This article is more than 5 years old. Information may no longer be current.
Mysteries remain in disease progression of extreme type 1 diabetes
Click Here to Manage Email Alerts
The life expectancy for those diagnosed with childhood-onset type 1 diabetes has improved dramatically since the 1950s, and the survival gap between type 1 diabetes and the general US population is diminishing, according to experts.
Researchers, however, are still investigating the mystery as to why this is the case, and the rising prevalence of diabetes and its complications remain a global public health issue.
“We have made tremendous strides in diabetes. Overall control has improved, and rates of retinopathy, amputation and so on are dropping,” Vivian Fonseca, MD, president-elect of medicine and science at the American Diabetes Association, told Endocrine Today.
Hillary A. Keenan, PhD, of Harvard University, said research should focus not only on risk factors, but also on protective factors in these patients.
Used with permission by: Joslin Diabetes Center
“However, life expectancy of the nondiabetic population has also gone up, so maybe those with diabetes have some catching up to do. Even so, not having blindness and amputation leads to a better quality of life. Although this has not been quantified, my opinion is that people with diabetes can look forward to a better quality of life,” said Fonseca, who is the Tullis-Tulane Alumni Chair in Diabetes, professor of medicine and chief of the section of endocrinology at Tulane University School of Medicine.
Hyperglycemia is a major cause of vascular and neuropathic complications that are seen in patients with type 1 diabetes. However, during the past few years, researchers at the Joslin Diabetes Center in Boston have identified a number of patients — known as the Joslin 50-year Medalists — who remain free from some of these common complications despite their 50-plus years of living with the disease.
Endocrine Today spoke with several experts in the arena to discuss the recent data that allude to possible causes of increased longevity in this aging population, as well as to highlight the Joslin Medalist Program and subsequent launch of the Medalist Study.
Recognizing survivors
Elliott P. Joslin, MD, founder of the Joslin Diabetes Center, started the Joslin Medalist Program in 1972 to recognize those who were successfully living with type 1 diabetes — mostly free of complications — for 25, 50 and 75 years. The program honors these patients’ accomplishments in diabetes management and care.
“Historically, no one expected people with type 1 diabetes to live this long. When you think about when this population was diagnosed, such a diagnosis was horrible, so the fact that these patients are living this long, complication-free is just phenomenal,” Hillary A. Keenan, PhD, co-principal investigator for the Joslin 50-Year Medalist Study and instructor of medicine at Harvard University School of Medicine, said in an interview.
Since then, there has been a revolution in the care of diabetes since the 1980s, when it became possible to measure blood sugar immediately and determine results in a matter of minutes, which ultimately led to improved control of blood sugar, experts said. Other improvements include the ability to measure long-term levels through HbA1c and advancements in insulin therapy.
“Maintaining good glycemic control in the 1970s was tough; to be complication-free at that time was going to be difficult. Dr. Joslin recognized how difficult this accomplishment was, which is why he made this award for people,” Keenan told Endocrine Today.
|
|
Over time, with the recognition of this group’s accomplishment, Joslin researchers identified unusual and positive health trends among this noted population of Medal recipients. This spurred them to launch the Medalist Study in 2005 to research and identify potential trends among this population. The study draws together investigators to analyze genetic or other factors that may be seen in this cohort.
“We wanted to understand the factors that can prevent complications from developing in diabetic patients, since these patients have lived such an extraordinarily long time. Could the reasoning be that environmental or genetic factors are helping them?” said George L. King, MD, principal investigator for the Joslin Medalist Study and Joslin’s chief scientific officer and professor of medicine at Harvard Medical School.
Medalist Study in depth
The goal of the Medalist Study was to understand and describe factors that allowed the extreme duration of type 1 diabetes in patients who have an average diabetes duration of 59 years (± 6.9 years). Participants’ average age at time of diagnosis was 11 years.
To date, researchers with the study have evaluated more than 680 patients with insulin-dependent type 1 diabetes to characterize genetic, environmental, psychological and physiological factors that may play a role in this finding of extreme duration of diabetes.
“We wanted to see whether they have complications from eye, kidney, nerve and/or heart disease, then perform an extensive survey and clinical and biochemical studies to determine any factors that could differentiate those who do have complications vs. those who don’t,” King said.
