Diabetes 2015. March 24, 2006 Report 06-10 and treatment of diabetes. diabetes related health disparities and enhancing health gains through the use …
Diabetes 2015
March 24, 2006 Report 06-10
Diabetes 2015
Introduction The Looming Crisis Advances in Type 2 Diabetes Prevention and Management The Biggest Challenge: Screening with Early Prevention Effective Management of Chronic Disease Biomonitoring Medicines for Controlling Glucose Metabolism New Insulins and New Delivery Methods Drugs for Obesity Will We Find a Cure for Diabetes? 3 3 5 5 6 7 8 9 11 12
Copyright 2006, Institute for Alternative Futures Preparation of this paper was assisted by a grant from the Robert Wood Johnson Foundation, Princeton, NJ Permission is hereby granted to use any or all of the material contained herein or on IAFs web site providing that: 1 reference to the source is made using the following format: wwwaltfuturescom/BFP/Platforms, Institute for Alternative Futures, Alexandria, Virginia, 2006; 2 an electronic copy is sent to futurist@altfuturescom and one copy of the publication or reproduction in which this material appears is sent to the Institute for Alternative Futures, 100 North Pitt Street, Suite 235, Alexandria, VA 22314
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Diabetes 2015
A forecast of likely incidence and treatment advances
Introduction
The Biomonitoring Futures Project BFP is exploring how biomonitoring related to diabetes and cancer might evolve over the next decade and its potential to reduce health disparities The BFP, funded by the Robert Wood Johnson Foundation, is a component of IAFs larger effort to identify and accelerate the most significant disparity reducing advances the DRA Project This document summarizes recent forecasts for the increasing incidence of diabetes, then explores likely developments in the prevention and treatment of diabetes A separate report will provide more detailed forecasts for developments in biomarkers and biomonitoring for diabetes and pre-diabetes There is great potential for reducing
diabetes related health disparities and enhancing health gains through the use of low cost, culturally appropriate and clinically efficient biomonitoring
This report provides two types of forecasts for 2015 The first type is likely forecasts given current trends or research they identify what will likely happen The second type of forecasts is optimistic they identify trends and potential changes which are desirable but are
less certain For example
prevention will become far more possible for diabetes that is highly likely What is uncertain is whether and how health care payors and providers will pursue prevention
The Looming Crisis
The prevalence of diabetes increased 5 annually over the past five years with an estimated 1,500,000 new cases in 2005 for a total of 208 million patients with the disease 146 million diagnosed and 62 million undiagnosed1 If this trend continues there will be at least 30 million2 and possibly even 35 million people3 with diabetes in 2015 The risk of an American male getting diabetes in his life time is 1 in 3 whereas females have a 2 in 5 chance4 Minorities have an even higher lifetime risk: 53 for a Mexican American female and 49 for a Black female5
The primary factor accelerating the incidence of diabetes appears to be the epidemic of obesity Currently two-thirds of American adults are overweight with almost one-third reaching the obese level greater than 30 body fat6 A new Framingham heart study concludes that 80 of White Americans
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will become overweight during
their lifetimes with 40-50 going on to obesity7 This is likely to be higher in minorities Obesity is becoming a disease of the young with 15 of 6-19 years being overweight 23 for Blacks and Hispanics 8 Type 2 adult onset diabetes was until recently unheard of in children, but now it makes up 40-50 of cases with the rest being type 1 diabetes Children as young as four have been found with abnormally high insulin levels and 13 of all children have elevated cholesterol levels9 These trends portend rising numbers of young adults with diabetes and cardiovascular disease
The disease burden is significant and will increase as more patients develop the disease at an earlier age People with diabetes tend to have hypertension and dyslipidemia leading to cardiovascular disease, the cause of their death 65-75 of the time Based on estimates from the American Diabetes Association and forecasts from the Centers for Disease Control, in 2015 at least 42,000 will develop blindness, 75,000 will go into renal failure and 144,000 will require a lower extremity amputation due to diabetic complications10 Depending upon age of onset, sex and race, people with diabetes lose between 15 and 30
