Close Concerns Weblog

MCAC meeting in Baltimore to have big time implications for continuous and traditional glucose monitoring reimbursement

Today, Wednesday, August 30, 2006, the Medicare Coverage Advisory Committee will hold a meeting to discuss glycemic control in patients with diabetes. The meeting will be held in Baltimore, MD with sessions from 8:00am to 4:30pm EST and the purpose of the meeting will be to determine the efficacy and need for self-monitoring of blood glucose (SMBG) for the Centers for Medicare and Medicaid Services (CMS). Importantly, the meeting will address the issue of reimbursement for continuous blood glucose monitoring. How there could be a need for a meeting to assess whether SMBG has efficacy is positively beyond us ... we are eager to see what the prevailing views are on CGM.

The MCAC meeting must fit a significant amount of information and discussion into one day - let's hope it starts out strongly and gains in strength! The Committee plans to review research on: glycemic control using a continuous glucose monitor, the relationship in glycemic control between outpatient and Medicare populations, the linearity of effects of glycemic control, and the correlation between an increase in hypoglycemic risk and clinical outcomes. As for desired clinical outcomes, the MCAC will be looking for a diminished progression of the disease, reversing of diabetic complications, and alteration of morbidity/mortality in the Medicare population. All these are hard to prove since long-term outcomes trials are needed. The Committee plans to not only review the available data but to identify topics that require further investigation, which will be very interesting.

On July 17, 2006, the MCAC posted questions for its panel on the topic of glycemic control. The responses to these questions will constitute the frame of tomorrow’s meeting. Many groups, including AADE, Abbott, and AAFP, submitted answers to these questions. We note that originally there were quesitons that didn't address continuous monitoring, but the more updated set does.

Many organizations and doctors and nurses have spent significant time in preparing presentations for the meeting, and they are all online at www.jdrf.org/mcac. By and large, we're blown away by the work that has gone in, though we are not that optimistic about the likely findings. We're frustrated that the government doesn't appear to be in "prevention pays" mode ~ we keep hoping that changes and with the slew of thought leaders on tap tomorrow - Irl Hirsch, Howard Wolpert, Ann Peters, Steve Edelman, Bruce Bode, Aaron Kowalski - can help change some prevailing views.

As to what the various organizations said! First, in their comments to the MCAC, AADE included a Position Statement on Self-Monitoring of Blood Glucose (SMBG): Benefits and Utilization, which will be published in the November/December, 2006 issue of “The Diabetes Educator,” the organization’s journal. AADE’s sentiments towards SMBG are clearly strongly felt, and extremely positive, unsurprisingly. The firmly-established organization of diabetes educators suggests that SMBG has revolutionized diabetes care by improving patients’ glycemic control. In fact, SMBG is an essential component to the AADE’s 7 Self-Care Behaviors. AADE cites the DCCT and UKPDS studies as having confirmed the numerous benefits of tight glycemic control for patients with diabetes, among them a reduction in both microvascular and macrovascular complications (shown through DCCT and EDIT).

The AADE comments for the MCAC meeting cite several studies to support the point that SMBG is successful in increasing glycemic control. Among many pieces of evidence, the AADE cites the Schwedes et al. study (2002), which showed that meal-related SMBG for patients with type 2 diabetes lowered their A1C levels. AADE recommends the use of SMBG to all individuals with diabetes and urges all healthcare professionals to support and use SMBG with their patients. AADE goes even further than recommending when they say that, “safe and appropriate blood glucose monitoring methods need to be taught…”

According to the AADE comments, SMBG is important for diabetes care because it allows for patients to learn more about their condition and to take a more active role in their care. A patient who is more focused on his or her care will be more likely to reach glycemic control goals. With all the additional information SMBG offers to patients about their blood glucose levels, patients gain an invaluable sense of their health and well-being. Not only is this important in motivating the patient to achieve their glycemic control goals, but it helps patients to discover a personal regimen that works for them.

Abbot, like AADE, confirms the benefits of SMBG and strict glycemic control, as measured by A1c levels. Abbot aims to present scientific-based evidence linking frequent testing and the improved glycemic control to a decrease in unfavorable outcomes of Type I and Type 2 diabetes among Medicare patients. Abbott has synthesized findings from multiple studies in an impressive, comprehensive white paper, entitled, “Clinical Value of Glucose Monitoring and Glycemic Control in the Medicare Diabetes Population and the Promise of Continuous Glucose Monitoring.”

Abbott maintains that existing evidence of the benefits of SMBG in the Medicare population is strong and ample enough to permit an adequate comprehensive assessment of outcomes. Abbot also references large clinical studies, such as the DCCT and UKPDS to make its case for SMBG. Referencing the updated analysis of the UKPDS study in 2000, Abbot also makes a strong case for the impact of reduced A1c levels in diabetes-related mortality.

However, the same confidence extended towards SMBG cannot yet be extended to Continuous Glucose Monitoring (CGM). Compared to SMBG, CGM, is new technology. Thus, Abbott maintains that, at this time, evidence for CGM among Medicare patients is only promising, as more research among the elderly population is required. While, a current assessment of CGM benefits among these patients is still premature, Abbott will discuss the emerging data in this arena.

While Abbott focuses much of the evidence on a reduction of A1c levels, AAFP’s Kevin A. Peterson paints a different picture regarding glucose monitoring and A1c levels. Taking into consideration the unique needs of and barriers faced by the elderly population, he insists that the measured impact of SMBG using A1c values provides a “very incomplete assessment” of the benefit of blood glucose monitoring. Further, in response to one of the questions posed by MCAC, Dr. Peterson, states that he is not confident that an increase in the frequency of glucose monitoring will automatically improve A1c levels in elderly patients.

Most of AAFP’S comments, as delivered by Dr. Peterson, are cautious in nature due to what the doctor believes is lack of evidence of glucose monitoring in large cohorts of elderly patients, as well as less faith in the patient’s A1c level as the single most important indicator of glycemic control. Personally, we believe strongly that A1c is important but not the only measure - we think it is crazy to even question whether SMBG reimbursement is too high.

