if you have questions related to your family history or if you are concerned that it might impact your risk of disease, it is important to talk to your physician about it,” he said.

Tips: Make sure you know possible signs, click here for more information.

Taking a Page From Homeopathy: Pharmacogenomics and Its Role In Drug Safety

Interesting quote in this FDA newsletter by Sir William Osler. Allopathic medicine continues to attempt to include [selected] homeopathic principles [treating the individual, the minimum dose, etc.] in its applications. However since the premise is incorrect (e.g. what is disease, who and what is man, the role of soil and diet in health, etc.) it won’t work.

FDA Drug Safety Newsletter
Volume 1, Number 2

Winter 2008

Feature Article: Pharmacogenomics and Its Role In Drug Safety

“Variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions which we know as disease…”
- Sir William Osler (1849-1919)

Pharmacogenomics is the science of determining how genetic variability influences physiological responses to drugs, from absorption and metabolism to pharmacologic action and therapeutic effect.1 With increasing knowledge of the molecular basis for a drug’s action has come the recognition of the importance of an individual’s genetic makeup in influencing how he or she may respond to a drug.


This understanding of the genetic variations in drug response opens the door to “personalized medicine” by (1) identifying patients who are more prone to experience adverse events from a drug and (2) identifying patients who are more likely to benefit from a particular therapy. This information has the potential to guide the selection of a drug for a particular patient and to tailor the drug dose to achieve the optimal therapeutic effect. In addition, knowledge of the genetic makeup of infectious agents is being used to guide treatment. For example, the identification of the specific drug resistance mutations in a patient’s human immunodeficiency virus (HIV) is used to select the therapy most suitable or best “targeted” for that patient. In these ways, pharmacogenomics has the potential to assist physicians in adapting drug treatments to the characteristics of individual patients, ultimately leading to safer and more effective prescribing and dosing.

Pharmacogenomics determines how genetic variability influences response to a drug.Potential applications in the clinic:

  • Tailor dosing to decrease risk of adverse events.
  • Identify patients for targeted therapy.
  • Detect viral drug resistance.

View the table2 of drugs with pharmacogenomics information provided in product labeling.

Improving Dosing and Decreasing Adverse Events

Genetic variants in drug metabolizing enzymes can have a significant effect on the way a person responds to a drug. They can speed up or slow down enzymatic activity, or even inactivate an enzyme. In some patients, known as rapid metabolizers, drugs are metabolized too quickly. As a result, the average dose of the drug may be broken down too quickly to be effective, and a higher dose may be needed. Conversely, where the metabolite of the drug is active, as in the case of codeine (see below), rapid metabolism may lead to excessive accumulation of the active metabolite, which may result in toxic levels. In slow metabolizers, a drug administered at the recommended dose can accumulate due to such slow metabolism, potentially reaching toxic levels in the patient’s system and leading to adverse reactions. Such patients may require a smaller dose. In conjunction with other factors, pharmacogenomics offers the potential to enable doctors to identify the patients who are rapid or slow metabolizers of certain drugs and to adjust dosing accordingly to achieve both effective and safe treatment.

Rapid metabolizers may break down a drug too quickly and require higher doses.Slow metabolizers may build up toxic levels of the drug and require smaller doses.

Clinical Applications of Pharmacogenomics

Warfarin (Coumadin and generics), an anticoagulant, is a recent example of the clinical use of pharmacogenomics to improve dosing. Warfarin has a narrow therapeutic window and a wide range of inter-individual variability in response, requiring careful clinical dose adjustment for each patient. Genetic variants in the warfarin target, the vitamin K epoxide reductase (VKORC1), as well as the warfarin metabolizing enzyme, cytochrome P450 2C9 (CYP2C9), influence the variation in patient response. Patients with certain variants of these genes eliminate warfarin more slowly and typically require lower warfarin doses. In those individuals, a traditional warfarin dose would more likely lead to an elevated International Normalized Ratio (INR), a longer time to achieve a stable warfarin dose, and a higher risk of serious bleeding events during the induction or dose-titration period of warfarin therapy.3 (FDA News)

Another recent example involves ultrarapid metabolizers of codeine, who have multiple copies of the gene for cytochrome P450 2D6 (CYP2D6), the enzyme that converts codeine into morphine, its active metabolite. Nursing mothers who are taking codeine and are ultra-rapid metabolizers could have high levels of morphine in their breast milk, increasing the risk of morphine overdose in their nursing infant.4 Although most nursing mothers can take codeine safely after childbirth, healthcare practitioners should prescribe the lowest dose for the shortest period of time to relieve pain and nursing infants should be carefully monitored when breastfeeding women receive this drug. (FDA Information to Healthcare Professionals)

Pharmacogenomic studies have recently identified a genetic marker in patients, the human leukocyte antigen (HLA) allele HLA-B*1502, which is associated with dangerous, sometimes fatal, skin reactions (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)) following treatment with the antiepileptic drug carbamazepine (Carbatrol PDF document, Equetro PDF document, Tegretol PDF document, and generics).5 Since the HLA-B*1502 allele is found almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians, healthcare practitioners should screen patients with ancestry in at-risk populations for the HLA-B*1502 allele prior to initiating treatment with carbamazepine.6,7,8,9 Patients who test positive for HLA-B*1502 should not be treated with carbamazepine unless the expected benefit clearly outweighs the increased risk of SJS/TEN. In weighing these risks and benefits, it is important to recognize that other antiepileptic drugs are associated with these serious skin reactions as well. (FDA Information for Healthcare Professionals Sheet)

Tests to identify the three genetic polymorphisms for warfarin, codeine, and carbamazepine described above are commercially available.

