Diabetes Core Update October 2015

Summary

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Diabetes Core Update – October 2015

Podcast: Diabetes Core Update
Host: American Diabetes Association
Date: September 24, 2015
Hosts: Dr. Neil Skolnik & Dr. John J. Russell

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Episode Overview

This episode presents and discusses six recently published, clinically relevant articles from the American Diabetes Association’s journals. The topics range from risk factors and lifestyle influences on type 2 diabetes to emerging interventions and a groundbreaking clinical trial on cardiovascular outcomes for diabetes medication. The hosts dissect the data, highlight key implications for clinical practice, and provide practical takeaways for healthcare professionals.

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Key Discussion Points & Insights

1. Body Weight, Metabolic Dysfunction, and Risk of Type 2 Diabetes

Source: Diabetes Care
Study: Prospective Secondary Manifestations of Arterial Disease Cohort Study
Timestamps: [02:03 – 04:46]

• Nearly 7,000 participants were classified by BMI and metabolic syndrome status; assessed for development of type 2 diabetes over 6 years.
• Key Findings:
  • Overweight without metabolic dysfunction: 2.5x increased risk.
  • Obesity without metabolic dysfunction: 4.3x risk.
  • With metabolic syndrome, risk increased dramatically:
    • Normal weight: 4.7x
    • Overweight: 8.5x
    • Obese: 16x
• Clinical Implications:
  • Metabolic syndrome is a stronger predictor than weight alone.
  • Emphasis on monitoring for metabolic syndrome components, not just BMI.

Notable Quotes:

• “The metabolic syndrome certainly is the quintessential American disease. I think it affects about 40% of American seniors.” – Dr. Russell [03:32]
• “If you have metabolic syndrome plus you're overweight, you’re much more likely to be a diabetic than overweight in its own right.” – Dr. Russell [04:17]

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2. Sedentary Time and Type 2 Diabetes Development

Source: Diabetes Care – CARDIA Study
Timestamps: [04:46 – 05:58]

• 20-year follow-up of 2,027 young adults, aged 38-50 at end, tracked with pedometers.
• Findings:
  • Average sedentary time ≈ 8 hours/day.
  • Each additional sedentary hour/day associated with 3% higher fasting insulin.

  • 10 hours sedentary/day doubled risk of impaired fasting glucose, nearly quadrupled risk of developing diabetes (OR 3.8).

Clinical Implications:

• Sedentary behavior is an independent risk factor, even in physically active people (“active couch potato” phenomenon).
• Clinicians should encourage breaking up sitting time with movement throughout the day.

Notable Quotes:

• “That sedentary time as a separate parameter from exercise incurs both cardiovascular and diabetes risk.” – Dr. Skolnik [05:58]
• “Active couch potato: someone who exercises their 150 minutes a week but sits at work... that grabs our attention.” – Dr. Skolnik [05:58]

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3. Breakfast Consumption and Metabolic Response

Source: Diabetes Care
Timestamps: [06:00 – 10:40]

• Randomized, crossover trial in 22 type 2 diabetics (mean A1C: 7.7).
• Compared days with vs without breakfast, measured metabolic parameters after subsequent meals.
• Results:
  • Skipping breakfast led to significantly higher (36-41%) postprandial glucose, free fatty acids, glucagon, and lower (17%) insulin after lunch/dinner.
  • Delayed insulin peaks by 30 min post-lunch and dinner on no-breakfast days.

Clinical Implications:

• Skipping breakfast worsens glycemic control for rest of day.
• Supports recommendation of at least a light breakfast for patients with diabetes.

Notable Quotes:

• “If you skip breakfast, you're setting yourself up metabolically to have a lot more mess after lunch and after dinner.” – Dr. Russell [10:25]
• “I think having at least a light breakfast... makes lots and lots of sense for our patients.” – Dr. Russell [10:40]

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4. Probiotics (Lactobacillus reuteri) and Insulin Response

Source: Diabetes Care
Timestamps: [10:44 – 12:00]

• Placebo-controlled study: Lactobacillus reuteri in 21 glucose-tolerant and 10 obese adults over 4 weeks.
• Major Findings:
  • Probiotic intake increased GLP-1 and GLP-2 secretion by 76% and 43%.
  • 49% higher insulin and 55% higher C-peptide secretion; no effect on BMI in short term.

Clinical Implications:

• Supports the intriguing link between the gut microbiome and metabolic regulation.
• Suggests future potential for microbiome-targeted therapies in diabetes.