In addition to AADE, Abbott and AAFP, we will listen to remarks by JDRF, Medtronic, IHPM, LifeScan, and several others. We look forward to reporting on tomorrow's MCAC meeting in our next issue of DCU - this has enormous implications for the health and future of traditional as well as continuous blood glucose monitoring and we are watching and waiting and will report back...

Even babies are getting fatter!

It seems that no one in America is immune to the obesity epidemic – not even infants!   A study published in the July issue of the journal Obesity found that the percentage of infants who are significantly overweight rose 73.5% over the past 2 decades.  Using medical records of more than 120,000 pre-school children from primarily middle-class families in Massachusetts who visited doctors from 1980-2001, researchers found that the observed prevalence of overweight increased from 6.3% to 10.0%.  Most striking, these increases were evident in all groups of children, including infants < 6 months of age!  More specifically, the percentage of overweight babies <6 months old (defined as weight-for-length ≥ 95^th percentile, specific for gender and age in months) jumped from 3.4% to 5.9%. 

Although the rate of overweight infants is still below the rate in older populations, the trend is very worrisome because there is accumulating evidence that accelerated weight gain in early life is a risk factor for weight problems and higher blood pressure later in life.  As Dr. Nicholas Stettler, assistant professor of pediatrics and epidemiology at Children’s Hospital of Philadelphia, explained, “If you look at weight gain early in life – during the first year, the first four months, even the first week -- and then you look at weight status in childhood and adulthood, you find a strong association.” Thus, the trend of increasing weight among young infants may predict a continued increase in childhood an adult obesity. 

This is an important study because this young age group is seldom included in weight studies. Although this study didn’t examine the reasons behind the increasing rate of fat babies, several other trends may partly explain it.  More babies are born large for their gestational age as more women are overweight before they become pregnant and more women develop gestational diabetes. In addition, more babies are rapidly gaining weight during the first few months of life. There are several plausible explanations behind these alarming trends.  It could be that overfeeding in early life reprograms a person to overeat by affecting the brain’s neurochemical development.  Alternatively, insulin secretion and metabolism could be altered by overfeeding during early development.  Another hypothesis is that the genetic component of being overweight may first express itself during infancy and remain a risk factor throughout life.  Or, humans may learn to override their innate feeling of being satiated if food is offered even when they are not really hungry. 

So, while those chubby cheeks may be cute, they may also indicate that, “even our youngest children are not exempt from the well-documented trends of over-weight seen among our older children and adults in the United Sates,” as this study concludes.  As Dr. Gillman, one of the study’s authors, says, “Our obesity prevention efforts need to start at the earliest stages of human development.” 

NYT on obesity - an infectious cause?

Obesity continues to infiltrate the news. Last week, we reported on one study linking the obesity epidemic to the consumption of sugar-sweetened beverages and another study documenting the increase in obesity among infants. Now this week the feature article in the NY Times Sunday magazine is all about “infectobesity,” the radical new theory that some forms of obesity may have infectious causes. This article has quickly become the most-read article in the NY Times, which isn’t at all surprising to us, but just goes to show the level of interest in the topic. Now if only something could be done about it!

While overeating is certainly one factor behind obesity, it is most likely not the only cause. Over the past decade, more than 50 genes have been found to contribute to obesity. Yet, if genes and eating control our weight, how is it possible for identical twins with identical genes and diets to have vastly different weights? The answer could lie in microorganisms living inside of us.

Out of all the cells in the human body, only one out of 10 is a human cell. Everything else is microbial. Beginning with our journey down the birth canal, we are constantly exposed to various microbes which populate our gut. These microbes aid in our digestion and absorption of nutrients. They create capillaries, produce vitamins, make enzymes which metabolize bile acid and cholesterol, break down plant polysaccharides, and extract and stores calories. Although we all have these microbes in our guts, the makeup of our microbe populations is different based on the microbes to which we are exposed and the antibiotics which we take. These small differences in the make up of our microbe populations can translate into huge differences between people. As Jeffrey Gordon of Washington University explains, although a bowl of Cheerios should theoretically have 110 calories no matter who eats it, different people will actually absorb different amounts of calories due to differences in their gut flora. “A diet has a certain amount of absolute energy,” he says, “but the amount that can be extracted from that diet may vary between individuals — not in a huge way, but if the energy balance is affected by just a few calories a day, over time that can make a big difference in body weight.”

In animal studies, microbe-free mice were found to be leaner than their normal counterparts. Without gut microbes, they could not extract calories from some of the food they ate, so the food passed through their bodies without being used or converted to fat. Thus, although they ate more food than the normal mice, the germ-free mice had 60% less fat. However, when gut microbes from normal mice were transplanted into the germ-free mice, the germ-free mice quickly gained weight and soon resembled their normal peers. In another experiment, Gordon compared normal-weight mice to mice with a genetic mutation that made them fat. Like humans, the microflora in both sets of mice predominantly consisted of two types of bacteria, Bacteroidetes and Firmicutes. However normal mice had more of the Bacteroidetes and the obese mice had far more Firmicutes. The role of these different proportions is still unclear, but Gordon and colleagues have been collecting stool samples from normal-weight and obese humans to determine whether a lean-type and obese-type microflora exists and whether weight loss results in a change in a person’s microflora..

In addition to bacteria, viruses may be another infectious cause of obesity. Nikhil Dhurandhar happened upon this idea while studying autopsies of chickens infected with the SMAM-1 virus. He noticed that these chickens had excess abdominal fat, which seems counterintuitive to their wasting away. Even more intriguing, the chickens had low levels of cholesterol and triglycerides despite their excess fat. The same thing happened to humans infected with the virus. Several human adenoviruses, which are closely related to the SMAM-1 chicken virus, have produced the same effects in humans, including AD-36, AD-5, and AD-37. It is still unclear exactly how these viruses cause obesity. They may affect fat cells directly, leading to increased fat cell numbers and sizes or they may impair the brain’s appetite control mechanism. Alternatively, viral infections may result in obesity via an indirect effect through inflammation.

