new perspectives in the management of type 2 diabetes herold merisier, md, faafp voluntary assistant...
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New Perspectives in the Management of
Type 2 DiabetesHerold Merisier, MD, FAAFP
Voluntary Assistant Professor of Family MedicineMiller School of Medicine, University of Miami
Plantation, FL
Diabetes 2010
Epidemiology
Diagnosis
Screening
Management of Type 2 Diabetes
Patient Education
Therapeutic Lifestyle Changes (TLC)
Pharmacotherapy
Treatment of co-morbid conditions
Diabetes in the US
23.6 million children and adults affected (7.8% of the population)
Diagnosed: 17.9 million people
Undiagnosed: 5.7 million people
1.6 million new cases in adults > 20y/o in 2007
4300 new cases every day
Pre-Diabetes: 57 million people
2-4 fold increase in cardiovascular mortality and stroke
Center for Disease Control and PreventionAvailable at: http://www.cdc.gov/diabetes/pubs/estimates07.htm#1
Diabetes in Canada1.8 million adults with Diabetes
Prevalence: 4.8% (1998): 1 054 000 adult Canadians
Prevalence: 5.5% (2005)
Available at: http://www.diabetes.ca/files/cpg2008/cpg-2008.pdf
23.0 M36.2 M↑57.0%
14.2 M26.2 M↑85%
48.4 M58.6 M↑21%
43.0 M 75.8 M ↑79%
7.1M15.0 M↑111%
39.3 M81.6
M
↑108%
M = million, AFR = Africa, NA = North America, EUR = Europe, SACA = South and Central America, EMME = Eastern Mediterranean and Middle East, SEA = South-East Asia, WP = Western Pacific
Diabetes Atlas Committee. Diabetes Atlas 2nd Edition: IDF 2003.
Global Projections for the Diabetes Epidemic: 2003-2025
World2003 = 194 M2025 = 333 M↑ 72%
AFR
NA
SACA
EUR
SEA
WP
19.2 M39.4 M↑105%
EMME
2003 2025
Diagnosis
Normoglycemia
Impaired Glucose
MetabolismDiabetes
FPG < 100 mg/dlFPG ≥ 100 mg/dl
< 126 mg/dlIFG
FPG ≥ 126 mg/dl(x 2)
2hPPG < 140 mg/dl
2hPPG ≥ 140 mg/dl< 200 mg/dl
IGT
2hPPG ≥ 200 mg/dl
or RPG ≥ 200 mg/dl w/ sx of
Diabetes
HbA1c ≥ 6.5 (x 2)
Adapted from Clinical Practice Recommendations. Diabetes Care, 2010
IFG: Impaired Fasting Glucose FPG: Fasting Plasma Glucose RPG: Random Plasma GlucoseIGT: Impaired Glucose Tolerance PPG: Post-Prandial Glucose
Screening All individuals ≥ 45y/o, particularly if BMI ≥ 25
if normal, repeat every 3 years
Start screening at younger age if BMI ≥ 25 and: physically inactive first-degree relative with Diabetes high risk ethnic group h/o IFG, IGT, Gestational Diabetes, PCOS Dyslipidemia or h/o cardio-vascular disease
Fasting glucose or 2-hour OGTT
Diabetes Risk Calculator
Diabetes Risk CalculatorGender
Age
Prior history of elevated blood glucose
Height and weight
Diet
Smoking history
Physical activity
Family history Diabetes Care. 2008 May;31(5):1040-5
Diabetes Risk Calculator
Available at: http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/
Diabetes Risk Calculator
Available at: http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/
QD Score (http://www.qdscore.org)
BMJ 2009;338:b880. Available at: http://bmj.com/cgi/content/full/338/mar17_2/b880
Management of Type 2 Diabetes
Patient Education
