Transcript Diabetes Mellitus 101 for Cardiologists, Part 15

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 15
Stan Schwartz MD,FACP
Affiliate, Main Line Health System
Emeritus, Clinical Associate Professor of Medicine,
U of Pa.
6105472000
MECHANISM OF ACTION OF
RANOLAZINE TO STIMULATE INSULIN
SECRETION
● Ranolazine inhibits late sodium current, resulting in decreased
calcium overload in myocytes
● The effect of inhibition of the sodium current on insulin
secretion in pancreatic beta cells is unknown
Ranolazine may be VERY
Beneficial in Patients With Diabetes
1. avoid
hypoglycemic agents- use
Metformin/Incretin/tzd//bromocryptine/ ranolazine for
CV/ glucose
2. In patients with TZD edema, diastolic dysfunction benefit
obviates Edema
3. Ranolazine / Incretins peri-op / peri-cath for cardioprotection
4. ?incretin/ranolazine similarities- heart/beta cell? no additional benefit, additive, supra-additive
Ranolazine may be a preferred Antianginal in Patients With Diabetes
1.
Beta-blockers increase blood sugar, decrease recognition of hypoglycemia,
and increase risk of claudication, increase risk overt DM in non-diabeticsonly have secondary outcome studies- decreases pulse/ bp
2.
Calcium channel blockers can increase edema in those patients- who may
have obesity-related venous insufficiency and may be on other meds that
have edema risk (eg: TZD)no outcome studies- decreases BP
3.
Nitrates prevent use of ED agents (high risk of ED in this population) – no
outcome studies- decreases BP
4. ? Additive reduction in ACS with tzd/ ranolazine
Use of Ranolazine in Patients With
Diabetes- ‘Issue of Silent Ischemia’
1. Real ‘Silent Ischemia’ -- in sense of neuropathy-related absence of chest
discomfort
2. But ‘false’ ‘Silent Ischemia’-- in sense of they are likely to have:
a. symptomatic anginal ‘equivalents’
b. progressive reduction in exercise capability, and patient then limits activity
to avoid symptoms
3. BOTH
ULTIMATELY,WITH MORE DATA, could
see Use of Ranolazine in a large number
of Patients With Diabetes who have (with better supporting data)
1. Symtomatic Ischemia
2. ‘Silent Ischemia’
3. ECHOS with decreased EF, diastolic dysfunctionedema with pio-
4. Hx CHF
5. History or risk for a.fib
6. Cardio-protection peri-op
Practical problem in increasing
Ranolazine’s use
1.
Overcome prior QT / arrhythmia worry
2.
Overcome their impression of ‘less effective’ given previous use
as last line agent where it worked ~50% of time
3.
How to get cardiologist to use as first line for ischemia, esp. in dmteach its glycemic benefit
4.
Get more data to use in other situations mentioned
5.
How to get primary/ endo’s comfortable in prescribing cardiac
med without ‘offending cardiologists’
Therapy for Type II
Diabetes
Targets for Glycemic Control
ADA
ACE
<7.0
<6.5
Fasting/Preprandial (mg/dL)
(plasma equivalent)
90-130
<110
Postprandial (mg/dL)
<180*
<140
A1C (%)
Normal: 4-6%
(2-hour)
* Peak
Goals for individual patients may vary.
Aim for the Lowest A1C Possible without
Hypoglycemia.
American Diabetes Association. Clinical Practice Recommendations. Diabetes Care. 2004,27:S15-S35
The American Association of Clinical Endocrinologists. Medical Guidelines for the Management of Diabetes Mellitus. Endocr Pract. 2002; 8(Suppl. 1):
40-82
Relative Contribution of FBG and PPG Varies
With A1C Range
Inc PPG
increases
Micro- and
macrovascular
disease
Thus , to get to glycemic goals, one must control PPG as well as FBS.
(incretins, alpha-glucosidase inhibitors, TZDs, glinides, fast-insulin
analogues)
Adapted from Monnier L, et al. Diabetes Care. 2003;26:881-885.
Non-Insulin Therapy for
Type II Diabetes
Non-Insulin Therapy for Hyperglycemia in Type 2 Diabetes,
Treating Defronzo’s Octet:
Match Patient Characteristics to Drug Characteristics
5.Gut CHO
Absorption:
8.Kidney-
SGLT2
-
Incretin,
Pramlintide,
Glucosidase inh.
1.Pancreatic
insulin
Secretion:
Incretin, ranolazine
2.Pancreatic
glucagon
Secretion- Incretin
7.BrainTZD,INCRETIN
bromocryptine
HYPERGLYCEMIA
De
-
-
3.MuscleTZD, Incretin
4.Liver
Hepatic glucose
production:
Metformin, incretin
Peripheral
glucose
uptake
6.Fat- TZD, metformin