Post on 09-Jun-2022
1
Naomi Berrie Diabetes Center
Type 1 Diabetes Update
2008
Robin Goland, MD
Type 1 diabetes is:
A manageable condition
A chronic condition
Often challenging
Entirely compatible with a happy
and healthy childhood and family
lif
Type 1 Diabetes Overview
Definitions
Epidemiology
Pathophysiology
Diagnosis
Prevention of Complications
Clinical Management
Experimental Treatment
Type 1 Diabetes: Historical Description
Two Main Types of Diabetes What is type 1 diabetes?
Auto-immune destruction of insulin-producing cells of pancreas.
People with type 1 diabetes are healthy and we expect them to remain healthy throughout their lives.
Chronic diabetes complications- microvascular and macrovascular damage. Complications only occur after many years of uncontrolled high blood sugars.
2
Type 1 Diabetes Epidemiology
24 million people in US (7% population) have diabetes
5-10% of total is type 1 diabetes
Staggering healthcare cost
Incidence increasing, particularly in young children
Type 1 Diabetes Epidemiology
1.9 per 1000 US school children
12-15 cases per 100,000
Male:female 1:1
Peak ages 5-7 and at puberty
Mostly Caucasians; African Americans at 20-30% less risk
Seasonal variation: peak in fall and winter
Why do people develop type 1 diabetes?
Combination of genetic and environmental causes
Children inherit diabetes-related genes from both their mother and father, even if no one in either family has diabetes.
There is also an environmental factor, not yet identified, such as a virus that tips over a genetically predisposed person into developing diabetes. Trigger often occurs years before diagnosis.
Type 1 Diabetes Incidence per 100,000 in Children < 14 years old
0
5
10
15
20
25
30
35
40
Chin
aVenezuela
Isra
el
Kuw
ait
Denm
ark
Lazio
Canda
USA
Sard
inia
Fin
land
Type 1 Diabetes Epidemiology
Prevalence in school-age children in US: 1.9 per 1000
Annual incidence: 12 to 15 cases per 100,000
Male: Female ratio: 1:1
Peak ages: 5 to 7 years puberty
Mostly Caucasians affected, African-Americans are at 20-30% less risk
Seasonal variation: peak in fall and winter
Genetic Risk in Type 1 Diabetes: Common HLA Haplotypes
High Risk DR3: DQB1*0201, DQA1*0501, DRB1*0301 DR4: DQA1*0301, DQB1*0302, DRB1*0401
Protective DR2: DQB1*0602, DQA1*0102,, DRB1*1501
DQB1
DQA1
DRB1 DRA 6p
BDC
3
Evidence that Type 1 Diabetes is Autoimmune
Autopsy studies documenting immune infiltration of islets
Preservation of beta cell function with immune intervention
Association with other autoimmune disease: thyroid disease, celiac, others
Progression of Type 1 Diabetes Progression to Type 1 Diabetes with Positive Antibodies
Clinical Presentation
Can occur at any age
Patients often lean and Caucasian although not always
Presentation often abrupt, can present in DKA; positive urine ketones
Not accompanied by metabolic syndrome
Positive antibodies against GAD, insulin, islet cells
Low or undetectable c-peptide and insulin level
Prevention of T1DM Complications
Acute: Hypoglycemia, DKA
Chronic: Microvascular
Chronic: Macrovascular and Neuropathic
Chronic: Psychosocial
4
Type 1 Diabetes: DCCT
Intensive therapy reduced
Retinopathy by 76%
Nephopathy by 57%
Neuropathy by 60%
Adverse effects included hypoglycemia and weight gain
EDIC study – progression of retinopathy after the DCCT
Goals of treatment in type 1 diabetes
Normal growth and development and a well-adjusted patient and family
Promotion of blood sugars near-normal most of the time - perfection not required to stay healthy
Reduction of high blood sugars
Reduction of low blood sugars
Optimal self-management to match insulin with food and activity
What we Measure in Type 1 Diabetes
BLOOD SUGAR (glucose) by fingerstick. Affected by food, particularly carbohydrate, and use by muscles in exercise.
Eating raises blood sugar. Stress and illness also raise blood sugar.
Skipping or delaying meals lower blood sugar. Exercise lowers blood sugar.
Hemoglobin A1C.
