Download Diabetes Mellitus 101 for Cardiologists (and Alike)

Practical Implementation as a
Discussion with the Patient
Practical Use of SGLT-2 Inhibitors in T2DM:
Clinical Pearls- Perlas de Sabiduria
Stan Schwartz MD, FACP
Affiliate, Main Line Health System
Emeritus, Clinical Associate Professor of Medicine,
U of Pa.
[email protected]
Structure of Our Discussion:
1. Following Flow of Discussion with Patient
1. General principles
2. SGLT-2 Principles
2. First Visit Process of Care
3. Follow-up Visit Process of Care
Updated Natural History of Type 2
Diabetes
E
P
I
G
E
N
I
T
I
C
S
E
P
I
G
E
N
I
T
I
C
Age
0-15
15-40+
15-50+
25-70+
Environmental Inflam. Triggers
eg: viral,endocrine disruptors, food AGE’s, biome
Macrovascular Complications
IR Phenotype
Disability
Resistance
inflammatory, adipokines
MI
CVA
Amp
Polygenic- other
Gene
β-Cell
secretion/mass
pp>7.8
Monogenic (HLA)
Polygenic
IGT
Monogenic – MODY
Resistance-FFA
Poor diet, inactivity
endocrine disruptors, food AGE’s ,biome
Environmental Triggers
ETOH
BP
Smoking
Risk of Dev.
Complications
DEATH
Type II DM
Eye
Nerve
Kidney
Blindness
Amputation
CRF
Disability
Microvascular Complications
Pearl
Treat Aggressively
to Delay or Prevent
Complications
Impact of Intensive Therapy in Type 2 Diabetes
Summary of Major Clinical Trials:
BUT Subset Evaluations Show Reduced CV Outcomes if shorter
duration of DM, without significant pre-existing complications
Initial Trial
Long Term Follow-up
Study
Microvascular
Macrovascular
Mortality
UGDP
↔
↔
↔
UKPDS
DCCT/EDIC*
ACCORD
ADVANCE
VADT
↓
↓
↓
↓
↓
↓
↔
↔
↔
↓
↓
↔
↔
↔
↔
↔
↓
↔
↑(unadj.), ↔ (adj.)
↔
↔
↑- likely due to hypoglycemia and weight gain
Pearl
Early Treatment Decreases Micro
and Macro Vascular RISK/
OUTCOMES
As long as do without Undue
Hypoglycemia or Weight Gain
Consequences of Hypoglycemia
• Prolonged QT- intervals– Can be of pronged duration
– Greater with higher catecholamine levels
Diabetologia 52:42,2009
IJCP Sup 129, 7/02
• Associated with Angina
changes
• Associated with Arrhythmias
• Associated with Sudden Death
Diabetes Care 26, 1485, 2003
Europace 10,860
/ Ischemic EKG
Porcellati, ADA2010
• Increased VariabiltyHgA1c in ACCORD
Endocrine Practice 16,¾ 2010
explains highest mortality in intensive group had highest
( increases inflammation, ICU
mortality Hirsch ADA2010)
• Sulfonylureas block Ischemic Preconditioning
There is No perfect Exogenous Insulin:
All result in HyperInsulinemia and Potential Hypoglycemia
Hypoglycemia/ Wt. Gain
CONCLUSION:
DELAY INSULIN
THERAPY;
AVOID BOLUS RX
if possible
NORMAL:
Insulin into portal system
and B-cell=
Exogenous Insulin
Perfect glucose sensorInsulin secretion modulator
Pearl
No more Sulfonylureas or Glinides
Delay Insulin
Most will not need Bolus Insulin
BETA CELL-CENTRIC VIEW OF DIABETES: Matching Rx with Etiology
use least number agents treating maximal # of modes of hyperglycemia
FOCUS on SGLT-2 Inhibition- addresses
5/11
MOH
2.
1.
11.
Immune System /
Inflammation
Anti-Inflammatories,
Immune
modulators
Decreased
insulin
secretion
Incretins
Ranolazine
Unsuppressed
glucagon
secretion
3. Decreased
incretin
effect
Incretins
Incretins
Pramlintide
CORE
DEFECT
5. Decreased
peripheral
muscle
uptake
Kidney
HYPERGLYCEMIA
9.
Brain
Incretin
Dopa agonist
Resistance Issues
New Construct
Older Construct
Islet Cell Issues
Increased
hepatic glucose
production
Metformin, TZDs
10.
SGLT2
Inhibitors
4.
Metformin,
TZDs
7.
8. Colon /
Biome
Incretins/Pro
biotics
Stomach/Sma
ll intestine
GLP-1 RAs
AGI
Pramlintide
6.
Adipose
Metformin,
TZDs