Diabetes Core Update August 2015

Summary

Diabetes Core Update – August 2015 (Released July 24, 2015)

Overview

In this episode of Diabetes Core Update, Drs. Neil Skolnik and John J. Russell discuss six key articles from the American Diabetes Association’s clinical journals, aimed at offering practicing clinicians insights with direct application to patient care. Topics range from the influence of socioeconomic status on diabetes outcomes, to the role of vitamin D, strategies to minimize hypoglycemia, the physiological variability of weight loss, telemedicine for youth diabetes management, and the impact of exercise on type 1 diabetes.

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Key Discussion Points & Insights

1. Socioeconomic Status and Outcomes in Type 1 Diabetes

[00:55–03:16]

• Study Details: Analysis of 24,947 Swedish patients with type 1 diabetes, mean age 39, followed for 6 years—examined the relationship between socioeconomic factors and rates of CVD and mortality.
• Findings:
  • Being married is associated with a 50% lower risk of death, cardiovascular death, and diabetes-related death versus being single.
  • Those in the lowest income quintiles have twice the risk of fatal/non-fatal CVD, coronary heart disease, and stroke, and three times the risk of death versus the highest quintile.
  • Individuals with college degrees saw a 33% lower risk of stroke compared to those with less education.
• Contextual Reflection:
  • “People who have more stable home lives are more likely to take better care of themselves…”
    – Clinician, [03:16]
  • Discussed access disparities in the U.S. vs. Sweden; highlighted how newer diabetes medications are less accessible to uninsured/underinsured.

2. Effect of Vitamin D Supplementation on Glycemic Control (The SUNNY Trial)

[03:32–05:34]

• Study Details: 275 non-insulin dependent type 2 diabetes patients randomized to vitamin D3 (50,000 IU/month) or placebo for 6 months; primary outcome: A1C change.
• Results:
  • No significant effect on A1C or glycemic outcomes in the overall group, despite increased vitamin D levels.
• Expert Commentary:
  • Dr. Skolnik warns against overinterpreting the value of vitamin D supplementation for glycemic control:
    “There are a lot of people out there who believe vitamin D is the cause of everything from hangnails to diabetes. But as the Wendy’s commercial said years ago, where’s the beef? We as clinicians want solid evidence.”
    – Dr. Skolnik, [05:34]
  • Suggests low vitamin D is more likely linked to unhealthy behaviors (e.g., less outdoor activity) than a direct cause of poor diabetes control.

3. Hypoglycemia Minimization in Diabetes

[05:34–11:50]

• Overview: Review of hypoglycemia classification, frequency, risk factors, and prevention strategies.
• Key Definitions:
  • Severe: Requires assistance (carbs/glucagon).
  • Documented symptomatic: Symptoms plus low glucose.
  • Asymptomatic: Low glucose, no symptoms.
• Epidemiology:
  • 30-40% of type 1 diabetics have 1-3 severe episodes/year.
  • Insulin-treated type 2 diabetics: ~⅓ of those rates.
• Physiology: As glucose falls, normal defense is decreased insulin and increased glucagon/epinephrine. In diabetes, these responses are blunted, especially with repeated hypoglycemia.
• Practice Recommendations:
  • Educate all diabetes patients about hypoglycemia.
  • Monitor for symptomatic events at every visit.
  • Adjust A1C targets and therapies (especially in patients with frequent or unrecognized hypoglycemia).
  • Favor insulin analogs, continuous glucose monitoring, and de-emphasize sulfonylureas where possible.
• Notable Commentary:
  • “Hypoglycemia can be very important…there’s an increased mortality when someone has hypoglycemia, especially elderly folks.”
    – Clinician, [11:50]
  • Emphasized individualized A1C targets, especially for older adults:
    “Are we setting an A1C goal for a 25-year-old or for a 75 or 85-year-old? They should be much different goals and that’s going to lead to a healthier population.”
    – Clinician, [11:50]

