D (2:27)

2 diabetes in youths are unknown.

E (2:29)

This study examined the effects of aerobic exercises versus resistant exercises without caloric restriction on abdominal adiposity, ectopic fat and insulin sensitivity and secretion in youth. 45 obese adolescent boys were randomly assigned to one of three three month interventions, aerobic exercise, resistance exercise or non exercise and control. Abdominal fat was assessed by MRI and intrahepatic lipid and intramyocellular lipid were assessed by proton magnesium resonance spectroscopy. Insulin sensitivity and secretion were also evaluated. Both aerobic exercise and resistant exercises prevented the significant weight gain that was observed in the controls compared with the control group. Significant reductions in total and visceral fat and intrahepatic lipid were observed in both the exercise groups. Compared with the control group, a significant improvement in insulin sensitivity, a 27% reduction was observed in the resistance exercise group. Collapsed. Across groups, changes in visceral fat were associated with changes in intrahepatic lipid and insulin sensitivity. Both aerobic exercise and resistant exercise alone are effective for reducing abdominal fat and and intrahepatic lipid in obese adolescent boys. Resistant exercise, but not aerobic exercise, is also associated with significant improvements in insulin sensitivities.

B (3:55)

Neil John clearly, the obesity epidemic in youth, which now a third of youth are considered obese or overweight, is a huge problem. Part of the problem is related to a lack of exercise, an increase in things like computers and video games. I remember growing up, when you and I grew up, there was no such thing as video games. I remember having a pair of barbells next to my bed, working out every day and then later hearing that that type of exercise, which is now termed resistance exercise, was nowhere near as healthy as aerobic or cardiovascular exercise. Over the last 10 years there have been a number of studies showing us that actually both aerobic and resistance exercises have a lot of benefit and this one now shows that same benefit in youth. In the American Association Standards of Care, they review that both that resistance exercises improve insulin sensitivity in adults and particularly in older adults, and that clinical trials have shown strong evidence that there's a 1C lowering associated with both aerobic and resistance exercises and in fact better lowering when both are combined. This is a nice reminder that the same sort of thing holds true for youth. Remember, in the Standards of Care, the recommendations are for adults that adults should perform 150 minutes per week of moderate intensity exercise or 75 minutes per week of vigorous aerobic exercise, but they should also include at least two days a week of resistance exercises. This study really supports that same idea for teenagers. One of the important points in this study that I thought was also very interesting is when they asked the teenagers how they liked doing exercise, more of them liked doing resistance exercises. So ultimately, when it comes to sustaining any form of lifestyle modification, the things that work are the things that we do. And this clearly puts resistance exercise strongly on the map as a point of emphasis for intervention with youth. Our next article is from the fall edition of Diabetes Spectrum on hypoglycemia after gastric bypass surgery. Nonspecific postprandial symptoms attributable to hypoglycemia are common in patients who have had gastric bypass surgery. It's important as we talk about this to recognize that the diagnosis of a true hypoglycemic episode requires that there's documentation of low plasma glucose, which is defined as less than 50 to 55 milligrams per deciliter in the presence of symptoms that are compatible with hypoglycemia. Most patients who have hypoglycemia shortly after gastric bypass surgery have that secondary to dumping syndrome. Dumping can occur postoperatively in up to half of gastric bypass patients when they ingest simple sugars. Early dumping, which is a result of rapid emptying of food into the jejunum because of surgically altered anatomy, is characterized by vasomotor symptoms, including flushing and tachycardia, as well as abdominal pain and diarrhea. Late dumping, a form of reactive hypoglycemia, occurs one to three hours after meal ingestion and is considered a consequence of the brisk insulin response to hyperglycemia that results from rapid absorption of simple sugars to from the proximal small intestine. Most patients with dumping respond to nutrition modification, which is basically comprised of small, frequent, low carbohydrate meals, in contrast to dumping, which tends to occur shortly after surgery and improves with time. Hyperinsulinemic hypoglycemia presents several months to years, often more than one year after gastric bypass surgery. The hallmark of this relatively rare syndrome is severe postprandial neuroglycopenia, which is characteristically absent in dumping.

