dr.

Muhammad Arif, SpPD

 Type 1 Type 2 Other specific type of Gestational
diabetes due to other
causes
 Cells destruction Progressive insulin
leading to absolute secretory defect on Diabetes
insulin deficiency background of diagnosed during
• Genetic defect on
insulin resistance pregnancy
 cell function
• Genetic defects in
insulin action
• Disease of the
exocrine pancreas
• Drug or chemical
induced diabetes
Natural History of Type 2 Diabetes
Insulin sensitivity Insulin secretion

Type 2
30% 50%
diabetes

50% IGT 70-100%

70% Impaired glucose 150%

metabolism
100% Normal glucose metabolism 100%

Diabetes Obes Metab 1999; 1(1): S1

 more 80% of patients type 2 diabetes
are low insulin secretion
Insulin sensitive;
low insulin secretion (16%)

Insulin sensitive;
good insulin Insulin resistant;
secretion (1%) low insulin secretion
(54%)

83%
Insulin resistant;
good insulin secretion (29%)

The 7-year follow-up of the San Antonio Heart Study

Haffner SM, et al. Circulation 2000; 101:975–980.
TREATMENT OF DIABETES

1. ORAL HYPOGLYCAEMIC AGENTS

2. INSULINS
 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
-Glucosidase inhibitors
DPP - 4 inhibitor Delay intestinal carbohydrate
4
absorption
GLP1 – analoque
Insulin, glucagon
enhancer
TREATMENT OPTIONS FOR TYPE 2 DIABETES
 Sulfonylureas  -Glucosidase inhibitors
 1st generation e.g. chlorpropamide,  e.g. acarbose
tolbutamide
 2nd generation e.g. glyburide,  DPP IV inhibitors
gliclazide, glipizide, gliquidone
vildagliptin ( Galvus)
 3rd generation e.g. glimepiride
 Modified release sitagliptin phosphate* (Januvia)
saxagliptin (ongliza)
 Glinides/meglitinides linagliptin (trajenta)
 Non-sulfonylureic e.g. repaglinide
 Amino acid derivatives e.g. nateglinide

 Biguanides  Fixed-dose oral antidiabetic

 e.g. metformin
drug combinations
 e.g. glyburide/metformin,
 Thiazolidinediones glipizide/metformin,
rosiglitazone/metformin
 e.g. rosiglitazone, pioglitazone
 ADA-EASD Position Statement Update:
Management of Hyperglycemia in T2DM, 2015

ANTI-HYPERGLYCEMIC THERAPY
• Therapeutic options: Insulins
Human Insulins
- Neutral protamine Hagedorn (NPH)
- Regular human insulin
- Pre-mixed formulations
Insulin Analogues
- Basal analogues (glargine, detemir, degludec)
- Rapid analogues (lispro, aspart, glulisine)
- Pre-mixed formulations
Diabetes Care 2012;35:1364–1379; Diabetologia 2012;55:1577–1596
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Insulin
human

15
Limitations of
Regular Human Insulin

1. Slow onset of activity

Should be given 30 to 45 minutes before meal
2. Long duration of activity
Lasts up to 12 hours
3. Potential for late postprandial hypoglycaemia
(4-6 hours)
Need for additional snack

16
Types of Insulin
Insulin Type (trade name) Onset Peak Duration
Bolus (prandial) Insulins
Rapid-acting insulin analogues (clear):
• Insulin aspart (NovoRapid®) 10 - 15 min 1 - 1.5 h 3-5h
• Insulin glulisine (Apidra™) 10 - 15 min 1 - 1.5 h 3-5h
• Insulin lispro (Humalog®) 10 - 15 min 1-2h 3.5 - 4.75 h
Short-acting insulins (clear):
• Insulin regular (Humulin®-R) 30 min 2-3h 6.5 h

Basal Insulins
Intermediate-acting insulins (cloudy):
1-3h 5-8h Up to 18 h
• Insulin NPH (Humulin®-N)

