Chapter 2 Psychological Issues In Adults With Type 2 Diabetes
Type 1 Diabetes in Adults Type 1 Diabetes in Adults Andrej Janež, MD PhD Dept. of Endocrinology...
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Transcript of Type 1 Diabetes in Adults Type 1 Diabetes in Adults Andrej Janež, MD PhD Dept. of Endocrinology...
Type 1 Diabetes in AdultsType 1 Diabetes in Adults
Andrej Janež, MD PhD
Dept. of Endocrinology Diabetes and Metabolic Diseases
University Medical Center Ljubljana
Undiagnosed diabetes
5.2 million
Prevalence of DiabetesPrevalence of Diabetesin the United Statesin the United States
Diagnosed type 2 diabetes
12 million
Diagnosed type 1 diabetes
~1.0 million
Centers for Disease Control. Available at: http://www.cdc.gov/diabetes/pubs/estimates.htm;EURODIAB ACE Study Group. Lancet. 2000;355:873-876; Harris MI. In: NationalDiabetes Data Group. Diabetes in America. 2nd ed. Bethesda, Md: NIDDK;1995:15-36; U.S. Census Bureau Statistical Abstract of the U.S.; 2001
US Population: 275 Million in 2000
Type 1 diabetes misdiagnosed as type 2 diabetes
~1.0 million
Incidence of Type 1 DiabetesIncidence of Type 1 Diabetes
• Incidence increasing by 3.4% per year• 50% of patients diagnosed before age 20 years• 50% of patients diagnosed after age 20 years
— Often mistaken for type 2 diabetes—may make up 10% to 30% of individuals diagnosed with type 2 diabetes
— Oral agents ineffective; insulin therapy required— Autoimmune process slower and possibly different— Can usually be confirmed by beta cell antibodies— Loss of c-peptide
EURODIAB ACE Study Group. Lancet. 2000;355:873-876;Naik RG, Palmer JP. Curr Opin Endocrinol Diabetes. 1997;4:308-315
American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S5-S10
*Requires confirmation by repeat testing
Making the Diagnosis of Type 1 DiabetesMaking the Diagnosis of Type 1 Diabetes
Symptoms of diabetes Polyuria, polydipsia,polyphagia, diabetic
plus ketoacidosis (DKA)
Random plasma glucose 200 mg/dL*
Fasting plasma glucose (FPG) 126 mg/dL*
Oral glucose tolerancetest (OGTT) with 2-hour value 200 mg/dL*
Loss of c-peptide c-peptide<0.8 ng/dL
Presence of islet autoantibodies GADA, ICA, IA-2A, IAA
Putativetrigger
Circulating autoantibodies (ICA, GAD65, ICA512A, IAA)Cellular autoimmunity
Loss of first-phase insulin response (IVGTT)
Abnormal glucosetolerance (OGTT) Clinical
onset
Time
-Cell mass 100%
-Cell insufficienc
y
Geneticpredisposition
Insulitis-Cell injury
Eisenbarth GS. N Engl J Med. 1986;314:1360-1368
Diabetes
Natural History of “Pre”Natural History of “Pre”––Type 1 Type 1 DiabetesDiabetes
Rationale for Intensive TherapyRationale for Intensive Therapyof Type 1 Diabetesof Type 1 Diabetes
Glucose Control Is CriticalGlucose Control Is Critical
Skyler JS. Endocrinol Metab Clin North Am. 1996;25:243-254
RetinopathyNeuropathyMicroalbuminuria
20
15
10
5
051
Relative risk
A1C (%)
6 7 8 9 10 11 12
Risk of Progression ofRisk of Progression of Microvascular Microvascular Complications vs A1C DComplications vs A1C DCCTCCT
A1C=hemoglobin A1c
*Not statistically significant due to small number of events.†Showed statistical significance in subsequent epidemiologic analysis.DCCT Research Group. N Engl J Med. 1993;329:977-986; Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28:103-117; UKPDS 33: Lancet. 1998;352: 837-853; Stratton IM, et al. Brit Med J. 2000;321:405-412.
