Highlights From the Barbara Davis Center’s July Keystone Conference

Recently I had the pleasure of attending the Barbara Davis Center’s “Management of Diabetes in Youth” conference, held every other year in beautiful Keystone, Colorado. The focus is on all of the latest and greatest in type 1, and it’s a real treat to have so many of the best names in this field gathered in one place. The Barbara Davis Center (BDC) is one of the premier programs in the world focusing on type I diabetes management, and the one (Dr. Peter Chase, to be precise) who brought us the famed” Pink Panther” book, Understanding Diabetes – the reliable handbook of type 1 diabetes that many parents of newly diagnosed kids rely on.

Peter Gottlieb, MD, Associate Professor of Pediatrics at the BDC and principal investigator in a number of diabetes prevention trials regarding the rise in incidence and types of diabetes-
• Due to increased longevity, about 23.5 million people (10.7% of the U.S. pop. over age 20) have type I
• Three phenotypes of adult type I’s seen when newly diagnosed:
• Classic T1DM – similar presentation to childhood type I, but occurring in adults
• Highest incidence for type I is in northern Europe, then Canada, followed by the U.S. and Australia.
• Currently seeing about 75, 800 new cases per year
• The “Promise of Tomorrow” for type I kids:
~ An improved understanding of epidemiology and natural history
~ Better technology- through sensors/pumps and the closed loop system
~ Immunotherapy being developed and tested
~ Beta cell regeneration therapies

Irl Hirsch, Diabetes Treatment and Teaching Chair at the Univ. of Washington-
~ LADA (Latent autoimmune diabetes in adults) – those who are able to still make some of their own insulin for a few years
~ Those known as “type 1.5” – the type 2’s who are antibody positive (but whose issues are different than the more classic type 1’s)

Georgeanna Klingensmith, MD, Chief of the Pediatric Clinic at the BDC and Professor of Pediatrics at the University of Colorado Denver
On type 2 diabetes in children-

• Recommends the following treatment guidelines: Hemglobin A1C <6.5 and FBS< 120, postprandial bgs < 140, and doing finger sticks twice a day, 3 to 5 days a week, and whenever ill (unless taking insulin, in which case they may need to do it more)
“To get a good HgbA1C you want to go as low as possible, as soon as possible, as safely as possible, and as rationally as possible.”
“As many of you already know, type I is not going away, but rather is increasing at a 3-5% rate per year. The best registries in Finland showed that the average age of diagnosis was 10-14 yrs. but the new shift has been to a much earlier age.”
“Lifestyle change must be a part of any intervention, but it needs to be used in combination with drug therapy. Only 10-15% of children with type 2 will be able to respond with lifestyle changes alone.”
Regarding monogenic forms of diabetes
• 1-3% of all pediatric diabetes are actually monogenic forms
• Many MODY (Maturity onset diabetes of youth) patients are misdiagnosed as type 1 or type 2.
• “You need to know when they have MODY so you can predict the clinical course and it will explain those other associated features. ”
• William Winter, MD, Professor of Pathology and Pediatrics at the University of Florida in Gainesville:
• Could MODY be the answer to why some people claim they are able to wean themselves off insulin and be cured?

David Kendall, Chief Scientific & Medical Officer for the ADAOn treating infants and toddlers-

• “These neonates may not have the regular antibodies; early onset diabetes can be caused by mutations in the insulin gene or in the MODY genes, or by different syndromes.”
• These babies should be tested for a genetic disorder right away and oral therapy instituted with sulfonylureas (being monitored very carefully and frequently)
• www.diabetesgenes.org, a lab in the UK, will perform this testing at no charge if DM onset is prior to six months of age.
• Since both hypoglycemia and hyperglycemia can have adverse effects on the developing brain, and can cause processing difficulties, parents need to be well educated on the risks of long term highs and lows
• Caring for the caregivers is important –
• Identify resources and support, and keep dad in the picture.
“Parents need to be told that they are not responsible for all of their child’s low or high blood sugars.”-

Tips on management
• Reminders about the importance of dosing adequately before meals to prevent postprandial highs:
• Test one hour prior to eating, and then follow this guide:
• If bg 200 or below, bolus 20 minutes pre-meal
• If bg 200-300, bolus 30 minutes before
• Try to take insulin 20 minutes before eating and give enough to cover 30 carbs to start, if you will eat at least that much, and then take the rest later, after you start eating.

