CURRICULUM VITAE

NAME : Soebagijo Adi Soelistijo, dr, SpPD,

K-EMD, FINASIM, FACP
SPECIALITY : Internist, Endocrinologist
NATIONALITY : INDONESIA
PLACE AND DATE OF BIRTH : Surabaya, April 1, 1958
ADDRESS : Mojoklanggru Kidul Blok B no. 5
SURABAYA 60285 Indonesia
CONTACT NUMBER : Phone (Home) : 62-31-5998724
(Office) : 62-31-5023866
Fax (Office) : 62-31-5012775
Email(Private):soebagijo@yahoo.com
(Office): diabetes@rad.net.id
 ACADEMIC RECORD
Medical doctor :
Medical Faculty Airlangga University Surabaya 1983

Internist :
Medical Faculty Airlangga University Surabaya 1997

Endocrinologist :
Medical Faculty Airlangga University Surabaya 2004

Fellow of Indonesian Society of Internal Medicine; 2009

Fellow of American Clinical Physician, 2017

 PRESENT POSITION
Staff of Endocrinology and Metabolism Division. The
Department of Internal Medicine, Dr.Soetomo
Teaching Hospital Faculty of Medicine Airlangga
University.

Staff of Diabetes and Nutrition Center Dr. Soetomo

Teaching Hospital, Faculty of Medicine Airlangga
University.

Member of Medical Committee RSUD Dr. Soetomo

Since 2014
 ORGANISATION and PROFESSIONAL ACTIVITIES

- Member of American Diabetes Association since 2010

- Member of American College of Physician since 2014

- Member of Indonesian Endocrinologist Association

- Chairman of Indonesian Diabetes Association Surabaya

- Secretary of Indonesian Medical Association Surabaya

- Chairman of Indonesian Association of Internal Medicine

Surabaya
Insulin therapy in emergency
and daily practice

Symposium and Workshop on

Emergency in Internal Medicine
FK-UHT, 14 Okt 2017

Dr. Soebagijo Adi SpPD, KEMD, FINASIM, FACP

Pusat Diabetes dan Nutrisi Surabaya
RSUD Dr. Soetomo - FKUA
In daily practice
“Fix the Fasting First”

Start with Basal Insulin

New Position statement of the ADA Guideline
PEDOMAN NASIONAL PELAYANAN KEDOKTERAN DIABETES MELITUS
KEMKES RI 2014, KONSENSUS PERKENI 2015
 Algoritme Pengelolaan DM Tipe 2 di Indonesia KONSENSUS PERKENI 2015

Modifikasi pola hidup sehat

HbA1c < 7.5% HbA1c ≥ 7.5% HbA1c ≥ 9.0%

Gejala (-) Gejala (+)

Monoterapi* dengan salah Kombinasi 2 obat* dengan
Kombinasi 2 obat
satu obat di bawah ini mekanisme kerja yang berbeda

Kombinasi 3 obat Insulin ± obat jenis lain

• Metformin • Agonis GLP-1

• Agonis GLP-1 Kombinasi 3 obat
• Agonis GLP-1 • Penghambat DPP-IV
• Penghambat DPP-IV

Metformin atau obat lini pertama yang lain +

• Penghambat DPP-IV • Tiazolidindion
Metformin atau obat lini pertama yang lain +

• Tiazolidindion
• Penghambat • Penghambat SGLT-2
• Penghambat SGLT-2
Glukosidase Alfa • Insulin Basal

Obat lini kedua +

• Insulin Basal
• Penghambat SGLT-2** • SU/Glinid
• Kolsevelam** Mulai atau intensifikasi Insulin
• Tiazolidindion • Kolsevelam**
• Bromokriptin-QR
• Sulfonilurea • Bromokriptin-QR
• Penghambat
• Glinid • Penghambat
Glukosidase Alfa
Glukosidase Alfa Keterangan
*Obat yang terdaftar, pemilihan dan penggunaannya
disarankan mempertimbangkan faktor keuntungan,
Jika HbAc1 > 7.0%
kerugian biaya, dan ketersediaan sesuai tabel 11
Jika belum memenuhi sasaran
dalam 3 bulan tambahan Jika belum memenuhi ** Kolsevelam belum tersedia di Indonesia
dalam 3 bulan, mulai terapi insulin
obat ke 2 (kombinasi 2 sasaran dalam 3 bulan, Bromokriptin QR umumnya digunakan pada terapi
atau intensifikasi terapi insulin
obat) masuk ke kombinasi 3 obat tumor hipofisis

Konsensus Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 di Indonesia. 2015.

