DIABETES AND

IT’S RELATED
COMPLICATIONS

Soebagijo Adi Soelistijo

Department of Internal Medicine
Faculty of Medicine Universitas Airlangga
Dr. Soetomo General Academic Hospital,
Surabaya
 DIABETIC COMPLICATIONS

ACUTE CHR O N I C
ca ti o ns: i ca ti o ns :
Compli Compl

Acute Complications:
1. Hypoglycemia
2. Hyperglycemic Crisis/Emergency
Hypoglycemia in
Diabetes
 Classification of hypoglycemia
Glycemic criteria/description
Level 1 Glucose <70 mg/dL (3.9 mmol/L) and >54 mg/dL (3.0 mmol/L)
Level 2 Glucose <54 mg/dL (3.0 mmol/L)
Level 3 A severe event characterized by altered mental and/or physical status requiring assistance
for treatment of hypoglycemia

• Level 1 hypoglycaemia. A blood glucose concentration of <70 mg/dL (3.9 mmol/L) has been
recognized as a threshold for neuroendocrine responses to falling glucose in people without
diabetes. Because many people with diabetes demonstrate impaired counterregulatory responses to
hypoglycemia and/or experience hypoglycemia unawareness, a measured glucose level <70 mg/dL
(3.9 mmol/L) is considered clinically important, independent of the severity of acute hypoglycemic
symptoms.
• Level 2 hypoglycaemia. Is the threshold at which neuroglycopenic symptoms begin to occur and
requires immediate action to resolve the hypoglycemic event. If a patient has level 2 hypoglycemia
without adrenergic or neuroglycopenic symptoms, they likely have hypoglycemia unawareness
• Level 3 hypoglycaemia. a severe event characterized by altered mental and/or physical functioning
that requires assistance from another person for recovery.

ADA. Diabetes Care 2020;43(Suppl. 1):S66–S76

 Clinical Features of Hypoglycemia

Neurogenic (or autonomic) and neuroglycopenic

responses to hypoglycemia
Neurogenic Neuroglycopenic
Palpitations Cognitive impairment
Tremor Behavioral changes
Anxiety/arousal Psychomotor abnormalities
Sweating Seizure
Hunger Coma
Paresthesia
Autonomic neural response failure --- unawareness hypoglycemia

Lavernia et al, Postgrad Med, 2015; Early Online : 1-7. DOI:

10.1080/00325481.2015.1086628 Cryer PE. J. Clin. Invest. 117:868–870 (2007)
 Who is at risk of Hypoglycemia?
Elderly
• Symptoms may be misinterpreted as neurological, psychiatric disease, or present as
cardiovascular events (e.g. myocardial infarction, ventricular arrhythmia, heart
failure)
• Severe hypoglycemic events may occur at higher blood glucose levels

Patient with Comorbidities

• Renal disease
• Malnutrition
• Chronic vascular disease
• Microvascular disease (e.g. peripheral neuropathy)
• Liver disease

Others
• The nighttime hours increasing the risk for hypoglycemia
(tend to be the longest interval between meals and time of maximal insulin
sensitivity)
• Irregular eating habits
• Reduced physical activity
• Heavy alcohol consumption

Modified from Lavernia et al, Postgrad Med, 2015; Early Online : 1-7. DOI: 10.1080/00325481.2015.1086628
 Hypoglycemia risk in diabetes management
 The risk of hypoglycemia increases further when two glucose-lowering medications are used in
combination or due to combination with concomitant non-glucose-lowering medication.

