Side Effects May Sway Drug Choices for Tough-to-Manage Diabetes Study looks at options for type 2 patients who need more than metformin or a sulfonylurea

Side Effects May Sway Drug Choices for Tough-to-Manage Diabetes Study looks at options for type 2 patients who need more than metformin or a sulfonylurea THURSDAY, May 19 (HealthDay News) -- When someone with type 2 diabetes needs a third medication to control blood sugar levels, the choice may come down to which drug has the least undesirable side effects, because the available medications all lower blood sugar in a similar manner. That's the conclusion of a new review of data that shows there were no great differences in the ability of various classes of medication to lower blood sugar among type 2 diabetics, when used as "third-line" treatment (after a first and second drug don't suffice). However, the study also found that some medications could cause weight gain, and some caused episodes of low blood sugar levels (hypoglycemia). In any event, "type 2 diabetes is a progressive disease and most patients will need the combination of two or three anti-hyperglycemic agents to reach good glucose control in the long-term," noted the study's lead author, Dr. Jorge Gross, a professor of medicine at the Hospital de Clinicas de Porto Alegre, Brazil. "The choice of the third agent should be individualized according to the characteristics of the patients and the undesirable effects of the medications, so you can't elect one agent to be used in all patients with type 2 diabetes," he explained. The study results were published in this week's issue of the Annals of Internal Medicine. Metformin, an older medication that's available as a generic, is generally recommended as a first-line treatment for type 2 diabetes, along with physical activity and diet changes. If metformin and lifestyle changes fail to control blood sugar well, a second drug is generally added. For this study, the researchers chose the commonly used combination of metformin and a sulfonylurea. Drugs in the sulfonylurea class are usually available as generics and include: glyburide, glipizide, chlorpropamide, tolbutamide and tolazamide. "This study looked at what's probably the most common combination of diabetes medications, but even the second-line therapy should be individualized based on the patient's needs," said Dr. Robert Henry, president of medicine and science for the American Diabetes Association. Third-line medications in the current study included alpha-glucosidase inhibitors (acarbose), thiazolidinediones (which include Avandia and Actos), glucagon-like peptide-1 (GLP-1) agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors. The review included 18 clinical trials with a total of more than 4,500 people. The studies lasted an average of more than 31 weeks. When the researchers compared reductions in hemoglobin A1C (HbA1C) levels, they found no statistically significant differences between the third-line medications. HbA1C is a blood test that measures long-term (about two to three months) blood sugar levels. Weight gain was more common in people taking insulin or a thiazolidinedione. The average weight gain for those on insulin was about six pounds, according to the study. For those on thiazolidinediones, the average weight gain was more than nine pounds. An average weight loss of 3.6 pounds was seen in people taking GLP-1 agonists, reported the study. Insulin was most likely to reduce blood sugar levels too much, raising the odds for hypoglycemia, according to the study. Dr. Joel Zonszein, director of the clinical diabetes center at Montefiore Medical Center in New York City, stressed, however, that "these are mostly drug company studies, and they're not long-term studies." This review "shows that giving a third agent can help, and it also shows us that these medications have both good and bad effects," he said. "But we really need long-term studies on combinations that aren't sponsored by the pharmaceutical companies." The bottom line, according to Zonszein: "Each patient should be treated individually. Are they obese? If yes, there are certain medications like insulin and thiazolidinediones that may cause weight gain we don't want." When it comes to third-line agents, Henry said, another factor may be price. Some medications aren't always available in generic form, which may make them significantly more expensive. If you have specific concerns, such as weight gain or cost, Henry said it's important to bring these concerns to your doctor's attention when you're talking about adding another diabetes medication. "If a third medication is needed because glucose control isn't adequate, get one that's tailored to your unique needs," he advised. "We think that the results of this study offer a wide range of choices of anti-hyperglycemic agents that might be used as the third option in patients with type 2 diabetes not controlled using metformin and sulphonylurea based on efficacy. The final decision would depend on the effects in weight and risk of hypoglycemic episodes," said Gross. SOURCES: Jorge Gross, M.D., Ph.D., professor, medicine, Hospital de Clinicas de Porto Alegre, Brazil; Joel Zonszein, M.D., director, clinical diabetes center, Montefiore Medical Center, New York City; Robert Henry, M.D., president, medicine and science, American Diabetes Association; May 17, 2011, Annals of Internal Medicine