A table2 describing the valid genomic biomarkers that are currently part of FDA-approved drug labels can be found at http://www.fda.gov/cder/genomics/genomic_biomarkers_table.htm The table provides a list of these markers, links to pharmacogenomic data that support their validity, and recommendations for the clinical use of some of these biomarkers.

Pharmacogenomics Leads To More Effective Targeted Therapies

The incorporation of genomics in the preclinical and clinical research of anticancer drugs has resulted in significant progress in the development of new drugs. Discovering targeted therapies that are specifically directed at tumor cells with particular protein characteristics that differ from those of normal cells has been a primary focus of innovation in cancer treatment. Targeting drugs specifically to tumor cells can decrease the toxic effects of anticancer drugs on normal cells. For some targeted therapies, diagnostic genetic tests that can help identify the tumors that are likely to respond to those particular treatments have been co-developed with the drug. Examples of these drugs and their targets include:

  • Imatinib (Gleevec PDF document) for bcr-abl tyrosine kinase in several tumor types
  • Cetuximab (Erbitux PDF document) for epidermal growth factor receptor (EGFR) in head and neck cancer and colorectal cancer
  • Trastuzumab (Herceptin PDF document) for variants in the Her2 receptor in breast cancer
Targeted therapies are directed at tumor cells with particular protein characteristics that differ from normal cells.

Pharmacogenomics Can Detect Drug Resistance in Viruses

The HIV genomes are constantly and rapidly evolving. Changes in targeted viral proteins may cause the HIV virus to become resistant to anti-viral drugs or vaccines. HIV patients often have to try different drug combinations when the virus becomes resistant to drugs they are taking. An FDA-approved kit, the TRUGENE HIV-1 Genotyping Kit PDF document, is now commercially available to detect several drug-resistance gene variants in the protease and reverse-transcriptase regions of the HIV virus. These two regions are targets of anti-retroviral treatments. If drug resistance is found to be present, the physician can alter the treatment regimen accordingly.

FDA’s Role in Pharmacogenomics and Personalized Medicine

Pharmacogenomics holds the promise to individualize our healthcare and to improve drug safety and effectiveness for the population as a whole. FDA is in a unique position to promote pharmacogenomics and personalized medicine. It encourages the incorporation of pharmacogenomics in the drug development process (Genomics at FDA). In 2004, FDA launched the Critical Path Initiative, a national effort to stimulate and facilitate the modernization of the sciences through which regulated products are developed, evaluated, and manufactured. The Critical Path Initiative is aimed at facilitating development of innovative tools, such as predictive genetic tests, valid biomarkers, assays, and information technology, to enable the efficient development and evaluation of safer and more effective drugs and promote the safe use of FDA-regulated products.

As part of the Critical Path Initiative, FDA is working to develop guidance for the pharmaceutical industry on co-development of drugs and diagnostic tests. FDA is also collaborating with the National Institutes of Health (NIH) and other research institutions in applied research efforts to study the genetic basis of drug-related toxicities. These research networks are working to improve the safety profiles of drugs in preclinical and clinical development as well as those, like warfarin and carbamazepine, that are already in the marketplace. Much work remains in understanding the role that genetics plays in achieving the goal of tailoring therapeutics to the individual patient.

References

  1. Lesko LJ, Woodcock J. Translation of pharmacogenomics and pharmacogenetics: a regulatory perspective. Nat Rev Drug Discov. 2004;3(9):763-9.
  2. Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels, available at : http://www.fda.gov/cder/genomics/genomic_biomarkers_table.htm, Accessed on January 23, 2008
  3. Gage BF, Lesko LJ. Pharmacogenetics of warfarin: regulatory, scientific, and clinical issues. J Thromb Thrombolysis. 2007;25(1):45-51.
  4. Koren G, Cairns J, Chitayat D, et al. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 2007;368(9568):704.
  5. Chung WH, Hung SI, Hong HS, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004;428(6982):486.
  6. Alfirevic A, Jorgensen AL, Williamson PR, et al. HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics. 2006;7(6):813-818.
  7. Hung SI, Chung WH, Jee SH, et al. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics. 2006;16(4):297-306.
  8. Lonjou C, Thomas L, Borot N, et al., RegiSCAR Group. A marker for Stevens-Johnson syndrome …: ethnicity matters. Pharmacogenomics J. 2006;6(4):265-268.
  9. Man CB, Kwan P, Baum L, et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia. 2007;48(5):1015-1018.

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