4. Individual Variability in Weight Loss: The “Thrifty Phenotype”

[13:43–14:42]

• Study Details: 15 healthy individuals confined and monitored for 77 days; measured changes in energy expenditure during caloric restriction and overfeeding.
• Findings:
  • Major inter-individual differences (>50%) in metabolic adaptation to the same calorie deficit/overfeeding.
  • Some lose less than expected due to marked reductions in metabolic rate and daily movement.
• Clinical Takeaway:
  • “That person who tells you in the office that ‘I really have decreased my caloric intake…but I’m not losing weight’ may actually be telling the truth.”
    – Dr. Skolnik, [14:42]
  • Weight loss is not purely mathematical; both metabolic adaptation and activity levels matter.
  • Recommends emphasizing increased physical activity alongside dietary change to counteract metabolic adaptation.

5. Telemedicine for Youth Diabetes: Skype vs. In-Person Behavioral Therapy

[17:00–18:52]

• Study Details: Adolescents aged 12–18 with type 1 diabetes (A1C >9%), and caregivers, randomized to family therapy via Skype or face-to-face in clinic.
• Outcomes:
  • Both groups saw significant improvements in glycemic control and adherence.
  • No difference between the delivery modes.
• Implications:
  • “Care was not necessarily better with Skype, but it was equivalent...As people are busier, this certainly seems to be a very convenient way to do the exact same thing.”
    – Dr. Russell, [18:55]
  • Telemedicine can increase access to best practices, especially for families distant from specialty care.
  • Main barrier is payor acceptance and reimbursement for virtual care.

6. Exercise and Type 1 Diabetes Outcomes

[20:00–21:22]

• Study Details: >18,000 adults (18–80) from Germany/Austria, categorized by self-reported exercise frequency.
• Findings:
  • More physical activity was associated with better A1C, lower rates of ketoacidosis, obesity (BMI), dyslipidemia, hypertension, and fewer microvascular complications (retinopathy, microalbuminuria).
• Expert Perspective:
  • “If we had one drug to give people and only one choice, it would probably be exercise.”
    – Dr. Skolnik, [21:22]
  • Exercise should be a cornerstone of diabetes care, but motivating patients remains challenging.

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Notable Quotes & Memorable Moments

• Vitamin D skepticism:
  “As the Wendy’s commercial said years ago, where’s the beef? We as clinicians want solid evidence before we start using information to treat patients.”
  – Dr. Skolnik, [05:34]

• On hypoglycemia in elderly patients:
  “There’s an increased mortality when someone has hypoglycemia, especially elderly folks.”
  – Clinician, [11:50]

• Lived reality of patients with “thrifty” metabolism:
  “That person who tells you in the office that ‘I really have decreased my caloric intake…but I’m not losing weight the way I expected’ may actually be telling the truth...”
  – Dr. Skolnik, [14:42]

• Telemedicine equivalence:
  “Care was not necessarily better with Skype, but it was equivalent...for diabetic education, this could put best practices available to lots and lots of segments of the American population.”
  – Dr. Russell, [18:55]

• Value of physical activity:
  “If we had one drug to give people and only one choice, it would probably be exercise rather than a lot of the other things we prescribe.”
  – Dr. Skolnik, [21:22]

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Timestamps for Important Segments

• Socioeconomic status in type 1 diabetes: [00:55–03:16]
• Vitamin D and glycemic control (SUNNY trial): [03:32–05:34]
• Minimizing hypoglycemia: [05:34–11:50]
• Thrifty phenotype and variable weight loss: [13:43–14:42]
• Skype vs. in-person therapy for youth diabetes: [17:00–18:52]
• Exercise in type 1 diabetes: [20:00–21:22]

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Summary

This episode highlighted practical, evidence-based insights for diabetes clinicians:

• Social/financial resources and education protect against negative outcomes in type 1 diabetes.
• Vitamin D supplementation does not improve glycemic control in type 2 diabetes without deficiency.
• Hypoglycemia is frequent and dangerous—prevention, education, and individualized targets are essential, especially in older adults.
• Weight loss responses to diet are highly individual; exercise is a critical tool to counter adaptation.
• Telemedicine, specifically Skype, is effective for behavioral interventions in youth with type 1 diabetes and expands access.
• Exercise remains one of the most powerful interventions for improving outcomes in type 1 (and all) diabetes.

