PERKEMBANGAN TERKINI

PENATALAKSANAAN
DIABETES MELLITUS

CLASSIFICATION OF
DIABETES
MELLITUS

Type 1 diabetes, -cell destruction, usually leading

to absolute insulin deficiency

Immune mediated or idiopathic

Type 2 diabetes mellitus - 90%

Other specific types, drug induced, endocrinopathies, disease of the exogen pancreas, etc

Diabetes mellitus gestational

Diabetes Care. 1997; 20: 1183 - 1197

PATHOGENESIS OF TYPE 2 DIABETES

Diabetes mellitus is a group of metabolic
diseases characterized by hyperglycemia
resulting from defect of insulin action,

insulin secretion or both

Insulin
resistance

Type 2 diabetes

cell
dysfunction

DeFronzo et al. Diabetes Care 1992;15:318-68

Type 2 Diabetes: a chronic progressive disease

Obesity

IGT

Diabetes

Postprandial

Plasma
Glucose
(mg/dl) 126

-cell
function
(%)

[uncontrolled]

Fasting
Insulin Resistance

100

Insulin Level
-20

-10

10

20

30

Diabetes duration (years)

Adapted from IDC, Minneapolis

CRITERIA FOR THE DIAGNOSIS OF

DIABETES MELLITUS
1. Symptoms of diabetes
200

Casual plasma glucose concentration >

mg/dl

or

2. Fasting plasma glucose > 126 mg/dl.

FPG, no caloric intake for at least 8 hours
or

3. 2-h post-OGTT > 200 mg/dl

75 gram glucose dissolved in water

KENAPA DIABETES MELITUS

HARUS DI TERAPI ??

Penelitian EPIC Norfolk

Semua penyebab
kematian (%)

6
5
4

3
2
1

<5

5 - 5.4

5.4 6.9

>7

DM

A1C (%)
Hubungan antara kadar A1C dengan semua penyebab kematian pada
penelitian EPIC-Norfolk. DM = diabetes mellitus; EPIC = European
Prospective Investigation of cancer and nutrition; A1c = glycated
hemoglobin. Khaw et al. BMJ 2001; 322: 15 18

THE HONOLULU HEART PROGRAM

28.8

30

25

20.4
20

15

14

13

14.1
8.8

10

6.3

5.9

5
1.7

3.7
Total Mortality

0
Low Normal (120 mg/dl) High Normal (181mg/dl)

Asymptomatic
Hyperglycemia (262*
mg/dl)

Know n Diabetes (254*

mg/dl)

The Honolulu Heart Program. Diabetes Care 22:1262-1265,1999

CHD Incidence
CHD Mortality

The Diabetes Control and

Complications Trial (DCCT)

60

Retinopathy primary prevention

50

Percentage of
patients

Conventional
Intensive

40
30

20
10
0
0

Time after beginning of study (years)

Conventional: n = 348
Intensive:
n = 354

324
335

128
79
136
93

Cumulative incidence of a sustained change in retinopathy in patients with type 1

diabetes in the primary prevention cohort. Adapted from the diabetes control and
complications research group. N Engl J Med 1993; 329: 977 - 986

The Diabetes Control and

Complications Trial (DCCT)

60

Retinopathy secondary intervention

50

Percentage of
patients

Conventional
Intensive

40
30

20
10
0
0

Time after beginning of study (years)

Conventional: n = 348
Intensive:
n = 354

324
335

128 79
136 93

Cumulative incidence of a sustained change in retinopathy in patients with type 1

diabetes in the secondary intervention cohort. Adapted from the diabetes control and
complications research group. N Engl J Med 1993; 329: 977 - 986

30

Percentage of
patients

Conventional
Intensive

25
20

p < 0.04

15
10
p = 0.4

0
50

40

Year of study

Conventional
Intensive

Percentage of
patients

30

p < 0.001

20
p = 0.01

10
0
0

Year of study
Cumulative incidence of urinary albumin excretion.
300 mg per 24 hours (Dashed line) and 40 mg per 24 hours (solid line)
patients with IDDM receiving intensive or conventional therapy.