Therapeutic Lifestyle Changes (TLC)
Pharmacotherapy
Treatment of co-morbid conditions
Pharmacotherapy: Oral Agents
Class Drugs Mechanism of action
α-Glucosidase Inhibitor
AcarboseMiglitol
Decrease carbohydrate absorption in GI tract
Biguanides Metformin Decrease hepatic neoglucogenesis
Secretagogues Sulfonylureas Meglitinides
Glyburide, Glipizide, GlimepirideRepaglinide, Nateglinide
Stimulate β-cell to increase insulin output
ThiazolidinedionesPioglitazone (Actos®)Rosiglitazone (Avandia®)
Improve insulin sensitivity, decrease insulin resistance
DDP-4 InhibitorsSitagliptin (Januvia®)Saxagliptin (Onglyza®)
Slow incretin metabolism, Increase insulin synthesis/release, Decrease glucagon levels
Rosiglitazone (Avandia®)
Contraindicated in patients with CHF
Meta-analysis of 42 clinical studies: Mean duration 6 months; 14,237 total patients Rosiglitazone vs. placebo Increased risk of risk of myocardial ischemic events
Three other studies Mean duration 41 months; 14,067 total patients Rosiglitazone vs. other oral diabetes medications or
placebo Increased of MI neither confirmed nor excluded this
risk
18
Progressive -cell Failure in Type 2 Diabetes
-12 -6 0 6 120
20
40
60
80
100
-ce
ll Fu
nct
ion
(%
)
Based on data of UKPDS 16: conventional (diet) treatment group. Diabetes. 1995.
Years
Diagnosis
Pharmacotherapy: Non-Insulin Injectables
Class Drug Mechanism of action
GLP-1 Analog(Incretin Mimetic)
Exenatide (Byetta®)
Liraglutide (Victoza®)
increases beta-cell responsedecreases glucagon secretiondelays gastric emptying
Amlynomimetic
Pramlintide (Symlin®)
slows gastric emptyingdecreases glucagon secretionearly satiety → weight loss
Insulin Preparation Onset Peak Duration
Short actingRegular 30-60
min. 3-4h 6-8h
IntermediateNPHLenteUltralente
2-4h3-4h4-6h
6-10h6-12h10-16h
14-18h16-20h20-24h
Combinations70% NPH / 30% reg75% NPH / 25% reg
30-60 min.
15-60 min.
DualDual
14-18h14-18h
Pharmacotherapy: Insulin(Older Agents)
Pharmacotherapy: Insulin(Newer Agents: Insulin Analogs)
Insulin Preparation Onset Peak Duration
Rapid actingLispro (Novolog®)Aspart (Humalog®)Glulisine (Apidra®)
15-30 min.
15-30 min.
15-30 min.
30-90 min.
30-90 min.
30-90 min.
4-6h4-6h4-6h
Long actingGlargine (Lantus®)Detemir (Levemir®)
1-2h1-2h
flatflat
24h24h
Combinations70% / 30% lispro75% / 25% aspart50% / 50% aspart
30-60 min.
15-60 min.
15-60 min.
DualDualDual
14-18h14-18h14-18h
Therapy for Type 2 Diabetes: Sites of Action
Liver
Pancreas
Glucose
Hyperglycemia
↑HGO*
↑Sulfonylureas↑RepaglinideTZD
↑Metformin±Thiazolidinediones
Gut
Muscle↑Metformin↑Thiazolidinediones
↓ α-Glucosidase inhibitors
Adiposetissue
↓ Glucoseuptake
AcarboseMiglitol
RosiglitazonePioglitazone
*HGO=hepatic glucose output.Adapted from DeFronzo RA. Ann Intern Med. 1999;131:281-303.
Package Inserts for AVANDIA® (rosiglitazone maleate, GlaxoSmithKline), Actos® (pioglitazone HCl,
Takeda), Prandin® (repaglinide, Novo Nordisk), Precose® (acarbose tablets, Bayer), Glyset® (miglitol, mfd. by Bayer for Pharmacia & Upjohn).
