Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to...
-
Upload
andrea-powell -
Category
Documents
-
view
214 -
download
0
Transcript of Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to...
![Page 1: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/1.jpg)
Diabetes Mellitus 101 for Medical Professionals
An Aggressive Pathophysiologic Approach to An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes:Cardiometabolic Therapy for Type 2 Diabetes:
Stanley Schwartz, MD, FACE, FACPEmeritus, Clinical Associate Professor of Medicine, University of Pennsylvania
Affiliate, Main Line Health System, Wynnewood, [email protected]
6105472000
Part 1
![Page 2: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/2.jpg)
Natural History of Type 2 Diabetes
IR phenotypeAtherosclerosisobesityhypertensionHDL,TG,
HYPERINSULINEMIA
Endothelial dysfunctionPCO,ED
Envir.+ Other Disease
Obesity (visceral)
Poor Diet Inactivity
Insulin Resistance
Risk of Dev. Complications
ETOHBPSmoking
EyeNerveKidney
Beta Cell Secretion
Genes
BlindnessAmputationCRF
Disability
Disability
MICVAAmp
Age 0-15 15-40+ 15-50+25-70+
Macrovascular Complications
IGT Type II DM
Microvascular Complications
DEATHpp>7.8
![Page 3: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/3.jpg)
![Page 4: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/4.jpg)
Natural History of Type 2 Diabetes
IR phenotypeAtherosclerosisobesityhypertensionHDL,TG,
HYPERINSULINEMIA
Endothelial dysfunctionPCO,ED
Envir.+ Other Disease
Obesity (visceral)
Poor Diet Inactivity
Insulin Resistance
Risk of Dev. Complications
ETOHBPSmoking
EyeNerveKidney
Beta Cell Secretion
Genes
BlindnessAmputationCRF
Disability
Disability
MICVAAmp
Age 0-15 15-40+ 15-50+25-70+
Macrovascular Complications
IGT Type II DM
Microvascular Complications
DEATHpp>7.8
![Page 5: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/5.jpg)
Why Bother to Treat Agressively?
![Page 6: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/6.jpg)
![Page 7: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/7.jpg)
One third of adults with diabetes are undiagnosed
~10% of US adults have diabetes/~20 million persons in 2005
Nearly one third don’t know they have diabetes
26% of US adults have impaired fasting glucose (IFG)*
*100–125 mg/dLCowie CC et al. Diabetes Care. 2006;29:1263-8.
NIDDK. National Diabetes Statistics. www.diabetes.niddk.nih.gov.
Total: 35% of US adults with diabetes or IFG~73.3 million persons
![Page 8: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/8.jpg)
Considering the Epidemic of Metabolic Syndrome, Considering the Epidemic of Metabolic Syndrome, Prediabetes, Prevention Data, Undiagnosed Diabetes-Prediabetes, Prevention Data, Undiagnosed Diabetes-
ER Office and Pre-Admission ER Office and Pre-Admission IDENTIFICATION IS CRITICAL!IDENTIFICATION IS CRITICAL!
• Family history: whether parents or siblings have had diabetesFamily history: whether parents or siblings have had diabetes
• Obesity: especially with an increase in abdominal girthObesity: especially with an increase in abdominal girth
• High-risk ethnic group: African Americans, Hispanics,High-risk ethnic group: African Americans, Hispanics,Native Americans, Asians, and Pacific IslandersNative Americans, Asians, and Pacific Islanders
• Age: Age: we’re looking at all ages, if patient seems at riskwe’re looking at all ages, if patient seems at risk
• Impaired fasting glucose or impaired glucose toleranceImpaired fasting glucose or impaired glucose tolerance
• Hypertension: blood pressure ≥ 140/90 mm Hg in adultsHypertension: blood pressure ≥ 140/90 mm Hg in adults
• High density lipoproteins < 35 mg/dL or triglyceride High density lipoproteins < 35 mg/dL or triglyceride levels ≥ 250 mg/dLlevels ≥ 250 mg/dL
• Gestational diabetes or given birth to an infant Gestational diabetes or given birth to an infant weighing > 9 poundsweighing > 9 pounds
• Pre-adm , pre-cath, pre-op , pre-CABG Pre-adm , pre-cath, pre-op , pre-CABG
FBS >100, ppg >140, POC HgA1c >6.0FBS >100, ppg >140, POC HgA1c >6.0
![Page 9: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/9.jpg)
9
Hyperglycemia
SpikePPG
ContinuousA1C
Acute toxicity Chronic toxicity
Tissue lesion
Diabetic complications (Brownlee hypothesis)
Microvascular Macrovascular
Retinopathy Nephropathy Neuropathy PVD MI Stroke
American Diabetes Association. At: http://www.diabetes.org/diabetes-statistics/complications.jsp.Brownlee M. Diabetes mellitus: theory and practice. Elsevier Science Publishing Co., Inc; 1990:279-291.
Ceriello A. Diabetes. 2005;54:1-7.