Risk of inducing
Glucose Lowering Therapy Concomitant Drug
hypoglycemia

Pentamidine High
• Metformin • Glinide
• DPP4i Disopyramide Moderate
• SGLT2
• TZD ACE inhibitor Low
• GLP1a
β-Blockers Low
Neutral Middle
Chloramphenicol Low
Chloroquine Low
• SU
• Insulin Clofibrate Low
Quinolones Low
Salicylates Low
Moderate
Tramadol Low

Modified from Lavernia et al, Postgrad Med, 2015; Early Online : 1-7. DOI: 10.1080/00325481.2015.1086628
 Pathophysiological CV consequences of hypoglycemia

 CRP  VEGF  IL-6

Effects last up to 7 Persists for up to
days 48 hours
Inflammation

 Neutrophil
activation Blood coagulation Endothelial
abnormalities HYPOGlycemia
dysfunction

 Vasodilatation
 Platelet  Factor VIII
activation
Sympathoadrenal response
 Epinephrine
Rhythm abnormalities Hemodynamic changes

Heart rate variability  Heart workload

 Contractility
 Output

CV: cardiovascular; CRP: C-reactive protein; IL-6:

interleukin 6; VEGF: vascular endothelial growth factor.
Adapted from: Desouza et al. Diabetes Care 2010; 33: 1389; Frier et al. Diabetes Care 2011; 34 (Suppl 2): S132
RISIKO KARDIOVASKULER HIPOGLIKEMIA BERAT DIBANDING NON HIPOGLIKEMIA

Yun et al. Cardiovasc Diabetol (2019) 18:103

 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
Hyperglycemic Crisis
Emergency:
Diabetic Ketoacidosis (DKA) and
Hyperglycemic Hyperosmolar State (HHS)
 Diagnostic criteria for DKA and HHS
DKA HHS

Mild Moderate Severe Plasma glucose >600

(plasma glucose >250 (plasma glucose >250 (plasma glucose >250 mg/dl
mg/dl) mg/dl) mg/dl)

Arterial pH 7.25–7.30 7.00–<7.24 <7.00 >7.30

Serum bicarbonate 15–18 10-<15 <10 >18

(mEq/l)

Urine ketone* Positive Positive Positive Small

Serum ketone* Positive Positive Positive Small

Effective serum Variable Variable Variable >320 mOsm/kg

osmolality†

Anion gap‡ >10 >12 >12 Variable

Mental status Alert Alert/drowsy Stupor/coma Stupor/coma

*Nitroprusside reaction method. †Effective serum osmolality: 2[measured Na + (mEq/l)] + glucose (mg/dl)/18. ‡Anion gap: (Na +) –
[(Cl- + HCO3- (mEq/l)].
Kitabchi AE et al. ADA Consensus Statement. Diab care 2009; 32: 1335-1343
Protocol for management of adult patients with DKA and HHS recommended by the ADA

Umpierrez G and Korytkowski M. Nature Rev 2016; 12: 222-232

 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
 Pengobatan Krisis Hiperglikemik

Intravenous fluids
20

1000–2000 ml 0.9% NaCl over 1–2 h for prompt recovery of hypotension and/or hypoperfusion. Switch to 0.9% saline or 0.45%
saline at 250–500 ml/h depending upon serum sodium concentration. When plasma glucose level ~11.1 mmol, change to
dextrose in 5% saline.
Insulin
Regular human insulin intravenous bolus of 0.1 U/kg followed by continuous insulin infusion at 0.1 U/kg/h. When glucose level
≤13.9 mmol/l, reduce insulin rate to 0.05 U/kg/h. Thereafter, adjust rate to maintain glucose level ~11.1 mmol/l. Subcutaneous
rapid-acting insulin analogues might be an alternative to intravenous insulin in patients with mild-to-moderate DKA.
Potassium
Serum potassium level >5.0 mmol/l (no supplement is required); 4–5 mmol/l (add 20 mmol potassium chloride to replacement
fluid); 3–4 mmol/l (add 40 mmol to replacement fluid); <3 mmol/l (add 10–20 mmol/h per hour until serum potassium level >3
mmol/l, then add 40 mmol to replacement fluid).
Bicarbonate
Not routinely recommended. If pH <6.9, consider 50 mmol/l in 500 ml of 0.45% saline over 1 h until pH increases to ≥7.0. Do
not give bicarbonate if pH ≥7.0.
Laboratory evaluation
Initial evaluation should include blood count; plasma glucose; serum electrolytes, urea nitrogen, creatinine, serum or urine
ketone bodies, osmolality; venous or arterial pH; and urinalysis. During therapy, measure capillary glucose every 1–2 h.
Measure serum electrolytes, blood glucose, urea nitrogen, creatinine and venous pH every 4 h.
Transition to subcutaneous insulin
Continue insulin infusion until resolution of ketoacidosis. To prevent recurrence of ketoacidosis or rebound hyperglycaemia,
continue intravenous insulin for 2–4 h after subcutaneous insulin is given. For patients treated with insulin before admission,
restart previous insulin regimen and adjust dosage as needed. For patients with newly diagnosed diabetes mellitus, start total
daily insulin dose at 0.6 U/kg/day. Consider multi-dose insulin given as basal and prandial regimen.