Notable Quotes:

• “It's pretty mind-boggling to think that we're looking at a study that's assessing whether Lactobacillus would increase insulin response.” – Dr. Skolnik [12:00]
• “The potential therapies... are both exciting and hard to imagine. So it's important to keep an open mind about this.” – Dr. Skolnik [12:00]

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5. Monetary Incentives for Adolescent Type 1 Diabetes Self-Monitoring

Source: Diabetes Care
Timestamps: [12:00 – 15:33]

• 12-week pilot with 10 adolescents with poorly controlled type 1 diabetes; paid per glucose test, with bonuses.
• Findings:
  • SMBG frequency increased from 1.8 to 4.9 tests/day.
  • Mean A1C reduced from 9.3 to 8.4.
  • Both adolescents and parents reported high satisfaction.

Clinical Implications:

• Monetary incentives may effectively improve disease management in some adolescents.
• May be a cost-effective strategy for high-risk groups.

Notable Quotes:

• “I think it's very hard for us to have fine teenagers and we can get to do anything. But... if we can have better control of diabetics by partnering with our adolescents, in the long run will be cheaper for the healthcare system.” – Dr. Russell [14:23]
• “Some thinking outside the box approaches... might make a difference for some of the kids that we can pull back from the abyss.” – Dr. Russell [15:25]

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6. EMPA-REG OUTCOME: Empagliflozin and Cardiovascular Outcomes

Source: New England Journal of Medicine, Sept 17, 2015
Timestamps: [15:33 – 20:39]

• 7,020 type 2 diabetes patients with existing CVD assigned to empagliflozin (10 or 25 mg) or placebo; mean follow-up 3.1 years.
• Outcomes:
  • Major CV events: 10.1% (empagliflozin) vs 12.1% (placebo)
  • Death: 3.7% vs 5.9% (38% relative reduction)
  • Hospitalization for heart failure: 2.7% vs 4.1% (35% reduction)
  • Death from any cause: 5.7% vs 8.3% (32% reduction)
  • Number Needed to Treat (NNT): 39 over 3 years

Clinical Significance:

• First diabetes drug trial showing significant reduction in CV deaths and all-cause mortality in the short-term.
• Effects were above and beyond standard-of-care (antihypertensives, statins, etc.)
• Raises clinical questions: class effect vs. drug-specific; applicability to broader diabetes populations.

Notable Quotes:

• “When Silvio Andzucci announced the results... the audience roared with applause, which is an unusual occurrence at a scientific meeting.” – Dr. Skolnik [16:48]
• “This is the first outcome study for any medicine that is primarily for diabetes that has showed a short term... positive effect on total mortality and cardiac outcomes.” – Dr. Skolnik [16:48]
• “Number needed to treat of 39 over three years. To compare that number... original Simvastatin trial... NNT of 30 over five years.” – Dr. Skolnik [19:28]

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Memorable Moments

• The 'active couch potato' concept: Even those who meet exercise recommendations can be at high risk if much of their day is sedentary ([05:58]).
• Audience applause for EMPA-REG: The enthusiasm in the diabetes research community when the empagliflozin trial results were revealed ([16:48]).
• Historical breakfast trivia: A light interlude on how breakfast became a modern staple, adding depth to the breakfast-skipping discussion ([09:44]).

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Final Takeaways

• Metabolic syndrome assessment is crucial in diabetes risk evaluation, more so than weight alone.
• Sedentary habits warrant direct intervention, distinct from advice to increase exercise.
• Breakfast is vital in glycemic control; skipping can have detrimental metabolic effects.
• Microbiome research is promising, though clinical applications remain in early stages.
• Behavioral economics (incentivization) may improve self-management, especially in adolescents.
• Empagliflozin’s CV benefits mark a paradigm shift for type 2 diabetes treatment, with broad implications for practice and upcoming guidelines.

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Further Information

For article links and more, visit www.diabetesjournals.org

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Summary compiled by PodcastAI — covering the latest in diabetes clinical research and practice for healthcare professionals.

Transcript

[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 core science and medical journals Diabetes, Diabetes Care, Clinical Diabetes and Diabetes Spectrum. Joining us for this program are Dr. Neal Skolnick, 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.

[B]

Thank you.

[C]

It's a pleasure to be here.

[A]

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.

[D]

Thank you. I'm looking forward to going over this week's articles.

[A]

And now for the articles.

[E]

We have another excellent issue this month, beginning with an article from Diabetes Care on weight, metabolic dysfunction and risk of type 2 diabetes, then an article on the relationship between sedentary time and type 2 diabetes development, followed by an article discussing the metabolic effects of breakfast versus no breakfast, then an unusual article discussing the effect of lactobacillus insulin response and an article on testing the concept of rewards for self monitoring of blood glucose. And we will end with a seminal article that just came out a few days ago and was announced at the European association for the Study of Diabetes as well as simultaneously published in the New England Journal on empagloflozin and its effect on cardiovascular outcomes and mortality in type 2 diabetes. We are saving this article for last because this is going to become a classic, important article and we want you.