Health Alert For People With Diabetes Affected By Tornadoes

Health Alert For People With Diabetes Affected By Tornadoes The recent tornadoes that devastated communities in the South have affected thousands. Natural disasters can put Alabamians with diabetes at special risk, whether they were directly affected by the tornadoes or helping in relief efforts. For information on getting medications or supplies, contact your doctor's office or pharmacy. In the affected areas pharmacies may allow you to get your medicines without a prescription if you have the pill bottles. Many people with diabetes take medicines for high blood pressure and cholesterol as well. These should also be restarted as soon as possible. Medical Advice for People with Diabetes in Emergency Situations The American Diabetes Association has received a number of questions concerning what a person with diabetes should do in an emergency situation. It is very difficult to give advice that will be correct for every person involved as each person’s situation may be very different from another person with diabetes. This being said, we do offer the following suggestions: 1. Identify Yourself as Having Diabetes The most important priority should be to identify yourself as having diabetes so that you can get the care you need. In situations such as a hurricane, the relief workers making decisions as to where a person should go and how they should be cared for will be based in part on the seriousness of their medical condition. Identifying yourself as having diabetes, and any diabetes-related complication you might have (such as heart or kidney problems) will significantly increase the chance that you will get the care you need. 2. Dehydration A major concern in some emergency situations for people with diabetes is the effect of on-going hyperglycemia (high blood sugar) leading to dehydration. When the blood glucose (sugar) level is abnormally high, the body attempts to reduce the glucose level by dumping glucose into the urine so it can then be eliminated from the body. In order to do this, water must leave the body with the glucose. Over time, this can lead to dehydration unless a person is able to drink enough fluids to keep up with the increased urination. Additional fluid loss can occur through perspiration or sweating. With on-going dehydration, serious medical problems can occur. Therefore, one of the most important things that a person with diabetes can do is to make sure that they take in enough fluid to meet the body’s needs. Obviously this must be done safely and the best choices for fluid intake would be clean water or noncarbohydrate containing fluids. Dehydration can also be a particular problem for those taking the diabetes medication called metformin (Glucophage). 3. Hypoglycemia A second short-term complication of diabetes is hypoglycemia (low blood sugar). This will only occur in a person who is taking medications that lower their blood glucose (insulin and/or pills which cause the body to make more insulin). If at all possible, a person with diabetes should try to keep something containing sugar with them at all times to treat hypoglycemia should it occur. Each person reacts to hypoglycemia differently, but some symptoms include: Shakiness Nervousness Sweating Irritability, sadness, or anger Impatience Chills and cold sweats Fast heartbeat Light-headedness or dizziness Drowsiness Stubbornness or combativeness Lack of coordination Blurred vision Nausea Tingling or numbness of lips or tongue Headaches Strange behavior Confusion Personality change Passing out Due to serious concerns regarding hypoglycemia and the unusual circumstances faced in the aftermath of hurricanes witnessed recently in our country – particularly if a patient is not able to monitor their blood glucose level because they do not having access to a blood glucose meter – it may be best to not strive to keep blood glucose levels as close to normal as possible (as we generally advise for people with diabetes) but to allow your glucose levels to be somewhat higher. It is important to consider that the requirements for the various medications used to treat diabetes may be very different in somebody in a situation such as a hurricane due to significant changes in diet and activity levels. 4. Prevent infections A third area of concern is the prevention of infectious disease, particularly foot infections. People with diabetes are at higher risk to develop infections of the feet due to nerve and blood vessel problems so it is very important that they do their best to avoid walking through contaminated water or injuring their feet. Feet should be inspected visually on a regular basis to look for any cuts, sores, or blisters so proper care can be obtained. Should any of the usual signs of infection (swelling, redness, and/or discharge from a wound) be seen, immediate medical help should be obtained. 5. Medications In response to questions about what a person with diabetes should do if they do not have access to their usual diabetes medications, only general advice can be given. Obviously, people with type 1 diabetes are at greatest risk because they are completely dependent on injected insulin. These patients usually take insulin a number of times per day. If insulin is not available, the consumption of carbohydrates should be reduced if possible. If a person with type 1 diabetes does not have any access to insulin, the most important priority should be to maintain adequate intake of fluids to avoid dehydration (as discussed above). As quickly as insulin becomes available, these individuals need to return to their usual insulin regimen, keeping in mind, as noted above, that their requirements for insulin may be quite different at this particular time. If one’s usual type and brand of insulin is not available, using a different type or brand of insulin as directed by medical personnel is quite safe. For a person with type 2 diabetes, who may or may not be on insulin, not receiving their medications on a regular basis presents fewer problems than in the person with type 1 diabetes but should be restarted as soon as possible. Again, avoiding hyperglycemia, which can lead to dehydration, is the most important priority. As medications become available, they should be restarted cautiously, keeping in mind that a person’s needs for a particular medication and dosage may have changed if significant weight loss has occurred or a person has gone without adequate intake of food for a significant period of time.