Umpierrez G and Korytkowski M. Nature Rev 2016; 12: 222-232

IDF, Diabetes Atlas 2019
Diabetes is a lifelong condition with potentially
devastating consequences
MACROVASCULAR MICROVASCULAR
COMPLICATIONS COMPLICATIONS

Diabetic retinopathy
Heart disease and stroke causes 12,000 to 24,000
account for ~65% of new cases of blindness each
diabetes-related deaths year, especially in adults
aged 20–74 years

Diabetes is a leading cause

of kidney failure; 44% of
new cases during 2002
Diabetes causes > 60%
of non-traumatic
lower-limb amputations
~60–70% of patients have
mild to severe nervous
system damage

Source: American Diabetes Association, Diabetes statistics

http://www.diabetes.org/diabetes-statistics/complications.jsp. Last accessed 25 January 2007
Macrovascular Complications
 Modifiable CV risk factors are common in patients with T2D1,2

Hy Hy Dy
pe pe sli Ob
rg lyc rte pid es
ae n s io ae ity
mi mi
a n a

Almost a third of diabetes patients were current smokers 2

CV, cardiovascular; T2D, type 2 diabetes
1. Svensson MK et al. Diab Vasc Dis Res 2013;10:520; 2. Das SR et al. Am Heart J 2006;151:1087
 Type 2 Diabetes and Cardiovascular Disease
T2D and CVD
Hypercoagulation Metabolic Environmental
Dyslipidemia
Platelet Activation Dysfunction Pollutants

Physical Inactivity

Poor Diet
T2 Diabetes
CVD
Mellitus
Smoking

Obesity

Endothelial
Arterial Stiffness Inflammation Oxidative Stress
Dysfunction

Newman JD et al. J Am Coll Cardiol 2017; 70: 883-893

Atherosclerosi
s
Cardiovascula
r Disease
Atherosclerosis Cardiovascular Disease
 Global estimates of the association and impact of diabetes on
cardiovascular diseases

Outcome Impact
Prevalence of cardiovascular diseases Any cardiovascular disease: 32%
Coronary heart disease: 21%
Myocardial infarction: 10%
Stroke: 7.6%
Coronary heart disease 160% increased risk
Ischaemic heart disease 127% increased risk
Haemorrhagic stroke 56% increases risk
Cardiovascular diseases death 132% increased risk
Years of life lost 5.8 years for men age 50
6.4 years for women age 50

IDF DIABETES ATLAS Ninth edition 2019

Life expectancy is reduced by 12 years in diabetes patients with previous CVD*

60 yrs
End of life

No diabetes

Diabetes
–6 yrs

Diabetes + MI –12 yrs

In this case, CVD is represented by MI or stroke

*Male, 60 years of age with history of MI or stroke
24
CVD, cardiovascular disease; MI, myocardial infarction
Peripheral
Artery
Disease
Risk factors for peripheral artery disease in HICs and LMICs

HIC, high-income country, LMIC, low-income and middle-income country

Fowkes FGR et al. NATURE REVIEWS | CARDIOLOGY 2016. doi:10.1038/nrcardio.2016.179