Recent results of a cross-sectional, observational analysis of 351 Medalist participants, published in the April 2011 issue of Diabetes Care, showed that 86.9% of patients remain free from nephropathy, 51.5% from cardiovascular disease, 42.6% from proliferative diabetic retinopathy and 39.4% from neuropathy.
“These were minimal rates of complications compared to the general population of type 1 diabetic patients,” Keenan said.
Although some of this improvement in risk for complications may be due to advances in technology, screening and management, these findings led the researchers to conclude that genetic or other protective factors not yet identified may also play a role.
Additionally, Joslin researchers have identified that 66% of participants have measurable levels of insulin-peptides. Study results published in Diabetes in November 2010 showed that some participants have insulin-positive cells in the pancreas.
“We don’t know why, and we don’t yet know what this actually means,” Keenan said. “This was very surprising because type 1 diabetic patients aren’t expected to have any insulin, period.”
|
|
In addition, King said these findings did not correlate with whether patients would develop complications. The researchers said two factors may be at play in the patients’ longevity: They take good care of their diabetes management and overall health, and an endogenous protective factor is underlying.
“The Medalist Study relates to a ‘select’ few, essentially self-selected through mechanisms we don’t understand that has kept them free of complications, as well as living longer,” Fonseca said. “They are important because if we can understand these mechanisms, we could develop similar strategies that will keep all people with diabetes free of diabetes and living longer.”
Life expectancy is increasing
Survival rates are soaring and complication rates are diminishing not only in this cohort of Medalist participants, but also in others.
|
|
Recent study results indicate that the life expectancy of those diagnosed with type 1 diabetes has dramatically increased during a 30-year period, according to results of the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a long-term prospective study of childhood-onset type 1 diabetes, which was initiated in 1986. Trevor J. Orchard, MD, professor of epidemiology, medicine and pediatrics in the department of epidemiology, Graduate School of Public Health, University of Pittsburgh, presented the results in June at the 71st Scientific Sessions of the American Diabetes Association in San Diego on behalf of co-researchers Rachel Miller, MS, a doctoral student, and Aaron Secrest, PhD, a recent graduate from the department.
“There aren’t any recent data available on life expectancy in this population, and that was the major stimulus to do this analysis,” Orchard said. “The goal was to provide an up-to-date assessment of life expectancy and to compare that to the life expectancy data of those diagnosed from 1950 to 1980.”
Participants (n=933) in the EDC study, who were an average age of 28 years when entering and 44 years at completion, were diagnosed with type 1 diabetes between 1950 and 1980. Researchers compared two cohorts based on year of diabetes diagnosis: 390 people diagnosed from 1950 to 1964 and 543 diagnosed from 1965 to 1980.
The life expectancy for participants diagnosed with type 1 diabetes between 1965 and 1980 was 68.8 years — a 15-year improvement compared with those diagnosed between 1950 and 1964, according to the study results. These results were consistent in both sexes and independent of age at onset of diabetes.
Additionally, those in the 1965 to 1980 diagnosis cohort had a life expectancy approximately 4 years less than that estimated of the general US population (72.4 years), whereas the 1950 to 1964 diagnosis cohort had a life expectancy approximately 18 years less than the general US population (71.5 years).
“We weren’t surprised they were living longer and having fewer complications, but we were surprised by the magnitude of the change,” Orchard said. “We didn’t anticipate that it would be so close to that of the general population.”
|
|
The 30-year mortality of those diagnosed with type 1 diabetes from 1965 to 1980 was 16% — a significant decline from the 23% seen in those diagnosed from 1950 to 1964, according to results of the study.
“Those with type 1 diabetes are still living approximately 4 years less than those without the disease, but the survival gap is shrinking,” said Miller, who is senior data manager and analyst in the department of epidemiology, Graduate School of Public Health, University of Pittsburgh.
The researchers are currently conducting follow-up studies to try to identify protective factors such as genetics and lifestyle that protect these patients from complications and improve their survival.
A separate study published in the June 25 issue of The Lancet showed that the prevalence of diabetes has risen or perhaps remained unchanged during the past 3 decades. According to data from the study, the number of adults with diabetes reached 347 million in 2008, more than double the number in 1980.
Conducted by researchers from Imperial College London and Harvard School of Public Health, in collaboration with the World Health Organization, the study results showed that from 1980 to 2008, the number of adults with diabetes rose from 153 million to 347 million.