What Protects Some Against Diabetes Complications? Researchers Find Protective Mechanism Exists for Cohort Living with Type 1 for More Than 50 Years; Proteins Known to Increase Risk May Also Be Protective

What Protects Some Against Diabetes Complications? Researchers Find Protective Mechanism Exists for Cohort Living with Type 1 for More Than 50 Years; Proteins Known to Increase Risk May Also Be Protective Dayle Kern Some people with diabetes possess yet-unidentified factors that reduce the risk for and even prevent them from developing diabetes-related complications, despite living with the disease for decades, a study published in the April issue of Diabetes Care has found. The study, conducted by the Joslin Diabetes Center on people who have lived with type 1 diabetes for more than 50 years, presents a strong case for the existence of a protective mechanism in some individuals that allows them to live relatively free of the problems typically associated with long-term duration of diabetes. These mechanisms, the study found, may be different for microvascular (such as kidney, nerve and eye disease) than macrovascular complications (such as heart disease). "If we can identify what constitutes this protective mechanism, we have the potential to induce such protections in others living with diabetes," said lead researcher George King, Chief Scientific Officer of the Joslin Diabetes Center and Professor of Medicine at Harvard Medical School. "That’s huge." Researchers looked at 351 U.S. residents known as the “Medalist” cohort and found that a subgroup of people who had lived with type 1 diabetes for more than 50 years remained free from such complications as proliferative diabetic retinopathy (PDR), a serious eye disease that can lead to blindness (42.6 percent of them); nephropathy, or kidney damage (86.9 percent of them); neuropathy, or nerve damage (39.4 percent); and cardiovascular disease (51.5 percent). Of those who did not develop PDR, 96 percent with no retinopathy progression in the first 17 years of their disease never experienced a worsening of symptoms, meaning that they likely possessed some type of protection specific to this complication. Surprisingly, glycemic control was not a factor in providing this protective mechanism. "That doesn’t mean of course that glycemic control doesn’t help to prevent complications. Numerous other studies have shown that it unquestionably does. In this case, it means only that there is a separate, protective mechanism in play that is not related to glycemic control that also helps to protect against diabetes-related problems. We are still working on identifying just what that is," King said. It’s important to note that most of the people in this study developed type 1 diabetes before strict glycemic control was even possible or used as the standard of medical care, the researchers write. The people in this study likely lived for several decades, therefore, without maintaining strict control. The study also found that those with high plasma carboxyethyl-lysine and pentosidine, or advanced glycation end products (AGEs), were 7.2 times more likely to have some kind of complication than those who had low levels of this combination of AGEs. AGEs are compounds that develop in the body after long exposure to high glucose levels and have generally been regarded as playing a role in diabetes-related complications. However, those with other types of AGE molecules exhibited protective features. Thus, this study suggests that not all AGEs are alike in their actions and raises the exciting possibility that some AGEs may be markers for protection against one or more diabetic complications. In an accompanying editorial, Dr. Aaron Vinik, Director, Eastern Virginia Medical School Diabetes Research Center, writes that "the accumulation of AGEs may be one of the important factors in metabolic memory," a phenomenon in which an initial period of good glycemic, lipid and blood pressure control results in a prolonged period of health benefits that last beyond the period of control. However, while it is clear that for some there is a protective mechanism at play, it’s unclear whether metabolic memory is playing a role because glycemic control was not considered important until 1993, long after the study began. What’s most interesting, Vinik points out, is that sRAGE (the circulating soluble receptor for AGEs) is deficient in those who have the most severe complications, and is present at high levels in those with the most longevity. "If this is the missing link, it is huge for the possible emergence of a new biomarker and the potential for therapy that might increase circulating sRAGE or sRAGE itself," he said.

