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Diabetes Core Update
Diabetes Core Update July 2016
00:21:22
Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes...
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Welcome to the American Diabetes Association Diabetes Core Update, where we will regularly keep you up to date on the latest clinically relevant articles from the American Diabetes Association's four science and medical journals, Diabetes, Diabetes Care, Clinical Diabetes and Diabetes Spectrum. Joining us for this program are Dr. Neal Skolnick, who is a professor of Family Medicine at Temple University School of Medicine and Associate Director in the Family Medicine Residency Program at Abington Memorial Hospital. Welcome, Dr. Skolmik.
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Thank you. It's a pleasure to be here.
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And Dr. John Russell, who is a Professor of Family Medicine at Temple University School of Medicine and Director in the Family Medicine Residency Program at Abington Memorial Hospital.
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Thank you. I'm looking forward to going over this week's articles.
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And now for the articles.
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We have an excellent issue this month, beginning with a study on roux en Y vs laparoscopic gastric banding and diabetes remission rates from Diabetes Care. Next, a study from Diabetes Care on a new glucagon receptor antagonist, followed by a study from Diabetes on the artificial pancreas in children, then a discussion of diabetes and years of disability published in Diabetes Care. Then a really interesting study on brain response to glucose ingestion studied by functional MRI in adolescents and finally a study from Diabetes Care on the persistent effects of intensive glycemic control on retinopathy in type 2 patients with diabetes in the Action to Control Cardiovascular Risk and Diabetes. A querred follow up study. Our first article today is titled Type 2 diabetes remission rates following laparoscopic Gastric Bypass and Gastric Banding Results of a Longitudinal Assessment of Bariatric Surgery published in Diabetes Care. The goals of this study were to determine baseline and post bariatric surgical characteristics associated with type 2 diabetes remission after controlling for differences in weight loss between patients receiving a Roux en Y gastric bypass and and those receiving laparoscopic gastric banding. This was an observational cohort of obese participants studied using a mixed models effect to examine the association of bariatric surgery type and diabetes remission rates for up to three years. A total of 466 patients with diabetes underwent Roux en Y procedures and 140 underwent a laparoscopic gastric banding after three years. Two thirds of patients with Roux en Y procedures and one third of patients with laparoscopic gastric banding were in diabetes remission. Baseline factors associated with diabetes remission included a lower weight for laparoscopic gastric banding and greater fasting C peptide levels as well as lower leptin to fat mass ratios for Roux en Y procedures and a lower hemoglobin A1c without the need for insulin for both procedures. Following both procedures, greater post surgical weight loss was associated with remission. Even after controlling for differences in the amount of weight loss, relative diabetes remission rates remain nearly twofold higher following Roux En Y than laparoscopic gastric banding.
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JOHN so we don't have to go far in our practices to find patients who would qualify for bariatric procedure with diabetes. And certainly we have tons of patients. When you look at really the remarkable ability to cure diabetes through a procedure, that's pretty remarkable. And if it was some other type of surgical procedure, I think more and more people would be going towards it. But somehow people feel having some kind of gastric bariatric procedure is a little bit of a loss and changes things forever for patients, which is certainly true. Now, as we're on the advent of seeing even more bariatric procedures come about, we need to be able to tell our patients which one to have done. And I think the interesting thing in this study is not that people who lost a lot of weight were less likely to be diabetics. And certainly that's intuitively obvious. There was a difference in the procedures and it wasn't purely related to how much weight loss. So certainly in this particular study we found that having a Roux en Y procedure translated to a larger percentage of people being cured of their diabetes than a band procedure with the same amount of weight loss. So I think as we're talking with our patients going for a bariatric procedure mainly to try to get off their diabetes medicines, we have a little bit more of informed knowledge to share with them. Our next article is from Diabetes Care and this is a randomized double blind placebo controlled phase 2 trial of the glucagon receptor antagonist LY24 09021 in patients with type 2 diabetes. LY24 09021, which I will now refer to as GRA, is a potent selective smallmolel glucagon receptor antagonist that lowers glucose and it was evaluated for efficacy and safety in patients with type 2 diabetes. This randomized double blind placebo controlled trial looked at efficacy and safety and the efficacy was measured through A1C and safety through elevation of serum transaminases. It's a once daily oral administration of this GRA. Patients had to have an A1C between 6.5 and 10. They were either naive to anti diabetic medications or receiving metformin treatment. They were then randomized to receive either 10, 30 or 60 milligrams of this GRA or placebo for 12 weeks. At the end of 12 weeks it was found that A1C levels were significantly different from placebo. Over the 12 week period there was a decrease of 0.83 in the 10 milligrams, 0.65 in the 30 milligrams and 0.66 in the 60 milligrams dose compared to 0.11 in the placebo. The increases in the level of serum transaminases, fasting glucose and total fasting glucagon like one prepatite were observed. All the levels returned to baseline after drug washout. The mean increases in alt was about 10 units per liter. The incidence of hypoglycemia overall with this drug was minimal and there were no differences between placebo and the GRA treatment groups in adverse event frequency.