 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 and as soon as possible

Inadequate
+ 1 OAD + 2 OAD + 3 OAD
lifestyle

INITIATE INSULIN
 How To Start Basal Insulin?

Start Titrate

Titrate the dose every 3 days, if

Insulin basal
10 U or 0.1-0.2 U/kg Average FPG > 130mg/dl = increase 10-15% or 2-4U
Average FPG < 80 mg/dl = decrease 10-20% or 4U

Once daily injection, anytime injection but in same time per each day

Meneghini L et al. Diabetes Obes Metab, 9, 2007, 902-913

ADA 2015
 Insufficiency of oral + basal Insulin
- Current Opinions
The individual is not meeting glycemic targets on
basal insulin1-4
and:

FPG with basal

A1C still not at Elevated A1C insulin is within Further increases
goal with 0.5 despite normal targeted range, in basal insulin
U/kg/day of daily FPG with basal but PPG is result in
basal insulin3 insulin2,3 persistently hypoglycemia3
above goal3,4

1. Skyler JS. In: Lebovitz HE, ed. Therapy for Diabetes Mellitus and Related Disorders.
Alexandria, VA: American Diabetes Association, Inc.; 2004:207-223.
2. American Diabetes Association.
Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. 2011:1-68.
3. Inzucchi S, et al. Diabetes Care. 2012;35:1364-1379.
4. Davidson MB, et al. Endocr Pract. 2011;17:395-403.
PEDOMAN NASIONAL PELAYANAN KEDOKTERAN DIABETES MELITUS
KEMKES RI 2014
20
 Prandial insulin dose adjustment

Preprandial blood glucose value Dose change

<80 mg/dl -2U

80-110 mg/dl 0
110-140 mg/dl +2 U
141-180 mg/dl +4 U
>180 mg/dl +6 U
 Diabetes Emergency

Hyperglycemic Diabetes in
Hypoglycemia
crises critically ill

DKA HHS Surgical Non

Surgical

Major Minor
 Hyperglycemic
crises

DKA HHS
Pathogenesis of DKA and HHS: stress, infection, or insufficient insulin. FFA, free fatty acid.

DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

 DKA
(Diabetic Keto Acidosis)

Characterized by the triad of

• uncontrolled hyperglycemia,
• Metabolic acidosis
• increased total body ketone concentration

DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

 DKA
(Diabetic Keto Acidosis)

Clinical presentation
• the metabolic alterations typical of ketoacidosis usually
evolve within a short time frame (typically 24 h)
• History of polyuria, polydipsia, weight loss, vomiting,
dehydration, weakness, and mental status change.
• Physical findings may include poor skin turgor, Kussmaul
respiration, tachycardia, and hypotension.

DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

 DKA
(Diabetic Keto Acidosis)

Clinical presentation
• Mental status can vary from full alertness to profound
lethargy or coma
• Although infection is a common precipitating factor,
patients can be hyperthermic, normothermic or even
hypothermic primarily because of peripheral
vasodilation. Severe hypothermic has poor prognosis
• Nausea, vomiting, diffuse abdominal pain are frequent

DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

 DKA
(Diabetic Keto Acidosis)
Laboratory findings
- The diagnostic criteria for DKA and HHS are shown in
Table 1.
- The initial laboratory evaluation of patients include
- plasma glucose
- BUN, creatinine, urinalysis
- electrolytes (with calculated anion gap), osmolality
- serum and urinary ketones
- arterial blood gases
- complete blood count with a differential
- ECG, chest X-ray, and urine, sputum, or blood
cultures should also be obtained
DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009
 Terapi
Terapi KAD
KAD -- Revisi
Revisi 1998
1998
(Askandar Tjokroprawiro, 1991-2006)

1 Rehidrasi : NaCl 0.9% atau RL, 2 L / 2 jam pertama, lalu 80 tt/m

selama 4 jam, lalu 30 tt/m selama 18 jam (4-6 L/24 jam),
diteruskan sampai 24 jam berikutnya ( 20 tt/m) : Rumus 2,4,18-24
2 IDRIV : 4-8 unit/jam i.v (Rumus Minus Satu )
FASE-I 3 Infus K+ : 25 mEq (bila K+ = 3.0-3.5 mEq/l), 50 mEq (K+ = 2.5 - 3.0),
per 24 jam 75 mEq (bila K+ = 2.0-2.5), dan 100 mEq (bila K+ < 2.0 mEq)
4 Infus BIK : bila pH < 7.2 - 7.3 atau BIK <12 mEq/l : 50-100 mEq drip
dalam 2 jam (bolus BIK 50-100 mEq diberikan bila pH < 7.0)
5 Antibiotika : up to date dan dosis adekuat
Glukosa Darah + 250 mg/dl atau reduksi +
1 Maintenance : NaCl 0.9% atau Pot. R (IR 4-8u) , Maltosa 10% (IR 6-12u)
bergantian : 20 tt/m (Start Slow, Go Slow, Stop Slow)
FASE-II 2 Kalium : p.e (bila K+ < 4 mEq/l) atau per os (air tomat/kaldu)
3 IR : 3 x 8-12 U sc (ingat : Rumus Kali Dua)
4 Makanan lunak Kbh kompleks per oral

