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Type 1 Diabetes Update 2008 Robin Goland, MD€¦ · Type 1 diabetes is: A manageable condition A...
Transcript of Type 1 Diabetes Update 2008 Robin Goland, MD€¦ · Type 1 diabetes is: A manageable condition A...
Naomi Berrie Diabetes Center
Type 1 Diabetes Update2008
Robin Goland, MD
Type 1 diabetes is:
A manageable conditionA chronic conditionOften challenging
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Entirely compatible with a happy and healthy childhood and family life
Type 1 Diabetes Overview
Definitions
Epidemiology
PathophysiologyPathophysiology
Diagnosis
Prevention of Complications
Clinical Managementg
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 livesto remain healthy throughout their lives.
Chronic diabetes complications- microvascular and C fmacrovascular damage. Complications only occur after many
years of uncontrolled high blood sugars.
Type 1 Diabetes Epidemiology
24 million people in US (7% population) have diabetesp p ( p p )
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 winterSeasonal variation: peak in fall and winter
Wh d l d l t 1Why 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.
T 1 Di b t I id 100 000Type 1 Diabetes Incidence per 100,000 in Children < 14 years old
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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 yearspuberty
Mostly Caucasians affected, African-Americans are at 20-30% less risk
Seasonal variation: peak in fall and winterSeasonal variation: peak in fall and winter
Genetic Risk in Type 1 Diabetes:Genetic Risk in Type 1 Diabetes: Common HLA Haplotypes
DQB1 DRB1
Hi h Ri k
QDQA1
DRB1DRA6p
High RiskDR3: DQB1*0201, DQA1*0501, DRB1*0301 DR4: DQA1*0301, DQB1*0302, DRB1*0401, ,ProtectiveDR2: DQB1*0602, DQA1*0102,, DRB1*1501
BDC
E id th t T 1 Di b t iEvidence 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
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339339 275275 197197 138138 7979 2727 11Number at RiskNumber at Risk
00 11 22 33 44 55 66 77Years FollowedYears Followed
Clinical Presentation
Can occur at any age
Patients often lean and Caucasian although not always
Presentation often abrupt can present in DKA; positive urine ketonesPresentation 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
Type 1 Diabetes: DCCT
Intensive therapy reduced R ti th b 76%Retinopathy by 76%Nephopathy by 57%Neuropathy by 60%
Adverse effects included hypoglycemia and weight gain
EDIC study progression ofEDIC 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 sugarsReduction 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 b h d t d b l i icarbohydrate, 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.
H l bi A1CHemoglobin A1C.
Normal insulin and glucose levels
Blood sugar problems can beBlood 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
R i i l bl dRecognizing low blood sugar
Sh ki P l i i S iShakiness Palpitations Sweating
Anxiety Dizziness Hungery gSevere untreated hypoglycemia can cause seizure or loss
Headache Fatigue Irritability
cause seizure or loss of consciousness
T f l bl dTreatment of low blood sugar1
Check blood sugar
2If <70-80 mg/dl, treat with 15 grams of carbohydrate
If using pump, suspend or disconnect
2
Check glucose again after 15 minutes
If glucose remains under 70 mg/dl
3
If glucose remains under 70 mg/dl, repeat treatment with 15 grams of carbohydrate
In unlikely case of low blood sugar 4
u e y case o o b ood sugaemergency (unconsciousness or seizure), use glucagon emergency kit.
Prevention of low blood sugar
Lows often occur because of mismatch between insulin and either food or exerciseinsulin and either food or exerciseAfter taking rapid-acting insulin, the meal should not be delayedExercise acts to lower blood sugar so reduce insulin or eat a snack with exerciseF t bl d h k d t t t tFrequent blood sugar checks and prompt treatment of low blood sugar will prevent serious lows
Recognizing high blood sugar
Frequent Urination Extreme Thirst
Blurred Vision Hunger Severe untreatedBlurred Vision Hunger Severe untreated hyperglycemia for many hours to days can cause dehydration and
Drowsiness Nausea
diabetic ketoacidosis
T f hi h bl dTreatment of high blood sugar
Check blood glucose
Check urine ketones if blood sugar > 300 mg/dl and advised by parent (ketones are breakdown
d t f f t th t l t i t t fproducts of fats that accumulate in states of insulin deficiency)
Gi i li (“ ti d ”) d i d bGive insulin (“correction dose”) as advised by parent
Give non sugary fluids as advised by parentGive 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 afterbetween insulin and food. High blood sugar after meals usually occurs because of inadequate pre-meal bolus insulin - increase for next timeHi h f i bl d bl d i h b fHigh 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 increasedThe stress of illness raises blood sugar. Insulin doses often need to be temporarily increased indoses often need to be temporarily increased in times of illness.
Hemoglobin A1c is the gold standard measurement for assessment of diabetes management
Hemoglobin A1c specifically refers to the Amadori productOf the N terminal valine of each beta chain of HbA with glucoseOf the N-terminal valine of each beta chain of HbA with glucose
Glucose Schiff Base Amadori+
Hemoglobin A
Schiff Base(reversible)
AmadoriProduct
It is a reliable index of average blood glucose concentrations over the preceding 6 8 weeksthe preceding 6 – 8 weeks.
