Type 1 Diabetes: Updates and Future Directions

Carey Driscoll, APRN,CDE

10/29/19

OBJECTIVESBrief HistoryDiagnosis of T1DMPathophysiologyManagement ComplicationsTechnology and Future directions

Nothing to disclose

• May 3, 1922: University of Toronto, Discovery of Insulin

• 1923 Nobel Prize awarded for discovery of Insulin

BANTING AND BEST

Insulin: “A miracle drug”

What is diabetes ?

• A chronic condition where the pancreas can no longer make insulin or the body cannot properly use the insulin it produces

• Insulin: a hormone made by the pancreas that helps glucose get into your cells to be used as energy

Type 1 vs Type 2

Signs and Symptoms

Diabetes Mellitus Diagnosis

1. Fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/L)

2. Plasma Glucose ≥ 200 mg/dl (11.1 mmol/l) two hours after 75 Gm* oral glucose load

3. Symptoms of hyperglycemia and casual plasma glucose ≥ 200 mg/dl (11.1 mmol/L)

4. Glycosylated hemoglobin (HgbA1c) ≥ 6.5 %

*Pediatric dose is 1.75 g glucose/kg of body weight

Pathophysiology of Type 1 Diabetes

• Autoimmune destruction of insulin producing Beta Cells in the Islets of Langerhans

• Happens in patients with genetic predisposition and unknown trigger (likely environmental)

• Genetic markers are present at birth and immune markers are detectable after the onset of the autoimmume process

Pathophysiology

• Serological

o> 90% of individuals with newly diagnosed T1DM have one or more positive autoantibodies

– Insulin (IAA)

– Glutamic acid decarboxylase (GAD)

– Islet cell/insulinoma-associated autoantigen 2 (IA2)

– Zinc Transporter 8 (ZnT8A)

oPeak incidence before 2 years of age in genetically susceptible individuals

– months to years before onset

o<5% of individuals with 1 autoantibody progress to T1DM

Atkinson, et al. Lancet 2014: 383, 69-82.

Couper, JJ . et. al. ISPAD Clinical Guidelines 2018

• Incidence varies with:o Age

– Peaks between 4-6 years and 10-14 years

– Most recent studies show incidence in children < 5 years is rising fastest and expected to double between 2005 and 2020 *

o Gender- Slight increase in males in select populations

o Family History- risk in offspring of parent with T1DM

o Ethnicity

o Geography

o Seasonal changes -Increased in autumn and winter

Epidemiology

* Levitsky, L and Misra, M., Up to Date Online 10/9/19

• Prevalence (per 100,000)

o Finland >60

o Sardinia 40

o China 0.1

o India 0.1

o Venezuela 0.1

Atkinson, et al. Lancet 2014: 383, 69-82.

Monitoring glycemic control:Where we started…

Urinalysis for glucose using a modified copper reagent tablet

Monitoring glycemic control:Glucose meters

1965: development of first blood glucose test strip

1970: First glucose meter was used.

Monitoring glycemic control:Continuous Glucose Monitors

Dexcom G6 Freestyle Libre

Medtronic GuardianEversense-implantable

• Device that automatically tracks blood glucose values

• Sensor is inserted under the skin to measure interstitial glucose levels

• Tests glucose levels every few minutes

• Sends values wirelessly to a monitoring device (meter, pump, phone)

• Alerts for highs and lows

• Waterproof

• Directional arrows and trends

• Ability to “look back on data to determine trends

Continuous Glucose Monitoring-CGM

Benefit

• Must be worn AT ALL TIMES

• Expensive and concerns re: insurance coverage

Disadvantage

• Better monitoring of blood glucose values

• Some systems : no fingersticks and can be used to dose insulin

• Less frequent episodes of hypoglycemia

• Improved accuracy over glucose meters

Benefits/Disadvantages of CGM

• Analysis of 2 diabetes registries with participants < 18 years with T1D > 1 year.

• Compared use and A1c between 2011 and 2016 to analyze change in rates of scanning and how it impacts glycemic control

• Result: CGM use increased across all age groups, regardless of gender, ethnic minority status or insulin delivery method from 2011-2016

• Greatest increase: youngest patients

• Usage rates remain lowest among adolescents

• A1c was lower among CGM compared to pump only or injection only users regardless of insulin delivery methods (P< 0.001)

CGM Use by Age in T1D Exchange Registry

Monitoring glucose control: HgbA1C

• “Gold standard” used to assess diabetes management and control over 3 month period of time

• Can be used as predictor for long term complications

• Normal A1c: 4-6 %

• A1c target for children with T1DM : < 7.5 % without frequent episodes of hypoglycemia

Diabetes Control and Complications Trial

- Major clinical study conducted from

1983 – 1993 in patients with IDDM.