Rumus : 2,80,30,20 ; Rumus 2,4,18,24 ; Minus Satu; Kali Dua; Rumus 5-1 ; Rumus 2,5-1 ;

ASK-DNC
 Regulasi Cepat Insulin I.V. : APLIKASI FORMULA x12 , –1 , x2
Kasus Gawat Darurat : Sepsis - ACS - Stroke Akut – Krisis Hiperglikemia - Dll
(Pengalaman Klinik : Tjokroprawiro 1993-2006)

Kasus DM : Glukosa Darah 720 mg/dl

Pasang Infus RL 15 tt/m : Insulin AR I.V. 4 Units/jam

Regulasi Cepat Insulin Pump

Formula Minus Satu (-1) Formula x12

7 Minus Satu = 6 7 x 12 = 84
6 Kali 4 u AR IV/jam 84 u AR/24 ml/24 jam

Reevaluasi Sesudah 3-6 Jam : Glukosa Darah, Dosis & Kecepatan Pump

Dosis Insulin SC : 7x2 = 14

Ulangan Regulasi Cepat Glukosa > 250 mg/dl Glukosa < 250 mg/dl
Formula Kali Dua (x2)

Nutrisi Enteral dengan Regimen E1–E6

Dosis Insulin AR : 3x14 u sebelum E1, E3, E5 atau, pada NPE : AR dalam Botol
ASK-DNC
 HHS
(Hyperglycemic Hyperosmolar State)

Characterized by:
• severe hyperglycemia,
• Hyperosmolality
• dehydration
• In the absence of significant ketoacidosis.

These metabolic derangements result from

the combination of absolute or relative insulin
deficiency and an increase in counterregulatory
hormones (glucagon, catecholamines, cortisol, and
growth hormone).
DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009
 HHS
(Hyperglycemic Hyperosmolar State)

Clinical presentation
• Mental status can vary from full alertness to profound
lethargy or coma
• Focal neurologic signs (hemianopia and hemiparesis) and
seizures (focal orgeneralized)
• Patients can be hyperthermic, normothermic or even
hypothermic. Severe hypothermia refletcs poor prognosis
• Nausea, vomiting, diffuse abdominal pain are uncommon

DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

 HHS
(Hyperglycemic Hyperosmolar State)

Clinical presentation
• The process of HHS usually evolves over several days to
weeks
• History of polyuria, polydipsia, weight loss, vomiting,
dehydration, weakness, and mental status change.
• Physical findings may include poor skin turgor, tachycardia,
and hypotension.

DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

 DIABETIC NON-KETOTIC HYPEROSMOLAR SYNDROME
(HONK-DIABETIK)
(Summarized : Tjokroprawiro 1991-2006)

Pathogenesis Diagnosis : 1 YES, 3 NO Therapy

Precipitating Factors : Clinical Dx (Suspect): Supporting Findings : 1 Tx DKA

1 Thiazide
(Tetralogy HONK : 1 (pH > 7.30) 2 a Plasma Na <150 mEq/l
2 Glucose Drinks 1 YES, 3 NO) 2 Neurological Sign +
3 Infection 1 YES: Glycemia >600 mg/dl 3 Prerenal uremia Normal Saline
4 Corticosteroid 2 NO: DM History - or + 4 Mental Impairment +
5 Beta Blocker 3 NO: Kussmaul - , 5 Severe Dehydration b Plasma Na >150 mEq/l
6 Phenytoin 4 NO: Ketonuria - or + 6 More than 60 years old
7 Cimetidine Hypotonic Saline
8 Chlorpromazine TETRALOGY HONK (1 YES, 3 NO) : 1H + 3 NO
Pathophysiology
Glucose (mg/dl) Ureum (mg/dl)
l Grossly Elevated Glucagon 5 Osm/l = 2x (Na + K) + + > 325
18 6
l Relative Insulin Deficiency
l Sufficient Insulin to inhibit lipolysis
Tetralogy + 5 = PENTALOGY HONK (Definite Dx)
ASK-DNC
Management of DKA and HHS

DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

 Diabetes in
critically ill

Non
Surgical
Surgical

Major Minor
 Recommendations: BG Targets
• Critically ill 140-180 mg/dL

–More stringent goals, such as 110-140

mg/dL (6.1-7.8 mmol/L), may be
appropriate for selected patients, if
achievable without significant
hypoglycemia
39
ADA. Diabetes Care in Specific Settings. Diabetes Care 2012;35(suppl 1):S44.
 Critically Ill Patients:
IV Insulin Protocol

• Achieve BG within target range

• Include a clear algorithm for making
corrective changes
• Minimize hypoglycemia; provide specific
directions if it occurs
• Provide guidelines for transition to SC insulin

40
 Preoperative Patient Evaluation

• Metabolic control: glycemic control and

nutritional status

• Neurological status

• Renal function

• Risk analysis (next slide)

 Risk Analysis: Surgical Risk Factors

• CV risk factors
– May or may not be diagnosed

• Obesity

• Chronic kidney disease

• Undiagnosed autonomic dysfunction

• Reduction in pulmonary function

Meneghini LF. Cleve Clin J Med 2009;76:S53-9.

 Insulin Therapy During Surgery

• Insulin should never be discontinued in

insulin-treated patients, specifically basal
insulin with T1 or T2DM.

• Insulin requirements can increase during major

surgery with general anesthesia.

• IV insulin provides the most flexibility and

durability in maintaining desired glycemic
control during prolonged surgical procedures.
 Perioperative Insulin Procedure: General
Guidelines

Supplemental/Correc
Basal Prandial/Nutritional
tional
Will eat post-op
Intermediate-acting: ½- When resumes eating: Until eating:
⅔ usual a.m. dose
Restart prior dose Regular: every 4-6 hrs
Long-acting: regular or rapid-acting
usual dose p.m. prior Rapid-acting: every 4 hrs

Clement S, et al. Diabetes Care 2004;27:553-91.

 Perioperative Insulin Procedure: General
Guidelines (cont’d)
Prandial/Nutrit Supplemental/Correc
Basal
ional tional
Will not eat (e.g. major surgery)
Insulin drip N/A Until eating:
Regular: every 4-6 hrs Regular: every 4-6 hrs
Rapid-acting: every 4 hrs Rapid-acting: every 4 hrs
Intermediate-acting:
½ usual a.m. dose
Long-acting:
usual daily dose

Clement S, et al. Diabetes Care 2004;27:553-91.

 Diabetes
Perioperative management

Diabetic on
Diabetic on diet alone Insulin therapy

Diabetic on OAD
treatment
 Patients on diet alone

• If the blood sugar is well controlled, no specific intervention

is needed
• Check the blood sugar prior surgery
• Supplementation dose with 4-10 unit sc of short acting
insulin could be administered if necessary
• In case of uncontrolled blood sugar level, and blood sugar
>180 mg/dl, in major surgery procedure, iv insulin is
necessary. Major surgery is a surgery with general
anaesthesia of more than 1 hour
 Perioperative Management algorithm for Pts with OAD
(Jacober and Sowers 1999)
Hyperglycemia Discontinue
Compensated with Oral Agent
No Suplemental Insulin SC
Yes Prolonged
IV Insulin Protocol
Fasting?
No Resume
Eating?
Yes

Devise Alternative No Normal Yes

Preoperative
Regimen Renal Function? Metformin?

No
Yes
Resume
Preoperative
Regimen
 Insulin IV kontinyu pada perioperative

Ceck GD tiap 1-2 jam

140-180 mg/dL >180 mg/dL

GD<60 GD 60-80 GD 81-

mg/dL mg/dL 99mg/dL

Stop insulin IV Stop insulin IV Stop insulin IV

Bolus D40% 1 f l Bolus D40% 0.5 f l Infus D5%/8 jam
Infus D5%/8 jam Infus D5%/8jam

Ceck GD tiap 15 menit

GD≥100  cek setelah 1 jam dan tetapl ≥ 100

 mulai lagi insulin IV dg dosis 50% dosis terakhir
Stop D5% infus
 Postoperative Assessment
and Management
• Metabolic: insulin should be continued until
metabolic condition is stable and patient can
tolerate feeding
– Transition plan should be implemented for
patients on IV insulin

• Postoperative evaluation of CV, renal and

wound should be conducted

Lingvay I, et al. “Management of Surgery and Anesthesia”. Ch. 30 in Medical Therapy for Diabetes Mellitus. 5th Ed.
American Diabetes Association, 2009.
 Converting from IV to SC insulin