Gluten not linked to babies' risk of diabetes: study

Gluten not linked to babies' risk of diabetes: study By Adam Marcus NEW YORK (Reuters Health) - For babies at higher risk of childhood diabetes because of family history or genes, a gluten-free diet in the first year of life does not lower the chances of developing the disease, German researchers report. The findings undercut previous studies, including work from the same scientists, suggesting that babies exposed to gluten as part of their early diet might be more likely to develop type 1 diabetes later in childhood. Although the new study included only 150 children, Dorothy Becker, director of the diabetes program at Children's Hospital of Pittsburgh, told Reuters Health the results are reasonably clear. "It doesn't mean that it if you did a huge study there wouldn't be an effect (of gluten)," said Becker, who was not involved in the study. "But it makes it unlikely." Gluten is the protein in wheat and other grains that makes dough elastic and gives bread its chewiness. Roughly 1 percent of people in the United States have a condition called celiac disease, in which immune reactions to gluten damage the intestines. Each year about 20 kids per 100,000 under the age of 10 in the U.S. are diagnosed with type 1 diabetes, according to the National Institutes of Health. In contrast with type 2 diabetes, which is usually a disease of adults and associated with old age or obesity, type 1 diabetes typically strikes children. Many of them likely inherited a genetic predisposition to the disease from their parents. Yet genes alone don't fully explain why people develop the condition. Other factors, such as environmental exposures, are thought to be necessary to trigger it. In the latest study, the researchers followed 150 babies with at least one parent or sibling who had been diagnosed with type 1 diabetes -- marked by the death of islet cells in the pancreas that secrete the hormone insulin. The body requires insulin to convert dietary sugars into energy. Half of the children were exposed to gluten in their diet for the first time at the age of six months. For the rest, exposure to the protein was delayed until after their first birthday. The different diets appeared to have no impact on the babies' ability to grow or gain weight. By age 3, three children exposed to gluten early had developed type 1 diabetes, compared to four in the late-exposure group. Signs that the children had developed immune reactions to their own islet cells - a possible precursor to diabetes, especially in those with a genetic predisposition for the disorder - appeared in 11 children given gluten at six months of age, compared to 13 who first ate gluten when they were 12 months old. Some research has suggested that delaying exposure to gluten can increase the risk of developing celiac disease. However, the German scientists said they found no evidence for such a link. Roughly 30 percent of parents said they did not strictly follow the diet plan. Still, the researchers said, the results of the study show that although delaying the introduction of gluten into a baby's diet causes no harm, it doesn't appear to reduce the risk of diabetes or immune-related early-indicators of insulin problems. The researchers did not respond to requests for comment on their study, which appeared online last month in the journal Diabetes Care. Research into other potential food triggers for type 1 diabetes is ongoing. Last November, researchers in Finland reported that babies with a genetic predisposition for type 1 diabetes who were fed an infant formula called Nutramigen were about half as likely as those given conventional cows' milk formulas to show signs of islet cell autoimmunity later in childhood. The milk proteins in Nutramigen (sold as Enfamil by Mead Johnson & Co.) are altered in a way that makes them more tolerable to the immune system. Becker is helping to lead a large international trial funded by the National Institutes of Health to further explore the Finish findings. The results of that study, which includes nearly 2,200 babies, are expected in 2017, she said. SOURCE: http://bit.ly/hzGutn Diabetes Care, online April 22, 2011.