Critics of infectobesity feel that there are other, more plausible, biological causes of obesity, such as the thrifty genotype hypothesis. According to this theory, humans who were able to store food during years of plenty for use during periods of scarcity had an evolutionary advantage. However, now that food abounds, that advantage has turned into a disadvantage.

However, if microbes do turn out to be relevant, it could change the way the public thinks about obesity. This new research will challenge the idea that fat people are lazy and not as virtuous as thin people. It might also help non-obese people understand how difficult it is for obese people to lose weight and maintain that weight loss. However, the danger of any biological explanation of obesity – be it genetics or microbes – is that people will fall into the predeterministic trap and dismiss behavior as irrevelent. Since we are still years away from developing therapies to deliberately manipulate the gut microflora or interfere with the offending microbes, behavior modification remains the most effective weapon that we have in the fight again obesity, whatever its cause.

AADE - day three/four

#1:  REIMBURSEMENT IS A BARRIER TO CONTINUOUS GLUCOSE MONITORING.  We spoke to Medtronic, Dexcom, and Abbott about reimbursement, but none of them were willing to discuss specifics.  Dexcom said that they filed for codes right after getting FDA approval in March and they are hoping for reimbursement as soon as possible.  However, they could not give a specific time estimate on reimbursement because it is up to the insurance companies, not Dexcom.  They did mention that individuals have gotten reimbursed on a case-by-case basis.  As far as indications, Dexcom wants to cast a wide net in terms of its customer base.  Even though their FDA approval is for insulin users only, they want to attract everyone, including Type 2 patients on orals or diet and exercise.  This is in contrast to Medtronic’s focus on pump users.  Dexcom is pushing CGM for real-time patient analysis for instantaneous adjustments more than retrospective analysis by healthcare providers since glucose profiles are so variable from day to day.  However, the Dexcom rep was also in favor of physicians buying CGM devices and loaning them to patients for short periods of time, especially for Type 2 patients. 

Gary Schenider gave a talk on interpreting CGM data where he said that he thinks CGM has been over-promoted as a panacea.  However, he conceded that all of his 300+ CGM patients have learned something from CGM because there is always room for fine-tuning their regimens.  During Gary Schneider’s talk, a lot of CDEs bemoaned the lack of training in interpreting CGM data.  Marcia Draheim commented that it surprised her that some health care providers do not like CGM because it provides them with more information than they are ready to handle because from her perspective, the beauty of CGM is that you can get as much data as you prefer. 

#2:  THERE IS A GROWING EPIDEMIC OF TYPE 2 DIABETES IN CHILDREN AND YOUTH.  In Dr. Francine Kaufman’s session on type 2 diabetes in children, she described “hybrid diabetes,” or beta cell failure with impaired fasting glucose tolerance. This is due to the increasing number of patients with type 1 diabetes who are also overweight.  Dr. Kaufman emphasized that the prevention of type 2 diabetes is as much about social and environmental factors as it is about diet and genetics. She suggested a tax on products that cause obesity.

#3: THE RENIN-ANGIOTENSIN SYSTEM MAY HOLD PROMISE FOR DIABETES PREVENTION.   ACE-1 and ARB inhibitors may reduce the appearance of type 2 diabetes by preserving beta cell function, enhancing insulin sensitivity and changing microcirculation and potassium and magnesium status, which increases islet insulin secretion and cellular insulin action.  In the ALLHAT study, the largest hypertension trial ever conducted, an ACE-inhibitor was shown to be more effective in reducing the percentage of new onset diabetes than a diuretic or a calcium channel blocker. Subjects on ACE-inhibitor lisinopril showed a 5.8% incidence of new onset diabetes after two years and an 8.1% incidence at a four-year followup, as compared to subjects on the thiazide diuretic chlorthalidone (9.6% incidence at two years and 11.6% incidence at four years) or the calcium channel blocker amlodipine (7.4% incidence at two years and 9.8% incidence at four years).  In the DPP study, metformin with diet and exercise reduced diabetes incidence by 39% while just diet and exercise alone reduced diabetes incidence by 31%.

#4: THERE IS A BRAND NEW LANDSCAPE OF TREATMENT OPTIONS FOR TYPE 2 DIABETES.  Nathan Painter presented a very thorough overview of the treatment options for type 2 diabetes.  When he asked the audience whether they thought inhaled insulin would replace injected insulin, most people shook their heads no.  Dr. William Cafalu thinks that the patients who might benefit most from inhaled insulin are the subset of Type 2 patients who are trying to control their diabetes with diet and exercise alone.  Painter mentioned that Byetta might confer beta cell protection and/or regeneration.  As for Levemir, he does not consider it a me-too drug, but he doesn’t like it because of the wide variability of duration indicated on the label (12-24 hours).  In contrast, he does consider Apidra a me-too drug, though he did not mention tumors.  Dr. Cefalu also talked about metformin, saying that, “probably every person in the country should go on metformin.”  Metformin and glitazones work in conjunction with insulin to increase its efficacy.  However, despite all of these new treatment options, few patients achieve their target A1C.  Dr. Cefalu attributes this problem to “clinical inertia,” or the lack of understanding of efficacy/time activity profiles of currently available agents.    

#5: INPATIENT MANAGEMENT OF HYPERGLYCEMIA IS STILL A STRETCH GOAL.  Of the 300+ people who attended Dr. Etie Moghissi’s talk on the subject, none felt that they were where they needed to be in terms of inpatient hyperglycemia management.  However, about half have started putting protocols in place and started discussing the issue in their hospitals.  Moghissi discussed the ADA/AACE consensus statement on inpatient hyperglycemia management in great detail.  She was very adamant that the sliding scale should be abandoned, and the audience clapped in response.  As for the cardiothoracic ICU in particular, Norbert Knack found that the most effective insulin protocol was the one created by Dr. Bruce Bode and refined by Dr. William Biggs; it uses the Glucomander formula (see www.adaendo.com for Dr. Bode’s work and www.amirillomed.com for Dr. Biggs’ work).