 History and/or Physical Examination Findings Suggestive of PAD

History
• Claudication
• Other non–joint-related exertional lower extremity symptoms (not typical of claudication)
• Impaired walking function
• Ischemic rest pain
Physical Examination
• Abnormal lower extremity pulse examination
• Vascular bruit
• Non healing lower extremity wound
• Lower extremity gangrene
• Other suggestive lower extremity physical findings (eg, elevation pallor/dependent rubor)
Gerhard-Herman MD et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral
Artery Disease. Circulation. 2017;135:e726–e779. DOI: 10.1161/CIR.0000000000000471
 Clinical Examination
• Assessment: Temperature, Color, Pulse Pattern, Auscultation

Common Femoral Artery Popliteal Artery Dorsalis Pedis Artery

Posterior Tibial Artery Auscultation on Artery

Palpation Auscultation
Normal ++ No bruit
Mild stenosis ++ Soft bruit
Significant stenosis +/- Harsh bruit
Critical stenosis -/+ Soft bruit
Occlusion - No bruit
Measurement and calculation of ankle–brachial index (ABI) in diagnosing peripheral
artery disease

AAA = abdominal aorta aneurysm; ABI = ankle-brachial index; BP = blood pressure; CAD = coronary artery disease; CKD = chronic kidney disease; CV = cardiovascular; ESC =
European Society of Cardiology; LEAD = lower extremity artery disease; PADs = peripheral arterial diseases; SBP = systolic blood pressure. aSubjects with: markedly elevated
single risk factors; diabetes mellitus (except for young people with type 1 dia- betes without other major risk factors); a calculated SCORE >_5% and <10%.
Aboyan V et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). European Heart
Journal (2018) 39, 763–816.
 Clinical stages of lower extremity artery disease

Fontaine classification Rutherford classification

Stage Symptoms Grade Category Symptoms
I Asymptomatic ←→ 0 0 Asymptomatic
I 1 Mild claudication
IIa Non-disabling intermittent claudication
II I 2 Moderate claudication
←→
IIb Disabling intermittent claudication I 3 Severe claudication
III Ischemic rest pain ←→ II 4 Ischemic rest pain
III 5 Minor tissue loss
IV Ulceration or gangrene ←→
III 6 Major tissue loss

CLI: Critical Limb Ischemia

Aboyan V et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). European Heart
Journal (2018) 39, 763–816.
PAD:
treatment approach

• Two aspects:
1. to address specific symptoms of any
localization and the risk related to a specific
lesion.
2. related to their increased risk of any CV
event

• Exercise
• Smoking cessation
• Lipid-lowering drugs
• Antithrombotic drugs
• Antihypertensive drugs

Aboyan V et al. 2017 ESC Guidelines on the Diagnosis and Treatment of

Peripheral Arterial Diseases, in collaboration with the European Society for
Vascular Surgery (ESVS). European Heart Journal (2018) 39, 763–816
Microvascular
Complications
Diabetic Eye
Diseases
(diabetic
retinopathy)

Diabetes complications
(IDF Diabetes Atlas 2017)
People with diabetes are at Diabetic retinopathy affects over one-
higher risk of developing
periodontal disease
third of all people with diabetes and is
the leading cause of vision loss in working-
age adults.
Pregnant woman with People with diabetes are 2
diabetes or at high risk for
GDM should manage their to 3 time of more likely to
glycemia throughout their have cardiovascular disease
pregnancy to avoid long- (CVD)
term consequences for
themselves, and
transgenerational
effects (higher risk of The prevalence of end-stage
obesity, diabetes, renal disease (ESRD) is up to
hypertension and kidney
disease in the offspring)
10 time higher in people
with diabetes
Every 30 seconds a lower limb or part of a
lower limb is lost to amputation somewhere in
the world as a consequence of diabetes
 Screening Recommendation for Diabetic Retinopathy
(ADA, 2022)

• Adults with type 1 diabetes should have an initial dilated and comprehensive eye
examination by an ophthalmologist or optometrist within 5 years after the onset of
diabetes. B
• Patients with type 2 diabetes should have an initial dilated and comprehensive eye
examination by an ophthalmologist or optometrist at the time of the diabetes diagnosis. B
• If there is no evidence of retinopathy for one or more annual eye exams and glycemia is
well controlled, then screening dilated retinal exa every 1–2 years may be considered. If
any level of diabetic retinopathy is present, subsequent minations should be repeated at
least annually by an ophthalmologist or optometrist. If retinopathy is progressing or
sight-threatening, then examinations will be required more frequently. B

ADA. Diabetes Care 2022;45:S185–S194.

