The study, conducted by the Joslin Diabetes Center on people who have lived with type 1 diabetes for more than 50 years, presents a strong case for the existence of a Some people with diabetes possess yet-unidentified factors that reduce the risk for and even prevent them from developing diabetes-related complications, despite living with the disease for decades, a study published in the April issue of Diabetes Care has found.

The study, conducted by the Joslin Diabetes Center on people who have lived with type 1 diabetes for more than 50 years, presents a strong case for the existence of a protective mechanism in some individuals that allows them to live relatively free of the problems typically associated with long-term duration of diabetes. These mechanisms, the study found, may be different for microvascular (such as kidney, nerve and eye disease) than macrovascular complications (such as heart disease).

“If we can identify what constitutes this protective mechanism, we have the potential to induce such protections in others living with diabetes,” said lead researcher George King, Chief Scientific Officer of the Joslin Diabetes Center and Professor of Medicine at Harvard Medical School. “That’s huge.”

Researchers looked at 351 U.S. residents known as the “Medalist” cohort and found that a subgroup of people who had lived with type 1 diabetes for more than 50 years remained free from such complications as proliferative diabetic retinopathy (PDR), a serious eye disease that can lead to blindness (42.6 percent of them); nephropathy, or kidney damage (86.9 percent of them); neuropathy, or nerve damage (39.4 percent); and cardiovascular disease (51.5 percent). Of those who did not develop PDR, 96 percent with no retinopathy progression in the first 17 years of their disease never experienced a worsening of symptoms, meaning that they likely possessed some type of protection specific to this complication.

Surprisingly, glycemic control was not a factor in providing this protective mechanism.

“That doesn’t mean of course that glycemic control doesn’t help to prevent complications. Numerous other studies have shown that it unquestionably does. In this case, it means only that there is a separate, protective mechanism in play that is not related to glycemic control that also helps to protect against diabetes-related problems. We are still working on identifying just what that is,” King said.

It’s important to note that most of the people in this study developed type 1 diabetes before strict glycemic control was even possible or used as the standard of medical care, the researchers write. The people in this study likely lived for several decades, therefore, without maintaining strict control.

The study also found that those with high plasma carboxyethyl-lysine and pentosidine, or advanced glycation end products (AGEs), were 7.2 times more likely to have some kind of complication than those who had low levels of this combination of AGEs. AGEs are compounds that develop in the body after long exposure to high glucose levels and have generally been regarded as playing a role in diabetes-related complications. However, those with other types of AGE molecules exhibited protective features. Thus, this study suggests that not all AGEs are alike in their actions and raises the exciting possibility that some AGEs may be markers for protection against one or more diabetic complications.

In an accompanying editorial, Dr. Aaron Vinik, Director, Eastern Virginia Medical School Diabetes Research Center, writes that “the accumulation of AGEs may be one of the important factors in metabolic memory,” a phenomenon in which an initial period of good glycemic, lipid and blood pressure control results in a prolonged period of health benefits that last beyond the period of control.

However, while it is clear that for some there is a protective mechanism at play, it’s unclear whether metabolic memory is playing a role because glycemic control was not considered important until 1993, long after the study began.

What’s most interesting, Vinik points out, is that sRAGE (the circulating soluble receptor for AGEs) is deficient in those who have the most severe complications, and is present at high levels in those with the most longevity. “If this is the missing link, it is huge for the possible emergence of a new biomarker and the potential for therapy that might increase circulating sRAGE or sRAGE itself,” he said.

Source:
American Diabetes Association in some individuals that allows them to live relatively free of the problems typically associated with long-term duration of diabetes. These mechanisms, the study found, may be different for microvascular (such as kidney, nerve and eye disease) than macrovascular complications (such as heart disease).

“If we can identify what constitutes this protective mechanism, we have the potential to induce such protections in others living with diabetes,” said lead researcher George King, Chief Scientific Officer of the Joslin Diabetes Center and Professor of Medicine at Harvard Medical School. “That’s huge.”