D (8:19)

John so hypoglycemia overall is something that's a fairly rare event outside of the setting of someone taking some diabetes medicines. And the mnemonic I always talk about with the residents is the mnemonic explains Ex for exogenous, P for pituitary insufficiency, L for liver failure, A for adrenal insufficiency, I for insulinoma, N for neoplasm, and S for starvation.

C (8:49)

So this is something that seems to.

D (8:51)

Happen about one in every 500 people who have a gastric bypass surgery. And we're going to talk about another article a little later in this edition about an overall the issue of gastric bypass surgery. But I think there's over 200,000 cases that are happening in the United States, which would probably put us about 400 people in the United States would be having this fairly rare symptom.

C (9:15)

And I'm not sure this would be.

D (9:17)

Something that I would automatically piece together someone having some hypoglycemia, taking no diabetes medicine So I think it is something that we need to put a little bit on our radar. I think as our patients have bariatric surgeries, oftentimes they are just following up with us and having some very kind of vague symptoms. So it is something we might be thinking about at some point as a rare thing that's different from the dumping syndrome that people are going to see when they have that very kind of sweet meal with simple sugars that are going to lead to these symptoms directly after having. So I think it's an interesting point. It probably wouldn't prevent me from recommending this procedure to patients because we do know the natural outcome of people who have morbid obesity enough to need the surgery is going to cause problems much more often than one in every 500 patients.

C (10:15)

Our next article is from the November 2012 edition of Diabetes and it's the FTO genotype and a two year change in body composition and fat distribution in response to weight loss diets the Pounds Loss Trial Recent evidence suggests that fat mass and obesity associated gene the FTO genotype may interact with dietary intakes in relation to adiposity. This study tested the effect of FTO variant on weight loss in response to two year diet interventions. The FTO RS 1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets that that differed in the proportions of fat, protein and carbohydrate. Body composition and fat distribution were measured by DEXA and computerized tomography. They found significant modification effects for intervention varying in dietary protein on two year changes in fat free mass, whole body, total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass and superficial adipose tissue mass. For all interactions, caries of the risk allele had a greater reduction in weight body composition, fat distribution in response to a high protein diet where an opposite genetic effect was observed on changes in fat distribution in response to a low protein diet. Likewise, significant interaction patterns also were observed at six months in this particular study. The data suggested that the high protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals who have the certain at risk allele.

B (11:51)

Neil John I find this study intriguing and it portends a future filled with personalized medicine. We've heard a lot about genomics over the last five to 10 years. It's still a ways from reaching prime time, but we've increasingly come to realize that simply one size does not fit all. So a couple of brief examples Metabolism Warfarin depending on your and this is actually now in product label. There are slow and fast metabolizers, similarly with clopidogrel and a number of other medications where there's increasing evidence of different rates of metabolism for drugs. Not entirely clear always how we're going to use that information. I never thought that we'd be seeing that with regard to diet. It's clear clinically that some people do better on a high protein diet, some people do better on a low protein diet. I've always thought it had to do more with personal preference and adherence to diet more than anything else. And while that may still be a correct assessment, what this study suggests is that there are genetic reasons why some people may actually achieve better weight loss on one diet than another. By no manner is this yet ready for prime time, but I think this is exciting information and suggests what we may be seeing more of 10 years from now, which is personalized recommendations based on someone's genomic makeup Our next article is from the fall edition of Diabetes Spectrum on a comparison of bariatric surgical procedures for diabetes remission. In 2009, over 220,000 bariatric surgery procedures were performed in the United States, so it's important for us in primary care to understand the different types of bariatric procedures that are available. There are essentially two types of bariatric procedures. The first are restrictive procedures which dramatically reduce the volume of the stomach to limit gastric capacity and promote early satiety but don't alter intestinal anatomy. The second type are gastrointestinal divergentary procedures which bypass segments of the small bowel. Examples of restrictive procedures are the adjustable gastric banding procedure, where an inflatable silicone band is placed around the fundus of the stomach, and it's believed to be the most commonly performed restrictive procedure worldwide. In that procedure, the GI anatomy essentially remains intact and and the rate of gastric emptying is not altered. The adjustable gastric band is rapidly being supplanted by vertical sleeve gastrectomies, which is a newer restrictive procedure that removes about 75% of the stomach and virtually all of the hormonally rich gastric fundus. Although vertical sleeve gastrectomy is conceptually a restrictive procedure, the removal of the endocrine rich gastric tissue and the accelerated rate of gastric emptying caused by this procedure is thought to have significant physiologic implications and may account for its superior efficacy compared to adjustable gastric banding. The other main type of procedure are GI diversionary procedures, of which the roux en Y procedure is the most commonly used performed. Two randomized controlled trials reported greater weight loss with the roux en Y procedure than with adjustable gastric bands. In addition, it appears that the vertical sleeve gastrectomy appears to induce superior weight loss compared to banding procedures. Let's now talk briefly about their effect on remission of diabetes. And a number of observational studies suggest that bariatric surgery is associated with between a 45 to a 95% rate of diabetes remission, depending on the type of procedure that's used. And the largest meta analysis done, which included over 3,000 patients with type 2 diabetes who underwent bariatric surgery, the disease resolved in 78% and resolved or improved in 87% of people. Weight loss and diabetes remission were greatest for the roux en Y procedure over the gastric banding procedure.

