1. Diabetes Mellitus 101 for Cardiologists (and Alike): 2015
An Aggressive Pathophysiologic Approach to Therapy of Type 2 Diabetes in Cardiometabolic Patients:
Looking at Diabetes Medications with a Cardiologists Eye
Part 2
Stan Schwartz MD,FACP
Affiliate, Main Line Health System
Emeritus, Clinical Associate Professor of Medicine,
U of Pa. 1

4. Type 2 diabetes – the microvascular and macrovascular burden is already present at diagnosis
21%
Retinopathy1
50%
ASVD
Nephropathy2
18%
20%
Erectile dysfunction1
Complications start early in the development of Type 2 diabetes
CORE SLIDE
Increasing blood glucose levels are associated with an increased risk of several debilitating microvascular complications.1-3
People with diabetes are at least 15 times more likely to undergo lower limb amputation than the general population.4,5
More than 50% of patients with Type 2 diabetes have complications at diagnosis and this figure rises to 70% if hypertension and impotence are included.1
Patients with Type 2 diabetes are also at greatly increased risk of cardiovascular disease.6
Link to next slide:
How do complications occur?
References
1. UKPDS Group. Diabetes Res 1990; 13: 1–11.
2. The Hypertension in Diabetes Study Group. J Hypertens 1993; 11: 309–317.
3. Stratton IM et al. BMJ 2000; 321: 405–412.
4. King’s Fund. Counting the cost. The real impact of non insulin dependent diabetes. London: British Diabetic Association, 1996.
5. Most RS et al. Diabetes Care 1983; 6: 87–91.
6. Stamler J et al. Diabetes Care 1993; 16: 434–444.
12%
Neuropathy1
1. UKPDS Group. Diabetes Res 1990; 13: 1– The Hypertension in Diabetes Study Group. J Hypertens 1993; 11: 309–317.

5. 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

6. Cardiovascular disease and diabetes
No A1C threshold
is apparent
Finnish study by Kuusisto et al;
UKPDS epidemiologic analysis;
EPIC-Norfolk Study
~65% of deaths are due to CV disease
Cardiovascular complications of T2DM
Coronary heart disease deaths 2- to 4-fold
Stroke risk
2- to 4-fold
Cardiovascular disease and diabetes
Cardiovascular (CV) disease is the primary complication of diabetes; approximately 65% of deaths in people with diabetes are due to heart disease and stroke.
Adults with diabetes have higher rates of coronary heart disease (CHD), stroke, and heart failure (HF) than nondiabetic adults:
CHD death rates are 2 to 4 times higher
Risk of stroke is 2 to 4 times higher
HF occurs twice as frequently in men and 5 times more frequently in women aged 45 to 74 years
In 2004, the estimated prevalence of physician-diagnosed diabetes among adults was million; the prevalence of undiagnosed diabetes was 5 million. According to the most recent government statistics, approximately one-third of the US population with diabetes is undiagnosed.(1)
Impaired glucose tolerance (IGT)
and postprandial hyperglycemia
are CV risk factors
Funagata Diabetes Study;
Honolulu Heart Program;
DECODE Study;
Rancho Bernardo Study
Heart failure 2- to 5-fold
Bell DSH. Diabetes Care. 2003;26:
Centers for Disease Control (CDC).
T2DM = type 2 diabetes mellitus
1. American Heart Association. Heart Disease and Stroke Statistics Update.

8. A1C Predicts Coronary Heart Disease in Type 2 Diabetes30
Men
28.4
Women 25
21.9 20
(events/100 persons)
CHD events
16.7
16.2
15.7 15
10.2
9.6 10
8.7
6.4
7.3 5
3.8 3
1.7
2.1
A1C Predicts Coronary Heart Disease in Type 2 Diabetes
Accumulating evidence suggests that there is a relationship between blood glucose concentrations and cardiovascular risk, even at levels below the diagnostic cutoff for type 2 diabetes.
Khaw and colleagues examined the relationship of A1C level to cardiovascular disease (CVD) and mortality in adults with and without diabetes in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk). This 6-year cohort analysis involved 4,662 men and 5,570 women between the ages of 45 and 79 who were residents of Norfolk, United Kingdom.
Persons with known or undiagnosed type 2 diabetes had a greater risk for all-cause mortality and CVD and coronary heart disease (CHD) than did those without diabetes. In both men and women, the risk for CHD increased throughout the whole range of A1C concentrations, as shown in this slide. Patients with A1C concentrations less than 5% had the lowest rates. Among men, a gradient of increasing rates through the distribution was apparent. Among women, odds ratios for CVD or CHD did not increase significantly until the A1C concentration reached 6%.
Additionally, in both men and women, there was a continuous and statistically significant (P<0.001) relationship between A1C levels and CVD (806 events), as well as between A1C levels and total mortality (521 deaths) throughout the whole distribution. This relationship was observed even in persons without known diabetes.
It cannot be determined if A1C concentrations and CVD or CHD are causally related from this observational study. These findings support the need for randomized trials of interventions to reduce A1C concentrations among persons without type 2 diabetes.
Khaw KT et al. Ann Intern Med. 2004;141:
<5.0%
5.0%-
5.5%-
6.0%-
6.5%-
³7.0%
Known
5.4%
5.9%
6.4%
6.9%
diabetes
A1C concentration*
*P<0.001 for linear trend
across A1C categories.
Khaw KT et al. Ann Intern Med. 2004;141:

9. Incidence (# of New Cases)
THE PREVALENCE OF CHRONIC ANGINA POSES A SIGNIFICANT BURDEN TO THE US HEALTH CARE SYSTEM
New Cases of Stable Angina Per Year (Among Americans ≥ 45 Years of Age)
~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
Incidence (# of New Cases)
500,000
320,000
180,000
Men
Women
Total
American Heart Association. Heart Disease and Stroke Statistics, 2008 Update. Pepine CJ, et al. Am J Cardiol. 1994;74:

11. Pathophysiology of Diabetic Complications: Implications for Goals of Therapy
Epidemiology
Hyperglycemia is a continuous
Risk Factor
No A1C threshold is apparent
Worse >A1C, longer duration DM II
Individual Susceptibility
Genetic/ethnic
?Acquired IV
Early
Metabolic
a\memory I
Metabolic Disorder
Glucose, insulin hormones, enzymes, metabolites, etc. (i.e., control)
Delayed Complications
Retinal, renal neural, CV, cutaneous, etc.
Point of metabolic “no return”
Eg:
Macro-
albuminuria;
Proliferative
retinopathy
Mechanisms
Unified Theory of Brownlee
Oxidative stress
AGE, PKC, Hexosamine, Aldose Reductase
III
Modulating Factors
Hypertension, diet, smoking, etc. V
Late 11 11 11