Researchers looked at 351 U.S. residents known as the “Medalist” cohort and found that a subgroup of people who had lived with type 1 diabetes for more than 50 years remained free from such complications as proliferative diabetic retinopathy (PDR), a serious eye disease that can lead to blindness (42.6 percent of them); nephropathy, or kidney damage (86.9 percent of them); neuropathy, or nerve damage (39.4 percent); and cardiovascular disease (51.5 percent). Of those who did not develop PDR, 96 percent with no retinopathy progression in the first 17 years of their disease never experienced a worsening of symptoms, meaning that they likely possessed some type of protection specific to this complication.

Surprisingly, glycemic control was not a factor in providing this protective mechanism.

“That doesn’t mean of course that glycemic control doesn’t help to prevent complications. Numerous other studies have shown that it unquestionably does. In this case, it means only that there is a separate, protective mechanism in play that is not related to glycemic control that also helps to protect against diabetes-related problems. We are still working on identifying just what that is,” King said.

It’s important to note that most of the people in this study developed type 1 diabetes before strict glycemic control was even possible or used as the standard of medical care, the researchers write. The people in this study likely lived for several decades, therefore, without maintaining strict control.

The study also found that those with high plasma carboxyethyl-lysine and pentosidine, or advanced glycation end products (AGEs), were 7.2 times more likely to have some kind of complication than those who had low levels of this combination of AGEs. AGEs are compounds that develop in the body after long exposure to high glucose levels and have generally been regarded as playing a role in diabetes-related complications. However, those with other types of AGE molecules exhibited protective features. Thus, this study suggests that not all AGEs are alike in their actions and raises the exciting possibility that some AGEs may be markers for protection against one or more diabetic complications.

In an accompanying editorial, Dr. Aaron Vinik, Director, Eastern Virginia Medical School Diabetes Research Center, writes that “the accumulation of AGEs may be one of the important factors in metabolic memory,” a phenomenon in which an initial period of good glycemic, lipid and blood pressure control results in a prolonged period of health benefits that last beyond the period of control.

However, while it is clear that for some there is a protective mechanism at play, it’s unclear whether metabolic memory is playing a role because glycemic control was not considered important until 1993, long after the study began.

What’s most interesting, Vinik points out, is that sRAGE (the circulating soluble receptor for AGEs) is deficient in those who have the most severe complications, and is present at high levels in those with the most longevity. “If this is the missing link, it is huge for the possible emergence of a new biomarker and the potential for therapy that might increase circulating sRAGE or sRAGE itself,” he said.

Source:
American Diabetes Association
Diabetes From Medical News Today

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Treating type 2 diabetes patients with a cholesterol-lowering drug called fenofibrate cuts the risk of a first diabetes-related limb amputation by 36%, according to a new study published this week in The Lancet.

“I would call that a substantial reduction in risk,” says James Best, MD, professor of medicine at the University of Melbourne in Australia and a co-author of the study.

The reduction in limb amputation risk is probably not directly related to the cholesterol-lowering effects of the drug, he tells WebMD, but rather to some of the other effects, such as improving the functioning of small blood vessels.

Amputation & Type 2 Diabetes: Background
People with diabetes are more likely than people without the condition to have a foot or leg amputation, according to the American Diabetes Association.

That’s because people with diabetes are likely to have peripheral artery disease, reducing blood flow to the lower legs and feet, and to have nerve disease called diabetic neuropathy, boosting their risk of getting ulcers and infections that can result in a need for amputation.

Fenofibrate & Amputation Risk: Study Details
Best and his colleagues looked at 9,795 patients in Australia, New Zealand, and Finland with type 2 diabetes, aged 50 to 75, who had taken part in the FIELD study (Fenofibrate Intervention and Event Lowering in Diabetes). The patients were assigned to get either fenofibrate at a dose of 200 milligrams a day or placebo for five years.

FIELD is a clinical trial that previously analyzed the drug’s effect on heart disease death and nonfatal heart attack and showed it did not have a significant effect on those outcomes, but it did help with other problems, such as reducing risk of diabetic retinopathy, a diabetes-related eye problem.