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John I think it's very exciting to see work being done on a glucagon receptor antagonist. In many ways glucagon is like the quiet cousin of insulin that is an important part of the family but no one is really familiar with. Remember, the alpha cells in the pancreas make glucagon and glucagon leads to gluconeogenesis, the production of glucose by the liver, increasing glucose levels in the serum, essentially the opposite of what insulin does. So it really fits in as an important part of the ominous octet and an area where there hasn't to date been productive drugs that work on that mechanism. If we look at the way we evaluate medicines, its effect on a 1C effect on hypoglycemia and side effects. This really seems like an exciting potential area of a class of medicines. It has good effect on a 1C. It doesn't have a lot of hypoglycemia. The question is what will emerge in larger trials looking at liver side effects because some patients did have elevated transaminases. But it certainly is an exciting area of study and certainly an area where we'll stay tuned to see what other things develop. Our next article is titled Randomized Summer Camp Crossover Trial in five to nine year old Children. The outpatient wearable artificial pancreas is feasible and safe. In this study, 35 to 9 year old children with type 1 diabetes completed an outpatient open label randomized crossover trial using three days with an artificial pancreas, comparing that to three days of patient managed sensor augmented pump. Overnight time in hypoglycemia was reduced with the artificial pancreas and with no instances of overnight hypoglycemia versus 2.2% of time with the sensor augmented pump. There was no significant difference in time in target for glucose ranges overall, that is daytime and nighttime. The artificial pancreas had a threefold reduction in time in hypoglycemia at the cost of decreased time in target 57% versus 63% and an increased mean glucose 169 milligrams per deciliter versus 147 with the sensor augmented pump.
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Shawn So I certainly think we are at the advent of some very exciting times for type one diabetics. And certainly with insulin pumps we've really seen a kind of change from where we were, you know, 15, 20 years ago with regard to our patients with type 1 diabetes. And I think this is certainly where the world is going and certainly when we worry about taking care of folks on insulin, hypoglycemia is a huge issue. And certainly this product seems superior to the insulin pump technology, especially overnight. I think as parents kind of people are worried that something's going to happen to their kid when they're sleeping and they're not necessarily going to know that. So I think that this will, if this progresses, this would certainly be something that would kind of ease the minds of parents that it's not the sensing is not going to drop sugars down real low in the middle of the night. It didn't overall seem to be as effective with regard to glucose lowering. And I think that that's often kind of the two ends of the swords that we're kind of following is kind of trading off tighter control for hypoglycemia. This is early on in the advent and certainly products are rolling out with regard to this. So I think we're going to be seeing kind of more and more of this. But it's very exciting to imagine what the technology is going to be like two or three years from now when they actually kind of figure out all the subtleties that goes along with any new technology. Our next article is from Diabetes Care and it looks at disability free years lost among adults over the age of 50 with and without diabetes. So this study looked at over 20,000 adults aged 50 years and older who were followed from 1998 to 2012 in the health and Retirement Study. This was a prospective biannual survey of national representative sample of adults. Diabetes and disability status defined by mobility loss, difficulty with instrumental mental activities of daily living, IADL or difficulty with activities of daily living ADL were self reported. The study looked at the lifetime disability related outcomes between people who did and did not have diabetes. What they found is from age 50, adults with diabetes died 4.6 years earlier, developed disability six to seven years earlier, and it spent one to two more years in a disabled state than adults without diabetes. With increasing baseline age, diabetes was associated with significant reductions in number and total years of disability free life. Men with diabetes spent about twice as much of the remaining years disabled 20 to 24% of the remaining life as men without diabetes who spent about 12 to 16% of their remaining life. There were similar associations between diabetes status and disability free and disobeyed years observed in young women.