Fracture Risk in Diabetes

Advanced Imaging Reveals Secrets of Increased Fracture Risk in Diabetes
Dateline: San Francisco, Calif.

Thomas Link, M.D., needn’t have worried that he might have to close down an imaging system critical to his work on fragility fractures in people with type 2 diabetes mellitus (T2DM). A grant from the American Recovery and Reinvestment Act (ARRA), has "reinvigorated" his osteoporosis imaging program, allowing him and his team of researchers at the University of California, San Francisco, to better understand why individuals with the T2DM have these fractures, despite the absence of low bone mineral density (BMD). The answer, he says, may be found in bone structure and composition features that his imaging facility identified.
Normal BMD, as measured by a standard imaging procedure called dual x-ray absorptiometry (DXA), does not usually indicate a higher risk for fractures. But when studies showed that women with T2DM had both normal or higher BMD and fractures, Dr. Link decided to investigate further. Using a different imaging modality called high-resolution peripheral quantitative computed tomography (hr-pQCT), he looked at bone structure in a group of elderly women with type 2 diabetes mellitus. This type of imaging system was able to reveal increases in the porosity of cortical bone (an indicator of impaired bone strength) among the T2DM women, as compared with women without the disease. Furthermore, they found a trend toward higher bone marrow fat in the women with diabetes, in particular, in those whose diabetes was not well controlled. Dr. Link now plans to expand his studies and further explore these findings.
Given the project’s success, the scientist is excited about the potential of hr-pQCT to join BMD as a possible bone biomarker for fracture risk. "Finding a strong, noninvasive bone-quality biomarker for fragility fractures in people with diabetes is clearly a major challenge area," says Dr. Link. "Based on our preliminary data, we believe that our novel biomarker may be able to better characterize fracture risk in these patients."

General information on diabetes and prediabetes

National Diabetes Fact Sheet, 2011
      Citation
Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
CS217080A
FAST FACTS ON DIABETES
Diabetes affects 25.8 million people 8.3% of the U.S. population
Among U.S. residents aged 65 years and older, 10.9 million, or 26.9%, •     had diabetes in 2010.
About 215,000 people younger than 20 years had diabetes (type 1 or •     type 2) in the United States in 2010.
About 1.9 million people aged 20 years or older were newly •     diagnosed with diabetes in 2010 in the United States.
In 2005–2008, based on fasting glucose or hemoglobin A1c levels, •     35% of U.S. adults aged 20 years or older had prediabetes (50% of
adults aged 65 years or older).  Applying this percentage to the entire U.S. population in 2010 yields an estimated 79 million American adults aged 20 years or older with prediabetes.
Diabetes is the leading cause of kidney failure, nontraumatic lower-•     limb amputations, and new cases of blindness among adults in the
United States.
DIAGNOSED 18.8 million people
UNDIAGNOSED 7.0 million people
Diabetes is a major cause of heart disease and stroke.•  
Diabetes is the seventh leading cause of death in the United States.•  
National Center for Chronic Disease Prevention and Health Promotion Division of Diabetes Translation
All ages, 2010
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