Relationship of A1c to Blood SugarRelationship of A1c to Blood Sugar
Diabetes: A Systemic DiseaseDiabetes: A Systemic Disease
Leading causeof blindness
2- to 4- fold increase in cardiovascularmortality
DiabeticRetinopathy
in working ageadults1 Stroke
mortality and stroke2
CardiovascularDisease
DiabeticNephropathy
Leading cause of 3end-stage renal disease3 Diabetic
NeuropathyLeading cause of non-traumatic
lower extremity amputations4lower extremity amputations
National Diabetes Information Clearinghouse. Diabetes StatisticsNational Diabetes Information Clearinghouse. Diabetes Statistics––Complications of Diabetes.Complications of Diabetes. (website)(website)http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#comp. http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#comp.
Relationship of Diabetes C li ti t H l bi A1Complications to Hemoglobin A1c
IntensiveN (%)
StandardN (%) HR (95% CI) PN (%) N (%) HR (95% CI) P
Primary 352 (6.86) 371 (7.23) 0.90 (0.78-1.04) 0.16
SecondarySecondary
Mortality 257 (5.01) 203 (3.96) 1.22 (1.01-1.46) 0.04
N f t l MI 186 (3 63) 235 (4 59) 0 76 (0 62 0 92) 0 004Nonfatal 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 D th 135 (2 63) 94 (1 83) 1 35 (1 04 1 76) 0 02CVD 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 therapeuticwith 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 timeintervention on the primary outcome at this time
Ongoing follow-up and ongoing analyses (bothOngoing 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 supportIt s important for the patient and the whole family (and support network) to be able to talk about their feelings about diabetes
I li t t t i t 1 di b tInsulin 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
I li b i b lti l i j ti bInsulin 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-insulin. Additional shorts of rapid acting insulin (lispro humalog or aspartnovolog) 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 catheterincrements 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.”
P l ith t 1 di b t h i di id li dPeople with type 1 diabetes have an individualized insulin:carbohydrate ratio that helps guide how much insulin to take with each meal and snack.
The “Bad Old Days of Type 1 Diabetes”Prior to 1980
1 or 2 injections of NPH and regular insulin per day
Rigid rules for composition and timing of meals
Urine tests for glucoseUrine tests for glucose
Aggressive therapy unsafe and of unknown benefits
H l bi A1 11 12%Hemoglobin A1c 11-12%
Inevitable eye and renal complications
Inevitable “noncompliance”
Advances in Type 1 Diabetes Treatment
Evidence supporting glycemic controlEvidence supporting glycemic control
Means for achieving glycemic control– Insulin analogues allowing basal/bolus therapy– Carbohydrate counting– Advances in monitoring – Insulin delivery systems– Integrated systems
Basal-Bolus Insulin Treatment of Type 1 Diabetes 2008
• 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, dietingp y g , pp g , g
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
Insulin Delivery Systems: Insulin Pens
Insulin Pens– DisposableDisposable– No syringes and vials– Convenient– Small doses in 0.5 u increments
Improved Blood Sugar Monitoring
Technologic AdvancesSmaller metersSmall blood sample (0.3 ul) Short test time (<5 secs)Self-contained stripsAlternate site testingAlternate site testing
Non-Randomized Trials of CSII:Non Randomized Trials of CSII: Adolescents, Adults, Children
Switching to CSII results in:
Lower HbA1cL H l iLess HypoglycemiaGreater Patient Satisfaction
Insulin Delivery in Pump Compared toInsulin Delivery in Pump Compared to Multiple Daily Injections
• Lispro/aspart insulin is given in a programmable “basal rate”every few minutes. Additional insulin is given in adjustable “boluses” to cover meal related glucoseadjustable 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
Early Insulin Pump
Continuous Subcutaneous Insulin Infusion(CSII
ANIMAS
MINIMED
ANIMAS
COZMO
Closed-Loop Insulin Pumpp p
• Implantable insulin pump coupled to glucoseImplantable insulin pump coupled to glucose sensor
Algorithm for ins lin deli er based on gl cose• Algorithm for insulin delivery based on glucose level
Experimental Treatment of Type 1 Diabetes
Immune Therapy: Rituximab, anti-CD3, CTLA4Ig, SYK inhibitor, GAD vaccine
• Islet and Pancreas Transplant
Closed loop system• Closed loop system
• Stem Cell-based Therapy
.
Experimental Treatment of Type 1 Diabetes: The Challenge
An intervention that can arrest the ongoing immune response and induce toleranceand induce tolerance
• Beta cell replacement with tolerance to the graft –h i l h i l i l l t?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
.
interventions that will block the effects of hyperglycemia directly or the associated abnormalities.
Anti-CD3 Preservation of Beta Cell Function
ControlDrug treated
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0 12
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A
00 12
Time (months)
Anti-CD20 Preservation of Beta Cell Function
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Embryonic Stem Cell Research
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Somatic Cell Nuclear Transfer Creation of ALS
NeuronsNeurons
Induced PleuripotentialStem Cells
Type 1 diabetes is:
A manageable conditionA chronic conditionOften challenging
QuickTime™ and adecompressordecompressor
are needed to see this picture.
Entirely compatible with a happy and healthy childhood and family life