#6: INFORMATION TECHNOLOGY WILL PLAY AN INCREASING ROLE IN DIABETES MANAGEMENT AND EDUCATION.  Bonnie Pepon and Caille Wendekier presented the findings from a study that compared effects of online diabetes education for patients who had private internet access with those who had public internet access. In the study, public internet access consisted of kiosks with privacy screens at Uniontown Hospital.  All study participants used MyCareTeam, an interactive website developed by Georgetown University that included a program that compiled uploaded glucose meter information and a program that allowed the CDE and patients to send messages to each other.  The differences in A1c change, quality of life change, and problem areas score change between the two groups were insignificant, and these areas improved for both groups. While there was more deviation among those with public internet access, a public kiosk proved to be an effective medium for online diabetes education.

In her talk on the use of technology in diabetes education, Marcia Draheim predicted that the approaching shift in customer base to the new baby boomer seniors will change the way diabetes education is done. These patients are going to be busier and more technologically savvy, and health informatics will help diabetes education adjust. Health informatics will allow information to be sent rapidly from hospital to hospital.  Furthermore, databases will be created to store data that has become too complex for paper-based methods.  Finally, Draheim predicts that reimbursement will shift to meet the upcoming needs of patients.  She hopes that educators will soon be able to bill for reviewing e-mails and doing other work on line.  Welcome to the 21st century!

#7: IN ANOTHER ALARMING TREND, GESTATIONAL DIABETES IS INCREASING AMONG YOUNGER WOMEN, MANY OF WHOM ARE UNDER TWENTY.  The HAPO study is currently underway to develop outcomes-based criteria for the diagnosis and classification of gestational diabetes mellitus. The MiG study is being conducted to compare the safety and effectiveness of insulin versus metformin in gestational diabetes mellitus. Both are slated to end in 2007.  Women with gestational diabetes mellitus who used various intervention therapies to prevent complications in their babies and themselves showed the highest decreases in serious complications and macrosomia-and postpartum depression.

#8: DIABETIC NEUROPATHY IS CURRENTLY UNDER MANAGED.  In her talk on diabetic neuropathy, Virginia Valentine estimated that the annual cost of diabetic neuropathy is $13 billion.  Valentine recommended that CDEs use the Michigan Neuropathy Screening Instrument (MNSI) (which can be found at http://med.umich.edu/mdrtc/survey/survey_svi.html) to assess whether a patient has peripheral neuropathy.  About 30% of diabetes patients are referred to neurologists for neuropathy, but the experience is rarely rewarding.  Not only does it often take up to 6 months to get a [very expensive] appointment with a neurologist, but neurologists often do not have any solutions.  As far as pain treatment options, Valentine thinks that neurontin is no more effective than TCAs, though neurontin causes fewer side effects.  In addition, generic neurontin is now available, so it should no longer cost more.  In addition, aldose reductase inhibitors are almost here - Fidarestat is in trials, and Epalrestat is now being marketed in Japan. Finally, ruboxistaurin has been fast-tracked by the FDA for retinopathy because the clinical data were so good.  While ruboxistaurin was less convincing on the neuropathy front, it will hopefully be the first effective drug to treat the pathology underlying diabetic neuropathy and not just the pain.

AADE - day two!

Day 2 in LA was another exciting day with several additional themes emerging:

#1: NOT SURPRISINGLY, THERE IS A LOT OF INTEREST SURROUNDING INHALED INSULIN. The Exubera booth was probably the hottest booth at the exhibit today. One could barely approach the exhibit for information. There were demonstrations of the inhaler for the crowd, as well as a video presentation of a physician walking people through the inhaler’s technology. The inhaler itself is about flashlight size, but the technology is very visually impressive. There are four [relatively simple] steps: open inhaler, exert pressure, release cloud, and then inhale cloud. Ginger Kanzer-Lewis also gave a talk to introduce inhaled insulin to the diabetes education community. She said that Exubera is scheduled to launch in the first week of September, and as of this week, 16 states have approved Medicare reimbursement for Exubera with no prior authorization needed. She mentioned that in practice, pulmonary function tests (PFT) can be limited to spirometry tests for FEV since the DLCO test usually just gives the same result as the FEV test. CDEs in the audience were disappointed by (1) Exubera’s incremental titration - Exubera must be titrated in minimum increments of 3 units since this is the lowest blister size; (2) the nonintuitive conversion formula of 1 mg blister = 3 units, 3 mg = 8 units, (3) the inconvenience of having to administer multiple blisters sequentially, and (4) the weekly cleaning requirement, which is unrealistic for many patients. One CDE said she was “much less enthused about [Exubera] now” and another said there were “too many exceptions.”

#2: THE USE OF INSULIN PUMPS IN CHILDREN AND ADOLESCENTS REDUCES HYPOGLYCEMIA AND SAVES MONEY, THOUGH A1C TARGETS ARE STILL TOO HIGH. Dr. Lynda Fisher of Children’s Hospital L.A. recently surveyed Medtronic, Disetronic, and Animas and concluded that roughly 35,000 patients under age 21 use pumps. In her review of the few studies that have been done in pediatrics, all studies show fewer hypoglycemic incidents, but A1c results are mixed with some studies, but not all, showing that pumps are better with respect to A1c reduction. Dr. Fisher attributes the mixed A1c results to overly-high A1c targets for kids. She believes the targets for kids in general (A1c, pre-meal BG, and bedtime BG) are too high because of the desire to avoid hypoglycemia. Dr. Fisher also reported results from an experiment that she did with 9 kids who were in and out of the hospital and ER because of DKA – in other words, not the ideal pump candidates. She put them on pumps and their DKA incidents stopped. She calculated that pump therapy resulted in $22,000 in yearly savings per kid, including the cost of the pump and all of its supplies!