[C]

To hear about it in detail. Our first study is on body weight, metabolic dysfunction and risk of type 2 diabetes in patients at high risk. A total of almost 7,000 patients participating in the Prospective Secondary Manifestations of Arterial Disease cohort study were classified according to BMI and metabolic dysfunction. Risk of type 2 diabetes assessed with biannual questionnaires was estimated. During a median follow up of 6 years. 519 patients developed type 2 diabetes in the absence of metabolic dysfunction that is less than 2 criteria for metabolic syndrome. Adiposity increased the risk of type 2 diabetes compared with normal weight patients with a hazard ratio of 2 and a half for overweight and 4.3 for obesity in the presence of metabolic dysfunction and that was defined as greater than OR equal to three criteria for metabolic syndrome. An increased risk of type 2 diabetes was observed in patients with normal weight and who had metabolic syndrome but not obesity of 4.7 of a hazard ratio, overweight, a hazard ratio of 8.5 and obese with metabolic syndrome. A hazard ratio of 16.

[D]

John so the metabolic syndrome certainly is.

[F]

The quintessential American disease. I think it affects about 40% of American seniors. It affects about 25% of the US adult population.

[D]

This study kind of to me echoes.

[F]

The WOSCOPS trial, the west of Scotland Prevention study, which was a Pravastatin study that looked at metabolic syndrome and see are people more likely to have a cardiovascular event, which they were. One of the arms looked if someone had metabolic syndrome. And metabolic syndrome includes an impaired fasting glucose of one of its five parameters, also including elevated triglycerides, low HDL, increased waist circumference greater than 40 in a man, greater than 35 in a woman, and hypertension.

[D]

So this study would say that if you have metabolic syndrome plus you're overweight.

[F]

You'Re much more likely to be a diabetic than overweight in its own right. But being overweight in its own right isn't increased rate of having diabetes. So certainly probably not a shocker to any of us that people who have kind of started down that metabolic road are going to eventually kind of find themselves in a diabetes arm, which is what they found in the, in the WOSKOPS trial is the people who had three of the metabolic syndrome parameters were much more likely to go on to become overt diabetics.

[D]

Our next article is from Diabetes Care. Its cross sectional and longitudinal association between objectively measured sedentary time and metabolic disease. The Coronary Artery Risk Development in Young Adult study, the Cardia study, which was in Diabetes Care. So in this particular study was a 20 year follow up of 2027 young adults who were first studied in 1985 and 86 who are now 38 to 50 years of age. They're 57% female and they have a mean BMI of 29. They followed these folks with pedometers and measured 20 year follow ups of a variety of metabolic factors.

[F]

Glucose, insulin, two hour glucose.

[D]

What they looked at was how much sedentary time a person has and the average Sedentary time was 8.1 plus or minus 1.7 hours per day. Each additional hour per day of sedentary time was cross sectionally associated with a 3% higher fasting insulin having more than 10 hours per day versus less than 6 hours a day of sedentary time was associated with an odds ratio of 2.74 of having impaired fasting glucose and an odds ratio of 3.8 for having diabetes.

[C]

Neil John, this is really interesting. We know and have known for a long time the relationship between poor exercisers and an elevated risk of diabetes and heart disease, and actually a relationship between a lack of exercise and increased mortality in both young, middle aged and older adults. Recently, this idea of sedentary time has emerged as a related but separate issue with regard to cardiovascular risk and risk for diabetes. And essentially what it says is that you can exercise, but if you're sedentary all day long as separate from exercise. The term that's been coined is the active couch potato, someone who exercises their 150 minutes a week but sits at work, sits on the train, sits in the car, and sits and watches TV at night. That sedentary time as a separate parameter from exercise incurs both cardiovascular and diabetes risk. This study is pretty impressive in support of that concept. And here when we see that sedentary time of greater than 10 hours a day compared to less than 6 hours a day leads to an increased risk of diabetes of almost fourfold, that grabs our attention. What does that mean from a practical point of view? From a practical point of view, it means that we ought to, when we find ourselves sitting for a prolonged period of time, try to, when possible, break that up with periods of walking around. The next study is titled Fasting until noon triggers increased postprandial hyperglycemia and impaired insulin response after lunch and dinner in individuals with type 2 diabetes. We know that skipping breakfast has been consistently associated with a high A1C in patients with type 2 diabetes. This study looked at a crossover design of 22 patients with diabetes who had a mean diabetes duration of eight years, a BMI of 28 and average A1C of 7.7, and they were randomly assigned to two test days, one day with breakfast, lunch and dinner, another day without breakfast but a normal lunch and dinner. Postprandial glucose, insulin C, peptide free fatty acid, glucagon and intact glucagon peptide were assessed compared with eating breakfast lunch area under the curve for 0 to 180 minutes for plasma, glucose free fatty acids and glucagon were 36, 41 and 14% higher, whereas the area under the curve for insulin was 17% lower on the no breakfast days, reaching a significant P value. Similarly, dinner areas under the curve were also higher for glucose free fatty acids and glucagon and area under the curve for insulin response was lower on no breakfast days compared to days when people ate breakfast. Furthermore, peak Insulin was delayed 30 minutes after lunch and dinner on the days where people didn't eat breakfast.