Intensive Therapy for Diabetes:Intensive Therapy for Diabetes:Reduction in Incidence of ComplicationsReduction in Incidence of Complications
T1DM DCCT
T2DMKumamoto
T2DMUKPDS
A1C 9% 7% 9% 7% 8% 7%
Retinopathy 63% 69% 17%–21%
Nephropathy 54% 70% 24%–33%
Neuropathy 60% 58% –
Cardiovascular disease
41%* 52* 16%*
T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
Long-term Microvascular Risk Reduction Long-term Microvascular Risk Reduction in Type 1 Diabetesin Type 1 DiabetesCombined DCCT-EDICCombined DCCT-EDIC
DCCT/EDIC Research Group. JAMA. 2002;287:2563-2569
0
0.1
0.2
0.3
0.4
0.5
0 1 2 3 4 5 6 7
Years in EDICNo. EvaluatedConventional 169 203 220 581 158 192
200Intensive 191 222 197 596 170 218
180
DCCTEnd of
randomized treatment
EDICYear 1
EDICYear 7
6%
8%
10%
12%
A1C Retinopathy progression(incidence)
Intensive Conventional
P<0.001
P<0.001
P=0.61
Cost-Effectiveness of IntensiveCost-Effectiveness of IntensiveTherapy in Type 1 Diabetes Therapy in Type 1 Diabetes DCCT Modeling StudyDCCT Modeling Study
Years Free From Complication(Projected Average)
Conventional treatment
Intensivetreatment
Proliferative retinopathy 39.1 53.9
Blindness 49.1 56.8
Microalbuminuria 34.5 43.7
End-stage renal disease (ESRD)
55.6 61.3
Neuropathy 42.3 53.2
Amputation 39.1 53.9
DCCT Research Group. JAMA. 1996;276:1409-1415
Principles of Intensive Therapy Principles of Intensive Therapy ofof
Type 1 DiabetesType 1 Diabetes
TargetsTargets
Current Targets for Glycemic ControlCurrent Targets for Glycemic ControlADA ACE LA IDF
A1C (%) Normal: 4%–6%
<7.0 6.5 <6.5 6.5
Fasting/Preprandial (mg/dL)
(plasma equivalent)
90-130 <110 110 <100
Postprandial (mg/dL)
(2-hour)
<180* <140 140 <135
*PeakAmerican Diabetes Association. Diabetes Care. 2004,27:S15-S35.The American Association of Clinical Endocrinologists. Endocr Pract. 2002; 8(suppl. 1):40-82.Chacra AR, et al. Diabetes Obes Metab. 2005;7:148-160.IDF (Europe) European Diabetes Policy Group. Diabet Med. 1999;16:716-730.
Principles of Intensive Therapy Principles of Intensive Therapy ofof
Type 1 DiabetesType 1 Diabetes
Insulin OptionsInsulin Options
Action Profiles of InsulinsAction Profiles of Insulins
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Plasmainsulinlevels
Regular 6–8 hours
NPH 12–16 hours
Ultralente 18–20 hours
Hours
Glargine ~24 hours
Aspart, glulisine, lispro 4–5 hours
Detemir ~14 hours
Burge MR, Schade DS. Endocrinol Metab Clin North Am. 1997;26:575-598; Barlocco D. Curr Opin Invest Drugs. 2003;4:1240-1244; Danne T et al. Diabetes Care. 2003;26:3087-3092
Polonsky KS et al. N Engl J Med. 1988;318:1231-1239
0600 0600
Time of day
20
40
60
80
100 B L D
Normal Daily Plasma Insulin ProfileNormal Daily Plasma Insulin ProfileNondiabetic Obese IndividualsNondiabetic Obese Individuals
B=breakfast; L=lunch; D=dinner
0800 18001200 2400
U/mL
4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:0012:008:00
Time
Basal
Pla
sma
insu
lin
Basal/Bolus Treatment Program with Rapid-Basal/Bolus Treatment Program with Rapid-acting and Basal Analogsacting and Basal Analogs
Rapid RapidRapid
• Basal insulin— Controls glucose production between meals and overnight
— Near-constant levels
— Usually ~50% of daily needs
• Bolus insulin (mealtime or prandial)— Limits hyperglycemia after meals
— Immediate rise and sharp peak at 1 hour postmeal
— 10% to 20% of total daily insulin requirement at each meal
• For ideal insulin replacement therapy, each component should come from a different insulin with a specific profile or via an insulin pump (with one insulin)
Physiologic Multiple Injection RegimensPhysiologic Multiple Injection RegimensThe Basal-Bolus Insulin ConceptThe Basal-Bolus Insulin Concept
Basal-bolus Therapy:Basal-bolus Therapy:
— More frequent decision making, testing, and insulin dosing
— Allows for variable food consumption based on hunger level
— Ability to skip meal or snack if desired (bedtime)
— Reduced variability of insulin absorption
— Easy to adapt to acute changes in schedule (exercise, sleeping in on weekends)
Insulin Injection DevicesInsulin Injection Devices
Insulin pens• Faster and easier
than syringes— Improve patient
attitude and adherence
— Have accurate dosing mechanisms, but inadequate resuspension of NPH may be a problem
0.1 110