quality-adjusted life years QALY and die 10 to 20 years prematurely11 Diabetes is now the 6th leading cause of death and will directly contribute to about 400,000 deaths in 201512 The cost to society from diabetes will be over 225 billion in constant 2002 dollars13
This is a realistic picture of the magnitude of the diabetes epidemic if American society and the healthcare system do not change To dramatically reduce this disease burden of diabetes we must change our communities to promote more exercise and our food industry and lifestyles to prevent obesity Our healthcare system must shift to aggressive prevention and effective early intervention with proven methodologies for managing multiple chronic diseases Society must also find ways to ensure healthcare access for all Americans and to address inequities of the social determinates of health By 2015, unless current trends change, the twin epidemics of obesity and diabetes will be the biggest challenge in public health and for the healthcare system Minorities and the underserved will be impacted the most Community health centers will devote a major portion of their resources and efforts in addressing the multiple comorbidities of
these twin problems
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Advances in Type 2 Diabetes Prevention and Management
Prevention A large proportion of all ethnic groups carry genes permitting diabetes to develop if the environment and lifestyle are conducive, as we have recently seen Society and the medical professions are becoming aware of the need for action using as a model the effective campaigns against smoking and encouraging seat belt usage The most comprehensive approach for reducing the potential disease burden would be to address the major risk factors simultaneously obesity, physical inactivity, smoking, hypertension, hyperglycemia, hyperlipidemia that predict the development of several major chronic diseases diabetes, cardiovascular disease, cancer and dementia14 successfully modify behavior Interventions must include ways to
Of course, a bigger challenge is for society to address the social
determinants of health such as the elimination of poverty An optimistic forecast would be: By 2015 effective measures are available to change behavior and randomized, controlled trials demonstrate efficacy Efforts
by health plans, community health centers, and state and federal agencies are beginning to reduce the incidence of diabetes and obesity It is a work in progress that will take many years for a significant reduction in societal disease burden
The Biggest Challenge: Screening with Early Intervention
In 2005 the ADA estimates there are 41 million adult Americans with prediabetes which will lead to clinical diabetes about 50 of the time within 10 years15 Modest weight loss and moderate daily activity have been shown to prevent this progression to diabetes in 58 for at least a few years16 Few people at risk are screened since test results are not immediately available, thus making follow-up visits necessary There are not enough qualified health interventionists nurses, dietitians, health educators, community health workers with the required training to effectively intervene in changing lifestyles Moreover, payors seldom reimburse treatment of predisease In this context an optimistic forecast would be: By 2015 people with risk factors for diabetes are screened routinely Aggressive primary prevention is undertaken when they are found to have prediabetes Health care payors routinely pay
for effective health/behavior intervention from a range of health care providers, including CHCs
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Currently there is an estimated 9-12 year delay in diagnosis for those who have progressed to true diabetes so around 30 of all those with the disease are undiagnosed and therefore not under treatment Given this current delay in diagnosis, it is likely that 20 of patients already are experiencing eye, nerve or kidney damage, and many have developing atherosclerosis by the time their diabetes is diagnosed An optimistic forecast for changing this situation is: By 2015 inexpensive noninvasive screening tests for glucose and lipids are available Electronic health records make it easy to identify those at risk who have not been tested so opportunistic screening tests are given when a person checks into the clinic or ER for another problem High risk patients who do not seek care are located through screening at church, work, soup kitchens, homeless shelters, and health fairs at malls and sporting events Noninvasive testing is fast, pleasant and provides immediate feedback for timely
intervention
Effective Management of Chronic Diseases17 18 19
