International Society for Pediatric and Adolescent Diabetes (ISPAD)

October 30-November 2, 2019; Boston, MA; Days #3-4 Highlights

Executive Highlights

  • ISPAD featured an international focus in its second half over the weekend, with Dr. Thomas Danne showing promising data from the SWEET type 1 registry (Europe, Australia, Canada, and India). Over the past ten years, the median A1c in the registry dropped by 0.4%, from 8.2% to 7.8% and pump use increased from 8%.

  • Dr. Graham Ogle from Life for a Child shared some inspiring data on the potential for “intermediate” levels of diabetes care in low-resources countries to hugely change mortality and complications rates: in Mali, Dr. Ogle estimated that moving from minimal care to intermediate care could improve 30-year survival rates by more than five times.

  • Dr. Revital Nimri from DreaMed presented the design of the Advice4U study, a multi-center trial comparing glycemic outcomes using pump setting recommendations from Advisor Pro and a trained physician, and results from a physician satisfaction questionnaire. After six months of use, physicians rated Advisor Pro as “intuitive and safe,” “reliable,” “safe,” and “saved time,” on a 5-point Likert scale. Eleven out of thirteen physicians stated they would want to keep using Advisor Pro as part of their routine practice. 

  • Sanofi presented results from the EDITION JUNIOR trial of Toujeo (insulin glargine U300) in a pediatric population, with Toujeo demonstrating non-inferiority against Lantus in A1c reduction, severe hypoglycemic events, and hyperglycemic DKA. Results of this trial, the first RCT comparing insulins in a pediatric population, may lead to an EMA approval for Toujeo to treat type 1 diabetes in children ages six and over in the EU.

  • Other noteworthy presentations centered on the socio-behavioral and psychological aspects of type 1 diabetes management. Dr. Colin Hawkes discussed the promise in community health worker interventions that go beyond diabetes management education to improve glycemic control. Dr. Regitze Pals outlined the challenges pre-teens with type 1 diabetes and their families face in diabetes care, while Drs. Angela Galler and Julia Blanchette talked about the benefit of psychological care for type 1 and the burden finances may have on preventing emerging adults from accessing this ancillary treatment, respectively.

Greetings from Boston, the home of the first US chocolate factory, public park, and American lighthouse! Even though ISPAD 2019 has come to a close, the last few days were equally as full of excitement and learning as the first two – see our top highlights below!

ISPAD Day #1 Highlights - Lessons and strong results from telehealth-driven CoYoT1 care model; Kelly Close looks back and ahead; KOLs galore: Ms. Laurel Messer, Prof. Chantal Mathieu, and Dr. Simeon Taylor

ISPAD Day #2 Highlights - AI-model to predict A1c rises, Roy Beck on beyond A1c, impressive Basal-IQ real-world data, Jeff Hitchcock shares severe hypo stories, and more

Top Six Highlights

1. 10-Year SWEET Type 1 Registry (Europe, Australia, Canada, and India) Data: Median A1c Dropped 0.4% and Pump Use Increased From 38% to 46%

Dr. Thomas Danne (Hannover Medical School), seemingly present everywhere at ISPAD, gave a quick update on data from the SWEET type 1 registry, showing median A1c dropped from 8.2% to 7.8% from 2008-2010 to 2016-2019. The SWEET registry data, compiled from 21 centers across Europe, Australia, Canada, and India from type 1s under the age of 25, also showed an increase in pump use from 38% to 46% over the ten years. The first observation period, from 2008 to 2010, was composed of 4,772 patients (mean age 11 with diabetes duration of 3 years). The second observation period, from 2016 to April 2019, had data from 12,750 patients (mean age 13 with diabetes duration of 4 years). Notably, the mean A1c showed statistically significant decreases across all age groups, as shown in the table below. Lastly, during Q&A, Dr. Danne shared that data from the first ~1,000 patients on CGM had been gathered, showing an average time-in-range of 51%.

Age Group

Median A1c, 2008-2010

Median A1c, 2016-2019

<6 years

7.9%

7.4%

6-<12 years

8%

7.5%

12-<16 years

8.3%

7.9%

>16 years

8.4%

8.2%

Questions and Answers

Q: Have you looked at the lag between change in A1c and pump use. You would think A1c changes on a clinic-visit to clinic-visit basis, while pump use is probably more systematic. If pump is leading A1c change, you should see pump use increase before the A1c decline.