Some thoughts from Gary Scheiner, MS,CDE, nationally-recognized diabetes speaker and author of Think Like a Pancreas:
• With or without all of the technological data we now have, we still need to always look at the bg patterns and individualize the plan of care.
• Tailor your program to the patient’s needs, their interests, and their abilities.
“I am not a big fan of HgbA1C’s; it’s better to look at the percentage of bgs within range.”
” Make sure that the patient’s goals and yours are the same!”
“Spend time learning about the latest devices and methods.”
“Fine tune basals first – respect the basals; it is the foundation of the whole management program.”
“Monitor and adjust often, and do a 3am [test] at least once weekly to know what’s going on in the middle of the night.”
• Attitude is everything. “Be aggressive from the get-go.”

• While you can let kids be kids, there are certain ‘non-negotiable’ responsibilities:
~ Bg monitoring
~ Taking your insulin
~ Preventing hypos
~ Keeping up with and getting professional care

Grace Shih, RD, who has extensive experience with type I diabetic children with eating disorders through her work at Stanford’s Packard Children’s Hospital and in private practice presents on Diabulimia-
• While there is a certain criteria to identify it (ED-DMT 1, Eating Disorders and Type I Diabetes), there is still no official diagnosis to date.
“Strong family support makes all the difference.”
“Start with getting them to take their basal insulin again – to take it once a day (hopefully being observed by a family member).”
“Then get them to check their blood sugars and start doing corrections again.”
“The final step – bolusing insulin again per their carbohydrate intake!”

Johnny Ludvigsson, MD, Professor of Pediatrics and Head Physician at the Div. of Pediatrics in Linkoping Univ. Hospital in Sweden, and principal investigator of the GAD trials in Europe-
• Reiterated the importance of treating based on a patient’s bg patterns.
• Everyone must be on the same page, and work collaboratively as a team.
“A diary can be of great value. Once a week – just looking at the pattern.”
“With modern techniques, and a bit of intelligence, diabetes doesn’t have to be such a problem,” said Johnny, “but treatment policies and attitudes can be!”
“Avoid double messages. Look at how you communicate – do your words say one thing but the message is another?”
“Give honest information, but also give hope and optimism”
Marian Rewers, MD,PhD, Clinical Director of the BDC and Professor of Pediatrics at the Univ. of Colorado at Denver On celiac disease and type I
• Celiac is not exclusively a GI disease, but rather a “multi-organ autoimmune disease”. 90% have no GI symptoms.
• It can manifest in conditions affecting several organs, such as:
~ The skin and mucosa -causing recurrent canker sores, hair loss, or severe pruritis, amongst others
~ Central nervous system and psychological disorders – although controversial, ataxia, seizures, and depression may all be symptoms that clear up after a gluten-free diet
~ Bone disorders – osteoporosis and osteopenia can be hallmarks of it if left untreated for a long time
~ Anemia, low ferritin levels, and low vitamin D250H
~ Fertility problems
~ Unexplained lows and poor HgbA1Cs
• Screening should be done at diagnosis of type I, and biannually until age 10, or if symptomatic.
• Recommends two transglutimase (TG) tests three months apart to confirm before doing a biopsy.
• Autoantibodies are believed to precede the development of intestinal injury and the TG levels do fluctuate.
“Go with the TG marker, not the deaminated gliadin peptides (DGP),which reflects more about the amount of wheat someone is eating and resolves soon after starting a gluten-free diet.”
“50% of biopsies are negative, so don’t order them unless really necessary.”