An estimated 125 million Americans live with chronic diseases and half of them have multiple chronic diseases, very often including diabetes Unfortunately, American healthcare is still focused on acute care delivered episodically on-site by physicians without reimbursement for effective team management and continuity There is recent emphasis on disease management, but it is not coordinated for effective management of multiple complex chronic diseases, and the focus is on controlling cost with little effort to improve quality of life
Ninety percent of those with diabetes receive the majority of care in primary care practices This is the perfect setting for multidisciplinary care teams directed by evidence-based guidelines and supported by electronic health records and performance feedback to practice coordinated continuous care Attention goes beyond current diseases and addresses risk factors for future comorbidities Emphasis is placed on patient education and coaching to support self-management goals and home self-care This plays to the strengths of community health centers which have a culture of teamwork and caring,
usually have access to a single paper record, and have the need to focus on simple evidence-based activities, rather than a financial incentive to focus on high-tech procedures As a result many CHCs produce higher scores on performance measures compared to managed care plans
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The chart below summarizes the shifts that should be in place by 2015, again in an optimistic forecast, for effective management of chronic disease: Effective Management of Chronic Diseases Current Practices Effective Chronic Disease Care Episodic testing Extensive use of biomonitoring Engage when symptomatic Prospective prevention Focus on current medical problem Focus on all risks Primary care physician Cooperative team of providers Care based on periodic visits Continuous healing relationships Short visits with little information Emphasis on education and coaching Decisions by clinical autonomy Evidence-based decisions for team Information restricted Electronic information flows freely One size fits all Care customized to needs and values Patient a passive participant Patient/family active
participants
Biomonitoring20
This section provides a brief glimpse of what is possible Separate Biomonitoring Futures Project reports consider current best practices and future developments in diabetes biomonitoring People with advanced diabetes must test their blood sugar several times a day requiring many finger sticks Researchers have been trying for years to create effective noninvasive methods for determining blood glucose using infrared spectroscopy, iontophoresis and sonophoresis as ways to get serum to pass through the skin for sampling The Glucowatch was such a device, but it was expensive and of limited clinical usefulness It is realistic to expect that technical obstacles will be overcome with a suitable device likely available by 2015 Effective noninvasive testing devices with high accuracy will also dramatically improve screening for diabetes and hyperlipidemia
Inexpensive home test kits are now available for hemoglobin A1c, LDL HDL cholesterol and triglycerides It is important for patients to receive periodic feedback about how well they are managing glucose, blood pressure or lipids as they are usually asymptomatic and stop taking medications after a few months
because they cant tell that the drugs are making any difference
A Korean company makes a cell phone that has an internal glucometer and motion sensor for monitoring daily exercise The results are stored and can be sent to health providers The cell phone or personal computer or PDA can be used to give the patient reminders about care, to provide information from the Web and to easily consult electronically with a nurse With increasing artificial intelligence capabilities
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the glucometer, cell phone or computer will assess lab trends and give the patient recommendations for better management of glucose or lipids The Glucoboy is an example of a game that promotes effective management It is a Gameboy attached to a glucometer The patient gets access to higher levels of a game if her blood sugar is under better control from appropriate testing and insulin usage
Again, these are simply an indication of the range of biomonitoring that is likely to be available by 2015 It leads to the optimistic forecast that: By 2015 noninvasive testing will be used for rapid screening, speedy clinic
visits and by empowered patients for effective self-management of their diabetes and dyslipidemias
Medicines for Controlling Glucose Metabolism21 22 23 24 25 26 27
In 2006, there are five major classes of oral diabetes agents on the market They stimulate beta cells to produce more insulin, reduce the amount of glucose made in the liver, increase cellular sensitivity to insulin or slow intestinal conversion of ingested carbohydrates into glucose Major drawbacks are that many cause weight gain and none of the current drugs modify the disease to slow do 