D (16:33)

John so certainly this is an exciting, exciting new area when you're starting to think about it. So, you know, diabetes, we've never really used the term cure before. And even when we go back to the discovery of insulin by banting and best it was discovery of a treatment, it wasn't discovery of a cure for diabetes.

C (16:56)

And with some of these procedures now.

D (16:58)

We can actually have a cure for diabetes for folks. So certainly the recommendations for people who have BMIs greater than 35 with diabetes, we're going to think about people having some of these procedures. I think it's our role in primary care for talking about what some of the procedures are. So the issues related to the bands have started to fall out of favor, the gastric bands, and has been replaced by the vertical sleeve gastrectomy. And people do really well with these restrictive procedures. And going back, the mortality rates, which used to be somewhere in that one to 100 range, are now down into that one in a thousand range. And the more involved procedures, the classic roux en Y, which makes up over 50% of the procedures that are done in the United States, certainly is going to have a greater effect on weight loss and some of the incretin hormones that we deal with. And that's some of the difference between some of the restrictive procedures. Although having the vertical sleeve gastrectomy does seem to have some effect on glp, as does some of the more advanced procedures. The big procedure, the biliary pancreatic diversion with the duodenal switch procedure, which only makes up about 5% of the procedures in the United States, is a very complicated procedure. It only makes up about 5% of the bariatric procedures that we have in the United States, but it has about a 90% cure rate for diabetes. So the more complicated the procedure, the more likely that someone's going to have one of these home run responses. With the last procedure, though, there are much more extensive issues with regard to vitamin malabsorption and people really have to have a much closer relationship with kind of follow up care and different monitoring of different nutritional elements if you're going to have this last procedure.

C (18:59)

So if we do send a patient.

D (19:01)

Off to have one of these surgeries potentially for a diabetes cure, we need to let people know that they're not all the same. And I think one of the things we also need to tell people is the people who are more likely to have a very, very positive response are the people who aren't on insulin, people who have been on insulin for a shorter period of time, people who don't have insulin resistance. So our patients who are on 1, 2, 3 oral medications are people who are much more likely to achieve this cure for diabetes, which interestingly enough now is found in the hands of our surgeons.

