B (3:13)

Neil John this is intriguing. I mean 5 pounds less weight gain over 18 years improved metabolic parameters, all just from eating a good breakfast. You know, we were all told growing up, eat breakfast before you go to school. And we later forgot some of that later. I don't know if you've heard the expression eat breakfast like a king, lunch like a pauper, and lunch like a prince and dinner like a pauper. And that's based on a series of research and assumptions that over the years have supported the eating of a good breakfast in the health profession. Study Breakfast as reported by those in the study, those who ate Breakfast had about a 5 kilogram or 12 pound less weight gain over the 10 years of the study. This past June, at the American Diabetes association scientific meetings there, there was a fantastic study presented where participants had controlled diets with some receiving the bulk of their calories at breakfast, some later in the day, and those who received calories at breakfast had less weight gain than the equal caloric diet later in the day. I'm not sure why that's the case, but it seems like there might be something going on here that really supports what our mothers always told us, which is eat a good breakfast breakfast before starting the day. I think we're going to be hearing more about this diet over the years to come. Our next article is from Diabetes Care on the benefits of liraglutide treatment in overweight and obese older individuals with prediabetes. The objective of this study was to evaluate the use of liraglutide to augment weight loss and improve insulin resistance in a group of overweight and obese older patients. The authors randomized 68 older individuals with mean age of 58 years who were overweight and had prediabetes to either liraglutide 1.8mg daily versus placebo for a total of 14 weeks. It's important to note that 11 of 35 people, 31% assigned to the liraglutide group discontinued the study, compared with 6 out of 33 or 18% assigned to placebo. And while this didn't reach statistical significance, I think this difference in dropout rate is important. Subjects who continue to use liraglutide, which was 24 individuals, lost twice as much weight as those using placebo and that was a total of 6.8 versus 3.3 kg which did reach statistical significance. Liraglutide treated subjects also had significant improvements in glucose concentration, significantly greater lowering of systolic blood pressure, fasting glucose and triglyceride concentrations.

C (6:15)

John so this seems like a fairly extreme approach to a very common problem. So certainly we have lots and lots of folks in the United States who have impaired fasting glucose who are also overweight. It just seems to me that it is having our patients do an injectable medicine, you know, over a 14 week period of time. We don't know if the people kept this weight off kind of long term and what was the long term effect after stopping this medicine. So it's not clear from the study, does someone need to be on this forever and ever? They certainly lost some weight and the folks in both groups were instructed to decrease their intake by about 500 calories. The question for the overweight groups would have been more practical to have people exercise and maybe eat 700 calories less and still potentially achieve roughly the 15 pounds weight loss. So it does work. The question is doing an injectable medicine, is it just a practical approach for these patients? Our next article is from the October 2013 edition of Diabetes Care and it looked at the adverse outcomes after non cardiac surgery in patients with diabetes. This Taiwanese study was a nationwide population based retrospective cohort study. They looked at the use of reimbursement claims. From the Taiwanese National Health Insurance System performed a population based cohort study of patients with and without diabetes who underwent non cardiac surgeries. The outcome of postoperative complications, mortality, hospital stay and medical expenditures were compared between patients with and without diabetes. Diabetes was found to have increased 30 day post operative mortality with an odds ratio of 1.84, particularly among patients with type 1 diabetes or uncontrolled diabetes, or patients with preoperative disorders such as peripheral vascular disease, ketoacidosis, renal disease and coma. Compared with non diabetic control patients, coexisting medical conditions such as renal dialysis had a 5 fold increase, cirrhosis a 3.5 fold increase, stroke a 2.87 fold increase, mental disorders a 2.35% increase, ischemic heart disease 2.08, COPD 1.96 and hyperlipidemia 1.94 were associated with mortality for patients with diabetes undergoing non cardiac surgery. The patients with diabetes faced a higher risk of postoperative renal failure a 3.5 fold increase and acute myocardial infarction a 3.65 times increase. Furthermore, diabetes was associated with prolonged hospital stay and increase medical expenditures.

B (8:59)

