Diabetes Melitus
Diabetes Melitus
Diabetes Melitus
progressive therapy
Fajar Yuwanto
SMF Penyakit Dalam RSUD Abdul Moeloek
Bandar Lampung
Diabetes: A global emergency, particularly in Asia
Younger Onset
Of Diabetes
Lower Rates Of
Higher Rate Of Type 1 Diabetes
Renal Complications
and Stroke compare to
CV Death &
Major Coronary Event Lower BMI But
High Visceral Fat
Adapted from Chan JCN, Yeung R, Luk A. Diabetes Voice 2014. March 14, Volume 59
Diabetes in Asia :
Male
Starting at younger age
Female
Diabetes
Hypertension
Insulin Dyslipidemia
resistance
Damage to blood
vessels
Clotting
abnormalities
Inflammation
Atherosclerosis
Zimmet P. Trends Cardiovasc Med 2002; 12:354–362
Schrier RW et al. (2007) Appropriate blood pressure control in hypertensive and normotensive type 2 diabetes mellitus:
a summary of the ABCD trial Nat Clin Pract Nephrol 3: 428–438 doi:10.1038/ncpneph0559
Insulin resistance and -cell dysfunction are core
defects of type 2 DM
Genetic, obesity,
Western lifestyle
-cell
Insulin
resistance IR dysfunction
Type 2 diabetes
Rhodes CJ & White MF. Eur J Clin Invest 2002; 32 (Suppl. 3):3–13.
Criteria for the Diagnosis of Diabetes
A1C ≥6.5%
OR
Fasting plasma glucose (FPG)
≥126 mg/dL (7.0 mmol/L)
OR
2-h plasma glucose ≥200 mg/dL
(11.1 mmol/L) during an OGTT
OR
A random plasma glucose ≥200 mg/dL
(11.1 mmol/L)
ADA, 2015
AACE Recommendations for A1C Testing
• A1C levels may be misleading in several ethnic
populations (for example, African Americans)
• A1C may be misleading in some clinical settings
– Hemoglobinopathies
– Iron deficiency
– Hemolytic anemias
– Thalassemias
– Spherocytosis
– Severe hepatic or renal disease
• AACE/ACE endorse the use of only standardized,
validated assays for A1C testing
Heart disease
Pregnancy complications
Source: International Diabetes Federation. Diabetes Atlas, 5th Ed. www.diabetesatlas.org (accessed 25 June 2012).
Diabetes duration (years)
–10 0 10 20
IGT Type 2DM
Microvascular complications
CAD
Atherosclerosis Advance Amputation
atherosclerosis
STROKE
On-going Blindness
metabolic
CAD derangement
PAD Renal failure
The Diabetes Numbers
• Every 24 hours:
–New cases 4,100 cases
–Deaths 810 cases
–Amputations 230 cases
–Kidney failure 120 cases
–Blindness 55 cases
Derived from NIDDK, National Diabetes Statistics fact sheet. HHS, NIH, 2005.
Natural History of type 2 Diabetes
Prediabetes Diagnosed
250 (IFG, IGT) diabetes
Relative Amount
Diabetes
Years Representative depiction of time course
and function.
Onset
Islet -cell
Increased
Impaired Lipolysis
Insulin Secretion
Islet a-cell
Increased
HGP
Decreased Glucose
Neurotransmitter
Uptake
Dysfunction
DeFronzo RA. Diabetes 2009; 58: 773-795
Type2 Diabetes is progressive, aggressive and needs
polypharmacy
glycemic control …………………..
Normal IGT
GT Type 2 DM
Complications : CVD
CKD, NEUROPATHY
mortality
Non-pharmacologic
Polypharmacy, High cost
• Current management:
– two-thirds of patients do not achieve target HbA1c3,4
– majority require polypharmacy to meet glycaemic
goals over time5
A1C
1%
ADA, 2015
Approach to the Management of
Hyperglycemia
ADA,2015
Many diabetics in Asian population do not achieve
glucose target
• IDPMS (International DM Practice Study)¹
- 5 years survey involving 11,799 pts (9.901 T2DM)
Clinical profile of 3.687 Asian type 2 diabetic patients enrolled in the Joint Asia Diabetes
Eavaluation (JADE) program during comprehensive at baseline
Total Hongkong India Korea Philipines Singapore Taiwan Thailand
(n=3687) (n=832) (n=788) (n=295) (n=1186) (n=256) (n=55) (n=275)
Status of
ABC
targets (%) 35.3 61.8 13.8 40.7 31.3 35.2 25.5 29.8
HbA1c
<7%
.