BAGAIMANA
PENATALAKSANAAN
DIABETES MELITUS

TIGA PILAR UTAMA

PENATALAKSANAAN DIABETES
Non-farmakologis
perencanaan makan
olah raga dan perencanaan makan
Obat-obatan
obat oral dan insulin
Edukasi penderita
memantau gukosa darah sendiri

Dilatih melakukan sendiri

BAGAIMANA PENATALAKSANAAN
DIABETES MELITUS
Perlu dibuat suatu kesepakatan umum
sebagai pegangan bagi para dokter
praktek
Kesepakatan yang ada adalah EASD ADA
Dasar membuat algoritma:
- dari penelitian yang sudah ada
- efektif untuk menurunkan glukosa darah
- mudah dilaksanakan oleh dokter
- terjangkau oleh penderita

ADA/EASD: Metabolic
Management of Type 2
Diabetes

07/10/15

Page 19
Nathan DM et al. Diabetes Care 2009; 32(1) : 194-203

Step One
Lifestyle intervention and metformin
If HbA1c > 7%*
Add basal insulin
(most effective)

Add sulfonylurea
(least expensive)

Add TZD
(no hypoglycemia)

If HbA1c > 7%
Intensify
insulin**

Add TZD

Add basal
insulin**

Add
sulfonylurea

If HbA1c > 7%
Add basal or
intensify insulin
Intensive insulin + metformin +/- TZD
* Check HbA1c every 3 months until HbA1c <7%, and then at least every 6 months.
** Preferred based on effectiveness and expense.
Nathan DM et al. Diabetes Care 2009; 32(1) : 194-203

Step One: Lifestyle and Metformin

Lifestyle interventions:
- Weight loss, exercise,
- Diet should be implemented by registered dieticians

Nathan DM et al. Diabetes Care 2009; 32(1) : 194-203

Step One: Lifestyle and Metformin, contd

Since lifestyle interventions fail in most patients ,

initiate metformin at diagnosis

Metformin is recommended due to its:

Effect on glycemia
Absence of weight gain and hypoglycemia
Generally low level of side effects
High level of acceptance
Relatively low cost

Nathan DM et al. Diabetes Care 2009; 32(1) : 194-203

Step Two
Lifestyle intervention and metformin
If HbA1c 7%*
Add basal insulin
(most effective)

Add sulfonylurea
(least expensive)

Add TZD
(no hypoglycemia)

If HbA1c 7%
Intensify
insulin**

Add TZD

Add basal
insulin**

Add
sulfonylurea

If HbA1c 7%
Add basal or
intensify insulin
Intensive insulin + metformin +/- TZD
* Check HbA1c every 3 months until HbA1c <7%, and then at least every 6 months.
** Preferred based on effectiveness and expense.
Nathan DM et al. Diabetes Care 2009; 32(1) : 194-203
-.

Step Two: Adding a Second Agent

After 2 - 3 months, if Step 1 fails to achieve glycemic goals, add one of the following:
- Basal insulin (most effective)
- Sulfonylurea (least expensive)
- TZD (no hypoglycemia) - pioglitazone
Choice of medication depends on HbA1c

Choose insulin for HbA1c level >8.5 or

with symptoms secondary to hyperglycemia
Nathan DM et al. Diabetes Care 2009; 32(1) : 194-203

CONTROLLED AND UNCONTROLLED

DIABETES BASED ON A1C
Data from our Diabetes Clinic :*
791 patients had A1C
A1C < 7,0%

= 145 or 18,3%

A1C > 7,0% - < 8,5%

A1C > 8,5%

= 152 or 19,2%

= 494 or 62,5%

Around 60% of our diabetic patients

attending our Diabetic Clinic needed
combination therapy either two oral agents
or oral agent plus insulin

Step Three
Lifestyle intervention and metformin
If HbA1c 7%*
Add basal insulin
(most effective)

Add sulfonylurea
(least expensive)

Add TZD
(no hypoglycemia)

If HbA1c 7%
Intensify
insulin**

Add TZD

Add basal
insulin**

Add
sulfonylurea

If HbA1c 7%
Add basal or
intensify insulin
Intensive insulin + metformin +/- TZD
* Check HbA1c every 3 months until HbA1c <7%, and then at least every 6 months.
Nathan
DM et al. Diabetes Care 2009; 32(1) : 194-203
** Preferred based on effectiveness and expense.
.
-.