For further reference and full articles, visit www.diabetesjournals.org

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Episode Tone: Clinical, focused, evidence-based, practical, with accessible and sometimes candid commentary aimed at practicing healthcare professionals.

Transcript

[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 four 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. Skolmik.

[Dr. Neal Skolnik]

Thank you. It's a pleasure to be here.

[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.

[Dr. John Russell]

Thank you.

[Another Medical Expert/Clinician]

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

[Host]

And now for the articles.

[Dr. Neal Skolnik]

We have another excellent issue this month, beginning with an article from Diabetes Care on socioeconomic status and outcomes in patients with type 1 diabetes. Then an article looking at the effect of vitamin D supplementation on diabetic outcomes. Then an article from Diabetes Care on minimizing hypoglycemia, followed by an article from Diabetes that is fairly phenomenal on a very carefully done study under controlled conditions looking at individual responses to caloric restriction and overfeeding. Then an article from Diabetes Care on using Skype to improve diabetic outcomes in youth. Then also from Diabetes Care an article looking at the effects of exercise on outcomes in patients with type 1 diabetes. Our first article from Diabetes Care is on the impact socioeconomic status on cardiovascular disease and mortality in over 24,000 individuals with type 1 diabetes. Socioeconomic status is a powerful predictor of cardiovascular disease and death and this study used clinical data from the Swedish National Diabetes Register, linked to national registers, to look at outcomes. They included 24,947 patients. Mean age and follow up was 39 years of age and 6 years of follow up. Death and fatal and non fatal cardiovascular disease occurred in 926 people and 1378 people. Compared with being single, being married was associated with a 50% lower risk of death, cardiovascular death and diabetes related death. Individuals in the two lowest quintiles had twice as great a risk of fatal and non fatal cardiovascular disease, coronary heart disease, stroke and roughly three times as great a risk of death, diabetes, death and cardiovascular disease as individuals in the highest income quintile. Compared with having less than nine years of education, individuals with a college degree had a 33% lower risk of stroke.

[Another Medical Expert/Clinician]

John so not really all that surprising on lots of different reasons. So certainly people who have more stable home lives are more likely to take better care of themselves, etc.

[Dr. John Russell]

When you look at the landscape of.

[Another Medical Expert/Clinician]

Diabetes, there's probably never been a better time, medication wise to be a diabetic. That said, it's never been a better time to be a diabetic if you have insurance. We've seen a lot of new classes of medicines that have emerged over the last few years. So as physicians we have a lot more choices. But almost all these choices are running in that $300 a month range for patients. So folks who are uninsured or underinsured and can't avail themselves to some of these newer things, and these are type one diabetics, so we're not going to be using a lot of those medications. But certainly that is kind of proof of concept. When the Affordable Care act was approved, there was a 10 year old boy who was standing next to the President when he signed the act and it was a 10 year old boy whose mother died of a fibroid tumor, who worked cleaning motel rooms and she had no insurance and she died of a very preventable disease. So certainly Sweden, which would have a nationalized health system, probably feels less of this one than we do in the United States, but certainly an issue we should consider to talk about whether we are for or against the Affordable Care Act. Our next article is from Diabetes Care and it looked at the effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes was called the SUNNY trial which was a randomized placebo controlled trial of 275 adult patients with type 2 diabetes who were not on insulin. Patients were randomly assigned to receive either vitamin D3 at 50,000 IUs per month or or placebo for six months and the primary outcome measured was a change in A1C. The baseline 25 hydroxy increased from 60.6 to 101 in the treatment group in 59.1 to 59.8 in the placebo group. The baseline A1C was 6.8 in both groups. After six months, no effect was seen on A1C and other indication of glycemic control in the entire study population.

