← Diabetes Core Update
Diabetes Core Update
Diabetes Core Update March 2016
00:21:34
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...
Loading summary
Transcript12 lines
- [00:04]
Host
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 core 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 Associate Director in the Family Medicine Residency Program at Abington Memorial Hospital. Welcome, Dr. Skolnick.
- [00:38]
Dr. Neal Skolnik
Thank you. It's a pleasure to be here.
- [00:40]
Host
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.
- [00:50]
Dr. John Russell
Thank you. I'm looking forward to going over this week's articles.
- [00:53]
Host
And now for the articles.
- [00:56]
Dr. Neal Skolnik
We have another excellent issue this month, beginning with an article from Diabetes Care on the incidence of hypoglycemia in a large cohort of patients with type 2 diabetes. Then another article on vitamin D and blood sugar control, followed by an article from Diabetes Care on the relationship between potato consumption and the development of diabetes. Then an article from Diabetes on the effect of obesity on stem cells and obesity in offspring of both lean and obese micro mothers, followed by an article from Diabetes Care looking at diabetes in Asia and Pacific countries and lastly an article looking at the combination therapy tenagliflozin and metformin. Our first article is titled Severe Hypoglycemia requiring medical Intervention in a large cohort of adults with diabetes receiving care in a US integrated healthcare delivery system from 2005-11. We know that appropriate glycemic control is important, but aggressive glucose targets may unintentionally increase episodes of hypoglycemia. This was an observational cohort study and included over 900,000 adults with diabetes who received care from 2005 to 2011 in a large multi office diabetes network and system. Severe hypoglycemia rates were based on any occurrence of Hypoglycemia related to ICD9 codes from emergency departments or inpatient encounters. The annual rate of severe Hypoglycemia ranged from 1.4 to 1.6 events per 100 person years. Rates of severe hypoglycemia were higher among those who were older, who had chronic kidney disease, congestive heart failure, cardiovascular disease, depression and higher A1C levels, as well as in users of insulin, insulin secretagogues or who were on beta blockers.
- [03:09]
Dr. John Russell
John so I found this to be interesting and this is another in the series of articles we've talked about about the seriousness of hypoglycemia. And we've talked in other articles about hypoglycemia associated with worse outcomes. What I found kind of interest thing about this article is that about beta blockers and I for a long time had kind of poo pooed a bit of the beta blocker thing with regard to hypoglycemia. But in some people it does blunt the adrenergic response that people will have to hypoglycemia. So maybe it goes on a little bit longer. So maybe we should be a little bit smarter, especially in our elderly patients. I was also a little surprised that the hypoglycemic events were higher in folks that had higher A1Cs, which didn't make a whole lot of sense. And we've learned from a court in advance that sometimes tight control that's too tight in our elderly folks could be associated with worse cardiovascular outcomes. And in this particular study there was more hypoglycemia in people who had some baseline heart disease, congestive heart failure, et cetera. So again, it's something I think we should be talking about at every visit for our diabetic patients. Again, every time that we're looking at a med list with our patients, I think we need to assess are they at risk for hypoglycemia and reevaluate continuosol. Our next article is the effect of high dose vitamin D treatment on beta cell function, insulin sensitivity or glucose homeostasis in subjects with an abnormal glucose tolerance. So in this particular trial they looked at 44 folks who were randomized to either receiving 30,000 IUs of vitamin D3 once a week or placebo for eight weeks. Hyperglycemic clamp assessed the first phase from 0 to 12 minutes and second phase 12 to 120 minute insulin response, insulin sensitivity and disposition index. An oral glucose tolerance test assessed glucose tolerance in glycosylated hemoglobin assessed glycemic control. So there were 21 folks in the vitamin D arm and 22 folks in the placebo arm and they completed the study. The adjusted vitamin D levels were doubled in the active treatment group, but there was no effect of vitamin D treatment compared with placebo on either first or second phase insulin secretion. No group differences in insulin sensitivity or any other measure of glycemic control. There was no hypercalcemia or other adverse effects of the vitamin D subgroup. Analysis of those with the lowest basal and greatest increase in their vitamin D levels did not change these Results.