 Instruments for screening (WHO, 2022)

Direct ophthalmoscopy Indirect ophthalmoscopy Slit-lamp biomicroscopy

Optical coherence tomography (OCT) Retinal photography

(mydriatic and nonmydriatic
Diabetic retinopathy classification
(WHO, 2020)
Diabetic Nephropathy
 Diabetes Is the Leading Cause of
End-Stage Renal Disease
• Incidence is rising dramatically • Primary diagnosis for patients
who start dialysis

United States Renal Data System. Annual data report. 2000, 2009.
http://www.usrds.org/atlas.htm
http://www.usrds.org/adr_2000.htm
Kidney disease is associated with increased all-cause mortality
75

rates (per 1000 person-years) 60

All-cause mortality

45

30

15

0
Previous MI* Diabetes CKD (eGFR <60 Diabetes No diabetes
and CKD ml/min per 1.73 or CKD
m 2)

*Includes participants with or without diabetes and chronic kidney disease

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; MI, myocardial infarction
Tonelli M et al. Lancet 2012;380:807
 Diabetic
Neuropathy
 Classification for diabetic neuropathies
Diabetic neuropathies
A. Diffuse neuropathy B. Mononeuropathy (mononeuritis multiplex) (atypical forms)
1. Distal symmetric polyneuropthy (DSPN) • Isolated cranial or peripheral nerve (e.g., CN III, ulnar,
- Primarily small-fiber neuropathy median, femoral, peroneal)
- Primarily large-fiber neuropathy • Mononeuritis multiplex (if confluent may resemble
- Mixed small- and large-fiber neuropathy (most common) polyneuropathy)
2. Autonomic Cardiovascular C. Radiculopathy or polyradiculopathy (atypical forms)
- Reduced HRV • Radiculoplexus neuropathy (a.k.a. lumbosacral
- Resting tachycardia polyradiculopathy, proximal motor amyotrophy)
- Orthostatic hypotension • Thoracic radiculopathy
- Sudden death (malignant arrhythmia)
3. Gastrointestinal
- Diabetic gastroparesis (gastropathy)
- Diabetic enteropathy (diarrhea)
- Colonic hypomotility (constipation)
4. Urogenital
- Diabetic cystopathy (neurogenic bladder)
- Erectile dysfunction
- Female sexual dysfunction
5. Sudomotor dysfunction
- Distal hypohydrosis/anhidrosis, c Gustatory sweating
6. Hypoglycemia unawareness
7. Abnormal pupillary function
Nondiabetic neuropathies common in diabetes

• Pressure palsies
Chronic inflammatory demyelinating polyneuropathy
• Radiculoplexus neuropathy
Acute painful small-fiber neuropathies (treatment-induced)

Pop-Busui R. et al. Diabetes Care 2017;40:136–154 | DOI: 10.2337/dc16-2042

 Symptoms and signs of DSPN1

Large myelinated nerve fibers Small myelinated nerve fibers

Function Pressure, balance Nociception, protective sensation

Symptoms§ Numbness, tingling, poor balance Pain: burning, electric shocks, stabbing

Examination (clinically • Ankle reflexes: reduced/absent • Thermal (cold/hot) discrimination:

diagnostic)** • Vibration perception: reduced/absent reduced/absent**
• 10-g monofilament: reduced/absent • Pinprick sensation: reduced/absent**
• Proprioception: reduced/absent

§To document the presence of symptoms for diagnosis; **Documented in symmetrical, distal to proximal pattern.