[D]

John so I think this is very.

[F]

Interesting and I think for years we've been telling people if they're trying to lose weight that they should indeed eat some breakfast. And breakfast is really important. If you look at a lot of the commercial weight loss plans, they encourage.

[D]

People to eat breakfast. When you look historically, breakfast was really.

[F]

Not something that was eaten until the 17th century.

[D]

Queen Elizabeth was one of the first.

[F]

Folks who started to eat a breakfast. It was associated with gluttony, but back then people didn't have a whole lot of calories. So it really didn't matter if you didn't have your first meal until later in the day. Meals were a lot harder to come.

[D]

By when we think about kind of.

[F]

The advent a little more of the modern breakfast. Kellogg's cereal was founded by a physician. John Harvey Kellogg was a physician and was an advocate of a vegetarian diet, but certainly was an advocate of and started Corn Flakes cereal. So certainly we'd like people to eat some breakfast in the morning. And I think this is a very important paper that we can go to.

[D]

Our patients and say, look, if you skip breakfast, you're setting yourself up metabolically.

[F]

To have a lot more mess after lunch and after dinner. So I think having at least a light breakfast to kind of control a little bit of the metabolic storm that might be coming makes lots and lots.

[D]

Of sense for our patients.

[F]

Our next article is from Diabetes Care.

[D]

And it looked at the intake of Lactobacillus reuteri and its approval of incretin and insulin secretions in glucose tolerant humans. This was a prospective double blind randomized trial performed in 21 glucose tolerant humans who had a mean age of 49 and a mean BMI of about 23.6 and 10 obese patients with a mean age of 51 and a mean BMI around 35. The participants ingested 10 to the 10 bid Lactobacillus reuteri or placebo over a four week period. Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess the incredin effect in GLP1 and GLP2 secretions. They also used techniques to measure peripheral insulin sensitivity and endogenous glucose production. What they found was in the glucose tolerant volunteers that the daily administration of Lactobacillus reuteri increased glucose stimulated GLP1 and GLT release by 76 and 43% respectively compared against placebo along with a 49% higher insulin and 55% higher C peptide secretion. Although over this period of time they did not find any effect on body mass.

[C]

Neil John, it's pretty mind boggling to think that we're looking at a study that's assessing whether Lactobacillus would increase insulin response. There's all sorts of theories out there about the increase in diabetes over the last 25 years. One of them that has been talked a lot about is the effect the changing microbiome of Americans partly due to overuse of antibiotics both in cattle and in people. I think this study, which addresses the microbiome theory and also suggests some possible solutions, really only suggests to us that anytime we think we know what is going on, we're going to find out that we didn't and we're going to learn more and that the potential therapies that we may see in the future for diabetes are both exciting and hard to imagine. So it's important to keep an open mind about this. And this is some good data about insulin response to Lactobacillus. Our next study is on testing for rewards, a pilot study to improve type 1 diabetes management in adolescents. And this study sought to evaluate the effectiveness of monetary reinforcement to increase the frequency of self monitoring of blood glucose among adolescents. They looked at 10 adolescents with poorly controlled diabetes and they enrolled them in a 12 week program in which the teenagers earned monetary reinforcers based on the frequency of self monitoring of their blood glucose. They earned a dime per test with bonuses for greater than four tests a day with a maximum of $250 over the course of the 12 week study. What they found was that self monitoring of blood glucose increased from 1.8 to 4.9 tests per day. So that's a significant p value with 90% of the adolescents completing four more tests per day. Interestingly mean A1C fell from 9.3 to 8.4. Adolescent and parents reported high satisfaction with the protocol.