1 Chan Juliana C.N, et.al. Multifaceted determinants for achieving glycemic control. The International Diabetes
Management Practice Study (IDMPS). Diabetes Care 2009;32: 227-233.
2. SO Wing-Yee, et.al. Comprehensive risk assessments of diabetic patients from seven Asian countries: The Joint Asia Diabetes Evaluation (JADE) program.
Journal of Diabetes 2011;3: 109-118.
Rationale for combination therapy
• Age
• Weight
• Ethnic
• Race
• Genetic
• Comorbidity:
• CKD
• CAD,Heart failure
• Hypoglicemia
• Liver dysfunction
Multiple
Lowers HbA1c to Adverse Effects
Defects in Type 2 No Hypoglycemia
normal levels
Diabetes of Therapy
1. Nordin C. Diabetologia.2010; 53: 1552–61; 2. Alvarez Guisasola F, et al. Diab Obes Metab. 2008; 10 Suppl 1: 25−32
3. Leiter LA, et al. Can J Diab. 2005; 29: 186−92; 4. Jermendy G, et al. Health Qual Life Outcomes. 2008; 6: 88
5. Zammitt N, et al. Diabetes. 2008; 57: 732−6 ; 6. Labad J, et al. Diabetologia. 2010; 53: 467−71
Risk of hypoglycaemia increases as
therapy intensifies
Episodes accompanied by
‒ 10-50 fold increased secretion of
AACE/ACE (2015)
IDF (2011)
PERKENI (2015)
Noninsulin Agents Available for T2D
Class Primary Mechanism of Action Agent(s) Available as
a-Glucosidase Delay carbohydrate absorption from Acarbose Precose or generic
inhibitors intestine Miglitol Glyset
Decrease glucagon secretion
Amylin analogue Slow gastric emptying Pramlintide Symlin
Increase satiety
Decrease HGP
Biguanide Metformin Glucophage or generic
Increase glucose uptake in muscle
Decrease HGP?
Bile acid sequestrant Colesevelam WelChol
Increase incretin levels?
Canagliflozin Invokana
SGLT2 inhibitors Increase urinary excretion of glucose Dapagliflozin Farxiga
Empagliflozin Jardiance
GLP-1 = glucagon-like peptide; HGP = hepatic glucose production; SGLT2 = sodium glucose cotransporter 2.
Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379.
37
Continued from previous slide
ADA, 2015
Diabetes Care: Management
Diabetes
Years Representative depiction of time course
and function.
Onset
Resistensi Insulin
Produksi
Insulin
Onset Diabetes
Penurunan sekresi insulin ada hubungannya dengan progresivitas dari Diabetes
Mellitus Tipe 2 itu sendiri
Awal mula dari diabetes, hanya terjadi setelah fungsi sel beta di pankreas
mengalami penurunan secara bemakna UKPDS
Pharmacotherapy Tailored for the
Multiple Defects of Type 2 Diabetes
Meglitinides
THIAZOLIDINEDIONES
Increase insulin secretion
1 Increase glucose uptake in
from pancreatic -cells
skeletal muscle and
decrease lipolysis in
adipose tissue
SULFONYLUREAS
Increase insulin secretion
2
from pancreatic -cells BIGUANIDE (METFORMIN)
Decreases hepatic
production and
increases uptake
Insulin
a-Glucosidase inhibitors
DPP - 4 inhibitor Delay intestinal carbohydrate
4
absorption
GLP1 – analoque
Insulin, glucagon
enhancer
Consideration For Selecting Combination
Therapy
Two (or more) oral blood glucose-lowering
medicines that have different mechanisms of
action
MonoTherapy
75
Combination
-Cell
50 Therapy
Function
(% )
Type 2 Insulin
25 Diabetes
Phase I Type 2
Diabetes
Phase II Phase III
0
-12 -10 -6 -2 0 2 6 10 14
Inadequate
+ 1 OAD + 2 OAD + 3 OAD
Lifestyle
INITIATE INSULIN