Mealtime Insulin and Severe HypoglycemiaMealtime Insulin and Severe HypoglycemiaAspart vs Regular InsulinAspart vs Regular Insulin
All severe hypoglycemia
Nocturnal event
Nocturnal, glucagon required
4–6 hours postmeal
Favors Aspart
Favors RegularInsulin
Relative risk
Home PD et al. Diabet Med. 2000;17:762-770
P Values
NS
0.076
<0.050
<0.005
Variable Basal Rate Continuous Subcutaneous Insulin Variable Basal Rate Continuous Subcutaneous Insulin Infusion (CSII)Infusion (CSII)
4:004:00
2525
5050
7575
16:0016:00 20:00 20:00 24:0024:00 4:004:00
BreakfastBreakfast LunchLunch DinnerDinner
Pla
sma
Insu
lin
P
lasm
a In
suli
n µ
U/m
l)
U/m
l)
8:008:0012:0012:008:008:00
TimeTime
Basal Infusion
Bolus Bolus Bolus
Insulin PumpsInsulin PumpsContinuous Subcutaneous Insulin Infusion Continuous Subcutaneous Insulin Infusion (CSII)(CSII)
• For motivated patients
• Expensive
• External, programmable pump connected to an indwelling subcutaneous catheter
—Only rapid-acting insulin
—Programmable basal rates
—Bolus dose without extra injection
—New pumps with dose calculator function
—Bolus history
• Requires support system of qualified providers
-2 -1 0 12
CSII vs Multiple Injections of InsulinCSII vs Multiple Injections of InsulinMeta-analysesMeta-analyses
Blood glucose concentration
Glycated hemoglobin
A1C
Insulin dose
InjectionTherapyBetter
PumpTherapyBetter
Mean difference
Pickup J et al. BMJ. 2002;324:1-6;Weissberg-Benchell J et al. Diabetes Care. 2003;26:1079-1087
Pickup et al. 12 RCTs Weissberg-Benchell et al. 11 RCTs
RCT=randomized controlled trial
Balancing Risk of Severe Hypoglycemia Against the Risk of Balancing Risk of Severe Hypoglycemia Against the Risk of ComplicationsComplicationsDCCTDCCT
DCCT Research Group. N Engl J Med. 1993;329:977-986
2
0
A1C (%)
4
6
8
10
12
14
16
5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.510.010.5
100 patient-years
0
100 patient-years
5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.510.010.5
20
40
60
80
100
120
A1C (%)
Severe Hypoglycemia
Retinopathy Progression
HypoglycemiaHypoglycemiaRisk FactorsRisk Factors
Patient FactorsPatient Factors• Hypoglycemia unawarenessHypoglycemia unawareness• History of previous History of previous
hypoglycemiahypoglycemia• Defective glucose Defective glucose
counterregulationcounterregulation
• Long duration of diabetesLong duration of diabetes
• Erratic insulin absorptionErratic insulin absorption
• Age less than 5 to 7 yearsAge less than 5 to 7 years
Behavioral FactorsBehavioral Factors• Dietary inconsistencyDietary inconsistency
– Prolonged fastingProlonged fasting
– Missed meal or snackMissed meal or snack
• Strenuous exerciseStrenuous exercise
Medical FactorsMedical Factors• Drug side effects (Drug side effects (-blockers)-blockers)
• Dosing errorsDosing errors
• Unpredictable insulin kineticsUnpredictable insulin kinetics
• Inappropriate insulin Inappropriate insulin distributiondistribution
Weight Gain Weight Gain
• Insulin therapy reverses catabolic effects of diabetes—Glycosuria reduced
—Normal fuel-storage mechanisms restored
• Risk of hypoglycemia often causes patients to increase caloric intake and avoid exercise
• Risk of weight gain decreases with more physiologic insulin administration—Flexible insulin dosing to meet dietary and exercise
needs
Future Glucose Monitors Future Glucose Monitors
• Minimally invasive continuous glucose monitors
• Implanted glucose sensors
• Implanted insulin pumps
• “Closed-loop” systems
External Closed-Loop
Implanted Closed-Loop
Guardian™ CGMS
Freestyle Navigator™
4
5
6
7
8
9
Can Type 1 Diabetes Be “Cured?”Can Type 1 Diabetes Be “Cured?”Islet Cell TransplantationIslet Cell Transplantation
7 Type 1 Patients, Aged 29 to 54 Years, With History of Severe Hypoglycemia and Metabolic Instability
Shapiro AMJ et al. N Engl J Med. 2000;343:230-238
Baseline 6 monthsafter
transplant
MeanA1C (%)
0
1
2
3
4
5
6
Baseline
6 monthsafter
transplant
MeanC-peptide(ng/mL)
Fasting 90 min postmeal
8.4%
5.7% 0.48
2.5
5.7
*
*
*P<0.001 vs baseline
*
Loss of first-phase insulin response
Newly diagnosed diabetes
Genetically at riskMultiple antibody positive
Opportunities for Intervention inType 1 Diabetes
TrialNet
-Cell insufficienc
y
Geneticpredisposition
Insulitis-Cell injury Diabete
s
Time
-Cell mass