#3: DESPITE EVIDENCE ABOUT THE CRITICAL IMPORTANCE OF GLYCEMIC CONTROL IN ACUTE CARE SETTINGS, HUGE BARRIERS REMAIN. The educational barriers to insulin use in acute care settings seem staggering. Fear of hypoglycemia is a huge barrier to insulin use in acute care settings. As a result, insulin is rated as a top 5 most dangerous drugs in almost all hospitals across the country! When we asked Carol Manchester of the University of Minnesota Medical Center about the role of CGM in the acute care setting, she said that she was a huge fan, but cost is the biggest barrier. She is currently working with Medtronic on a pilot study looking at CGM in critical care and transplant units. In addition, she said that patients who are admitted with CSII face challenges because it is tough to get floor nurses up to speed and an ill patient isn’t qualified to figure out how to adjust dosing appropriately. Implementing strong systems and processes across her hospital system took cooperation across all specialties, many champions, and diligent follow through. But the effort has paid off - the rate of hypoglycemic events in her system has dropped to 1.2% overall, and many months are 0%.

#4: DESPITE THE IMPORTANCE AND CLEAR BENEFITS OF DIABETES EDUCATION, REIMBURSEMENT IS COMPLEX. Medicare pays for diabetes self-management training (DSMT) by CDEs, but with restrictions that can be debilitating to patients. For example, DSMT is only reimbursed when “service is needed,” which means a fasting blood glucose of over 126 mg/dl. Peggy Bourgeois suggested that what they should really be checking is 2-hour postprandial glucose, as it is too easy for patients with diabetes to fall within a healthy range for FPG. Medicare reimburses for 10 hours of DSMT per 12 month period, where one of those hours is one-to-one and the rest are group classes. In addition, CDEs can only bill in 30-minute increments, which means they often have to round their time down. Medicare is looking into this now, and may change this. Charlene Postigo strongly recommended that CDEs coach patients on how to call their insurance companies and ask the right questions. It is also important for CDEs to list codes in the right order—if diabetes is not put as the primary diagnosis and something like pump training second, coverage will be rejected. Medicare will reimburse for CGMS, but it is only $150. Medicare does not reimburse for any code having to do with pre-diabetes or obesity since they are not considered medical conditions (wow!). Peggy Bourgeois also made a passionate plea for attendees to call their legislators to encourage them to roll back cuts on physician payments planned by Medicare for January 1, 2007. Bush asked congress to roll these cuts back, but it is unclear if they will.

#5: NON-COMMUNICABLE DISEASES, SUCH AS DIABETES, HAVE REPLACED INFECTIOUS DISEASES AS THE MOST CRITICAL UNMET GLOBAL HEALTH ISSUES. Linda Siminerio offered some truly grim projections about the global rise in diabetes: the prevalence of diabetes in 2003 was 194 million globally but is projected to rise to 330 million by 2025. She cited lack of funding as the major road block to prevention. Linda thinks the global epidemic is worst for developing countries due to the decrease in productivity associated with obesity/diabetes. She emphasized the extremely important role of nurses and diabetes educators in developing countries and asserted that nurses will have to be given more responsibility in order for diabetes patients to get the care they need.

#6: WE CAN REDUCE THE RISK OF TYPE 2 DIABETES SIGNIFICANTLY. JaNellyn Hannah and Carolyn Leontos reviewed the results of the Diabetes Prevention Program (DPP) clinical trial, which demonstrated that rigorous lifestyle intervention was very successful in preventing and slowing the development of type 2 diabetes in people with impaired glucose tolerance (IGT). Dr. Pamela Allweiss of the University of Kentucky and the CDC also reviewed results from the public private partnership of GE Energy, the CDC, and the National Business Group on Health for the primary prevention of diabetes in GE employees. The group identified employees at risk of diabetes and CVD, developed interventions to reduce their risk, and calculated the return on investment (ROI) for prevention therapy, using serial (annual) cardiovascular risk assessments (CRAs) to measure the efficacy of the program. CRAs filled out in year 1 (2002) and year 2 (2003) showed reductions in serum glucose, blood pressure, waist circumference, total cholesterol, LDL, and serum triglycerides. They estimated that the program prevented four cardiovascular events every five years for every 1000 people screened. GE’s ROI was $992,000 - 24.8 events were averted in the entire GE screened population at a savings of $40,000 per event.

Even simple interventions can be effective in preventing diabetes complications. Washington Medical Center in Southwestern Pennsylvania saw a sizeable decrease in their diabetic patients’ A1c percentages and blood pressure just by color-coding the charts of their diabetic patients so that all diabetic patients had yellow folders. They feel this changed their residents’ approach to diabetic patients so that they were considering their acute needs in the context of their diabetes rather than just considering the diabetes as an afterthought.

What do you mean I can't wear my pump on the plane?

Normally, we like to think ourselves as people, not patients, those of us with diabetes here at Close Concerns. Mostly, we think that we should be able to look after ourselves so well that we do better than others without a chronic illness because with ours, if we eat well, pursue exercise, and do everything we can to reduce our A1cs safely, we can do better than the average person (yes, mortality was what we were thinking, but also morbidity).

Alas, today, we were reminded that we take so much for granted. Three people with diabetes on pumps here in the US tried to board planes this morning and were told that they needed to check the pumps. Check it!?!?!? Pumps are what keep us alive. Pumps also, I realized, just make me feel reassured, like life is going my way, when I feel my pump. It's part of me. If someone told me to take it off and check it, I'd think they were certifiably insane.

We were reminded all day today of Jose Saramago's Blindness. Things felt like they did after the first person went blind ... how crazy will this get? How nonsensical? How will we adapt? How won't we?