A: It’s difficult to adjust for all these things. I’d guess your hypothesis is right, but I cannot support it yet with data. We will certainly look into that. Just to give you a feel, we have the initial 1000 patients’ data on CGM, and it has an average time-in-range of 51%.

Q (Dr. Tadej Battelino): The T1D Exchange showed a worsening A1c, and the SWEET is showing a significant improvement, yet there are actually more pumps used in the T1D Exchange. Do you have explanation?

A: One point is that the T1D Exchange is not necessarily representative of the centers. They have select data in their centers and for any type of benchmarking, the completeness of data and looking at things like loss to follow-up are very important. Also, SWEET has peer-review to look into how centers are collecting their data and their healthcare delivery. This is also a point of improvement within the center, which is extremely important. There’s a whole package that SWEET is offering. The T1D Exchange is now starting a quality improvement initiative also that we hope will be successful. We’re looking for possibilities to work together and I’m very optimistic that we’ll find ways to do so.

2. Intermediate Care (2-3 Fingersticks/Day, Human Insulin MDI, Diabetes Education) Is Cost-Effective and Can Increase Survival Rates by Five Times in Low-Resource Countries

Australia’s Dr. Graham Ogle (Life for a Child) shared powerful data showing that moving the state of diabetes care in low-resource countries from “minimal” (fingerstick testing only at clinic, human premixed insulin only, minimal education) to “intermediate” (2-3 fingersticks/day, human insulin MDI, diabetes education) could greatly improve A1c, reduce complications, and mortality. While, ideally, all people with diabetes would receive “comprehensive” care (i.e., the standards of care in ISPAD guidelines), Dr. Ogle performed an analysis examined the effectiveness of intermediate care in six countries: Azerbaijan, Bolivia, Mali, Pakistan, Sri Lanka, and Tanzania. By reducing A1c from 12.5% to 9%, the rate of blindness as a diabetes-related complication dropped from ~50% to ~10%. More drastically, rates of end-stage renal disease fell from ~70% to ~5%. The 30-year survival rate was most dramatically increased in Mali, from 8% to 50%. Azerbaijan, which saw the least improvement, would see a 30-year survival rate jump from 62% to 89% by raising its level of care to “intermediate.” A study of 20 children from Mali in 1999 found that all but two had died after three years. As of 2007, Mali had more than 550 people with type 1 diabetes older than 30. While prevalence of diabetes in Mali is “screaming up,” this is largely due to improved diagnosis. Impressively, Dr. Graham also pointed at countries like Bolivia and Mexico, which have been able to achieve mean A1cs around 8%-9.5% with intermediate care – “just as good as the T1D Exchange data.”

Table 1. 30-Year Survival Rates Under Minimal and Intermediate Care

 

Minimal Care

Intermediate Care

Mali

8%

50%

Tanzania

10%

53%

Pakistan

39%

77%

Sri Lanka

46%

83%

Bolivia

26%

73%

Azerbaijan

62%

89%

  • Importantly, Dr. Ogle also recently published a cost-analysis, finding that intermediate care was “extremely cost-effective.” Unsurprisingly, providing intermediate care was more expensive than minimal care, though Dr. Ogle noted this was primarily because “providing healthcare for a dead child doesn’t cost anything.” By indexing cost against a country’s GDP per capita, Dr. Ogle called intermediate care “extremely cost-effective” in four Azerbaijan, Bolivia, Pakistan, and Sri Lanka) of the six countries analyzed with the cost of a healthy-life year generated much lower than the GDP per capita. In the other two countries (Mali and Tanzania), intermediate care was still fairly cost-effective.


Questions and Answers

Q: This would be very persuasive if you show it to ministers of health in different countries. Is that the plan?

A: That is the intention. We are planning to combine this with other advocacy materials. Countries are already incrementally improving care. People from Ecuador at this meeting have reported the government is about to start providing analogs. More importantly, to me, they will provide more test strips to their [type 1] children. We’re all working with the governments and this will help us to have more results.

Q (Dr. Thomas Danne): We need data to show what is really effective in improving those outcomes: is it analogs, test strips, pumps?

A: We have increasing data from Bolivia and Mexico. I think they’re blood glucose monitoring and diabetes education. I think analogs are nice, but no one has ever shown that analogs, in a full analysis, improve A1c. They do reduce hypoglycemia. I think the key things are blood glucose monitoring and diabetes education. My dream is that flash glucose monitoring will become cheaper and cheaper, and we can directly jump from no glucose monitoring.