23
+ +
Diet &exercise
Oral monotherapy
Oral combination
Oral plus insulin
Insulin
+
Stepwise Management of Type 2 Diabetes
Adapted from Williams G. Lancet 1994; 343: 95-100.
PharmacotherapyStepwise Management
Glycemic targets often not met
Monotherapy often not effective long term
Therapy fails to address multiple impairments
Step-wise approach tends to perpetuate “failure”
New Treatment ParadigmTreatment designed to address multiple
impairments
Simultaneous rather than sequential therapy
Combination therapy from the outset
Early titrations to meet glycemic targets
Combination Oral Diabetic Agents
Glucovance® ( Glyburide + Metformin)
Metaglip® (Glipizide + Metformin)
Avandamet® (Rosiglitazone + Metformin)
Avandaryl® (Rosiglitazone + Glimepiride)
ActoPlus Met® (Pioglitazone + Metformin)
Janumet® (Januvia + Metformin)
ADA/EASD Consensus Algorithm 2009
Nathan and Associates: Diabetes Care, Vol. 32, Number 1, January 2009
At Diagnosis
Lifestyle+Metformin
Tier 1: Well-validated core therapies
Step 1
Lifestyle + Metformin+Sulfonylurea
Lifestyle + Metformin+Basal Insulin
Step 2
Lifestyle + Metformin+Pioglitazone
Lifestyle + Metformin+GLP1- Agonist
Tier 2: Less well validated therapies
Lifestyle + Metformin+Intensive Insulin
Step 3
Lifestyle + Metformin+Pioglitazone+Sulfonylurea
Lifestyle + Metformin+Basal Insulin
Type 2diabetes
Postprandial hyperglycemia
Basal hyperglycemia
Glucose Dynamics: Basal and Prandial
Riddle MC. Am J Med. 2004;116(suppl):3S-9.
Plasma glucose (mg/dL)
Time of day
200
250
150
100
50
0
0600 1200 1800 06002400
Normal
Basal-Bolus Combination Therapy
4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:0012:008:00
Time
Bolusinsulin
Bolusinsulin
Bolusinsulin
Plasma Insulin Levels
Basalinsulin
Diabetes CV Risk Calculator (Canada)
http://www.diabetes.ca/documents/about-diabetes/FINAL_PATIENT_TOOL_FOR_WEBSITE.pdf
The ABCs of Diabetes CareA1C
ADA recommends < 7% in general, < 6% for selected individuals
AACE/IDF recommend ≤ 6.5%
Blood pressure < 130/80 mm Hg
Cholesterol LDL-C: < 100 mg/dL (< 70 mg/dL in very high-risk
patients) HDL-C: > 40 mg/dL in men and > 50 mg/dL in women Non-HDL-C: < 130 mg/dL (< 100 mg/dL in high-risk
patients) Triglycerides: < 150 mg/dL American Diabetes Association. Diabetes Care. 2007;30(suppl 1):S4-S41.
American Association of Clinical Endocrinologists. Endocr Pract. 2007;13(suppl 1):3-68. International Diabetes Federation. Diabet Med. 2006;23:579-593.
Additional Recommendations
Individualized Medical Nutrition Therapy
Exercise
Aspirin (75-325 mg/d)
Smoking cessation
Screening for microvascular complications (eyes, kidneys, feet)
Immunization ( Flu vaccine, Pneumovax)
Recommended cancer screening
ADA. Diabetes Care. 2005;28(suppl 1):S1-79.
• Proper nutrition
• Physical activity program
• Smoking cessation
• Weight control
• HbA1c <7%
• Glucose (mg/dL): Preprandial 90–130Postprandial <180
• Dyslipidemia: Statin
• Hypertension: ≥2 drug classes, include ACEI or ARB
• Microalbuminuria:ACEI or ARB
• Use of aspirin
• CHD: ACEI, β-blocker
• CVD/high risk: ACEI
Lifestyleinterventions
Intensive glycemic control
Aggressive Rx forCV risk reduction
Optimal Care of the Diabetic Patient