C (3:54)

John so metabolic syndrome, as defined in ATP3, has three of the five following criteria. You would have a low HDL, you would have an elevated triglyceride, you would have elevated by blood pressure, you would have an elevated fasting glucose, and you would have an increased waist circumference. So three of the five following would classify you for metabolic syndrome. The waist circumference they talk about is greater than 40 inches in a man and greater than 35 inches in a woman. And the HDL has different numbers. It has 40 less than 40 in man and less than 50 in a woman. So metabolic syndrome affects 40% of US seniors. It affects 25% of the US population. In general, metabolic syndrome is linked with having an increased chance of going on to have diabetes. And if you look at the west of Scotland prevention trial, which was a Pravastatin trial, you had a threefold higher chance of having a cardiovascular event. So ATP3 talks about using these bony landmarks for measuring waist circumference. And this study would point out that that using this midway point would make more sense. Although when we try to measure something on our own walls, we like to find some bony landmark of our walls. We tend to go from the side or the top, et cetera, and measure down 2ft or 3ft. So I think using our own natural landmarks on our body makes it much easier to have consistent measurement. You have this bony landmark and you can measure across as opposed to saying, find this bony landmark, find this bony landmark and go halfway in between. I think if you thought office to office and this was a very well done study, I think you're going to have more variation. And I'm not really sure that there's a ton of difference between the two when it boils down to it. Our next study is from the June edition of Diabetes Care, and it looked at the effect of type 2 diabetes on 12 new year cognitive change. So this study from the Netherlands looked at close to 1300 individuals who were over 40 years of age. The participants had cognitive studies done at baseline. After 6 years and 12 years, there were 68 participants who had type 2 diabetes at baseline and 54 and 57 had incident diabetes at the 6 and 12 year follow up. Changes in performance on tests of information processing speed, executive function and verbal memory from baseline to to the 6 and 12 year points were compared between the two groups using linear models. The effects of diabetes on cognitive decline were adjusted for demographic variables that included a history of smoking, alcohol intake, comorbid conditions including hypertension, cardiovascular disease, depression and elevated bmi. The participants who had baseline diabetes had a larger decline in information processing speed, executive function and delayed word recall over the 12 year follow up compared with controlled subjects. Compared with controlled subject participants with incidence, diabetes showed subtle early decline in information processing speed only. Interestingly, they did not show larger decline in any other cognitive domain.

B (7:09)

Neil John I thought that this was an interesting study. I mean a three times larger decline in information processing spend and a four times larger decline in executive function among patients with diabetes at baseline is impressive and scary. We know that diabetes causes cardiovascular disease, renal disease, retinopathy, an increased rate of cerebrovascular disease, but we don't typically think of it as affecting higher cognitive function separate from large strokes and it turns out that this this suggests that it really does. Another I add that to the list of long term consequences of diabetes. We don't know how to affect this consequence yet and unlike vascular disease we don't have a sense of what are the things that we can do about Might be though that this effect on cognitive function is through an effect on macro and particularly microvascular disease in the cerebral circulation. We know that multi infarct dementia, which this study didn't look specifically at, is the second most common cause of dementia among the elderly. And it might be that the cognitive decline that we're seeing here is secondary to a vascular effect. Whatever that may be the case, it clearly is something that is important to be aware of and another reason to try to address as aggressively as possible and reasonable the different risk factors blood glucose, hypertension and cholesterol. Our next study is from the June edition of Diabetes Care on the prevalence of diagnosed cancer according to duration of diagnosed diabetes and current insulin use among US adults with diagnosed diabetes. These findings were from the 2009 Behavioral Risk Factor Surveillance System. There's a growing body of evidence that suggests that diabetes may be associated with an increased incidence or prevalence of certain cancers. This study looked at Results of over 25,000 adults over 18 diagnosed with diabetes who participated in the Behavioral Risk Factor Surveillance System. After adjustment for potential confounders, the authors found that the greater the duration of diagnosed diabetes, the higher was the prevalence of diagnosed cancers with a P value of less than 0.0001. For a linear trend among adults with diagnosed type 2 diabetes, the prevalence estimate for cancer of all sites was higher among men and among women, 60 to 80% higher who reported being diagnosed with diabetes greater than or equal to 15 years ago. Compared to those diagnosed less than 15 years ago. The prevalence for cancers of all sites was 30% higher among type 2 diabetes patients who currently used insulin than among those who did not use insulin.