Normal insulin and glucose levels Blood sugar problems can be fixed and prevented
How to recognize low blood sugar (hypoglycemia)
How to treat low blood sugar
How to prevent low blood sugar
How to recognize high blood sugar (hyperglycemia)
How to treat high blood sugar
How to prevent high blood sugar
5
Recognizing low blood sugar
Shakiness Palpitations Sweating
Anxiety Dizziness Hunger
Headache Fatigue Irritability
Severe untreated
hypoglycemia can cause seizure or loss
of consciousness
Treatment of low blood sugar
Check blood sugar
If <70-80 mg/dl, treat with 15 grams of carbohydrate
If using pump, suspend or disconnect
Check glucose again after 15 minutes
If glucose remains under 70 mg/dl, repeat treatment with 15 grams of carbohydrate
In unlikely case of low blood sugar emergency (unconsciousness or seizure), use glucagon emergency kit.
1
2
3
4
Prevention of low blood sugar
Lows often occur because of mismatch between insulin and either food or exercise
After taking rapid-acting insulin, the meal should not be delayed
Exercise acts to lower blood sugar so reduce insulin or eat a snack with exercise
Frequent blood sugar checks and prompt treatment of low blood sugar will prevent serious lows
Recognizing high blood sugar
Frequent Urination
Blurred Vision
Drowsiness
Hunger
Nausea
Extreme Thirst
Severe untreated
hyperglycemia for many hours to days
can cause dehydration and diabetic
ketoacidosis
Treatment of high blood sugar
Check blood glucose
Check urine ketones if blood sugar > 300 mg/dl and advised by parent (ketones are breakdown products of fats that accumulate in states of insulin deficiency)
Give insulin (“correction dose”) as advised by parent
Give non-sugary fluids, as advised by parent
Prevention of high blood sugar
High blood sugars often occur because of mismatch between insulin and food. High blood sugar after meals usually occurs because of inadequate pre-meal bolus insulin - increase for next time
High fasting blood sugar or blood sugar right before a meal usually occurs because of inadequate long-acting or basal insulin - if this is a pattern, basal insulin can be increased
The stress of illness raises blood sugar. Insulin doses often need to be temporarily increased in times of illness.
6
Hemoglobin A1c is the gold standard measurement for assessment of diabetes management
Hemoglobin A1c specifically refers to the Amadori product
Of the N-terminal valine of each beta chain of HbA with glucose
Glucose
+
Hemoglobin A
Schiff Base
(reversible)
Amadori
Product
It is a reliable index of average blood glucose concentrations over
the preceding 6 – 8 weeks.
Relationship of A1c to Blood Sugar
Cardiovascular
Disease
Diabetic
Retinopathy
Leading cause
of blindness
in working age
adults1
Diabetic
Nephropathy
Leading cause of
end-stage renal disease3
Stroke
2- to 4- fold increase in cardiovascularmortality and stroke2
Diabetic
Neuropathy
Leading cause of non-traumatic
lower extremity amputations4
Relationship of Diabetes Complications to Hemoglobin A1c
7
Intensive
N (%)
Standard
N (%) HR (95% CI) P
Primary 352 (6.86) 371 (7.23) 0.90 (0.78-1.04) 0.16
Secondary
Mortality 257 (5.01) 203 (3.96) 1.22 (1.01-1.46) 0.04
Nonfatal MI 186 (3.63) 235 (4.59) 0.76 (0.62-0.92) 0.004
Nonfatal Stroke 67 (1.31) 61 (1.19) 1.06 (0.75-1.50) 0.74
CVD Death 135 (2.63) 94 (1.83) 1.35 (1.04-1.76) 0.02
CHF 152 (2.96) 124 (2.42) 1.18 (0.93-1.49) 0.17
In people with type 2 diabetes at high risk for CVD, with an A1C of 7.5% or more, a therapeutic strategy that targets an A1C <6% vs. 7.0-7.9% increases mortality over 3.5 years
There is no significant effect of the glycemic intervention on the primary outcome at this time
Ongoing follow-up and ongoing analyses (both epidemiologic & within baseline subgroups) will add further insight and generate more hypotheses
Coping with diabetes
A diagnosis of type 1 diabetes is a big deal
Feelings of sadness, guilt, loneliness, and blame are common
It’s important for the patient and the whole family (and support network) to be able to talk about their feelings about diabetes
Insulin treatment in type 1 diabetes: Replacement treatment
Background or basal insulin given over 24 hours
Meal-related, or bolus, or prandial insulin is given to cover the carbohydrates in the food
Insulin can be given by multiple injections or by pump
With injections, 1 shot is long-acting basal insulin, usually glargine (lantus) insulin. Additional shorts of rapid-acting insulin (lispro-humalog or aspart-novolog) are given right before meals and snacks.