(enrollment >13 years of age)

- Keeping blood glucose levels as close

to normal as possible slows the onset

and progression of complications

- Intensive diabetes treatment reduced the

risk of:

Eye disease by 76%

Kidney disease by 50%

Nerve disease 60%

CV events by 42-57%

• Captures blood glucose variation

• Target range is typically 70-180 mg/dl

• Goal TIR is 70 %

• Strong relationship between TIR and diabetes complications

Time in Range

www.diatribe.org/time-range

Management: Insulin therapy

Basal/ Bolus Concept

• BASAL INSULIN

oYour liver secretes glucose even if you are not consuming food

oBasal insulin supports your baseline insulin needs to allows cells to take in glucose for energy

oA long or intermediate insulin is used

• BOLUS INSULIN

oA “burst” of insulin typically given when we have elevated blood glucose values or consume foods which raise the blood sugar

oA rapid acting insulin is used

Duration of Insulin Action

NODM Insulin DosesTotal Daily Dose (units/kg/day)

• Take clinical status (obesity, acanthosis nigricans, intercurrent infection), and if possible A1c into account.

No DKA DKA

Pre-pubertal 0.25 – 0.5 0.75 – 1

Pubertal 0.5 – 0.75 1 – 1.2

Post-pubertal 0.25 – 0.5 0.8 - 1

Correction Factor

• Amount of insulin given to cover the amount of food consumed

• Typically covers total grams of carbohydrates *

• Calculation

Total carbs/ Carb ratio

Carbohydrate Coverage• The amount of insulin required to bring the blood

sugar down to the target

• Targets can vary based on age

• Calculation:

(Blood sugar- Target)/ Correction factor

Pre Meal Bolus Dose

Insulin Administration: MDI therapy

Advantages

• Multiple injections per day

• Site hypertrophy with overuse

• “Lots of work”

Disadvantages

• Closely matches how body would secrete insulin

• Allows for flexibility with meal timing

• Allows for flexible food intake (portion/sizes)

MDI: Multiple Daily Injections

Insulin pump therapy

Medtronic 670G Omnipod DASH Tandem Tslim X2

• Small device that delivers continuous and customizable doses of rapid acting 24 hours per day

• Mimics bodies insulin needs

• Insulin given via Basal/Bolus concept

o Basal rate: can be adjusted every hour

o Bolus dose: Utilizes dose calculator based on blood sugar and carbs

Insulin Pump therapy

Advantages

• Something always attached to you

• Site irritation

• Pump failure

• Alerts or Alarms

• Cost and Insurance Coverage!

Disadvantages

• Customizable long acting insulin doses based on body’s metabolic needs

• Site change every 2-3 days

• Flexibility with snacking

• Can administer VERY small doses

• Less injections

• Ability to reduce/dose suspend basal insulin

Pump Advantages and Disadvantages

• Approved in 2016- first semi automated insulin pump

• Called a “Hybrid Closed Loop”

• Automatically adjusts basal insulin every 5 minutes based on your CGM reading and trend

• Target blood sugar is 120 mg/dl but can be set to 150 mg/dl for exercise

• Helps minimize hypoglycemia: will suspend basal rate if blood sugar is predicted to go low within 30 minutes

• Must enter in carbohydrates to notify pump to give additional insulin for food

Artificial Pancreas and Pump Automation-Medtronic 670G

• 984 reports

• 24 randomized controlled trials for outpatient use

• 585 participantso 219 adults

o 265 pediatric

o 101 combined

“Artificial pancreas systems uniformly improved glucose control in outpatient settings”

Weisman A, et al. Lancet. July 2017

More Pump Automation

#Wearenotwaiting

• Founded by group of parents/individuals with T1DM who believed they deserved more from T1DM

• Do it Youself System

• Non-FDA approved Hybrid Closed loop

• Uses temp basal rates to adjust YOUR CURRENT BASAL SETTINGS based on current BG, BG direction, active insulin and active carbohydrates

• Glucose responsive insulin that are being designed to turn on when needed and turn off when not needed

• JDRF funding 9 studies across the world currently- others that are not JDRF funded as well

• Prevents all hypoglycemia

Smart Insulin

Encapsulation

• Currently being tested in human trials

• Transplantation of insulin producing cells which are encapsulated in a protective device

• Obstacles:o Cell supply

o Cell health and survival

o Protection from the body’s immune response

• Teplizumab (Anti-CD3) :immumotherapy drug shown to delay the diagnosis of T1DM a median of 2 years in children and adults at high risk

• First drug to do so!

• All study participants were relatives of individuals with T1DM and had 2 positive autoantibodies and abnormal blood sugar levels

• Presented at ADA June 2019

Prevention

• Atkinson MA, Eisenbarth GS & AW Michels. Overview and Pathophysiology. Type 1 diabetes. Lancet 2014: 383, 69-82.

• Beck, R.W et al. “Validations for Time in Range as an Outcome Measure for Diabetes Clinical Trials” Diabetes Care Mar 2019; 42 (3) 400-405

• Couper , JJ et al. “Stages of type 1 diabetes in children and adolescents”. ISPAD Clinical Practice Consensus Guidelines 2018, www.ISPAD.org, 10/9/19\

• DeSalvo, D. et al. “Continuous glucose monitoring and glycemic control among youth with type 1 diabetes; International comparison from the T1D Exchange and DPV Initiative” Pediatric Diabetes 2018; 19; 1271-1275

References

THANK YOU

cdriscoll@connecticutchildrens.org