- [05:48]
Dr. Neal Skolnik
Neil John, I really like this study and I hope it's the last study on vitamin D that we'll need to see. Everyone gets excited about the idea of a natural substance, a vitamin, helping disease. In the 1990s, it was vitamin E leading to decreased coronary disease and CVAS until a meta analysis showed that vitamin E increased mortality in a large group. META ANALYSIS over the last 10 years, there's been a lot of excitement about vitamin D, low vitamin D causing a lot of things ranging from asthma to pain syndromes to even diabetes. And again, often there's early excitement based on epidemiologic data that low vitamin in this case vitamin D levels were associated with diabetes. And now a number of trials, this one being the one we're talking about today, that shows no relationship between supplementing people whose levels are low with vitamin D and improvement and no improvement in their blood sugar control with supplementation. We talked about a similar trial by Mayor Davidson about two years ago showing similar results. So I think at this point we can say very clearly that while low vitamin D levels may be associated with diabetes, that association is not causal. It's likely because it presents those people not going outside as much, not exercising as much, perhaps, perhaps an issue of healthy living. But there's no value of supplementing vitamin D with the goal of improving blood glucose control. Our next trial is on potato consumption and the risk of type 2 diabetes. In this trial, the authors analyze data from from three different cohorts consisting of United States male and female professionals without diabetes, cardiovascular disease or cancer. Baseline There were over 70,000 women from the Nurses Health Study, 87,000 women from the Nurses health Study too, and over 40,000 men from the Health Professionals Follow up study. During over 3 million person years of follow up, there were over 15,000 new cases of type 2 diabetes. Higher consumption of total potatoes and that include baked, broiled mashed potatoes and french fries was significantly associated with an elevated risk for type 2 diabetes. The pooled hazard ratio of type 2 diabetes compared with less than one serving a week was 1.07 or 7% increase for two to four servings, a 33% increase for greater than seven servings a week after adjustment for demographic, lifestyle and other values variables. In addition, the pooled hazard ratios for type 2 diabetes for every three servings per week were 1.04 for baked, boiled or mashed potatoes and 1.19 or 19% increase for French fries. They further estimated that the hazard ratio of type 2 diabetes, or rather to say it a way that makes More sense. The instance of type 2 diabetes was decreased by 12% for replacing 3 servings per week of potatoes with the same amount of whole grain foods.
- [09:22]
Dr. John Russell
John so the potato, really a quintessential American dining delicacy, right? So we eat lots and lots of potatoes. The average American eats about 126 pounds of potatoes a year. So that's an awful lot of potatoes. And so the question is, is it the potato or is what we do to the potato, is it that it's just an innocent baked potato, or is it the three pads of butter we put on it? Is it the shoestring French fry, or the fact that we cook the shoestring French fry in lots and lots of grease? So I certainly think the potato in its own right. And there was a study in the American Journal of Clinical Nutrition and actually showed that potatoes can cause as much excursion in our blood sugar as drinking a can of Coca Cola or having a hand of jelly beans. So the potato itself might not necessarily be all that innocent in its own right. And I think we need to look at, you know, if we're eating a lot of potatoes, could we replace a couple servings of them a week with something else? We're going to talk a little bit later in the show about an increase in diabetes in other parts of the world. And I think one of the things that's interesting to tie into that, in 2005, we changed that kind of more parts of the underdeveloped world grew more potatoes than the developed world. So the largest producer of potatoes in the world right now is China, followed by India, followed by the Russian Federation. So the United States no longer has the kind of the number one role as the potato producer of the world. And perhaps some of these countries producing potatoes, which are a relatively easy crop to grow, they don't need a whole lot of tending once you kind of get them growing under the. Under the soil. Certainly led to the Irish potato famine in the, you know, the 1840s, when there was a population that completely sustained themselves on the potato. So perhaps we're seeing some of these, this obesity in other parts of the world and parts of Asia, tied to increased potato consumption. Our next article is from Diabetes, and it looked at mesenchymal stem cells from infants born to obese mothers and their greater potential for adipogenesis. The Healthy Start Baby Bump Project. So overall, one in five children in the United States is obese. Maternal obesity increases the risk for pediatric obesity. The researchers hypothesized that mesenchymal stem cells from infants born to obese mothers would demonstrate a greater potential for adipogenesis and less potential for myogenesis. So overall, they cultured stem cells from the umbilical cords of infant born to normal weight pre pregnancy mothers with a bmi of about 21 and who had a pre pregnancy level of obesity with a BMI of 34.6. Overall, that they found that the cells from the obese mothers correlated with the percent fat mass in infants, saying that mothers who were more obese were more likely to have stem cells in their children that had a greater propensity to go on to become adipose cells.