John, this is interesting but at the same time really what it says is sicker people do worse than people who aren't sick. It's interesting as someone who likes looking at methodology, when I look at the conclusion of this study, it says diabetes increases post operative 30 day mortality and complications. When we go back and look at the methodology here, they actually didn't just include patients with diabetes, they just included patients with diabetes who had been admitted to the hospital at some point during the prior 24 months. So this really selects out an important and sicker subset of all patients with diabetes. That's a group who it wouldn't be entirely surprising that they don't do as well as an age matched population without diabetes who've been well previously. That said, what do we take of this? We well, I think one of the things to take is that when we're doing preoperative clearance of patients with diabetes, we're still going to clear them for needed surgery, but we want to be careful about the word cleared. What we're really saying is that the benefits of the surgery outweigh the risk and that patients are optimized with regard to both their glucose management and other comorbidities prior to going into elective surgery. What's the other thing we want to make sure of? We want to make sure we adhere to the standards of Care's recommendations about management of in hospital hyperglycemia. Aiming on the average for glucose is less than 180140 to 180 in order to minimize as much as possible the risk of post operative infections and wound infections and of course careful postoperative care with regard to cardiac care. Checking EKGs after surgery with the highest incidence of MI being 3 days after surgery. So this is a group that requires careful attention and this is a study that reminds us to give that careful attention to this group. Our next article is from Diabetes Spectrum on asthma therapy in patients with diabetes. An update on current recommendations Aspirin induced inhibition of cyclooxygenase leads to impaired platelet aggregation and is the likely cause of aspirin's cardioprotective effects. This was first shown in the Physician's Health study back in 1989 that was a randomized double blind placebo controlled trial in over 22,000 physicians and demonstrated a 44% reduction in the risk of MI in patients taking 325 milligrams of aspirin every other day. This is particularly important with regard to patients with diabetes for whom 68% of deaths are the result of coronary heart disease and 16% are secondary to stroke. Those benefits are clear and of course are weighed against the potential for bleeding side effects. Most commonly and most important, intracranial hemorrhage and GI bleed. Serious GI bleeding events are more common by about 40% in individuals taking aspirin. The American Diabetes association, putting all of this information together in the standards of Care, has suggested that aspirin therapy be used for primary prevention in patients with either type 1 or type 2 diabetes who have an increased risk of cardiovascular disease. And that was defined as a 10 year risk greater than 20 than 10%. They also state that this includes most men greater than 50 years of age and most women greater than 60. The standards also state that aspirin therapy should not be recommended for cardiovascular disease prevention in men less than 50 years of age or most women less than 60 years of age who are at low risk for cardiovascular disease with a 10 year risk less than 5% because the increased bleeding risk likely offsets the potential benefits of aspirin therapy.

C (13:24)

JOHN so aspirin use dates back to the time of the Sumerians. Aspirin was really a product of the Bayer company in the early part of the 20th century. I think one of the interesting facts about aspirin is aspirin is actually the brand name. It's acetylsalicylic acid. Aspirin was the brand name that Bayer had used. We are coming around close to the hundredth anniversary of the 19181919 flu epidemic. And when there was flu in Boston in 1918, the Boston newspapers actually suspected that it was germ warfare, that someone who was actually putting flu in the bare aspirin which was being made by our enemy Germany in World War I. So I think the overall takeaway point from this is aspirin is effective in higher risk folks and it's really more dangerous than effective in low risk folks. So we have a large cohort of folks with diabetes who are older who are certainly going to need it and are going to get by just as well with a baby aspirin as a full aspirin.

B (14:31)

Our final article for this issue is from Diabetes on Sugar, Uric Acid and the Etiology of Diabetes and Obesity. This article is a review of issues around the of effect of fructose intake on metabolism and obesity. Fructose intake has been shown to induce features of the metabolic syndrome. Findings have shown that when animals are fed sucrose or high fructose corn syrup, both of which contain fructose, there is a higher incidence of metabolic syndrome than when an equal caloric amount of glucose is given. Fructose may increase the risk for obesity by altering satiety and results in increased food intake. The intake of fructose is not effective in stimulating insulin and leptin secretion in humans, and therefore that may be one of the mechanisms by which high fructose corn syrup does not induce a satiety response. A recent study in humans documented that a reduction in resting energy expenditure occurs in overweight and obese subjects that fed fructose, but a similar reduction did not occur in those eating simply glucose. The study also reviews the fact that high fructose corn syrup can lead to an increase in intracellular uric acid that can be followed by a rise in uric acid levels in the circulation. Uric acid may in turn stimulate lipogenesis in hepatic cells, which appears to be one of the mechanisms by which high fructose corn syrup leads to fatty liver. The mechanisms reviewed in this study suggest that given the increase in high fructose corn syrup throughout the United States over the last 30 years, that this may be one of the important reasons or causes for the increase in obesity over the last 30 years.

C (16:36)

John so we saw an increase in the use of high fructose corn syrup in the 1970s, cane sugar, which a lot of that came from companies we had trade restrictions with, like Cuba. We started needing a substitute. We started using high fructose corn syrup, and we had a stark in sharp increase since the early 1970s. And now we're at a point where 7% of our calories in our diet come from sodas and high fructose corn syrup. I don't think it's completely that simple, though. I think this kind of gets blamed as the problem from all mankind. If you look, compared over the last 40 years, we have an increase in 458 calories in our diet compared to 40 years ago. And only 34 of those calories are actually coming from high fructose corn syrup. So that would equate to about three pounds a year, which is certainly significant. But I don't think that is kind of the only problem. That while we're having obesity in the United States, for those of us who like to go to Mexican restaurants, sometimes you can get Mexican Coke. And Mexican Coke still is made with sugar as opposed to corn syrup. And so you would think that Mexico, who has, you know, the regular, the old time coke with the sugar in it versus us who have the high fructose corn syrup, would be less obese. And actually Mexico recently passed, the United States is the fattest country in the world. So the sugar coke kind of loses out to the high fructose corn syrup. So I think, I really think calories are calories and we really need to be concentrating on these 500 extra calories we've picked up per day over the last 40 years.

B (18:25)

For more information and links to the articles that we discussed in this issue, just go to www. Diabetes journals.org until next week, keep listening and keep learning. Sam.