wn progression Under development are agents that: Improve or mimic metabolic actions of insulin to counter insulin resistance, Preserve beta-cell function and prevent loss of cell mass by either promoting neogenesis or preventing apoptosis, Stimulate insulin biosynthesis by beta-cells to support required increased secretion, Reduce the lipotoxic effects of chronically elevated triglycerides and fatty acids on beta-cell function and insulin action, Suppress gluconeogenesis and glucogenolysis eliminating glucotoxicity exacerbating insulin resistance and beta-cell failure, Address impaired glucose uptake and utilization by tissues,
Reduce obesity leading to reduction of hyperglycemia as weight is lost
New therapies based on these approaches are becoming available Exendtide is an incretin mimetic drug similar to the bodys glucagon-like peptide-1 GLP-1 hormone It was recently approved as an
8
adjunctive therapy given by injection twice a day to increase insulin secretion, lower plasma glucagon
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thereby reducing the amount of glucose produced by the liver, and bind to the hypothalamic appetite center telling the brain to stop eating These effects result in appetite suppression, progressive weight loss and sustained glucose control It also reduces inflammatory markers suggesting improvement in blood vessel endothelial function and it might preserve beta cells by stimulating regeneration and stopping cell death Dipeptidyl peptidase IV inhibitors are another class of drugs that target the incretin pathway They have similar effects, but can be given orally Multiple compounds are in development or clinical trials
Dual peroxisome proliferators-activated receptor PPAR alpha/gamma agonist drugs are in late clinical
trials They improve insulin sensitivity lowering blood glucose and hemoglobin A1c, and they also decrease triglycerides and raise HDL cholesterol a two-in-one solution for diabetes and lipid disorders However, the FDA is requesting additional studies because of concern with potential cardiac side effects These drugs or modified candidates may be on the market within the next few years Given these and several related developments a likely forecast is that: By 2015 there will be new classes of effective drugs for treating both diabetes and comorbidities The big question is whether the price will be too high to make them available for use by community health centers
New Insulins and New Delivery Methods28 29 30
There are new short- and long-acting insulin analogues for better glucose control as a result of advances in recombinant DNA technology Hepatoselective insulin that is selectively absorbed by the liver for delivery via the portal vein causes less build up in peripheral tissues and may cause fewer complications An insulin substitute is under investigation that is a novel insulin-mimetic heterodimer peptide which attaches to each of the insulin receptor binding sites to
activate the insulin pathway Other research developments include the creation of uniform nanometer size insulin particles that may be more efficient, as well as exploration of heat-stable insulins for easier storage and distribution This leads to the likely forecast that: By 2015 there will be even more effective insulins on the market, especially for new delivery systems
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New approaches to insulin delivery are under development to avoid the discomfort of injections, thereby improving compliance with better glucose control Promising examples: Inhaled insulin is under development by several companies and a dry power form using a special controlled nebulizer has just been approved by the FDA Currently inhaled insulin is short-acting for use just before meals, and longer-acting injectable insulin would have to be used at bedtime Longer-acting forms are being developed As the bioavailability of inhaled insulin is only about 10 of current injected forms, it will likely be expensive, and it is uncertain if payers will cover it Oral insulin would be ideal, but has been a difficult
challenge because it is broken down in the stomach and its large molecule is not easily absorbed into the bloodstream Work is ongoing on a gel-polymer coated version Another approach is oral spray insulin that is absorbed through the buccal mucosa It is uncertain whether technical challenges will be overcome to produce oral insulin Transdermal insulin is being considered using multiple minimally invasive methodologies such as microneedles, sound waves or electrical current to overcome the skin barrier If successful a patch could deliver continuous low dose insulin through a pump mechanism If the device had a glucose biomonitor and computer intelligence the dose could be continuously adjusted to automatically control blood sugar a closed loop system Insulin pump technology has been under development for a long time External pumps now in use provide better control of hemoglobin A1c in those with juvenile diabetes Implanted externally controlled pumps that infuse insulin directly into the peritoneal cavity are available in Europe and being considered by the FDA for use in the US The pump reservoir is refilled percutaneously every 90 days Work is progressing on a durable implanted