3. Results from EDITION JUNIOR: Toujeo Meets Non-Inferiority in A1c Reduction, Adverse Events in Youth Age 6-17 with Type 1 Diabetes

A Sanofi poster highlighted results from the EDITION JUNIOR trial in which treatment with Toujeo (insulin glargine U300) showed non-inferiority in A1c reduction and fewer severe hypoglycemic events compared to Lantus (insulin glargine U100). The EDITION JUNIOR trial (n=463) found similar reductions in A1c (RR: 0.99; 95% CI: 0.88 – 1.02) in patients age 6 to 17 years old with a baseline A1c of 7.5-11% taking Toujeo versus U100, confirming the study’s primary outcome. The secondary outcome of adverse effects was also comparable between both agents, with the number of patients experiencing severe hypoglycemia (6% of participants on Toujeo versus 9% on U100) and hyperglycemia with DKA (8% on Toujeo versus 11% on U100) lower in the Toujeo-treated group. This is the first RCT comparing Toujeo with U100 in a pediatric population, and six-month follow up data will be presented later. The EMA’s CHMP has given Toujeo a positive opinion and recommendation for expanding Toujeo’s label in the EU for the treatment of diabetes in children ages six and older. The EMA is expected to make a decision in the upcoming months. We’re thrilled to see further treatment options being investigated in this important population.

4. Education Alone May Not be the Best Intervention: The Role of Community Health Workers in Improving Type 1 Outcomes

Dr. Colin Hawkes discussed the unique problem solving required to treat high-risk children with type 1, highlighting the promise of a family-directed, social determinants of health focused community health worker (CHW) intervention. The intervention involved six months of intensive support then six months of reduced support from a CHW to help families with any and all issues that go beyond diabetes care. In the first six months, mean A1c fell 0.5% and appointment attendance improved. These results are impressive given the currently small sample size and the sample’s demographics: 11.3% mean A1c, $31,0000 median household income, and self-reported food insecurity and difficulties paying household bills. Due to the formally analyzed data set being so small, Dr. Hawkes shared a story of one family who received the intervention and greatly benefitted. For a single parent household struggling with food insecurity, bill and loan payments, and reading hospital materials, a CHW helped ensure utilities remained on, helped with loan refinancing, helped with reading hospital documents, and even enrolled the single parent in secondary education. These efforts helped the family’s teenager reduce his A1c to 7.6% from a baseline of 12.3% while improving quality of life and self-efficacy. Dr. Hawkes went so far to say that some families do not need more diabetes education to make improvements, meaning that social determinants can make optimal diabetes control unattainable despite knowledge of how to manage the condition. While early results are preliminary and anecdotal evidence is most impressive, quality improvement and a longitudinal study need to be performed to both enhance the program and determine if the CHW’s impact is sustained overtime.

5. Physicians View DreaMed’s Advisor Pro as “Safe,” “Reliable,” and “Useful”

Following an introduction from Dr. Lori Laffel (Joslin Diabetes Center) on the need for diabetes decision support systems, DreaMed’s Dr. Revital Nimri presented some strong early physicians’ satisfaction results from the Advice4U study. DreaMed’s Advisor Pro decision support software is CE-Marked and FDA cleared to provide insulin pump adjustment recommendations using BGM or CGM data. The Advice4U study is a seven-center, Helmsley-funded study, designed to compare glycemic outcomes using insulin pump adjustments based on CGM readings using Advisor Pro vs. experienced physicians. The six-month study, which randomized 122 patients (ages 10-21) to an Advisor Pro arm and physician arm, will read out ATTD 2020, with time-in-range and time spent below 54 mg/dl as primary outcomes. Physicians using Advisor Pro (n=13) also filled out a 50-item questionnaire on their satisfaction at 12- and 24-weeks. On a five-point Likert scale (1=”strongly disagree” and 5=”strongly agree”), physicians gave Advisor Pro a 4.8 for “intuitive and simple,” 4.5 for “reliable,” and 4.5 for “useful,” after 24-weeks. Notably, the physicians rated Advisor Pro 4.2 as “sufficiently dynamic to provide accurate advice in different situations,” even though they only gave the system a 3.5 rating for “similar to therapy adjustments I would have done.” Perhaps most telling, eleven of the thirteen physicians responded that they would want to keep Advisor Pro in clinical practice. In September, we heard that Advisor Pro has been used to delivery advice to more than 100 patients, with launch coming in Israel next.