Among the funding sources were Laboratoires Fournier SA, now part of Solvay Pharmaceuticals, which markets fenofibrate, and the National Health and Medical Research Council of Australia.

The researchers got information on amputation and whether they were minor, defined as below the ankle, or major, defined as above the ankle.

They also assessed whether large blood vessel disease or small blood vessel disease was found in the amputated limb.

Fenofibrate & Amputation Risk: Study Results
Over the course of the study, 115 patients had amputations of the lower limbs related to their diabetes. The researchers also found:

• Overall, the risk of first amputation was 36% lower for all patients given fenofibrate compared to those given placebo. Although 70 of those on placebo had amputation, 45 of those on the drug did.
• The risk of minor amputation in patients who did not have large vessel disease was even lower, 47%, for those who took the drug compared to those who got the placebo.
• Risks didn’t differ significantly between groups for major amputations.
• Height predicted risk of amputation. For every 4-inch increase in height, there was a 1.6-times boost in risk. (Best notes that this is not a new finding.)

Fenofibrate & Amputation: Take-Home Message
Best puts the study findings in perspective this way. “What we have to keep in mind is that amputation is not as common as heart attack [among those with type 2 diabetes].” Although the effect of the drug on amputation risk was significant, he says, “This doesn’t mean everyone with diabetes should start taking fenofibrate to prevent amputation. The therapy should be targeted to those at high risk for amputation.”

That includes those who have nerve damage in their feet from their diabetes, who have an ulcer on their foot, or who have had a previous amputation, Best says.

Fenofibrate & Amputation: Second Opinions
“It’s an interesting study that may change some people’s approach [to diabetes treatment],” says Richard Jackson, MD, senior physician at Joslin Diabetes Center and assistant professor of medicine at Harvard Medical School, Boston, who occasionally does prescribe the drug, typically to bring down high triglyceride levels.

But he adds a caveat. “The medication could be helpful, but it’s only one study.” More studies are needed, he says.

Another expert who reviewed the study findings for WebMD agrees. “We need to do a larger trial to understand its mechanism and confirm the findings,” says Richard M. Bergenstal, MD, president-elect of the American Diabetes Association and executive director of the International Diabetes Center at Park Nicollet Health Services in Minneapolis.

Meanwhile, he says, the study results point to the importance of preventive care. The researchers found that the strongest predictors of a first amputation included a history of previous amputation or diabetic skin ulcers, nerve problem, or a history of peripheral vascular disease. “Anybody who has neuropathy and a history of amputation or ulcer, we need to follow them very closely because they are at higher risk.”

WebMD Health News – By Kathleen Doheny

Living with Type II Diabetes?

Diabetes prevalence has doubled in the past decade, and the increases in diabetes-related eye disease poses a new challenge to eye specialists, according to an editorial in the March issue of Archives of Ophthalmology, one of the Journal of American Medical Association (JAMA)/Archives journals.

Two editorials and a research article in the issue focus on ophthalmologic implications of metabolic diseases and are being published in conjunction with a JAMA theme issue of diabetes, obesity, and their comorbidities.

“By 2050, the number of Americans with diabetic retinopathy [affecting blood vessels in the retina] is projected to triple from 5.5 million to 16 million, and the number of those with vision-threatening retinopathy will increase from 1.2 million to 3.4 million,” wrote Thomas W. Gardner, MD, MS, and Robert A. Gabbay, MD, PhD, of Penn State College of Medicine, Hershey, PA, in the first editorial. “The number of cataracts will increase by 235% and glaucoma among elderly Hispanic individuals with diabetes will increase 12-fold.”

According to Dr. Gardner and Dr. Gabby, effectively treating these conditions requires that ophthalmologists go beyond surgically treating late-stage eye disease and work with other clinicians to help patients control their diabetes before eye complications worsen.

“Ophthalmologists have a unique opportunity to influence patient behavior because vision loss is one of the most feared complications of diabetes. Helping patients make the connection between their eye disease and the ABCs of diabetes (A1C, blood pressure, and cholesterol) can motivate them to improve their health,” wrote the authors.

Ophthalmology Times

Living with Type II Diabetes?