glucose sensor, but an automatic closed-loop system using this implanted pump approach or a transdermal approach is still several years away Islet Cell Transplantation and the Bio-Artificial Pancreas are two experimental approaches to implant cadaver, xenograft or stem cell islets Islet cell transplantation done by injecting cadaver cells via the portal vein directly into the liver has been performed on more than 500 patients with about 80 remaining free of the need for insulin injections after one year However, they must be maintained indefinitely on immunosuppressive drugs with significant costs and side effects The bio-artificial pancreas is a microporous membrane containing islet cells that is inserted in the body Nutrients enter the membrane to sustain the islet cells and insulin passes out, however larger immune system components cannot enter to destroy the foreign islet cells Much more research is necessary before this technology could be approved for human use The gene pill is another novel idea in early animal research The gene for manufacturing insulin is inserted into a pill that is swallowed, permitting the gene to be taken up by the lining cells of the gut, which then
produce insulin that is absorbed into the blood stream As mucosal cells are continually sloughed off and replaced, a pill is needed every couple days The gene stays out of the blood stream so cells elsewhere do not start producing uncontrollable insulin Someday this process may be used to supplement the inadequate insulin production in many with type 2 diabetes
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The resulting likely forecast is that: It is reasonable to expect that noninvasive ways to administer insulin will be available by 2015 The big question is whether these will be effective and inexpensive enough for routine use, or only practical for special cases Ease of use and avoidance of painful injections could dramatically improve compliance with better control and fewer long-term complications
Drugs for Obesity31
Obesity is a strong risk factor with about 60 of new cases of diabetes being obese and an additional 30 being overweight Weight reduction and exercise are superior to oral anti-diabetes drugs in preventing the development of diabetes in those with impaired glucose tolerance Although there has
been tremendous research on the metabolic and neurohumeral pathways controlling metabolism and weight, targets showing great promise in research animals have frustratingly little impact when used in humans This will soon change
The only currently approved long-term drug effective in reducing weight is orlistat It is a lipase inhibitor that works in the intestine to block absorption of one-third of dietary fat It has also been shown to prevent and reverse early type 2 diabetes
Rimonabant is a selective CB1 receptor endocannainoid blocker that in phase III clinical trials is effective in producing sustained weight loss It also reduces hemoglobin A1c, triglycerides and blood pressure while raising HDL This is an example of a drug with multiple beneficial effects for reducing cardiovascular risk while treating diabetes and obesity It is expected to be approved in 2006, but it will take time to clarify its proper use in community health centers as well as availability based on its cost
Other drugs under development will control absorption, metabolism, energy expenditure and hunger They will probably have to be used in combination to prevent the body from working around one action to
maintain obesity This leads to the likely forecast that: By 2015 there will be more effective drugs for obesity, but they are likely to be expensive and continuous long-term use will be required to keep weight under control
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The logical approach to the obesity epidemic is a serious societal commitment to effective prevention programs New drugs would be better used for reversing established obesity when other measures have failed
Will We Find a Cure for Diabetes?