The researchers said 70% of this increase may be due to the growth of the population and aging; 30% is due to the increased prevalence. The proportion of adults with diabetes rose to 9.8% among men and 9.2% among women in 2008 compared with 8.3% among men and 7.5% among women 30 years prior.
“It is a possibility for many people with type 1 diabetes to live as long as those without it, if not longer,” Orchard said. “For some, having diabetes makes you follow better behaviors that may improve one’s overall health.”
Cause of increased longevity
Many of the experts who Endocrine Today interviewed said these improved survival rates and decreased rates of complications from type 1 diabetes may be attributed to advancements in technology and improved tools for monitoring and managing the disease.
|
|
The development of finger-stick home glucose monitoring revolutionized diabetes management, according to Thomas B. Repas, DO, FACP, FACE, CDE, clinical assistant professor in the department of internal medicine at University of South Dakota, Sanford School of Medicine. In addition, there have been improvements in the flexibility, ease of use and accuracy of blood glucose meters, overall, and improvements in delivery tools for insulin, in general.
“People with diabetes are now able to treat blood glucoses aggressively while minimizing risk of hypoglycemia,” Repas said.
Another reason for the increase in life expectancy may be due in part to the improved understanding of how to screen, prevent and treat diabetic complications.
Improvements in angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) play a role by controlling blood pressure and preventing diabetic nephropathy. In addition, there are better tools available for the early detection of microalbuminuria and agents to delay neuropathy and treatments for retinopathy.
“As we have gotten better at preventing, screening for and managing the complications of diabetes, not surprisingly life expectancy has also improved,” Repas told Endocrine Today. “The long-term complications typically associated with type 1 diabetes may not be inevitable, as seen among some of those in the Joslin Diabetes Center’s 50-Year Medal Program.”
Further, experts all agree that long-term success of living with type 1 diabetes is highly contingent on the patient’s ability to care for themselves, their access to health care and services needed, and how well they monitor and manage their diabetes on a continual, daily basis.
“The Medalist Study has illustrated that people with type 1 diabetes can do well in the long term,” said Howard Wolpert, MD, senior physician at the Joslin Diabetes Center. “This mirrors what we are seeing in the clinic, especially among those who tend to care for themselves better.”
|
Reprinted with permission from: Sanford Tyson Smith |
Caveats to these studies
Fonseca said it will take much time for a decrease in these rates seen in the aforementioned studies to translate into an improvement in life expectancy.
“One obvious reason is those who died recently may not have had the benefits of good control in the early phase of their disease; in contrast, those who were diagnosed more recently and who keep good control may well expect to live longer, but it will take many years to prove that,” he said.
King said most patients in the Joslin Medalist Study seem to have high health standards and are anxious to try new medical technologies that may improve their quality of life. These factors may play a role in the prolonged lives of many of these patients, along with extraordinary medical care.
“I am sure these patients are living longer, but this group could give us a lot more answers with continued research,” he said.
Although Wolpert said much of the natural history of type 1 diabetes has changed over the past several years, complications may be lower but are not inevitable.
“Considerably fewer people are ending up with retinopathy leading to visual blindness, and the rates of amputation are considerably lower than they were a few decades ago,” he said. “What is seen in these studies is generally reflected in the general population.”
Those with type 1 diabetes undergo different life phases that present unique challenges when it comes to lifelong management, according to Wolpert. For example, with adolescence, the challenges consist of distracting demands and physiological changes in the growing body. Those patients aged 18 to 30 years are a “vulnerable group” and present the challenge of dealing with life transitions (ie, graduating from school, getting a job, transition of insurance coverage, future goals, etc), which may cause them to lose focus on their individual health care.
However, those challenges seen in the elderly are mainly caused by lifelong effects of living with the disease. Hypoglycemia due to exposure to immunogenic insulin from earlier years, and CV comorbidities play a large role and remain “one of the biggest challenges in longer-standing individuals,” Wolpert said.
For clinicians who treat patients with type 1 diabetes, Orchard said to be aware of any underlying BP or liver problems.
“If there is a deficiency in care, it is probably because we focus on their glucose levels alone and we should focus on all risk factors. These patients require a broad approach to health care,” he said.
“The outlook has never been better for patients with type 1 diabetes, and given reasonable care and following major guidelines, there is every expectation that these patients can have a relatively normal lifespan and lead a normal life,” Orchard said.