Back a bit on the mundane side, relatively speaking - it's amazing that there is such lack of knowledge about diabetes and pumps ~ the tyrrany of course is far worse and far be it from me to complain about those trying to make the country and world safe. BUT, many more people would be on pumps if they were easier ... and if that were so, they might not be such an object of abject fascination and there might not be any threats like the ones this morning.

Kudos, and just plain gratitude to Animas for jumping on this issue very very early; as we understand from a number of HCPs, they informed pump competitors and worked with the higher-ups in the government (ringing the acting attorney general, for example, who has diabetes) to address this problem. Right now, no one's pump is being pulled out of their abdomen that we've heard of since the transportation sites have been taken care of. ... welcome news in this sobering time. As much as I'm worried about terrorism for everyone, short of terrorism, having someone taking away my pump would be about the most daunting thing I could imagine.

The influence of money on medical science

In light of several recent instances in which authors have failed to fully disclose their potential conflicts of interest, Dr. Catherine DeAngelis, JAMA’s Editor in Chief, wrote a very interesting editorial in this week’s journal about the ability of medical journals to enforce full disclosure policies. 

Dr. DiAngelia acknowledges that for-profit companies fund the discovery of new medications and devices.  However, conflicts arise when the quest for profits inappropriately influences research findings or the way in which the findings are presented, such as incomplete reporting of adverse events or concealing negative clinical trial data.

As Dr. DeAngelis points out, for-profit companies must have the best people working on medical problems, either as paid employees or consultants, if they hope to advance medical science. Yet, the majority of these experts are academicians, the same people who publish most of the research and articles in medical journals.  So, how can editors preserve the integrity of their journals while ensuring dissemination of scientific information?

First and foremost, journals must have rigorous peer review and editorial evaluation processes to ensure that all published articles are scientifically sound and as objective and unbiased as possible.  In addition, full disclosure of financial relationships and potential conflicts of interest is essential so that readers can interpret articles in the light of that information.  In an effort to present readers with reliable information, JAMA has combated such conflicts of interest with several policies. JAMA requires all industry-sponsored studies to undergo an independent statistical analysis by an academic researcher to ensure the data’s legitimacy. Also, JAMA requires that all authors sign a specific agreement disclosing all their financial sponsors. Just last month JAMA published a stronger statement of this policy and publicly announced the failures of some authors to make full disclosures. 

However, despite these efforts, Dr. DeAngelis contends that there is no way to guarantee that all potential conflicts of interest are disclosed.  It is not feasible to independently investigate the financial relationships of every author since there is no comprehensive, up-to-date source for this information.  Even if one journal bans an author who fails to appropriately disclose information, that author can send his or her articles to another journal.  One possibility is that a group of editors such as the International Committee of Medical Journal Editors could agree to share information about authors who have failed to report their funding and ban those authors across the board. Unfortunately, as Dr. DeAngelis points out, this solution might violate antitrust law.  Thus, Dr. DeAngelis concludes that the best solution is a full investigation by the deans of the author’s institution with appropriate corrective actions.    

While we certainly agree that disclosures MUST happen, the pursuit for full disclosure should not come at the expense of obtaining expert opinion.  Rather, journals need to develop a system whereby authors fully disclose their financial relationships (with meaningful penalties for non-disclosure) in enough detail so that readers can make their own judgments, just as they make their own judgments about the validity of trial results.  JAMA’s policies are a step in the right direction, but all journals must voluntarily follow suit in order to make this effort a success.  Furthermore, as Dr. DeAngelis suggests, academic institutions must share in the responsibility for full disclosure by instituting similar disclosure policies, investigating cases of non-disclosure, and implementing corrective actions as necessary.  Finally, full disclosure is only part of the solution.  The scientific community must also enact other measures, such as clinical trial registries, to ensure that complete results from clinical trials are reported, including all adverse events and negative results. 
 

Looking for perspective on Byetta pancreatitis cases

Investors have recently scrutinized Byetta’s potential to cause pancreatitis, a serious side effect associated with significant morbidity and mortality.  In his review of the FDA MedWatch Adverse Event Reports System (AERS) database for Byetta, Lehman Brothers analyst Jim Birchenough found 24 unique cases of pancreatitis associated with Byetta from August 2005 through January 2006.  Of these, 15 cases had no apparent confounding factors such as gallstones or other known causes of pancreatitis.  Birchenough estimates that this translates into an incidence rate of 65/100,000 overall, and 40/100,000 once patients with confounding factors are eliminated.  He argues that this rate is higher than the estimated baseline rate in the general population (17/100,000) as well as the AERS reported rate for Lantus (0.1/100,000) and TZDs (0.4/100,000 for Actos and Avandia) over the same time period.  Furthermore, the reported rate for Byetta is in between that associated with atypical anti-pyschotics, which have some mention of pancreatitis in their label, and valproic acid, which has a bolded black box warning about pancreatitis.   

Birchenough also argues that there is a strong temporal relationship between initiation of Byetta therapy and pancreatitis, which further supports a causal relationship.  In 9 of the cases, pancreatitis occurred within one week of initiation of Byetta therapy.  In 15 cases, it occurred within 1 month of Byetta initiation.  In 8 cases, symptoms improved after discontinuation of Byetta.  Furthermore, in 23 cases, Byetta was listed as the primary suspect drug by at least 1 report.

Birchenough also points out that it may be biologically plausible for Byetta to cause pancreatitis via a direct cellular effect since the pancreas is one of the primary sites of Byetta action.  Since Byetta is also associated with antibody formation, it could theoretically also potentiate an immune response in the pancreas.  (We are less impressed with Birchenough’s argument that pancreatitis is a theoretical concern based on Byetta’s origin in the saliva of the Gila Monster and documented pancreatitis associated with the Gila Monster bite.)      