With the pump, only rapid acting insulin is used. Basal insulin is given in small increments all day long and bolus insulin is given through the pump’s catheter right before meals and snacks.
Insulin Injections or Insulin Pump Food in type 1 diabetes
There is NO such thing as a diabetic diet.
People with type 1 diabetes eat normally and “cover” the carbohydrates in food with insulin.
This is called “carbohydrate counting.”
People with type 1 diabetes have an individualized insulin:carbohydrate ratio that helps guide how much insulin to take with each meal and snack.
8
1 or 2 injections of NPH and regular insulin per day
Rigid rules for composition and timing of meals
Urine tests for glucose
Aggressive therapy unsafe and of unknown benefits
Hemoglobin A1c 11-12%
Inevitable eye and renal complications
Inevitable “noncompliance”
The “Bad Old Days of Type 1 Diabetes”Prior to 1980
Evidence supporting glycemic control
Means for achieving glycemic control– Insulin analogues allowing basal/bolus therapy– Carbohydrate counting– Advances in monitoring – Insulin delivery systems– Integrated systems
Advances in Type 1 Diabetes Treatment
• Use of insulin:carb ratios to normalize postprandial meal glucose and allow flexibility in timing and content of meals
Use of corrective bolus to normalize glucose
Peakless insulin simpifies sick day management, skipping meals, dieting
Diabetes education promoting self-care especially day-to-day insulin dose adjustment
Hemoglobin A1c 6.5-7.5%
Eye and renal complications rare
“Noncompliance” redefined
Basal-Bolus Insulin Treatment of Type 1 Diabetes 2008 Insulin Delivery Systems: Insulin Pens
Technologic AdvancesSmaller meters
Small blood sample (0.3 ul)
Short test time (<5 secs)
Self-contained strips
Alternate site testing
Improved Blood Sugar Monitoring
Switching to CSII results in:
Lower HbA1c
Less HypoglycemiaGreater Patient Satisfaction
Non-Randomized Trials of CSII: Adolescents, Adults, Children
9
• Lispro/aspart insulin is given in a programmable “basal rate”every few minutes. Additional insulin is given in adjustable “boluses” to cover meal related glucose excursions.
Programmable basal rate offers advantage over injected basal insulin as it can be modified as necessary leading to enhanced lifestyle flexibility, especially helpful in managing dawn phenomenon and exercise.
CSII leads to more predictable insulin levels compared to MDI
Dual-wave and square wave bolus offers greater ability to match insulin to food
Insulin Delivery in Pump Compared to Multiple Daily Injections
Early Insulin Pump
ANIMAS
COZMO
MINIMED
Continuous Subcutaneous Insulin Infusion(CSII
Closed-Loop Insulin Pump
• Implantable insulin pump coupled to glucose sensor
• Algorithm for insulin delivery based on glucose level
.
Immune Therapy: Rituximab, anti-CD3, CTLA4Ig, SYK inhibitor, GAD vaccine
• Islet and Pancreas Transplant
• Closed loop system
• Stem Cell-based Therapy
Experimental Treatment of Type 1 Diabetes
.
An intervention that can arrest the ongoing immune response
and induce tolerance
• Beta cell replacement with tolerance to the graft – mechanical or even more physiological replacement?
• Is hypoglycemia preventable?
• Markers for individuals at risk for complications and interventions that will block the effects of hyperglycemia directly or the associated abnormalities.
Experimental Treatment of Type 1 Diabetes: The Challenge
10
Anti-CD3 Preservation of Beta Cell Function Anti-CD20 Preservation of Beta Cell Function
Embryonic Stem Cell Research
Somatic Cell Nuclear
Transfer Creation of ALS
Neurons
Induced Pleuripotential
Stem Cells
Type 1 diabetes is:
A manageable condition
A chronic condition
Often challenging
Entirely compatible with a happy
and healthy childhood and family
lif