[Dr. Neal Skolnik]

Neil John Basically this study looked at individuals whose diabetes was relatively well controlled who had vitamin D levels that were in the lower end of normal. People who are advocates of vitamin D repletion would have called these levels frankly low. But ultimately it didn't show any effect of vitamin D repletion on outcomes in patients with diabetes. We reviewed another paper about two years ago by Mayer Davidson on the effect of repleting vitamin D in patients with prediabetes who actually had low vitamin D levels. And that paper also showed no effect. There are a lot of people out there who believe that vitamin D is the cause of everything from hangnails to diabetes. But as the Wendy's commercial said years ago, where's the beef? We as clinicians want solid evidence before we start using information to treat patients. And there really is very little evidence showing that repletion of vitamin D helps diabetes outcomes. The evidence that's there relates low vitamin D levels to poor glycemic control or to an increased incidence of vitamin D. But that is simply a may be a confounding variable that it might be that people who are exercising less or outside less and have other less healthy behaviors also have low vitamin D levels. But it isn't the low vitamin D. It's the other unhealthy behaviors like a lack of exercise that are more related to diabetes outcomes. This study as well as others does not show any relation between vitamin D repletion and better diabetes outcomes. Our next article from from Diabetes Care is on minimizing hypoglycemia in diabetes. This paper emphasizes understanding both the classification as well as how to minimize the frequency of hypoglycemia in diabetes. It does not talk specifically about what to do once hypoglycemia occurs. The paper discusses classification and frequency of hypoglycemia in diabetes. Severe hypoglycemia is classified as an event requiring assistance of another person to actively administer carbohydrates or glucagon. Documented symptomatic hypoglycemia is an event which typically you have symptoms of hypoglycemia accompanied by a low measured plasma glucose and asymptomatic hypoglycemia is an event not accompanied by typical symptoms. Hypoglycemia is common in diabetes. Population based data indicate that 30 to 40% of people with type 1 diabetes experience an average of one to three episodes of severe hypoglycemia each year. Those with insulin treated type 2 diabetes experience about 1/3 that number. The rates of any type of hypoglycemia are actually about 50 fold higher than those of severe hypoglycemia. The pathophysiology of hypoglycemia is that as plasma glucose concentrations fall, the prevention or rapid correction of hypoglycemia normally involves physiologic defenses that include a decrease in insulin release and an increase in glucagon. In the absence of an increase in glucagon, an increase in epinephrine occurs. Hypoglycemia and diabetes is typically the result of the interplay of therapeutic interventions such as a sulfonylurea, a glynide or insulin and compromised physiologic and behavioral defenses against the resulting fall in plasma glucose. The compromised defenses, including a loss of decrease in insulin and a loss of increase in glucagon, are probably the result of beta cell failure. Attenuation of the sympathoadrenal response is believed to cause the clinical syndrome of impaired awareness of hypoglycemia, which increases as the risk of hypoglycemia, which increases the risk of hypoglycemia by about six fold. Defective glucose counter regulation and impaired awareness of hypoglycemia are components of an important syndrome called hypoglycemic autonomic failure that becomes more and more common as people experience more episodes of hypoglycemia, making it critical to avoid hypoglycemia. Recommendations the International Hypoglycemia Study Group include making sure that we educate all patients with diabetes about hypoglycemia, that we treat blood glucose levels less than 70 to avoid progression to clinical iatrogenic hypoglycemia, that we regularly ask patients at each visit are they having hypoglycemia and those developing symptoms at a glucose level less than 55 should be considered at significant risk and perhaps should have their goal a 1Cs relooked at and their therapies readjusted. When hypoglycemia becomes a problem, we ought to consider looking at thinking about compromised glucose counter regulation and changing someone's therapy to avoid sulfonylureas. If possible, we might consider using insulin analogs when insulin is required and even consider continuous glucose monitoring if that is available and appropriate for the patient. Sending a patient again for further diabetes self management education so they better understand what to look for. And while we always Try to balance a 1C control with avoiding hypoglycemia, that would be a time to pull back on a 1C control so as to minimize the frequency of hypoglycemia so someone can reset their counter regulatory and awareness mechanisms.