Hyperglycemia Leads to Complications:Risk Starts with Pre-Diabetes
21% 18% 12% % of pts. with complication at DX 60% ASVD
![Page 10: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/10.jpg)
FBS>126
Ppg>200
New Hyperglycemia
#223 (12%)
Known Diabetes
#495 (26%)
Normo- Glycemia
#1168
Mortality, total 16 3 1.7
Mortality, ICU 31 11 10
Mortality, non-ICU 10 1.7 0.8
LOS 9 5.5 4.5
ICU Admission 29 14 9
D/c Dispo.Home 56 74 84
Transition Care 20 15 10
Nursing Home 8 9 4
RISK OF UNRECOGNIZED HYPERGYCEMIA:Effect of Hyperglycemia on Mortality, LOS,
ICU admission, D/C Disposition
Umpierrez, JCEM 2002;87:978
![Page 11: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/11.jpg)
Metabolic Sydrome, IGT, Diabetes, CV Disease
1. Beginning at 83 mg/dL, rising 2-hr pp glucose levels correlated linearly with CHD mortality
2. Even mild glucose elevations (fbs >110) increase mortality in patients undergoing PCI
3. Almost 70% of patients with first MI have IGT or undiagnosed diabetes
4. In multiple studies stress hyperglycemia in AMI is associated with 3-10 x mortality risk in patients without known diabetes
5. In a group of >31,000 patients without known diabetes but with CV disease (CVD), patients, an 18 mg/dL-higher FPG was associated with a 23% increase in the risk of hospitalization for HF
6. Inc mortality in hosp if admitted wth CVA
![Page 12: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/12.jpg)
Cardiovascular disease and diabetes
Bell DSH. Diabetes Care. 2003;26:2433-41.Centers for Disease Control (CDC). www.cdc.gov.T2DM = type 2 diabetes mellitus
Cardiovascular complications
of T2DM
~65% of deaths are due to CV disease
Coronary heart disease
deaths2- to 4-fold
Stroke risk2- to 4-fold
Heart failure 2- to 5-fold
No A1C threshold is apparentFinnish study by Kuusisto et al;UKPDS epidemiologic analysis; EPIC-Norfolk Study
Impaired glucose tolerance (IGT) and postprandial hyperglycemia are CV risk factorsFunagata Diabetes Study;Honolulu Heart Program; DECODE Study; Rancho Bernardo Study
![Page 13: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/13.jpg)
A1C Predicts Coronary Heart Disease in Type 2 Diabetes
Khaw KT et al. Ann Intern Med. 2004;141:413-420.
3.81.7
6.4
2.1
8.7
3
10.2
7.3
16.7
9.6
28.4
16.2
21.9
15.7
0
5
10
15
20
25
30
<5.0% 5.0%-5.4%
5.5%-5.9%
6.0%-6.4%
6.5%-6.9%
7.0% Knowndiabetes
Men
Women
CH
D e
ven
ts(e
ven
ts/1
00 p
erso
ns)
A1C concentration*
*P<0.001 for linear trend across A1C categories.
![Page 14: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/14.jpg)
High Risk of Cardiovascular Events High Risk of Cardiovascular Events in Type 2 Diabetesin Type 2 Diabetes
Cardiovascular deaths
0
5
10
15
20
25
30
35
40
45
50
7-ye
ar in
cide
nce
of
card
iova
scul
ar e
vent
s (%
)
Myocardial infarction
Stroke - +
No diabetes
Type 2 diabetes
Prior myocardial infarction - + - + - + - + - +
Haffner, NEJM 1998, 229-234
![Page 15: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/15.jpg)
THE PREVALENCE OF CHRONIC ANGINA POSES A SIGNIFICANT BURDEN TO THE US HEALTH CARE SYSTEM
• ~16 million Americans have CHD
• ~9.1 million Americans have angina pectoris
500,000 new cases are reported annually
• Mean angina frequency is ~2 episodes per week> 18 million episodes each
week or ~30 episodes each second
American Heart Association. Heart Disease and Stroke Statistics, 2008 Update. Pepine CJ, et al. Am J Cardiol. 1994;74:226-231.
New Cases of Stable Angina Per Year (Among Americans ≥ 45 Years of Age)
Men TotalIn
cid
enc
e (
# o
f N
ew C
ase
s)
320,000
180,000
500,000
Women
![Page 16: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/16.jpg)
SEVERITY OF ANGINA SYMPTOMS PREDICTS POOR SURVIVAL MORTALITY IN
VA PATIENTS (N=8900) WITH CAD
Mozaffarian D, et al. Am Heart J. 2003;146:1015-1022.
Years
0
0.74
10 1 2 3 4
*p<0.001 for log-ranktest for equality ofsurvivor function
75-10050-7425-49
0-24
Survival According to Physical Limitation Due to Angina (Seattle Angina Questionnaire Score)
Little to no limitation
Greatest limitation: 2.5 fold higher risk of death
Mild limitation: 27% higher risk of death
Moderate limitation: 61% higher risk of death
After adjustment for potential confounders, greater physical limitation due to angina was associated with increased risk of death compared with patients with little or no limitation
![Page 17: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/17.jpg)
![Page 18: Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Stanley Schwartz,](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649f575503460f94c7c953/html5/thumbnails/18.jpg)
Pathophysiology of Diabetic Complications: Implications for Goals of Therapy
I Metabolic DisorderGlucose, insulin hormones, enzymes, metabolites, etc. (i.e., control)
IIIndividual SusceptibilityGenetic/ethnic?Acquired
IIIModulating FactorsHypertension, diet, smoking, etc.
Delayed ComplicationsRetinal, renal neural, CV, cutaneous, etc.
IVEarly
VLate
Point of metabolic“no return”
Epidemiology
1. Hyperglycemia is a continuous
Risk Factor
2. No A1C threshold is apparent
3. Worse >A1C, longer duration DM
Mechanisms
1. Unified Theory of Brownlee
2. Oxidative stress
3. AGE, PKC, Hexosamine,Aldose Reductase
Eg: Macro-albuminuria; Proliferative retinopathy