Diabette sorunlu vakalar Dr. Mustafa Kanat

Diabette sorunlu vakalar Dr. Mustafa Kanat

DİYABETTE SORUNLU
VAKALAR
Dr. Mustafa KANAT
İstanbul Medeniyet Üniversitesi
İç Hastalıkları Anabilim Dalı
İstanbul
2 yıl önce MI geçiren 46 yaşındaki erkek
hasta check-up sırasında kan şekerinin
yüksek çıkması üzerine değerlendiriliyor.
BMI:32 kg/m2, Glukoz: 216 mg/dl, A1C:
12.5 Trigliserid: 438 mg/dl, LDL: 136
mg/dl, HDL: 32 mg/dl, C-peptid: 3.2 ng/dl.
TA= 170/90 mmHg, Mikroalbümin: 88
mg/24 saat
Bu hastada tedavi olarak ne başlarsınız?
OMINOUS OCTET
Decreased
Incretin Effect
Decreased Insulin
Secretion
Increased
Lipolysis
Islet–a cell
ETIOLOGY OF T2DM
Impaired Insulin
Secretion
Increased Lipolysis
Hyperglycemia
Increased
HGP
Decreased Glucose
Uptake
DEFN75-3/99
HYPERGLYCEMIA
Increased
Glucagon
Secretion
Increased
HGP
Increased
Glucose
Reabsorption
Decreased Glucose
Uptake
Neurotransmitter
Dysfunction
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
TREATMENT OF TYPE 2 DIABETES: A SOUND
APPROACH BASED UPON ITS PATHOPHYSIOLOGY
Impaired Insulin Secretion
Metformin
TZDs
GLP-1
Increased
HGP

TZDs
GLP-1 analogues
DPP-IV Inhibitors
Sulfonylureas
Hyperglycemia
Increased
Lipolysis
TZDs