While Birchenough makes several compelling arguments, there are always other sides to examine. Hmm, where to start! Well, first, it is difficult to ascertain a direct causal role for Byetta since the AERS database contains limited information regarding the clinical history of the patients with pancreatitis, the accuracy of the diagnosis, and concomitant medications.  For example, we don’t even know whether pancreatitis diagnoses are based on elevated pancreatic enzymes or just on clinical symptoms of abdominal pain, which can often be confused with other diagnoses.  Second, adverse events tend to be reported much more frequently early in a product launch, and this reporting bias makes comparisons between different drugs in AERS flawed.  Furthermore, patients taking Byetta are likely to have more severe diabetes than those taking other diabetes medications since Byetta is indicated for patients who have failed oral drugs and are taking several concomitant medications.  In fact, in its own review of a large payor database, Amylin reported a lower reported rate of pancreatitis with Byetta than the rate in type 2 diabetics, contrary to Birchenough’s findings.  In addition, when the FDA updated the Byetta label in April 2006 (after they presumably had access to all of these reported cases), there were no additional Warnings or Precautions added to the label and there was no direct mention of pancreatitis under the Adverse Reactions section.  This seems to imply that the FDA did not find a causal relationship between Byetta and pancreatitis.  And, remember, Byetta got through the FDA without a panel review precisely because its safety profile was so pristine!

Also of note, of the 24 cases of pancreatitis that Birchenough found, only one of them was reported in 1Q06, which implies a decreasing incidence rate.  Taken alone, the rate in 1Q06 is actually much lower than the rate of pancreatitis in the general population.  This is contrary to what we would have expected since more people continue to start on Byetta over time.  If pancreatitis is actually associated with initiation of Byetta treatment, we would have expected the rate of pancreatitis to increase over time as more people initiate therapy.  This decrease in incidence rate may reflect better drug introduction since it coincides with the release of more information about adjusting meal size and composition when initiating Byetta.  Alternatively, it may reflect more accurate diagnosis of pancreatitis. In any case, this issue clearly needs to be further analyzed.      

Thomas Wei of PiperJaffray points out, “there are rare serious side effects associated with almost all diabetes drugs, including lactoc acidosis (and pancreatitis) with metformin, hypoglycemia with sulfonylureas and insulin, and edema/heart failure with TZDs, but all have been successful due to the overall benefit outweighing the risks.  We continue to believe that Byetta’s differentiated clinical profile, including weight-loss, post-prandial glucose control, and restoration of first phase insulin release, support continued adoption.” 

We will continue to monitor the situation and speak to thought leaders - the first one we called, Dr. Irl Hirsch gave us his bottom line tonight, “Rare side effects occur and aren’t seen until many people are on the drug.  I can’t speak for anyone else, but it won’t stop me from using the drug in people who can benefit.” We welcome the focus on patients ...

One soda a day = 15 pounds per year="That's ludicrous."

While there are undoubtedly many factors behind the increasing obesity epidemic in the U.S. (think super-sized fast food portions and decreased physical activity, to name a couple ~ energy in doesn’t equal energy out, etc.), a new scientific review suggests that sugar-sweetened beverages, particularly carbonated soft drinks, are a key contributor. In a report published Tuesday in The American Journal of Clinical Nutrition, Dr. Frank Hu and others at the Harvard School of Public Health reviewed 30 studies (15 cross-sectional, 10 prospective, and five experimental) on the relation between sugar-sweetened beverages and weight gain published over the past 40 years. Although not all studies conclude that beverages are at fault, the researchers found “an overwhelmingly strong case... for a causal relationship” between beverage trends and obesity, which “clearly justifies public health efforts to limit sugar-sweetened beverages.”

Soft drink consumption has increased dramatically over the past four decades, in parallel with the increase in obesity. According to this report, an extra can of soda a day can lead to 15 additional pounds in a single year. Scary. Experimental studies suggest that the mechanism by which sugar-sweetened beverages may lead to weight gain involves high-fructose corn syrup (HFCS), the main sweetener in these beverages. HFCS makes beverages less satisfying than other carbohydrate sources because it fails to stimulate insulin, which processes calories, and leptin, which helps regulate appetite.
Not surprisingly, the beverage industry is quick to point out that there is more than one factor contributing to the obesity epidemic. While this is almost certainly true, that does not mean that we should ignore it. As Dr. David Ludwig, director of the obesity program at Children’s Hospital in Boston put it, “Could you imagine someone saying we should ignore the contribution of hypertension to heart attack because there are many causes? It’s ludicrous.”

In addition to weight gain, sugar-sweetened beverages provide little nutritional benefit and may increase the risk of diabetes, fractures, and dental carriers. In one study, intake of soft drinks was significantly associated with an increased risk of diabetes, even after adjustment for BMI. The authors postulate that this association is probably due to the high amount of rapidly absorbable carbohydrates such as HFCS in soda, which contribute to a high glycemic load. Several studies have also suggested that rapidly digested and absorbed carbohydrates may exacerbate the proinflammatory process underlying diabetes, such as C-reactive protein and haptoglobin. Furthermore, consumption of sugar-sweetened beverages displaces milk and other more nutritious beverages from the diet. Reduction in consumption of milk, which contains high amounts of calcium, combined with the high phosphate content of cola, may also contribute to an increase risk of fractures. Low calcium intake during the adolescent years is particularly hazardous because it jeopardizes the accrual of peak bone mass.
The authors therefore conclude that “it is imperative that current public health strategies include education about beverage intake. Consumption of sugar-sweetened beverages such as soda and fruit drinks should be discouraged, and efforts to promote the consumption of other beverages such as water, low-fat milk, and small quantities of fruit juice should be made a priority.” Recent restrictions on the sale of sugar-sweetened drinks in schools are certainly a step in the right direction! (Go California, and thank you Dr. Kaufman!) However, far far more needs to be done and lots of politics stand in the way - we hope to see things change on this front as the dangers of the public health epidemic (diabetes and obesity) emerge.