B (19:44)

Our next article was released online in Diabetes Care and is published in the December issue of Diabetes Care on a consensus report on diabetes in older adults. We are going to actually have one of the authors, Mary Kurtosky, discuss this consensus report in detail in a few weeks in a special edition of Diabetes Core Update, but we wanted to cover it in our usual edition in brief as well. Essentially, more than 25% of the United States population age greater than 65 years has diabetes, and the aging of the overall population is a significant driver of the diabetes epidemic. Although the burden of diabetes is often described in terms of its impact on working age adults, diabetes in older adults is linked to higher mortality, reduced functional status, and increased risk of institutionalization. There are three major overriding points that are discussed in this report and will be expanded upon in more detail in our special issue. The first is individualization of goals with regard to A1C's when talking about older adults. And this individualization is the same in this report as discussed in the Standards of Care, which is simply that for younger individuals who have had diabetes for a shorter length of time and who have limited comorbidities, then A1C goals closer to normal than the usual goal is what makes sense. For older individuals who have a significant lifespan left and who have limited comorbidities, then the usual goal of an A1C less than 7 is what's recommended. But what's important to recognize and emphasize is that for older individuals who have multiple comorbidities, who may have limited lifespans because of data from a cord, as well as the increased concerns as individuals get older of the consequences of hypoglycemia, less lenient goals than the usual goal of seven should take hold. Point number two when treating lipids we should treat older adults aggressively in a manner similar to that which we treat younger adults because the period of time over which you see a benefit with aggressive lipid treatment is relatively short compared to the long period of time that needs to take place place to see the benefits with intensive glycemic control. Third point blood pressure goals the blood pressure goals for older adults are similar to that in younger adults if they can be achieved easily because again, the span of time that's required to see benefit, particularly with regard to stroke reduction in older adults is relatively short. Again, that's if we can achieve it with reasonable ease, we might want to be a little more relaxed a systolic of 130 to 140 instead of the usual systolic line in the sand of less than 130 that we have in younger adults. Again, we'll be talking about this in more detail in an upcoming special report of Diabetes Core Update. Our next article is from Diabetes Care November edition and is on the metabolic syndrome and the risk of cancer. There's accumulating evidence that the metabolic syndrome may be associated with the risk of some common cancers. In this article, the authors analyzed 116 data sets from 43 articles, including over 38,000 cases of cancer. In cohort studies in men, the presence of metabolic syndrome was associated with liver, colorectal and bladder cancer. In cohort studies in women, the presence of metabolic syndrome was associated with increased risk of endometrial, pancreatic, breast, rectal and colorectal cancer.

D (24:03)

John so the metabolic syndrome really is the quintessential American disease. So to qualify for having the metabolic syndrome described in ATP3, you're going to have three of the following you are going to have a waist Circumference Greater than 35 inches in a female, greater than 40 inches in a male. You're going to have elevated triglycerides, you're going to have a low hdl, you're going to have impaired fasting glucose, and you are going to have hypertension. So having three out of the five of the following would qualify someone as having metabolic syndrome. Metabolic syndrome affects probably about 25% of Americans, 40% of senior citizens. That said, we're faced with this study that says the metabolic syndrome has an association with cancer. And I do not think it is kind of all five of these things necessarily together, but probably a combination of all these things and increased adiposity in the central part of our body is associated with some cancers, and in this particular study, liver cancer. And you would argue that probably a lot of the people that have metabolic syndrome are more likely to have fatty liver, and fatty liver kind of can lead people to have cirrhosis, and having some cirrhosis can lead to having hepatocellular carcinoma. So that might make some sense. Certainly there have been some studies that have seen obesity being associated with colon cancer and breast cancer before. So none of these are really revelations. Overall, I think that we would say is we want people to not necessarily be obese, not necessarily have impaired fasting glucose, not necessarily be hypertensive if we could prevent it, and not purely because we want to prevent cancer. We just know the stigmata of all these other things that we're going to look at. There was a study called the west of Scotland Prevention Trial, the WOSCOPS trial, which is a trial that looked at pravastatin. And actually having three of the following conditions, really and qualifying for the metabolic syndrome, put people at risk for a threefold chance of having a myocardial infarction. So certainly these very small increases in some cancers, in some studies that were done worldwide, not necessarily in the US Population, we'd like to prevent metabolic syndrome because we don't want people to have heart attacks.

B (26:41)

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.