[Another Medical Expert/Clinician]

John so for many years as clinicians we've been very focused on hyperglycemia, but I think what we've learned over the last few years is hypoglycemia can be very very important. So six randomized controlled trials looked at hypoglycemia and its effect on cardiovascular health. And it was not good. There's an increased mortality when someone has hypoglycemia, especially elderly folks. So going back to the DCCT trial, there was a lot of hypoglycemia in these type 1 diabetics with better control, but they were younger folks. What we've learned in older folks is there could be increased mortality with tighter A1C controls. And that's why a court in advance did show some increased increased mortality with lower A1Cs. So hypoglycemia should come into play when we're thinking about giving medicines to patients. Do they understand the signs and symptoms of hypoglycemia? Can they test from hypoglycemia? Can they treat for hypoglycemia? So I think it's a big part of which medicines we select or do not select. And I think the sulfony areas are not a most favored nation as they once were for medications. And I think on the other end, we need to realistically look at our A1C goals. Are we setting an A1C goal for a 25 year old or are we setting an A1C goal For a 75 or 85 year old? They should be much different goals and I think that's going to lead to a healthier population. And thirdly, every time we see a patient in the office, we should ask them, since we last have seen them, have they had hypoglycemic events, symptomatic hypoglycemic events, and we need to make changes unless there's some some clear reason, clear transient reason on why that happened, otherwise we should be making changes to avert the next episode of hypoglycemia.

[Dr. John Russell]

Our next study is from diabetes and it looked at a human thrifty phenotype associated with less weight loss during caloric restriction. In this particular study that went on between 2008 and 2013, 50 healthy individuals.

[Another Medical Expert/Clinician]

Were evaluated during a weight maintaining period where they had 24 hour energy expenditure. Responses to both fasting and 200% overfeeding were measured in a whole room indirect calorie measuring situation volunteers that underwent six weeks of 50% calorie restriction. The researchers calculated daily energy deficit during caloric restriction. They incorporated energy intake and waste energy expenditure and daily activity. They found that a small reduction in 24 hour energy expenditure during fasting and to a larger response to overfeeding predicted.

[Dr. John Russell]

More weight loss over the six weeks.

[Another Medical Expert/Clinician]

Even after they accounted for age, sex, race and baseline weight.

[Dr. Neal Skolnik]