On the research end, studies should continue to focus on identifying and learning about potential protective factors among those with complications vs. those without, and then, ultimately, prevent or reverse those complications, King said.
“There is a lot of potential for these patients now compared to the past,” Keenan said. “Scientists should shift their research to not only focus on risk factors, but also on protective factors in this population. Diabetes is a multifaceted disease and the research needs to be so, too.” – by Tara Grassia
For more information:
- Danaei G. Lancet. 2011;378:31-40.
- Keenan HA. Diabetes. 2010;59:2846-2853.
- Miller RG. Abstract 78-OR. Presented at: American Diabetes Association’s 71st Scientific Sessions; June 24-28, 2011; San Diego.
- Rosolowsky ET. J Am Soc Nephrol. 2011;22:545-553.
- Sun JK. Diabetes Care. 2011;34:968-974.
Disclosure: The physicians quoted in this article report no relevant financial disclosures.
Research has demonstrated that
people with type 1 diabetes are still living approximately 4 years less than
those without the disease. Do you believe this survival gap is shrinking, or
are other factors at play?
Recently published studies only confirm what we all see in daily practice.
|
|
I can now see three, four or five patients with more than 50 years of diabetes in one clinic session. Twenty-five years ago, this was unheard of. Sixty years of type 1 diabetes duration is now commonplace.
The improvement in glucose control seen in the Pittsburgh Epidemiology of Diabetes Complications study is probably minor for older patients since they did not have this advantage in their early days. Rather, the use of statins and angiotensin-converting enzyme inhibitors, in addition to overall better cardiovascular (especially blood pressure) and general medical care, are responsible for this finding.
Another not-stated problem (a “good problem”) is the public health issues from this growing population of type 1 diabetes. It is my opinion that Medicare is not ready to care for the large numbers of Medicare recipients with type 1 diabetes. In fact, in general, Medicare does not acknowledge the difference between insulin-requiring type 2 diabetes and type 1 diabetes. Medicare only differentiates type 1 from type 2 for patients using insulin pumps. For instance, we now have to go through more paperwork to get enough test strips for those with type 1 diabetes. When considering the management of type 1 diabetes in nursing homes and rehab facilities, how do we do with insulin therapy in these institutions in type 2 diabetes? In general, not well. Moving this to a population of increasing patients with type 1 diabetes is a scary thought. I only hope someone else thinks about this.
Irl B. Hirsch, MD, is professor of medicine at University of Washington Medical Center-Roosevelt.
Disclosure: Dr. Hirsch does consulting for Roche, Johnson & Johnson and Abbott.
Survival gap may not be shrinking.
|
|
There has been a tremendous improvement in our recognition of the importance of improving glucose control in type 1 diabetes and in our ability to help those living with type 1 diabetes achieve good control with self-monitoring of blood glucose and with multiple-dose insulin therapy. We also have increasing recognition of the importance of blood pressure treatment, particularly using angiotensin-directed therapy; of cardiovascular risk reduction with statins and antiplatelet therapy; and of a myriad of other approaches, which, taken together, have greatly improved the medical management of this complex condition.
That said, I am not sure we really know if the survival gap is shrinking. This is difficult to study, and some articles suggest somewhat differently. For example, Rosolowsky and colleagues published a study in the Journal of the American Society of Nephrology last year looking at 423 patients with type 1 diabetes who developed albuminuria (J Am Soc Nephrol. 2011). The researchers found that during follow-up from 1991 to 2008, end-stage renal disease (ESRD) developed in 172 patients (incidence rate=5.8/100 person-years) and 29 died without ESRD (mortality rate=1/100 person-years). The majority of outcomes occurred when patients were aged 36 to 52 years and had durations of diabetes of 21 to 37 years. During 15 years of follow-up, the use of renoprotective treatment increased from 56% to 82% and blood pressure and lipid levels improved significantly; however, risks for ESRD and pre-ESRD death did not change. They concluded that “despite the widespread adoption of renoprotective treatment, patients with type 1 diabetes and macroalbuminuria remain at high risk for ESRD, suggesting that more effective therapies are desperately needed.”
Zachary T. Bloomgarden, MD, is clinical professor in the department of medicine at Mount Sinai School of Medicine. He is also an Endocrine Today Editorial Board member.
Disclosure: Dr. Bloomgarden reports no relevant financial disclosures.