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Diabetes Core Update
Diabetes Core Update 9/10/2012
00:18:04
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 Diabet
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- [00:04]
A
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 Skolnik, who is a professor of Family Medicine at Temple University School of Medicine and and associate Director in the Family Medicine Residency Program at Abington Memorial Hospital. Welcome, Dr. Skolnick.
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B
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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A
And now for the articles.
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B
We've got an excellent issue this month. First article that we're going to review is from Diabetes Care on The association of B12 deficiency and metformin therapy. The next article, also from Diabetes Care, is on the association between vitamin D levels and progression to diabetes in patients who are at high risk for diabetes. That is then followed by an article from Diabetes Spectrum and as the Kidney as a Target for treatment in patients with type 2 diabetes, followed by an article from Diabetes Care on the benefits and safety of phenofibrate therapy in patients with type 2 diabetes and renal impairment, then an article on isoflavones from Diabetes Care, and lastly an article reviewing the declining rates of hospitalization for non traumatic lower extremity amputation in patients with diabetes from 1988 to 2008 from Diabetes Care.
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C
Our first article in this edition is from the February 2012 edition of Diabetes Care. This study looked at the association of vitamin B12 deficiency with metformin therapy and vitamin B12 supplements. This study from the NHANES trial was an analysis of data of US adults more than 50 years of age with or without diabetes. There were 1,600 folks in the with diabetes and 6,800 in the without diabetes. Type 2 diabetes was defined as clinical diagnosis occurring after the age of 30 without initiation of insulin therapy within one year. Those with diabetes were classified according to their current metformin use. Biochemical B12 deficiency was defined as having a B12 concentration of less than 148 and borderline deficiency was defined as greater than 148 to less than 221. A biochemical B12 deficiency was present in 5.8% of those patients with diabetes using metformin compared to 2.4 of those not using metformin and 3.3% of those without diabetes. Among those with diabetes, the metformin use was associated with biochemical B12 deficiency with an adjusted odds ratio of 2.92. Consumption of any supplement containing B12 was not associated with a reduction in the prevalence of biochemical B12 deficiency among those with diabetes, whereas consumption of any supplement containing B12 was associated with a 2/3 reduction of among those without diabetes.
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B
Neil John, this is interesting. We know that both diabetes as well as B12 deficiency increase with age. With B12 deficiency you have only about a 2% prevalence when you look at 50 year olds. That goes up to about 5% when you look at people over 65 and I believe up to 10 or 15% in patients over 80. Add to that this current data that the prevalence of B12 deficiency is even higher in patients on metformin and we know that a lot of our older patients are on metformin as well. The risk for B12 deficiency goes up enormously and with that potentially the consequences of unrecognized B12 deficiency, particularly concerning there are the neurologic sequelae as one of the important potentially reversible causes of dementia, another common condition in the elderly. The other thing that this study shows us is that simply taking B12 doesn't seem to ameliorate the increase in B12 deficiency. So more to come on this issue. It's not clear whether we should be screening patients with diabetes who are on metformin for B12 deficiency, but certainly our attention for it should be heightened. We we may consider screening. It wouldn't surprise me if in the future we see recommendations about screening and clearly it's a fruitful area for more research. Our next article that we're going to review is also from diabetes care on plasma 25 hydroxy, vitamin D and progression to diabetes in patients at risk for diabetes. This study looked at the cohort of patients in the Diabetes Prevention Program, a trial that included three 3,000 individuals with prediabetes who were randomized to placebo intensive lifestyle modification or metformin. This particular trial focused on the thousand patients in the placebo group and the thousand patients in the intensive lifestyle group and looked at baseline plasma vitamin D levels and their relationship to the development of diabetes over time. The results showed that there was a 28% decrease in the development of diabetes in the highest tertile of vitamin D group compared to the lowest tertile.
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C
John well, vitamin D is certainly one of those things that seems to be the cause of and the solution to every problem that everyone has. And I always think vitamin D is A bit of a misnomer. And it really is not a vitamin in the truest sense of the word. It's a hormone. We can't make vitamin C, we can't make other vitamins, but certainly we can make our own vitamin D if we get enough sunshine. I think this is of interest, sake only. I'm not sure that suddenly I'm going to try to figure out who's going to go on to have diabetes in my patients who already have elevated blood sugar and by checking their vitamin D level and say, well, you're going to have diabetes because you have an elevated blood sugar already and you have a low vitamin D level. So I'm not really sure of how helpful this is going to be. I also think vitamin D, which we can synthesize if we're outside more, perhaps the people who are outside more and walking around more and getting a little more sunshine are going to have higher vitamin D levels. And because they're outside getting a little fresh air and exercise and sunshine, maybe they're less likely to progress to have diabetes. Our next article is from Diabetes Spectrum 2012, volume 25, number one. And this talks about the kidney as a treatment target for type 2 diabetes. So certainly we have an array of oral medicines for diabetes, but researchers are always looking for new ways to skin a cat, so to speak. So overall, our kidney reabsorbs 99% of filtered glucose and returns it to the circulation. Glucose reabsorption by the kidney is mediated by sodium glucose co transporters, the SGLTS, mainly SGLT2. SGLT2 inhibition is a potential site of treatment for diabetes by inhibiting how much reabsorption of glucose happens at the kidneys. So this particular study they looked at some new medicines that are in development that are SGLT2 inhibitors and how well they're going to work. And overall, looking at some various medicines that are in the pipelines, about five different SGLT2 inhibitors are potentially in the pipeline. For coming out, the medicines were fairly well tolerated. They they do not cause hypoglycemia. To the same array that we would with the sulfonylureas. They seem to work a 1C reduction, fairly comparable to medicines like glipizide. You get about a half point, a 1C reduction. They seem to work well with metformin side effects wise, the same array of vague side effects that one would get with a placebo. The only thing that the researchers found different in some of these trials is there was an increased rate of urinary and genital infections And I don't know if that might be secondary to having more sugar in our urine. Is that going to attract UTIs and things like that. But they felt that the infections were no more serious than ordinary infections and certainly responded to treatment. So, you know, something that's not ready for prime time, but potentially something that's of interest. Interest.