Step Three: Further Adjustments

If Step 2 fails to achieve glycemic goals
after 2 3 months ..
Start or intensify insulin (preferred choice)
- Usually means adding short or rapid acting insulin before selected meals to reduce PPG excursions
- Discontinue use of sulfonylureas or glinides
when short - or rapid - acting insulin injections are started (not considered synergistic)
If HbA1c is close to goal (<8.0%) add a third agent
(not the preferred choice due to higher cost and
lower efficacy)
Nathan DM et al. Diabetes Care 2009; 32(1) : 194-203

Efficacy-Cost Ratio of Adding a Third Oral

Therapy vs. Switching to Insulin + Metformin
Portion of patients achieving
HbA1c (%) at study endpoint

HbA1c values at study endpoint (Week 24)

p=n.s

70%
60%
50%
40%

p=n.s

30%
20%
10%
0%

HbA1c < 7%

HbA1c < 8%

Triple oral therapy ($10.40/day)

Insulin + metformin ($3.20/day)

Schwartz S et al. Diabetes Care 2003;26:2238 - 2243

Considerations for Selecting

Combination Therapy
Glucose - lowering effect
Secondary characteristics of the medications
- e.g., weight gain or loss, GI side effects,
injection, frequency, expense, other side effects
Synergy
- In general, different mechanisms of action will
have the greatest synergy

Nathan DM et al. Diabetes Care 2009; 32(1) : 194-203

ADA RECOMMENDED COMBINATIONS

Insulin + metformin
Insulin + TZD
- However, fluid retention must be considered
The combination of metformin and TZD has
shown only modest HbA1c reductions (i.e.,
0.3 - 0.8%)

Schwartz S et al. Diabetes Care 2003;26:2238 - 2243

Insulin + Metformin

Glycosylated
hemoglobin Value (%)

12-month reduction in HbA1c for bedtime

Intermediate acting insulin + metformin (2 g)
10
9
n=19
8
7
0

12

Time (mo)
Adapted from Yki-Jarvinen H, et al. Ann Intern Med 1999;130(5):389-3 96

Insulin + TZD
Reduction in HbA1c with dual (Week 0- 16)
and triple (Week 16- 32) therapy
9.0
Insulin + metformin
(+TZD at Week 16)
n=14

HbA1c (%)

8.5
8.0

Insulin + TZD
(+metformin at Week 16)
n=14

7.5
*

7.0
6.5
6.0
5.5

Week 0

Week 16

Week 32

* p<0.05 vs. baseline, p<0.05 vs. week 16, p<0.05 vs. INS + MET group.

Strowig SM, et al. 2004;27(7):1577- 83.

NASIHAT
Penderita kencing manis meninggal bukan
kare-na gulanya tetapi akibat komplikasi
Kencing manis tidak dapat disembuhkan,
tetapi
anda dapat menghindari komplikasi
dengan
- kendali gula darah sebaik mungkin
- kendali tekanan darah sebaik mungkin
- kendali kolesterol sebaik mungkin

Untuk itu perlu disiplin

RINGKASAN
Penatalasanaan DM tipe 2 mengacu pada algoritme yang ada saat ini
Oleh karena sebagian besar penderita DM tipe
2 ke dokter dengan kendali buruk, metformin
dapat segera dimulai terkecuali A1C < 8,0%,
dapat non-farmakologis
Kombinasi metformin insulin paling efektif
(insulin basal spt Levemir)
Kombinasi metformin sulfonilurea murah
Kendali diabetes harus menggunakan kadar
A1C