Using a monofilament (A) The correct way of applying pressure (For performance The monofilament test should be performed at the
of the 10 g monofilament test, the device is placed perpendicular to the skin, with
pressure applied until the monofilament buckles. It should be held in place for 1
highlighted sites while the patient’s eyes are closed.2
second and then released); (B) Monofilament which is worn out after use; (C)
Incorrect method of applying pressure. 2

1. Pop-Busui R. et al. Diabetes Care 2017;40:136–154 | DOI: 10.2337/dc16-2042

2. Mahesh DM et al. In A Practical Guide to Diabetes Mellitus (Thomas N et al. Eds). 2016
 Symptoms and signs associated with diabetic autonomic neuropathy
cardiovascular autonomic neuropathy (CAN) Gastrointestinal Urogenital Sudomotor

Resting tachycardia Gastroparesis (Gastropathy) Bladder dysfunction Dry skin

Abnormal blood pressure regulation • Nausea • Frequency • Anhidrosis
• Nondipping • Bloating • Urgency • Gustatory
• Reverse dipping • Loss of appetite • Nocturia sweating
• Early satiety • Hesitancy
• Postprandial vomiting • Weak stream
• Brittle diabetes • Dribbling
• Urinary incontinence
• Urinary retention
Orthostatic hypotension (all with standing) Esophageal dysfunction Male sexual dysfunction
• Light-headedness • Heartburn • Erectile dysfunction
• Weakness • Dysphagia for solids • Decreased libido
• Faintness • Abnormal ejaculation
• Visual impairment
• Syncope
Orthostatic tachycardia or bradycardia and Diabetic diarrhea Female sexual dysfunction
chronotropic incompetence (all with standing) • Profuse and watery diarrhea • Decreased sexual desire
c Light-headedness • Fecal incontinence • Increased pain during intercourse
c Weakness • May alternate with constipation • Decreased sexual arousal
c Faintness • Inadequate lubrication
c Dizziness
c Visual impairment c Syncope
Exercise intolerance Constipation
• May alternate with explosive
diarrhea

Pop-Busui R. et al. Diabetes Care 2017;40:136–154 | DOI: 10.2337/dc16-2042

PERAN FKTP DALAM PENCEGAHAN
KOMPLIKASI
• Kendali glikemik dan faktor
risiko lain
• Deteksi dini penyulit
• Penyuluhan
• Vaksinasi
• Influenza
• Hepatitis B
• Pneumokokus
• COVID-19
Sasaran Parameter Sasaran

pengendalian Indeks Masa Tubuh (IMT)

diabetes • IMT (kg/m2)

Tekanan darah
18.5-22.9

• TD Sistolik (mmHg) <140

• TD Diastolik (mmHg) <90

Kendali glikemik

• HbA1c (%) <7 atau individual

• Gula darah kapiler puasa/sebelum makan 80-130

(mg/dL)

A : A1c • Gula darah kapiler 1-2 setelah makan (mg/dL) <180

B : BP & BMI Lipid

C : Cholesterol • LDL-C (mg/dL) <100, <70 jika risiko tinggi PKV

D : Drugs to prevent Complications • Triglyceride (mg/dL) <150

E : Education • HDL-C (mg/dL) <40 untuk laki-laki, <50 untuk

perempuan
• Apo-B (mg/dL) <90
Hal.13
Hal.13
Hal.13
Hal.13
Hal.14
Hal.14
Hal.14
Hal.14
 Algorithm of Type 2 Diabetes management in Indonesia (PERKENI, 2021)
GOAL THERAPY : HbA1c <7% (Individualised)

HEALTHY LIFESTYLE MODIFICATION

Entry HbA1c Entry HbA1c Entry HbA1c
<7.5% >7.5% >9%

MONOTHERAPY DUAL THERAPY SYMPTOMS

(combination of 2 drugs TRIPLE THERAPY
Metformin (combination of 3 drugs with NO YES
with different
mechanism) different mechanism)
SU/Glinid If HbA1c
is not < SU/Glinid SU/Glinid DUAL INSULIN

Metformin or other first line drug

Metformin or other first line drug
AG-I THERAPY
7% in 3 If ±
AG-i If HbA1c
TZD months, AG-I HbA1c Other
is not < OR