AADE day one - high level themes

AADE Day One - High level themes
We're in LA! Excellent. Here are some quick initial themes from day one

#1 - LOTS MORE SYMLIN DISCUSSION: So for the first theme, this is sort of interesting - it's Symlin! This drug is definitely taking off a bit more - maybe due to the Byetta shortage, which we've been thinking is going to end soon (thankfully!) We've heard more people talking about Symlin - it also makes sense since more educators that we saw/spoke to today see intensively managed patients - but we also heard a lot about Symlin and pumping - we heard it at the Medtronic session that started off the day, where Dr. Fran Kaufman was extremely engaged as always; we heard it at one of the DPP4 sessions, and then we heard it tonight at Dex Com, which took place at the spectacular Disney Hall. 
This sort of surprised us. For a long time, we've been calling Symlin a sleeper drug, so from it to move from "sleeper" or just "small drug, right now" status to a drug where everyone is singing its praises and discussing how fabulous this alternative new delivery form is ... wow. Of course we personally concur with how excellent pumping Symlin is. Everyone was saying how practical that wasn't, but I think eventually there will be a way. Symlin is also probably getting more discussion points here because with the emergence of continuous monitoring, there's now an easier way to figure out the titration.  Most of all, we’re impressed with the reimbursement strategy  for Symlin. Would that reimbursement could be as easy for CGM…they are both such high potential tools.

#2: BYETTA IS BIG HERE TOO: CDEs we've spoken to so far don't seem to be concerned about pancreatitis.  There is also a lot of excitement about LAR.  Davida Kruger, who is part of the LAR trial, characterized the results as “amazing,” with more weight loss, better glucose control, and the same or less nausea than Byetta.

#3: PFIZER IS THE LATEST NEWEST BIG ADVOCATE OF POST-PRANDIAL TESTING TO IMPROVE ABILITY TO GET A1C UNDER 7. Complications from type 2 start long before diagnosis.  “We treat too late” is a becoming a flatter and flatter statement every year - the consequences of a younger population of type 2s living with complications much longer is a daunting prospect. Monnier showed us that controlling PPG gave the best bang for the buck in lowering A1cs compared to FBG for most, except those with very unacceptably high A1Cs. Also, powerhouse educator Catherine Gray (Diabetes Network, Inc. Albuquerque, NM) believes that PPG testing offers more encouragement to her patients – she believes they are more motivated, creative, and successful in their self management if they are on the PPG bandwagon. Very intriguingly - if the reimbursement piece works (and it does in her NM community) she believes in aggressively treating pre-diabetics.  Blonde also speculated that early insulin therapy may reduce atheroschlerotic processes and macrovascular complications and help preserve beta cells.  He mentioned the NAVIGATOR trial, which is investigating whether insulin for pre-diabetics and early diabetics reduces progression.

#4: CONTINUOUS GLUCOSE MONITORING IS CHANGING THE PARADIGM OF SELF-MANAGEMENT.  There is increasing evidence that glycemic variability contributes to morbidity and mortality, but A1Cs do not reflect this glycemic variability and fingersticks alone are not catching it.   Thus, Dr. Francine Kaufman of Children’s LA feels that CMG is “the next big breakthrough” because it is proactive rather than reactive.  Kaufman and her team have jumped on the CMG bandwagon as fast as possible, even prescribing it off-label in their pediatric patients.  CMG lowers the risk of hypoglycemia (due to alarms) and the discovery of blood glucose trends allows clinicians to correct easily correctable factors in insulin regimens. The most corrected factor in patients who have used CGM is an increase in meal boluses and the second is a decrease in basal insulin. A close third is a change the method of counting carbs—big changes!

#5: WE WERE REMINDED YET AGAIN OF THE FABULOUS VALUE AND LEARNING THAT COME FROM THE PHARMACIST RELATIONSHIPS in "Treatment of Type 2 Diabetes: Controversies, Challenges, and Opportunities." Curtis Triplitt, PharmD CDE, Texas Diabetes Institute, Clinical Assistant Professor of Medicine/Diabetes, University of Texas Health Science Center at San Antonio took the lead on this one and had some interesting thoughts:

On the DREAM trial. He expects the study results to be positive and that a shift in how TZDs are used will follow. We'll be watching in mid-September ...

On Byetta use in his clinic. His group is having lots of pre-authorization issues with respect to reimbursement. Some of his patients with nausea can't get past it no matter what they try with dosing, etc. Some people lose weight, some people don't.

On DPP4s. He likes that they are well tolerated but expects ongoing controversy around their long term impact on the immune system.

On Exubera. There was audible paper rustling when he turned started talking about Exubera. He expects some confusion as to where it "fits". Right, us too, since people who take inhaled insulin probably won't get it reimbursed initially.  As for the pulmonary function topic, he believes the work to date and ongoing work on collecting safety data will dampen the concerns over time.

#6: ON BALANCE, WE BELIEVE THERE IS AN INCREASINGLY COMPLICATED LANDSCAPE FOR THE DIABETES EDUCATOR AS NEW THERAPIES AND TECHNOLOGIES EMERGE. The CDEs will be the frontline and charged with knowing about everything that's happening – and often in more depth than the doctors. This speaks to fantastic opportunity, but also to our ongoing concern that the field hasn't created enough incentives for educators and thank heavens for their hearts – they are sadly in dire need of reimbursement funds for all the life-changing and life savings education they do.

#7: EMPOWERING PATIENTS AND INDIVIDUALIZING THERAPY are emerging themes, with caregivers talking less about what patients HAVE to do and more about figuring out what patients CAN do.  Educators can only advise patients, they can’t set their goals.  As star educator Davida Kruger put it when talking about the ACCORD trial, “There is no right way – it all depends on the patient.”  Caregivers must listen to patients and tailor therapy to how they behave.  Karmeen Kulkarni also emphasized the need for clinicians to integrate their therapies because patients rarely have diabetes alone – they also have hypertension, dyslipidemia, etc. 

…