Neil John, this is a mind boggling study that I think confirms with what many of us have believed to be the case based on our interaction with patients in the. The fact that they were able to get these 15 people to live in a room under incredibly controlled conditions for on the average 77 days is amazing. Measuring everything they ate during a period of both caloric restriction and overfeeding and then measuring every movement they made and energy expenditure is simply amazing. And the things we learn from that should be valued. And basically what this showed was that people respond differently to the same level of caloric restriction in terms of the change in their basal metabolic rate and overall energy expenditure. And there's greater than a 50% difference among different people on the same amount of caloric restriction to what the response is of their basal metabolic rate and energy expenditure. What that basically means is that person who tells you in the office that I really have decreased my caloric intake by whatever it is we set by a few hundred calories a day, but I'm not losing weight the way I expected may actually be telling the truth that it isn't. What we used to think of is if you decrease your caloric intake by 3,500 calories, calories, we'd lose a pound of body weight. But actually that doesn't appear to be the case because there's offsetting changes in our metabolic rate and energy expenditure. And remember, those are two different things. Our metabolic rate is a basal rate. Our energy expenditure is influenced by the amount we move around so that we all respond differently to the same amount of both caloric restriction and overeating. What does that mean for us from a practical point of view in the office, what it means is that we can't rely solely on diet to achieve weight loss goals in a predictable way. We really do have to use both diet and exercise. And since we can control the amount of exercise we do if we're enthused and motivated to. If you're not losing the weight that you anticipate, it may be because your body has lowered its metabolic rate that you're unconsciously moving around less. And then you have to dial up the amount of exercise you're doing to offset and I think that's the take home lesson for us in the office, that there's inner individual variability in response to changes in diet and that that may be able to be offset by increases in exercise level. Our next article is from Diabetes Care on using Skype to improve diabetes outcomes in youth. The objective of this study was to compare the Relative effectiveness of two different modes of delivering behavioral family systems therapy to improve adherence and glycemic among adolescents with type 1 diabetes and suboptimal glycemic control who had an average A1C greater than 9% and they compared face to face therapy in the office with Internet video conferencing through Skype. Adolescents aged 12 to 18 and at least one adult caregiver were randomized to receive therapy via the clinic or Skype. Participants completed up to 10 therapy sessions within a 12 week period using an intent to treat approach. No significant difference was detected between groups either before or after or during follow up assessments. Results identified that statistically significant improvements in adherence and glycemic control occurred from before to after intervention in both groups without any differences between groups and were maintained at three month follow up.

[Another Medical Expert/Clinician]

John so I think this is very interesting.

[Dr. John Russell]

I think if you talk to us old timers we're going to say you need to have the patient in front of you, you know, etc. Etc. But the world is changing and I think this is a good example that care was not necessarily better with Skype, but it was equivalent to Skype. And I think as we have a younger generation, I think as people are busier, as the world is more connected, this certainly seems to be a very convenient way to do the exact same thing. And certainly there are examples of doing CBT through video modules and things like that. So for diabetic education, for a lot of us in the United States, we don't necessarily live close to a place that is a great children's hospital for educating young people about diabetes and families are often traveling a great distance. So certainly this could put best practices available to lots and lots of segments of the American population through Skype. So I think it's something we should be thinking about and I think it's a way to kind of bring patient care to folks homes and really kind of take all the travel time and all the waiting time out a little bit and get the same level of care. Hopefully there'll be more consistent follow through when people are able to make appointments. But I think it's very interesting. The bottom line though, we need to figure out a way to pay for this. So we need to say that these are equivalent mechanisms, these are equivalent methods and we're going to pay for them the same way. Our last article is from Diabetes Care and it looks at the impact of physical activity on climate, glycemic control and prevalence of cardiovascular risk factors in adults with type 1 diabetes. So this was a study of over 18,000 adults between 18 and 80 years of age from Germany and Austria who had type 1 diabetes. The patients were stratified according to their self reported frequency of activity, either inactive, active one to two times per week or active more than two times per week. The researchers did Multivariable regression models were applied for glycemic control, diabetes related comorbidities and cardiovascular risk factors. There was an inverse association found between physical activity in A1C ketoacidosis, BMI, dyslipidemia and hypertension, as well as between physical activity and retinopathy and microabinuria.

[Dr. Neal Skolnik]

Neil John this study, I'll have to admit, was not surprising to me. We know that in patients with type 2 diabetes, exercise gives you better outcomes. We know that in middle aged individuals without diabetes, if you exercise, you have a lower risk of developing diabetes, you have a lower risk of developing heart disease. We know that exercise also gives you a lower risk of, interestingly, breast cancer and colon cancer, benefits that are not as well recognized, the lower risk of depression. It's if we had one drug to give people and only one choice, it would probably be exercise rather than a lot of the other things we prescribe. The challenge, of course, with exercise is motivating people to carry out the exercise that now an abundance of data tells us is so beneficial for them. For more information and links to the article that we discussed in this issue, just go to www.diabetesjournals.org until next week, keep listening and keep learning. It.