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B
Neal John, we've become used to thinking of the kidney as an organ that can be hurt as a consequence of uncontrolled diabetes. And we've over the last couple of years, just now become aware of it as a target of therapy for treating diabetes. SGLT2 is responsible for 90% of glucose reabsorption. And as you went over, increasing the amount of glucose spilling into the urine decreases glucose reabsorption. There's also some gluconeogenesis that goes on from the kidneys, so it becomes an important target of therapy. Recently, one of the new potential medicines in this area did not receive FDA approval. I believe that was partly because of the increased incidence of urine infections. It's certainly something that we'll be hearing more about and certainly helpful to have been made aware of. Our next article is from the February edition of Diabetes Care on the benefits and safety of long term phenofibrote therapy in people with type 2 diabetes and renal impairment. The field study the field study was a double blind randomized trial of fenofibrate, 200mg daily in over 8,000 patients looking at cardiovascular outcomes. This particular article focuses on the group that has GFRs between 30 and 60mls per minute. Results of the trial showed that fenofibrate reduced total cardiovascular events compared to placebo with a hazard ratio of 0.89. John?
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C
Yeah, I'm not so sure that this trial tells us a ton. I think if you really look at the standard of care is every diabetic, unless there's really strong reason not to, should be on a statin. And the patients in this trial were not on statins. And I don't think any of us would put someone on a fibrate in deference of having someone on a statin. There is a little bit of LDL reduction from fenofibrate and from other fibrates, but not a ton. So I think you might see a little bit of mortality. I think the one thing you could take away from this trial is we're always a little cautious in using the fibrates in someone who's got some kidney disease. And really looking at adjusting doses, they really found that there was not a negative impact on people who had poor kidney function to a point that you really had to decrease the dose of the fenofibrate, as we would expect here in the United States. So I think we should probably take a little bit of solace that we don't have to adjust the dose. But remember, as people's kidney function gets worse, oftentimes their triglycerides will go up. There was a trial last year, the Accord trial, looking at using fibrates in patients with diabetes and actually did not find that putting every patient on a fibrate made a difference. The only ones it really did make a difference on were the people whose triglycerides were already elevated. So that would be the population we'd use with this medicine. But I think we really want to have all our patients on a statin first. Our next article is from the February 2012 edition of Diabetes Care and this study looked at dietary flavonoids and insulin sensitivity and lipoprotein status in postmenopausal medicated women with type 2 diabetes. This one year double blind randomized control trial looked at 118 postmenopausal women with diabetes and randomized them to a diet that had supplemental flavonoids as a flavonoid. Enriched chocolate and 100 milligrams of isoflavones were matched. Placebo for a year. 93 women completed the trial and adherence was high, over 90% compared with the placebo group. The Compline flavonoid intervention resulted in a significant reduction in estimated peripheral insulin resistance and improvement in insulin sensitivity as a result of increased decrease in insulin levels. Significant reductions in total cholesterol to HDL ratio and ldl. LDL cholesterol was also observed.
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B
Neil John, this is an area that I've been following for years and love back in 2003 there was an article in JAMA on improved blood pressure in elderly who are eating chocolate, essentially cocoa. In 2006 in hypertension there was an article showing that cocoa improved blood pressure and insulin resistance as well as endothelial function. And then in Archives of Internal Medicine in 2006, they actually looked at a cohort trial, a cohort of over 470 older men, and they looked at the relationship between chocolate intake and blood pressure and cardiovascular mortality. And wouldn't you know it, those older men who ate more chocolate had lower blood pressures and lower age adjusted cardiovascular mortality. The trial that you just went over gives us even more excuse to have chocolate and seems to in a puzzling way speak to what may be some of the benefits of flavonoids, and the most common place that they appear is chocolate. On a more serious note, though, the important take home point is that while there may be beneficial effects, there are are increased calories that come along with that. So it's something that's actually hard to recommend to people as a therapeutic alternative, as likable as it may seem. Our next article also comes from the February edition of Diabetes Care on the declining rates of hospitalization for non traumatic lower extremity amputation in a diabetic population aged 40 years and older in the United States from 1988 to 2008. The authors here calculated the rate of non traumatic lower extremity amputation hospitalization by diabetes status. What they found was that the age adjusted rates per thousand persons among those with diabetes age greater than 40 decreased from 11 in 1996 to 3.9 in 2008, while the rates among persons who did not have diagnosis changed virtually not at all.
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John so like many other things in the United States, I think if you look back on things we were doing 20 years ago compared to things we're doing now, I think for a lot of things that have to do with circulation, we're doing a much better job. So diabetic amputations used to be about 1 in 100 adult diabetics. Now it's about 1 in 300. But certainly 20 years ago, you know, statins were fairly new medicines. We really don't have better medicines with regard to peripheral vascular disease per se, but I think we have better techniques. We weren't doing angioplasties way back when. We were only really doing fem phen bypasses. So I think we have more options with people with peripheral vascular disease. Certainly our patients with diabetes and peripheral vascular disease, we should be aiming for an LDL of less than 70. So certainly that might be one way to help decrease this. And certainly this is a number we'd like to see go lower and lower.
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So that's all of the articles for this week and until next week.
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Keep listening and keep learning.