- [12:34]
Dr. Neal Skolnik
Neil John, this is really interesting and we've known from epidemiologic studies that women who are obese have a higher chance of having kids who are obese. And it turns out that that obesity isn't just in the neonatal time, but all the way on through adolescence and adulthood. And here we're beginning to see the mechanisms by which that occurs elucidated. I think the main importance of this is recognizing that it's not just environmental, that if you're obese, your kids will be obese, but there actually is a physiologic mechanism that goes through stem cells that the kids have that differentiate into cells that create more adipocytes than muscle mass. How does that matter or how does that translate clinically? I think it's another thing that we can discuss with young adults as to why they should exercise and eat in a healthy way, both to feel better, to prevent the development of diabetes themselves, and also to pass on to their children healthy genes in order to allow their kids to grow up as healthy as possible. Our next article is on diabetes in the Asia and the Pacific. In 2013, the International Diabetes Federation estimated that approximately 400 million people had diabetes worldwide and that by 2035, this would increase to almost 600 million people. 80% of them live in low and middle income countries and of the total, more than 60% live in Asia and a third of those people live in China. The International Diabetes Federation estimated that in the Asia and Pacific area there were 138 million people with diabetes. Again, the largest single area with diabetes in China, having approximately 113 million adults with diabetes and an astonishing almost 500 million adults with prediabetes. That makes China the country with the most patients with diabetes, and that's followed closely by India. This rising trend in developing countries turns out to be a steeper increase in the incidence of diabetes compared to the developed countries. It is felt that the increase in diabetes prevalence is related to changes in dietary patterns, increased sedentary behavior, with more urbanization of the population and obesity superimposed on a background of both genetic and epigenetic sensitivity. When we look at prevention of diabetes in Asia and the Pacific, just as the Diabetes Prevention Program trial has shown that lifestyle matters in preventing progression to diabetes, here in the United States and in Finland, a number of studies have been carried out in China, Asia, showing that the same lifestyle issues can be utilized and lifestyle modifications can be utilized to decrease the progression from prediabetes to diabetes.
- [15:57]
Dr. John Russell
JOHN so I think as a concept, I think this is something that I probably would have gotten wrong. I always thought about folks who are going to eat kind of more traditional fare and a lot of these countries are going to be a lot healthier. And I view a lot of these foods as things that probably would be lower in a glycemic index, would have more vegetables, etc. I think what we're learning though is kind of as the westernization happens in Asia, I think we're seeing that populations that once upon a time walked and biked everywhere suddenly have access to automobiles. Suddenly having increased air pollution increases the rate of diabetes. About 50% of adults in many Asian countries, at least male adults smoke, which increases the chance of having kind of truncal obesity, which increases the chance of overall developing obesity. Rice is kind of the common staple in lots and lots of countries which has a high glycemic index. We're seeing fast food in populations that had never seen fast food before. And I think we have to remember that genetically not everyone is going to have the same glycemic response to the same amount of refined sugars. We think of the Pima Indians here in the United States, and the Pima Indians who live in the United States have an infinitely higher rate of diabetes than the Pima populations that live in some of the other countries. Some of the oils that they use in parts of Asia, they use some things like palm oils to cook, which are definitely really not all that good for folks. And often when there's poor nutrition, when a pregnant mother is pregnant means when the baby grows up, it's more likely to have higher blood sugars if they find themselves transitioning to a diet that has lots of refined sugars. Our next article is from Diabetes Care and it looked at an initial combination therapy with quinagliflozin plus metformin versus each component as monotherapy in drug naive type 2 diabetic patients. This was a 26 week double blind phase 3 trial that randomized close to 1200 patients to either canagulaflozin 100 plus metformin canagliflozin 300 plus metformin canaglifcozin 100 canagliflozin 300 were metformin as monotherapy. The primary endpoint was a change in A1C at week 26 for combinations versus monotherapy. Secondary endpoints that were also looked at included a non inferiority in hemoglobin A1c, changes in fasting plasma glucose, body weight and blood pressure and the overall proportion of patients that achieves an A1C under 7. The patients had a mean baseline A1C of 8.8. The combination of canagliflozin in both 100 and 300 with metformin significantly lower the A1C versus the metformin at 2000 milligrams per day at a 1.77 or 1.78 versus a 1.3 and versus the Conagl flows in 100 and 300 it was 1.37 and 1.47. In isolation there was a greater attainment of A1C of less than 7 and more weight loss. So overall the attainment of an A1C under 7 was in the 50 percentile 50% versus 43% with the metformin and there was more weight loss in the 3 kilogram range versus 1.9 kilogram range.
- [19:33]
Dr. Neal Skolnik
Neil John this is a good study to see and really it reflects the fact that with diabetes we're really moving toward a lot more patients getting combination therapy in a way that is easy to adhere to. So we've been doing this for years in hypertension management where we know that the majority of patients with hypertension need two or more agents and adherence is always a difficult issue for patients who are on multiple chronic medicines. The same is true in diabetes, that most patients with diabetes need more than one medicine and there's no question that adherence to those medicines is a challenge. In fact, the best data out there on adherence suggests that patients with diabetes only take about 50 to 75% of the medicines for diabetes that are prescribed. So the advent of combination therapy, two medicines in one pill, makes it easier for patients to adhere to. And clearly, as you went over in this study, this combination of metformin with canaglifloz and an SGLT inhibitor works effectively better than either one alone without more in the way of side effects and also accomplishing weight loss. 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. It.