文档介绍：INSULIN RESISTANCE AND BETA CELL DYSFUNCTION: A DYNAMIC DUET RESPONSIBLE FOR T2DM
Ralph A. DeFronzo, MD
Professor of M pathogenic mechanisms known to promote beta cell failure and cause insulin resistance
HYPERGLYCEMIA
Decreased Incretin Effect
Decreased Insulin Secretion
Increased
HGP
Islet–a cell
Increased Glucagon Secretion
OMINOUS OCTET
Increased
Lipolysis
Increased
Glucose
Reabsorption
Neurotransmitter Dysfunction
Decreased Glucose
Uptake
Diabetes 58:773-795, 2009
TREATMENT OF T2DM
(1) Will require multiple drugs in combination to correct multiple pathophysiologic defects
(2) Should be based upon known pathogenic abnormalities, and NOT simply on the reduction in HBA1c
(3) Must be started early in the natural history of T2DM, if progressive beta cell failure is to be prevented
Hyperglycemia
TREATMENT OF TYPE 2 DIABETES: A SOUND APPROACH BASED UPON ITS PATHOPHYSIOLOGY
Impaired Insulin Secretion
Hyperglycemia
Decreased Glucose
Uptake
Increased Lipolysis
DPP-IV Inhibitors
Sulfonylureas
Metformin
TZDs
TZDs
TZDs
GLP-1 analogues
Increased
HGP
TZDs
Metformin
Median HbA1c (%)
Time (years)
9
8
7
6
0
0
3
6
9
12
15
UKPDS: Effect of SU & Metformin Rx on HbA1c
37%
Conventional
Glibenclamide
Metformin
UKPDS 352:837-853 and 853-865, 1998
EXCESS
GLYCEMIC
BURDEN
-2
-1
0
1
Change in HbA1c (%)
TIME (years)
0
1
2
3
4
5
6
10
Hanefeld (n=250)
Charbonnel (n=313)
Chicago (n=230)
ADOPT (n=1,441)
UKPDS (n=1,573)
Gliclazide
PERISCOPE (n=181)
GLY
Glimepiride
Glyburide
Glyburide
Glyburide
Glyburide
SU
SU
Alvarsson (n=39)
Alvarsson (n=48)
RECORD (n=272)
Tan (n=297)
Gliclazide
DURABILITY OF GLYCEMIC CONTROL WITH SULFONYL