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Neil John this is really interesting. Typically we look at hard outcomes being both micro and macrovascular disease. When we assess the outcomes of treatment for diabetes, we also look at mortality. This study takes a different tact and says how does diabetes affect the life of people who have it? And it shows that people with diabetes have an incredibly higher rate of disability after middle age. People with diabetes, when compared with the general population, have disability earlier and for a much longer period of time from age 50 onward, affecting their life in a lot of ways. The question that it then leads to is what can we do to offset this large amount of time with disability? And there probably are two different approaches, neither of which have been specifically looked at with regard to disability. One is obviously better risk factor control. It's not a large leap in thought to think that if we can better control both micro and macrovascular consequences of diabetes by careful control of hypertension, high cholesterol and blood glucose levels, that will decrease the amount of time with disability. The other approach is a behavioral approach. There is some data from the Look Ahead trial which used a lifestyle management approach in patients with diabetes and showed a actual 50% decrease in the amount of disability in patients in the intensive lifestyle group. That intensive lifestyle modification, meaning exercise and diet, can also decrease disability. It's an important area to focus on and will become increasingly an important area to study with regard to out. Our next study from the journal Diabetes is titled Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents. In this study, the authors utilized functional magnetic resonance imaging to assess brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose in obese and lean adolescents. Marked differences were observed in response to drinking glucose. Obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function, the prefrontal cortex, and increased perfusion in the homeostatic appetite regions of the brain, the hypothalamus. Conversely, in response to drinking glucose, lean adolescents demonstrated increased prefrontal cortex brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum glaun and increased circulating insulin levels following glucose ingestion.
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JOHN so I find this a very fascinating article on so many different levels. One is, if you think about it, the, the adolescent young adult brain is still about developing until we're 25. This neuroplasticity that happens, and it's very interesting in how we treat our young people is the age of majority to vote is 18. To have a drink of alcohol in most states is going to be 21, to get a rental car is 25. So our brain is still developing for 25. So I would be very interested if they looked at the same in lean and obese adults to see is this a phenomenon that we're just seeing in children or is this something that in a developed brain is still happening? Because it really might impact how we, you know, allow soda to be introduced to kind of younger people who might kind of develop this kind of lifelong craving to it as their brain is still developing. If you kind of held off to have soda till you were later in life. Soda is also a very interesting thing. So spring of 2016, soda consumption in the United States reached its all time low over the last 30 years. So we're seeing people drinking less and less sodas, even though that the volumes of soda that can be consumed at any one time is getting bigger and bigger. And we're also seeing soda consumption to be a public health thing. So certainly the national news had Mayor Bloomberg kind of limiting sodas. Neil and I live outside of Philadelphia, which is just instituting a soda tax in the city in hope of, you know, X number of cents per ounce for soda and sugared beverage consumption to see if that can help make our folks healthier. So I think that this is a very interesting thing, but perhaps if this is something that is very, very dangerous to young people, we're not going to be as interested in allowing our kids to start soda at an earlier age. We're reaching a point where soda consumption is topping out milk consumption in a lot of young. I think we really need to think as parents, as clinicians is our discussion of sugar sweetened beverages. Our last article is from Diabetes Care and it looked at persistent effects of intensive glycemic control on retinopathy and type 2 diabetes in the Action to Control Cardiovascular risk in diabetes. The ACCORD Follow On Study so the ACCORD study, which went on from 2003 to 2009, randomized participants with type 2 diabetes to either intensive or standard treatment. The intensive group had a glycemic A1C level of less than 6 versus the standard treatment had 7 to 7.9. They also had an arm for blood pressure control 120 versus 140 and dyslipidemia, either adding fenofibrate to simvastatin or placebo to Simvastatin. In the ACCORD eye study, participants who had Baseline and Year 4 eye exams with fundus photographs were re examined four years following the CORD trial closeout. The results found that diabetic retinopathy progressed in 5.8% who had intensive glycemic control versus 12.7 with the standard which was an adjusted odds ratio of 0.42 in the blood pressure arms. 7.5% of the folks in the intensive arm versus 6% in the standard arm developed retinopathy or an odds ratio 1.21 and the phenofibrate arm was 11.8 versus 10.2% in the placebo with an adjusted odds ratio of 1.13.
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Neil John this study demonstrates what has become an incredibly important aspect of diabetes to pay attention to, which is called the legacy effect and that describes the fact that early treatment, early intensive treatment has an effect on both macro and and microvascular outcomes for years to come even after the groups are no longer that are studied are no longer separated with regard to effect. We saw the follow up study for dcct in type 1 diabetics reported in 2005 showing a legacy effect for macrovascular disease. We saw a similar legacy effect for UK PDS reported in the New England Journal in 2008 and essentially what these trials showed was that for macrovascular disease, even when the groups that were studied randomized and separated to intensive versus less intensive treatment, then after the study was done received the same care for years later there was still differences in outcome. We discussed this a bit two months ago on our podcast with a 30 year follow up for retinopathy of the DCC trial. And now we see in the ACCORD trial that intensive treatment of blood glucose has an effect on microvascular disease even years after the groups that were randomized to different care have received the same care. What is the take home point for us as clinicians? The take home point is that early intensive treatment has an important effect for years to come, so it really is worth spending the time talking with our patients, seeing them back, doing what we can to have as close to target or to target glucose control as possible to affect outcomes, both macro and microvascular outcomes, for years to come. For more information and links to the articles that we discussed in this issue, just go to www.diabetesjournals.org. until next week, keep listening and keep learning.