• Establish 24 hr Insulin Requirement

– Extrapolate from average over last 6-8 hr if stable
• Give One-Half Amount As Basal
• Start SC basal insulin 2 hours before stop IV
insulin
• Give One-Half Amount As Total Bolus
• Monitor a.c. tid, hs, and 3 am
• Correction Bolus for All BG >140 mg/dl
Hypoglycemia
 Definitions of hypoglycaemia (1)
• Any abnormalities of low plasma glucose
90
concentration that exposes the subject to potential
harm with a proposed plasma glucose < 70 mg/dl (<
65
3.9 mmol/l) with or without symptoms (American
Diabetes Association)
› The severity of hypoglycaemia can be defined by its
Glucose mg/dL

clinical manifestations2
55
 Mild
› Autonomic symptoms present – individual is able to self-treat
 Moderate
50 › Autonomic and neuroglycopenic symptoms present –
individual is able to self-treat
 Severe
› Unconsciousness may occur. Plasma glucose is typically
<50 mg/dL (2.8 mmol/L) – individual requires the assistance
of another person
 Currently no consensus exists to define a
biochemical threshold for hypoglycaemia2
1. Amiel SA, et al. Diabet Med. 2008;25:245-54. 2. CDA. 2008 Clinical Practice Guidelines. Can J Diabetes. 2008; 32(Suppl. 1).

Dejager. Diabetes Ther (2011) 2 (2): 51-66; Ahren. Vascular Health and Risk Management 2013:9 155–163
 Hypoglycemia
 The primary cause of hypoglycemia in type 2 diabetes is
diabetes medication, in particular, those which raise insulin
levels independently of blood glucose, such as Sulfonylureas
(SUs) and exogenous insulin
 The risk of hypoglycemia is increased in older patients
 Hypoglycemia may cause serious morbidity, provoking major
vascular events such as stroke and myocardial infarction;
severe hypoglycemia is associated with increased mortality

Amiel SA et al. Diabet Med 2008;25:245-54

 Hypoglycemia in T2DM
Risk factors and at-risk groups

RISK FACTORS AT-RISK GROUPS

 Exercise1  Renal impairment1
 Irregular eating habits1  Older people1
 Alcohol1  Lower HbA1c1
 Periods of fasting, e.g.  Prior hypoglycemia1
Ramadan2  Long-duration diabetes1
 Use of insulin and  hypoglycemia unawareness1
sulfonylureas3

1Amiel SA et al. Diabet Med 2008;25:245–54; 2Salti L et al. Diabetes Care 2004;27:2306–11;
3Nathan DM et al. Diabetes Care 2009;32:193–203
 Hypoglycemia is Common with SUs

25
Incidence of Hypoglycemia (%)

21.3%

20

15.3%
15 14%

11%
10

5%
5 2.9%*

0
Glyburide1 Chlorpropamide2 Glibenclamide3 Glimepiride3 Gliclazide4 Glipizide5

Sulfonylureas
*Hypoglycemia: fingerstick blood glucose measurement 50 mg/dL (2.75 mmol/L)
1. Glucovance [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2004. 2. UKPDS Group. Lancet
1998; 352: 837–853. 3. Draeger KE, et al. Horm Metab Res. 1996; 28: 419–425. 4. McGavin JK, et al. Drugs 2002;
62; 1357–1364. 5. Metaglip [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2002
Glucose-lowering agents classified
by risk of hypoglycaemia in type 2 diabetes

High risk1 Low risk1,2

Insulin Metformin

Sulphonylureas α-glucosidase inhibitors

Meglitinides Thiazolidinediones

GLP-1 receptor agonists

DPP-4 inhibitors

1. Nathan DM, et al. Diabetologia. 2009;52:17-306. 2. Cefalu WT. Nature. 2007;81:636-49.

Symptoms and defence mechanisms in relation to glucose levels in the subnormal range.

70
60

50

45
35
25

20

59 Ahrén B. Vascular Health and Risk Management 2013,9:155-163)

6
0
 PETUNJUK PRAKTIS TERAPI HIPOGLIKEMIA
DENGAN RUMUS 3-2-1
(Pengalaman Klinik : Askandar Tjokroprawiro 1996-2006)

Kadar Glukosa Glukosa

(mg/dl) Terapi Hipoglikemia Dengan Rumus 3-2-1 1 Flakon = 25 ml
40% (10 gram)

< 30 mg/dl : Injeksi I.V Dekstrosa 40%, bolus 3 Flakon Rumus - 3

30-60 mg/dl : Injeksi I.V Dekstrosa 40%, bolus 2 Flakon Rumus - 2

60-100*) mg/dl : Injeksi I.V Dekstrosa 40%, bolus 1 Flakon Rumus - 1

ASK-DNC