C (10:25)

John so the people in the United States are going to be more likely to get type 2 diabetes are going to overall tend to be people who are heavier. So is there links between weight and certain cancers? Certainly. So it's not news that breast cancer, prostate cancer and colon cancer might be more associated with people being overweight is which they found in the study. And those cancers tended to have an increased rate in the people that had diabetes. So that certainly makes sense. What I can't completely dissect away is the people there was an increased rate of skin cancer in the people who had diabetes, which doesn't necessarily kind of make sense that people who are heavier are necessarily going to have more skin cancer. The links between diabetes and cancer, though, I think we're going to see more and more in the news. There have been whispers in the news that GLP1 agonists and DPP4 medications might have some link to cellular changes that happen in the pancreas. So who knows if there's something, if anything's going to come about this. This is just some early whispers. There was one study out of the Mayo Clinic that looked at people who had ovarian cancer, and folks who had metformin in ovarian cancer actually had a higher survival rate than people had ovarian cancer and weren't on metformin. So I can't really tell you that there was a direct cause and effect between diabetes and cancers. It might be something we'll learn in the next few years that clearly there is some link. And it's going to be another argument for primordial prevention in preventing people from ever developing diabetes, because we can hopefully keep them healthier down the road. Our next study is from the June edition of Diabetes Care, and this was a prospective study of serum adiponectin and the incidence of metabolic syndrome. This was the ARIRANG study. So this prospective cohort study was done on over 2000 adults, of which 800 some were men and 1200 some were women who were aged 40 to 70. Years of age who did not have metabolic syndrome and they were evaluated in the 2005-2008 period and then again in 2008-2011 during an average of 2.6 years of follow up, 153 men and 199 women so between 16 and 18% in the two groups develop metabolic syndrome. In the multivariable adjusted models, the odds ratio for incident metabolic syndrome comparing the highest with the lowest quartiles of adiponectin level was 0.25 in men and 0.45 in women. While serum adiponectin did not improve the area under the curve for predicting new onset mild but metabolic syndrome. Based on information from metabolic syndrome components, the net reclassification improvement and the integrated discrimination improvement of prediction models including adiponectin were significantly higher compared with those models that did not include adiponectin among men and there was a significant difference found between men and women.

B (13:28)

Neil John I think this is a potentially confusing study but the important point here, the take home point, is that increased adiponethrin levels are independent predictors of for incident metabolic syndrome and potentially we're going to be seeing more about this down the road. Adiponectin is a protein that's secreted primarily by visceral and subcutaneous adipose tissue. Binding of adiponectin results in increased insulin sensitivity and improved glucose utilization. What happens with increased obesity is is that there's down regulation of adiponectin secretion so that in larger adults while you'd expect more adiponectin there's actually down regulation of that secretion. We know that more adiponectin leads to increased insulin sensitivity and according to this study, a decreased rate of development of metabolic syndrome. I think it's a hormone that we're probably going to be hearing a lot more about over the coming years, both with regard to its effect on obesity as well as potential effects on diabetes. Our next study is from the June edition of Diabetes Care on mercury exposure in young adulthood and the incidence of diabetes later in life. This was a prospective COHORT study of 3,875American young adults and aged 20 to 32 years who were free of diabetes in 1987 and were enrolled and followed six times until 2005. Baseline toenail Mercury levels were measured over this period of time. There were a total of 288 incident cases of diabetes over the 18 years of follow up intake of long chain N3 fatty acids and magnesium and toenail selenium. Toenail mercury levels were all positively associated with the incidence of diabetes. The hazard ratio of incident diabetes compared from the highest to the lowest quintiles of Mercury exposure was 1.65. Or to say it a different way, higher levels of mercury exposure led to a 65% increase in the development of diabetes.

C (15:56)

John so I find this very interesting. I'm not exactly sure I'm especially interested about mercury and it leading to diabetes because when we look and think about who is going to have mercury exposure in the United States, we're going to think about the people who eat lots of sushi, who tend to be kind of a healthier group in general. The actor Jeremy Piven supposedly had mercury poisoning not too long ago because he ate twice a day sushi. So I don't know if I would use this kind of small study to tell people to stay away from mercury. But mercury itself I find is a very fascinating subject. So we know the expression mad as a hatter. People who made hats during the 18th and 19th century were exposed to mercury in the felt and actually that led to the mad hatter expression. Abraham Lincoln, when he was president, before he was president, took a pill called blue mass to help his melancholy, which he took for many years. He ended up stopping it prior to being president because he did not like what it did to him emotionally. But he took a mercury compound for many, many years. In many years prior to the advent of antibiotics in the United States, people took mercury to treat syphilis. The expression used to be a night with Venus, the goddess of love, and a lifetime with mercury. So mercury kind of a very interesting thing. We all grew up when there were thermometers that had mercury in it and for the most part not really the source of mercury so much. So I think mercury itself is kind of an interesting thing, a dangerous thing. And certainly there continue to be small outbreaks of mercury toxicity that happens in people that does get people. I think one of the things that mercury still might touch our lives is fluorescent light bulbs, that we're all probably sitting under fluorescent light bulbs, perhaps listening to this in our offices right now. And too much exposure to the gas in broken fluorescent light bulbs can increase our mercury levels. There was a child, a case of a child who had a shed outside the nursery wall that had several broken fluorescent light bulbs in it, who developed a high level of mercury. So I find the mercury poisoning very, very interesting. I'm not so sure that I'm going to use this as a diabetes prevention thing in my office.

B (18:27)

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.