On diabetes technology:
• Medtronic has begun the first step in having a system with automatic shut-off for lows – where it will automatically suspend the basal insulin for two hours if too low to prevent a severe hypoglycemic reaction.
• Three ingredients are needed for a closed loop system: the pump, the CGM, and effective algorithms to vary insulin delivery.
“We have all three of these already available, but the first generation closed loop system has to be better than what we have now – by removing human error and computer malfunction. We have to remove the danger of over-infusing insulin delivery and then we are set!”
“No treatment of type I diabetes will ever be optimal unless there’s feedback controlled regulation of insulin delivery. Our goal? To get an FDA-approved commercially available product as soon as possible!”

Dr. William Tamborlane, MD, Professor and Chief of Pediatric Endocrinology at Yale School of Medicine, and Co-Chair of the JDRF CGM Study Monitoring Group-
• The mean HgbA1C for type I’s is 8%; current usual therapy does not achieve HgbA1C goals within 50% of children.
• CGMs can help but only if they are using it consistently, studies show.

On hypoglycemia and CGMs:
• 71% of patients who go low during the night don’t respond to the alarms
• In studies, they found that patients were <70mg/dl on 25% of nights for 1-2 hrs., <60 on 15% of those nights for 1-2 hrs., and < 50 on 80% of those nights for 1-2 hrs.
• 75% of nocturnal hypoglycemic events are due to increased activity earlier that day
• Check out the 2nd edition of Dr. Peter Chase’s book Understanding Insulin Pumps and Continuous Glucose Monitors (just released at this conference) He gives helpful recommendations of how to manage exercise to avoid lows as well as how to avoid over-treating lows. (Available through www.childrensdiabetesfdn.org)

Current research
• DirectNet (a network of clinical centers investigating the potential use of glucose monitoring technology and its impact on type I management in children)
• TEDDY ( an international effort to determine the causes and triggers of type I)
• TrialNet ( an international consortium studying ways to prevent, delay, and reverse the progression of type I)
• SEARCH study ((looking at the incidence and prevalence of type I in children in 6 areas of the U.S.)
• TODAY trial (a multi-center study designed to compare three different modalities for treating type 2 kids),
• Type I Diabetes Exchange Project ( Being started by the Helmsley Trust to further research of type I in adults and to create new research opportunities)

Aaron Kowalski, PhD, who leads the Artificial Pancreas Project at JDRF, spoke about what JDRF is up to these days –
~ is not just focusing on the cure for type I now, but is driving more on prevention and treatment now.” We want to prevent, arrest, and reverse complications.”
~ is funding a lot of work in beta cell regeneration – addressing the baby progenitor cells that grow up to become beta cells.
~ Biggest focus is on immune therapies, and working on long term immunoregulation
~ Partnering more with industry because “science was moving faster than industry was”
“Antigen-specificity is our real focus.”
• Today there is a “robust immunotherapy trial pipeline in recent onset type I” with several clinical trials now taking place for newly diagnosed type I’s, among them the Diamyd GAD, DEFEND-2, and Protégé Encore trials.
“We need quicker-acting insulin. Current ones work too slowly and last too long.”

• Amylin, the second beta cell hormone co-secreted with insulin
~ “I firmly believe it will be a major player in the years ahead”
• It is possible to minimize 80% of all nocturnal hypoglycemia. Initial studies have shown that the artificial pancreas can improve overnight control for a range of real-life situations.
• Can the GAD vaccine be used to prevent type I diabetes? – question asked by Johnny Ludvigsson, principal investigator of the European GAD trials
• Listed 20 interventions that have been, or are now being investigated for prevention which involved limitations or adverse side effects
• Demonstrated the strong safety profile of the Diamyd GAD vaccine and how it compares to the other anti-CD 3 therapies

Peter Gottlieb also stressed how important it is to intervene early in the disease process on all fronts-
• Probiotics, DHA, vitamin D, and Omega 3’s might play a role in helping to prevent type I. More studies are needed.
• “Antigen-specific therapies are important, as they work more as a ‘magic bullet’ approach, especially one where you have minimal toxicity.”
• “We really do think it’s a preventable disease.

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