Long-acting basal insulin analogues (clear)

• Insulin detemir (Levemir®) 90 min Not 16-24 h
• Insulin glargine (Lantus®) 90 min applicable 24 h
 Types of Insulin
Insulin Type (trade name) Time action profile

Premixed Insulins

Premixed regular insulin – NPH (cloudy): A single vial or

30% insulin regular/ 70% insulin NPH (Humulin® 30/70) cartridge contains a
30% insulin regular/ 70% insulin NPH (Novolin®ge 30/70) fixed ratio of insulin
40% insulin regular/ 60% insulin NPH (Novolin®ge 40/60) (% of rapid-acting or
50% insulin regular/ 50% insulin NPH (Novolin®ge 50/50) short-acting insulin
to % of intermediate-
acting insulin)
Premixed insulin analogues (cloudy):
30% Insulin aspart/70% insulin aspart protamine crystals
(NovoMix® 30)
25% insulin lispro / 75% insulin lispro protamine
(Humalog® Mix25®)

50% insulin lispro / 50% insulin lispro protamine

(Humalog® Mix50®)
 Adherence to Injection Recommendation

"When do you inject your insulin?"

100
% of Respondents

42%
32%
22%

4%
0
30–45 min 15–30 min 0–15 min 0–15 min

Before meal After meal

Roper Starch Canada,201998

Serum Insulin Level

Time
Human Basal: Humulin-N Human Bolus: Humulin-R
Analogue Basal: Lantus, Levemir Analogue Bolus: Apidra, Humalog, NovoRapid
Serum Insulin Level

Time
Human Premixed: Humulin 30/70
Analogue Premixed: Humalog Mix25, NovoMix 30
 Slide 24

Insulin can be initiated at any time…

• Traditionally, insulin has been reserved as the last line of therapy…
• …However, considering the benefits of normal glycemic status,
Insulin can be initiated earlier.

Inadequate
+ 1 OAD + 2 OAD + 3 OAD
Lifestyle

INITIATE INSULIN

Adapted from Nathan DM, et al. Diabetes Care 2009; 31:193-203

ALGORITHM
ADA–EASD ( 2015)

AACE/ACE (2015)

PERKENI (2015)
 ADA-EASD position statement management of T2DM

Inzucchi S, et al. Diabetes Care 2015

Kriteria pengendalian
American Diabetes Association. Approaches to Glycemic Treatment. Diabetes Care 2015;38(Suppl. 1):S41–S48
Effective control of type 2 diabetes reduces risk of
complications
1% decrease in HbA1c correlates with reduction in risk of:

Microvascular Peripheral Myocardial Stroke Heart Cataract Death

disease vascular failure extraction related to
disorders infarction
diabetes
0
–37% –43% –14% –12% –16% –19% –21%

–15
Relative Risk (%)

p = 0.035 p = 0.021 p < 0.0001 p < 0.0001

–30

–45
p < 0.0001

* Prospective observational analysis of UKPDS 35 patients (n = 4585, incidence analysis; n = 3642, relative risk analysis).
Median 10.0 years of follow-up.

Adapted from Stratton IM, et al. BMJ. 2000;321:405–412.

Figure 1. Modula on of the
intensiveness of glucose Approach to the management
lowering therapy in T2DM of hyperglycemia
more HbA1c less
stringent 7% stringent
PATIENT / DISEASE FEATURES
Risks potentially associated
with hypoglycemia and low high
other drug adverse effects

Disease duration
newly diagnosed long-standing

Usually not
Life expectancy modifiable
long short

Important comorbidities
absent few / mild severe

Established vascular
complications absent few / mild severe

Patient attitude and

expected treatment efforts highly motivated, adherent, less motivated, non-adherent, Potentially
excellent self-care capacities poor self-care capacities modifiable

Resources and support

Readily available limited
system
Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0