Our increasing understanding of diabetes at the genetic, molecular and cellular levels will result in many advances Identification of phenotypes at higher risk will lead to screening and early intervention for affected subpopulations The most effective therapies for the individual with diabetes will be selected based on the unique characteristics of the disease and the patients pharmacogenomic profile The approach may be genetic or biochemical manipulation, often as preventive measures It is possible that someday we will understand the underlying biomolecular pathophysiology well enough to create therapeutics that
block diabetes from occurring The obvious lesson at present is that it is much easer to prevent the disease in the first place
CDC, National Diabetes Fact Sheet: United States, 2005 http://wwwcdcgov/diabetes/pubs/pdf/ndfs_2005pdf accessed 10/26/05 2 Honeycutt, AA, et al A Dynamic Markov Model for Forecasting Diabetes Prevalence in the United States through 2050 Health Care Management Science 2003;6:155-164 3 Rowley, WR Bezold, C Diabetes Forecasts to 2025 and Beyond: The Looming Crisis Demands Change, Changing Diabetes Forum, Washington, DC, November 9, 2005, Novo Nordisk National Changing Diabetes Program 4 Narayan, KMV, et al Lifetime Risk for Diabetes Mellitus in the United States, JAMA 2003;290:1884-1890 5 Narayan, Opcit 6 Flegal, KM, et al Prevalence and Trends in Obesity Among US Adults, 1999-2000 JAMA 2002;288:1723-1727 7 Vasan, RS, et al Estimated Risks for Developing Obesity in the Framingham Heart Study Ann Intern Med 2005;143:473480 8 Narayan, Op cit 9 Davis, JL Childhood Obesity Seen Even in Preschool WebMD Medical News, May 5, 2003 http://mywebmdcom/content/Article/64/72383htm?printingtrue accessed 10/13/05 10 Based on American Diabetes Association 2000 data
extrapolated to 2015 using Amanda Honeycutts 2015 prevalence projection Honeycutt Op cit 11 Narayan, Op cit 12 Based on American Diabetes Association 2000 data extrapolated to 2015 using the average of Honeycutts Honeycutt Op cit and Rowleys Rowley Op cit prevalence projections 13 American Diabetes Association, Economic Cost of Diabetes in the US in 2002 Diabetes Care 2003;26:917-932 Data extrapolated to 2015 using Honeycutt prevalence projection Honeycutt Op cit 14 Tuomilehto, J Primary Prevention of Type 2 Diabetes: Lifestyle Intervention Works and Saves Money, but What Should be Done with Smokers? Ann Intern Med 2005;142:381-383 15 American Diabetes Association Frequently Asked Questions about pre-diabetes http://wwwdiabetesorg/prediabetes/faqjsp accessed 11/28/05 16 Centers for Disease Control and Prevention Primary Prevention Working Group Primary Prevention of Type 2 Diabetes Mellitus by Lifestyle Intervention: Implications for Health Policy Ann Intern Med 2004;140:951-957 17 Rothman, AA Wagner, EH Chronic Illness Management: What Is the Role of Primary Care? Ann Intern Med 2003;138:256-261 18 Anderson, Gerald, John Hopkins Bloomberg School of Public Health, Institute for
Alternative Futures Foresight Seminar, Washington, DC, 12/16/03
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Yach, Derek et al Barriers to Chronic Disease Care in the United States of America: The Case of Diabetes and its Consequences, Changing Diabetes Forum, Washington, DC, November 9, 2005, Novo Nordisk National Changing Diabetes Program 20 Briggs, AL Cornell, S Self-monitoring Blood Glucose SMBG: Now and the Future Journal of Pharmacy Practice 2004;17:29-38 21 Aroda, VR Henry, RR Incretion Hormones in Diabetes and Metabolism Medscape, 5/28/04, http://wwwmedswcapecom/viewprogram/3075_pnt accessed 6/24/04 22 Baily, CJ New Pharmacologic Agents for Diabetes Current Science 2001;1:119-126 23 Darves, B Muraglitazar May Help Lower Glucose and Cholesterol Levels in Type 2 Diabetes Medscape Medical News 6/13/05 http://wwwmedscapecom/viewarticle/506546 accessed 6/22/05 24 Darves, B Tesaglitazar Shows Promise in Controlling Lipid and Glucose Levels Medscape Medical News 6/13/05 http://wwwmedscapecom/viewarticle/506549 accessed 6/22/05 25 Luna, B Feinglos, MN Oral Agents in the Management of Type 2 Diabetes Mellitus
American Family Physician 2001;63:1747-1756 26 Moller, DE New drug targets for type 2 diabetes and the metabolic syndrome Nature 2001; 414:821-827 27 Richardson, K The Clinical Use of Exenatide: An Expert Interview With Ralph A DeFonzo, MD Medscape Diabetes Endocrinology 2005 http://wwwmedscapecom/viewarticle/506940 accessed 6/29/05 28 Kordella, T The Future of Insulin: Pills, patches, and puffs are slowly making their way down the pipeline http://wwwdiabetesorg/diabetes-forecast/mar2003/futurejsp accessed 1/25/05 29 Diabetes today novel approaches to management: Conference Highlights, European Association for the Study of Diabetes, 5-9 Sept 2004, Diabetes for Professionals, 9/22/04, wwwd4procom accessed 1/27/05 30 Begley, S Future Gene Pill May Supplant Shots, WSJ 6/29/05 31 Darves, B Rimonabant Reduces Lipids, Weight and Adiposity Medscape Medical News 6/14/05 http://wwwmedscapecom/viewarticle/506633 accessed 6/22/05
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Source:asbs.org