[D]

JOHN so I think this is very interesting and it's, I think it's very hard for us to have fine teenagers and we can get to do anything. But you know, if we're thinking about the big picture, if we can have.

[F]

Better control of diabetics by partnering with our adolescents in the long run will.

[D]

Be cheaper for the healthcare system.

[F]

So perhaps for this kind of subset.

[D]

Of a group it might be something to kind of think about as a long term.

[F]

In the book Freakonomics, they looked at.

[D]

A Chicago school system that kind of.

[F]

Found some struggling kids and whether they should get payment for grades. And it was not a hundred percent kind of win win. There were kids that were fail that really the financial incentive made no difference.

[D]

But there were some kids whose grades.

[F]

Were in that kind of CDF group, in the Freakonomics, that they made some financial incentives, that they swung all their grades to passing with a little financial incentive.

[D]

So perhaps there are incorrigible type 1.

[F]

Diabetics who we are not going to get to make some changes, but perhaps.

[D]

Some changes like this, some thinking outside.

[F]

The box approaches to this might make.

[D]

A difference for some of the kids.

[F]

That we can pull back from the.

[D]

Abyss and our last article is from the New England Journal of Medicine, the September 17, 2015 edition and it looked at empagliflozin cardiovascular outcomes and mortality in type 2 diabetes. In this particular study they took patients with existing coronary artery disease and diabetes. Of these 7020 patients, they were randomized to receive either 10 or 25 milligrams of empagliflozin or placebo and were followed for 3.1 years. The major outcome that they were looking for was major adverse cardiovascular events. They found that these major adverse Cardiovascular events happened 10.1% of the time in the patients on empagliflozin versus 12.1 in the patients on placebo. Death occurred in 3.7% of the patients in the empagliflozin group and 5.9% in the placebo group with a 38% risk reduction. They also found a decrease in risk for hospitalization for heart failure of 2.7 and 4.1% respectively, with a 35% risk reduction and overall a decreased death from any cause from 5.7 to 8.3% respectively, with a 32% relative risk reduction.

[C]

Neil John the results of this trial were announced at the European association for the Study of Diabetes Annual meeting and simultaneously published in the New England Journal of Medicine last Thursday. When Silvio Andzucci announced the results of this study, the audience roared with applause, which is an unusual occurrence at a scientific meeting. This is the first outcome study for any medicine that is primarily for diabetes that has showed a short term meaning three year old positive effect on total mortality and cardiac outcomes. What's interesting when you look at the graphs of when the effect began to occur, you actually see the placebo and the active empagliflozin group begin to diverge at about three months into the study, which is far shorter than what one would expect. Certainly if the reason for that divergence of curves is the effect of blood sugar on atherosclerotic disease. There was an improvement in blood sugar of about a half a point of a 1C in the empagliflozin versus the control group, there was an improvement in blood pressure also in the empagliflozin group. It's interesting when you look at the outcomes here, you have to also acknowledge that this was an improvement in heart failure and total mortality and cardiac mortality that occurred on top of existent optimal treatment. So these patients were all on medicines for hypertension, all on statins for treatment of the hypercholesterolemia and there still was a number needed to treat of approximately 39 over three years. To compare that number and that effect, let's go back to the original Simvastatin trial that was done in people at high cardiac risk but not already on a statin and that had a number needed to treat of 30 over five years. The Ramaprilace trial had a number needed to treat a 56 over five years and this trial has a number needed to treat of 39 over three years. So it fits into that collection of outcome studies with impressive outcomes that have become our standard of care. A question that is going to remain is which patients will best benefit from this? Is it all patients with diabetes or to be more strictly evidence based patients that fit the group of patients in this study which were those at very high cardiovascular risk. The other question that remains is is this a class effect of the SGLT2 inhibitors or is this something particular to empagliflozin? We will be seeing other SGLT2 cardiovascular studies come out, but we'll have to wait quite a while for those results because those are not coming out till 2017-19. For now, this study is incredibly exciting. It's the first study of a diabetes medicine to show a short term meaning three year effect on both cardiovascular mortality, macrovascular disease as well as total mortality. I look forward to seeing in January when the guidelines from the American Diabetes association comes out how this information will be integrated into our standard of care. And you know, we'll review the standards of care in January when they come.

[B]

Out.

[D]

And we'd like to just tell.

[F]

Our listeners if they are going to be at the National Family Medicine Convention in Denver at the end of September beginning of October. Neil and I will be doing a diabetes brain game on Thursday night at 7 o'.

[B]

Clock.

[D]

If you can join us for this.

[F]

Academic symposium, we'd love to meet you face to face.

[C]

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.

[B]

SA Sam.