Second line drugs

proceed is not < Agents
TZD 7% in 3 TZD
DPP-4i to DUAL 7% in 3
months, TRIPLE
THERA months,
DPP-4i proceed to DPP-4i THERAPY
SGLT-2i PY proceed
TRIPLE
to ADD
GLP-1 RA SGLT-2i THERAPY SGLT-2i OR
(combinati
Basal INTENS
on of 3 Basal Insulin
Insulin IFY
drugs) ADD OR INTENSIFY
Insulin
GLP-1 RA GLP-1 RA Therapy INSULIN

1. The selection and use of drugs consider drug cost, availability, effectiveness, cardiorenal benefits, safety profile, effects on body weight, and patients'
choice.
2. Management includes not only blood glucose, but also integrated management of other Cardio-Renal risk factors.
3. Some GLP-1 RA and SGLT-2i show benefits to patients with Atherosclerotic Cardiovascular Disease, Heart Failure, and Kidney Failure
comorbidities. Both classes are suggested as options for patients with mentioned comorbidities / complications.
4. If the HbA1C cannot be checked, then the average blood glucose is used as a guide which is then converted to HbA1C (Point 7 in algorithm explanation).

Pedoman Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 Dewasa - 2021

 Hal.32

RISIKO SANGAT TINGGI

RISIKO TINGGI

RISIKO SEDANG
 Hal.32-33

Pasien DM tipe 2 yang baru terdiagnosis maupun yang telah mendapatkan obat
Risiko
antihiperglikemik lain dengan risiko sangat tinggi dan risiko tinggi maka pilihan obat
sangat
tinggi & yang dianjurkan adalah golongan GLP-1 RA atau penghambat SGLT-2 yang terbukti
tinggi memberikan manfaat kardiovaskular

Risiko Pada pasien DM tipe 2 dengan PKVAS dominan pilihan obat yang dianjurkan adalah
sangat GLP-1 RA atau penghambat SGLT-2 yang terbukti memberikan manfaat
tinggi & kardiovaskular
tinggi

Pada pasien DM tipe 2 dengan gagal jantung terutama HfrEF (Heart Failure with
Risiko
reduced Ejection Fraction) dengan EF <45% maka pilihan obat yang dianjurkan
sangat
tinggi & adalah penghambat SGLT-2 yang terbukti memberikan manfaat untuk gagal
tinggi jantung.
 Hal.33

Pada pasien DM tipe 2 dengan penyakit ginjal kronik (PGK) :

• Penyakit ginjal diabetik (PGD) dan albuminuria : obat yang dianjurkan adalah
penghambat SGLT-2 yang terbukti menurunkan progresifitas PGK, atau bila
penghambat SGLT-2 tidak bisa ditoleransi atau merupakan kontraindikasi
maka dianjurkan GLP-1 RA yang terbukti memberikan manfaat
kardiovaskular.
• PGK (LFG <60 mL/min/1.73m2) tanpa albuminuria merupakan keadaan
dengan risiko kardiovaskuler yang meningkat maka obat yang dianjurkan
adalah GLP-1 RA yang terbukti memberikan manfaat kardiovaskular atau
penghambat SGLT-2 yang terbukti memberikan manfaat kardiovaskular.

Dalam hal penggunaan penghambat SGLT-2 perlu diperhatikan labelling dan aturan berkaitan dengan
batasan LFG untuk inisiasi terapi tidak sama untuk masing – masing obat, juga berbeda antar negara. Pada
keadaan dimana GLP-1 RA atau penghambat SGLT-2 tidak dapat diberikan atau tidak tersedia, maka
dianjurkan pilihan kombinasi dengan obat lain yang telah menunjukkan keamanan terhadap kardiovaskular
antara lain insulin.
Management of Hyperglycemia in
Type 2 Diabetes, 2022. ADA/EASD
2022 Consensus;
doi.org/10.2337/dci22-0034
Management of Hyperglycemia in
Type 2 Diabetes, 2022. ADA/EASD
2022 Consensus;
doi.org/10.2337/dci22-0034
 1984

1990