TZDs
Metformin
GLP-1
UKPDS: Effect of SU & Metformin Rx on HbA1c
Median HbA1c (%)
9
Glibenclamide
Conventional
8
Metformin
7
EXCESS
GLYCEMIC
BURDEN
6
0
0
3
UKPDS 352:837-853 and 853-865, 1998
6
9
Time (years)
12
15
DURABILITY OF GLYCEMIC CONTROL WITH
SULFONYLUREAS
Change in HbA1c (%)
1
Glyburide
Glyburide
Glimepiride
Glyburide
GLY
SU
Gliclazide
0
SU
Alvarsson (n=39)
Alvarsson (n=48)
RECORD (n=272)
Hanefeld (n=250)
Glyburide
Charbonnel (n=313)
-1
Gliclazide
UKPDS (n=1,573)
Chicago (n=230)
ADOPT (n=1,441)
PERISCOPE (n=181)
Tan (n=297)
-2
0
1
2
3
4
TIME (years)
5
6
10
DURABILITY OF GLYCEMIC CONTROL WITH
THIAZOLIDINEDIONES
Change in HbA1c (%)
1
0
Hanefeld (n=250)
Charbonnel (n=317)
Chicago (n=232)
ADOPT (n=1,456)
PERISCOPE (n=178)
Rosenstock (n=115)
RECORD (n=301)
Tan (n=249)
PIO
Rosiglitazone
PIO
ROSI
PIO
-1
PIO
PIO
-2
0
1
2
3
4
TIME (years)
5
6
Fat Topography In Type 2 Diabetic Subjects
Hi TG
Hi FFA
Intramuscular
Fat
Subcutaneous
Fat
Intrahepatic
Fat
Intra-arterial
Fat
Intraabdominal
Fat
Effect of Thiazolidinediones on Fat Topography
High TG
High FFA
Intramuscular
Fat
TG
FFA
TZD
Subcutaneous
Fat
Intrahepatic
Fat
Intra-arterial
Fat
Intraabdominal
Fat
Artery
Bays H, Mandarino L, DeFronzo RA. J Clin Endocrinol Metab. 2004;89:463-78..
EFFECT OF PIOGLITAZONE ON
ABDOMINAL FAT DISTRIBUTION
Visceral Fat
Baseline
After PIO
Deep SC Fat
Superficial SC Fat
126895-2/04
INCRETINS
In response to equivalent hyperglycemic
stimuli, ORAL glucose elicits a greater
insulin response than IV glucose
Glucagon-like Peptide 1 (GLP-1)
and
Glucose-Dependent Insulinotrophic
Polypeptide (GIP)
account for ~90% of the
incretin effect
GLP-1 ANALOGUES
● Exenatide BID
● Liraglutide
● Exenatide QW
● Albiglutide QW
● Dulaglutide QW
EXENATIDE AND LIRAGLUTIDE
● Effectively reduce HbA1c
● Preserve beta cell function
● Promote weight loss
● Correct known pathophysiologic
defects in T2DM
● Do not cause hypoglycemia
● Have an excellent safety profile
DPP-4 INHIBITORS
EFFICACY AND
MECHANISM
OF ACTION
DPP IV ACTION/INHIBITION
GIP
[1-42]
GLP-1
[7-36 amide]
(biologically
active)
DPP IV
action/
inhibition
GIP
[3-42]
127945-5/04
GLP-1
[9-36 amide]
(biologically
inactive)
EFFECT OF SITAGLIPTIN ON HbA1c:
CHANGE FROM BASELINE (HbA1c ~ 8.0%)
Diabetes Care 29:2638, 2006; Clin Ther 28:1556, 2006; Diabetolgia 49:2564, 2006
DHbA1c(%)
0
-0.5
-0.60
-0.67
-0.85
-1.0
Drug Naive
Metformin
Pioglitazone
ADDITION OF SITAGLIPTIN TO
THE KIDNEY PLAYS A
CENTRAL ROLE IN
THE PATHOGENESIS
OF T2DM
RENAL HANDLING OF GLUCOSE
(180 L/day) (1000 mg/L) = 180 g/day
SGLT 2
S1
S3
90%
S
G
L
T
1
10%
NO
GLUCOSE
INCREASED SGLT2 GLUCOSE TRANSPORTER mRNA
AND PROTEIN LEVELS IN HUMAN RENAL PROXIMAL TUBULAR
CELLS
2
1
1500
4
1000
*
2
500
0
0
CON
T2DM
Rahmoune et al, Diabetes 54:3427-34, 2005
2000
CON
T2DM
CON
T2DM
0
CPM
3
*
* P<0.05-0.01
Normalized Glucose
Transporter Levels
4
Fold Increase
6
*
5
AMG UPTAKE
SGLT 2 PROTEIN
SGLT 2 mRNA
SGLT2 INHIBITOR: WHERE DO THEY FIT
IN THE TREATMENT ALGORITHM
●
●
●
●
●
●
●
●
Monotherapy
Add-on to: MET, SU, PIO
Add-on to oral combo therapy
Double/Triple combo therapy
Add-on to insulin in T2DM
Add-on to insulin in T1DM
IGT/IFG
A1c > 10.0%
OMINOUS OCTET
Decreased
Incretin Effect
Decreased Insulin
Secretion
Islet–a cell
Increased
Glucagon
Secretion
Increased
Lipolysis
ETIOLOGY OF T2DM
Impaired Insulin
Secretion
Increased Lipolysis
Hyperglycemia
Increased
HGP
Decreased Glucose
Uptake
DEFN75-3/99
HYPERGLYCEMIA
Increased
Glucose
Reabsorption
Increased
HGP
TZDs
MET
GLP1
Neurotransmitter
Dysfunction
TZDs
GLP1
2 yıl önce MI geçiren 46 yaşındaki erkek
hasta check-up sırasında kan şekerinin
yüksek çıkması üzerine değerlendiriliyor.
BMI:32 kg/m2, Glukoz: 216 mg/dl, A1C:
12.5 Trigliserid: 438 mg/dl, LDL: 136
mg/dl, HDL: 32 mg/dl, C-peptid: 3.2 ng/dl.
TA= 170/90 mmHg, Mikroalbümin: 88
mg/24 saat
Bu hastada tedavi olarak ne başlarsınız?
Metformin 2x1000 mg
Pioglitazon 15 mg
Exenatide mcg 2x1
Ramipril 5 mg 1x1
Atorvastatin 10 mg
Coraspin 100 mg
12 ay sonra
BMI: 28
Glukoz 110 mg/dl
A1c: 6.4
Trigliserid: 136 mg/dl
LDL: 88 mg/dl
HDL: 44 mg/dl
68 yaşında erkek hasta, 15 yıldır T2DM+SVH+HT+DL
tanısı ile izleniyor. 1 yıl önce strok geçirmiş. Sol
hemiplejisi mevcut. BMI: 34 kg/m2 Glikoz
regülasyonundaki bozukluk nedeniye müracaat etti.
Glukoz: 216 mg/dl, A1C: 10.5, Kreatinin: 1.7 mg/kg,
Mikroalbiminüri: 1445 mg/gün, Albümin: 3.2 gr/dl
Trigliserid: 338 mg/dl, LDL: 136 mg/dl, HDL: 32 mg/dl
Tedavi olarak Detemir 2x30ünite, Lispro: 3x26
ünite,Clopidogrel 75, Coraspin 100, Perindopril 5
plus, Karvedilol 2x6.25 mg alıyor.
Bu hastada tedavi olarak ne başlarsınız?
Glargin insülin 32 Ü
Liraglutide 1.2 mg
Metformin 2x500 mg
Pioglitazon15 mg
Atorvastatin 20 mg
Clopidogrel 75 mg
Ramipril 10 mg plus
Coraspin 100
3 ay sonra
Glukoz: 124 mg/dl
A1c: 7.4
Trigliserid: 166 mg/dl
LDL: 68 mg/dl
HDL: 40 mg/dl
DON’T FORGET (ABCDE)
•
•
•
•
•
•
A
B
C
C
D
E
A1c
Blood Pressure
Cholesterol
Coraspin
Decrease Body Weight
Exercise
RAMAZANDA ORUÇ TUTABİLİR MİYİM
MÜSLÜMAN TOPLUMUN
DEMOGRAFİK YAPISI
Dünya nüfusu 7.3 milyar
Müslüman nüfus 1.85 milyar (~%25)
En az 1 milyar≥20 yaş
Diyabet prevelansı %14 = 150 Milyon DM
MÜSLÜMAN TOPLUMUN
DEMOGRAFİK YAPISI
Diyabetiklerin ne kadarı oruç tutuyor?
EPIDIAR ÇALIŞMASI
13 İslam ülkesi, 12243 kişi
T2DM %79
T1DM %43
~115 Milyon
RAMAZAN
Ay takvimi esas alınır.
Yıl =354-355 gün
Ay = 29-30 gün sürer
Ramazan yılda bir ay
Şafak vaktinden güneş batımına
RAMAZANDA ORUÇ TUTABİLİR MİYİM