  • Dr. Gregory Forlenza (Barbara Davis Center), one of the physicians in the study, walked through the way Advisor Pro analyzes CGM data. Both Advisor Pro and a clinician normally begin by analyzing areas in which the patient is doing well, i.e., times when the patient is consistently in-range. Then, the system analyzes periods with hypoglycemia and hyperglycemia. Then, it can analyze insulin dosing data to help identify causes. Dr. Forlenza noted that he would typically spend about one-third of his time in visits answering these types of questions, which takes away from the time left for face-to-face interaction. By using Advisor Pro, there is more time left over in a clinic visit to address concerns that the patient or their families want to talk about.

6. Key Findings on the Relationship Between Behavioral Health, Young Adulthood, and Type 1 Diabetes Care

This multidisciplinary section focused on the different aspects of behavioral health that could affect diabetes care in young adulthood, a period of time defined by the transition from parental to self-diabetes management. See below for some of the biggest takeaways from the session:

  • Dr. Regitze Pals discussed the challenges of adolescence in diabetes care and how interventions in pre-adolescence could help. Interventions focusing on both psychosocial aspects and self-care met more ISPAD recommendations  compared to programs that focused on self-care or psychosocial aspects alone. However, most interventions had small effects and did not specify for what reason and how theory was used to tailor and develop the interventions. Few interventions specifically  targeted pre-teens with type 1 diabetes and their families  and were primarily based on adult-centric, individual level psychological theories. Dr. Pals suggested co-producing interventions with the target group in order to increase their efficacy. 

  • Dr. Angela Galler talked about the connections between metabolic outcomes and psychological care in teens with type 1 in real world settings. Youth with type 1 diabetes are at higher risk for developing psychological problems than their peers, and psychological problems have been associated with poor glycemic control and higher rates of DKA. While interventions in controlled environments have improved glycemic control and reduced DKA and hospital admissions, data on the efficacy of these interventions in real world settings is sparse. Using data from the German DPV survey, Dr. Galler found that 40% of youth received psychological care, and a third of these youth also received continued care. After analyzing the data set, her group found that psychological care was preferentially given to children and teens with worse glycemic outcomes and higher rates of DKA. Glycemic control stayed stable during follow-up time of two years in HbA1c-matched children with and without psychological care and frequency of severe hypoglycaemia decreased in children supported by psychological care. Results offer preliminary evidence that more youth with type 1 should seek psychological care in order to better manage their diabetes.

  • Though receiving supplementary psychological care to help manage type 1 diabetes may be beneficial, it is expensive, and many emerging adults cannot afford it. Dr. Julia Blanchette focused on emerging adults (ages 18 to 25/30) in her presentation. As emergent adults are usually not working full time, financial stressors linked to insulin rationing and hospitalization costs cause 85% to not meet their glycemic goals. A survey given to emergent adults found that most have transitioned to adult health providers, half used CGM, 2/3 used pumps, and 2/3 were on private health insurance while 17% were uninsured (which is higher than figures reported in other studies). Mean reported A1c was 8.1%, and they reported low financial independence – which Dr. Blanchette speculates means that those with type 1 may not meet financial adulthood milestones because of the costs associated with living with diabetes. Overall, this age group has limited knowledge of healthcare finances, so future studies should look at the impact of personal finances on self-management outcomes. Dr. Blanchette urged providers to advocate for policies that support accessible care, assess financial stress in clinics, and deliver developmentally accurate diabetes education and care to emerging adults.

    • Mindfulness and self-acceptance may be low-cost options for treating depression, diabetes distress, and diabetes-related outcomes in teens with type 1. Dr. Hiba Abujaradeh shared that mindfulness focused on enhanced awareness of the present and attitudes of non-judgmental acceptance have been associated with lower levels of depression and diabetes distress and higher levels of self-management behaviors. With this, Dr. Eveline Goethals presented data that shows that increased mean levels of illness acceptance may lead to better diabetes management. She concluded with the point that understanding and recognizing how illness impacts daily life may help clinicians better target diabetes guidance and triage adolescents for psychological care if needed. 

 

--by Albert Cai, Ursula Biba, and Kelly Close