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DETEKSI DINI

KOMPLIKASI
DIABETES MELITUS
Harsinen Sanusi
Divisi Endokrin dan Metabolik
Bagian Penyakit Dalam FKUH
RS Wahidin sudirohusodo
Makassar

Workshop and symposium DPJS 1 September 2015


clarion hotel

TYPE 2 DIABETES
Characteristics
Progressive - not stable
Aggressive - not mild
Multipharmacy needed
antidiabetic
antihypertensive
antilipidaemic
anti-platelet

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.

Complications of
Diabetes Mellitus

Acute Complications
Hypoglicemia
Diabetic ketoacidosis
Hyperglycemic,
Hyperosmolar, nonketotic
state
Basic & Clinical Endocrinology
Chronic Greenspans
Complication
2007:722-5

Chronic
Complicatio
nt
Microangiopat
hy

Macroangiopat
hy

1.CVD
1. Diabetic
2.Stroke
Retinopathy
3.Peripher Arteri
2. Diabetic
Disease
Nephropathy
3.Diabetic
neuropathy Greenspans Basic & Clinical Endocrinology
2007:722-5

Diabetic microangiopathy
Leading cause blindness (12.5% of
cases)
Leading cause of ESRD (42% of
cases)
50% of all non-traumatic
amputations

Diabetic macroangiopathy
(cardiovascular disease - CVD)
Coronary heart disease (CHD)
myocardial infarction
coronary atherosclerosis (angina)
heart failure

Cerebrovascular arterial disease (stroke)


Peripheral arterial disease
intermittent claudication
ischaemic foot ulcer

UKPDS, DCCT
RISIKO KOMPLIKASI
MENINGKAT APABILA
KONTROL EUGLIKEMIK
JELEK

LESSONS FROM UKPDS:


BETTER CONTROL MEANS FEWER COMPLICATIONS
EVERY 1%
reduction in A1C

-43%

Peripheral vascular
disorders

-37%

1%

Microvascular complications

-14%

Heart attacks

-21%

Deaths from diabetes

UKPDS 35. BMJ 2000; 321: 405-12.


*p<0.0001

Target Euglycemic Controll


PARAMETE
R

ADA-EASD

AACE-ACE

IDF

PERKENI

FPG
(mg/dL
PPG
(mg/dL)

70-130

<110

<100

<100

<180

<140

<140

<140

HbA1c
(%)

<7.0

6.5

<6.5

<7.0

AACE=American Association of Clinical Endocrinologists; ACE=American College of Endocrinology; ADA=American Diabetes Association;
FPG=fasting plasma glucose; IDF=International Diabetes Federation; PPG=postprandial glucose.
aReference to a non-diabetic range of 4.0% to 6.0% using a DCCT-based assay.
1. American Diabetes Association. Diabetes Care. 2010;33(suppl 1):S11S61.
2. AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007;13(suppl 1):368. 3. Rodbard HW et al. Endocr Pract. 2009;15(6):540559. 4.
International Diabetes Federation. www.idf.org/webdata/docs/Guideline_PMG.pdf. Accessed September 2, 2010.

TARGETS
Multiple

Lowers
Defects in Type 2
HbA
1c to
Diabetes
normal
levels
Does not
cause
weight gain
Increases
or
preserves
beta-cell

Adverse
Effects
No
Hypoglycemia
of Therapy

Improves
Type 2
Glycemic
Diabetes
Control

Decreases
insulin
Hyperglycemia
resistance and
hepatic
glucose
production

Does not
cause edema
or
congestive
heart failure

Ophthalmopathy 25-30 X

DR blind
Kidney 20-30 X CKD HD
Heart 2-4 X CVD AMI
Cerebral 2-4 X stroke
Neuron 15-40 X
parestesi, amputation

Insulin resistance, DM and CVD


Diabetes duration (years)
10

IGT

10

20

Type 2 diabetes mellitus

CVD

Microvascular complications

Macrovascular
complications

Insulin
Resistance
HDL
TG
Blood
Presure
Blood
Glucose
Obesity

Atherosclerosis
On-going

Advance atherosclerosis
Retinopathy
derangement
Hypertension

metabolic
Nephropathy
Neuropathy

CHD
Amputatio
ns
Blindness
Renal
failure

---Eye Complications-- Higher risk of blindness.


Many have minor eye
disorders.
Early treatments critical

Leading cause blindness


(12.5% of cases)

Diabetic
Retinopathy
Microaneurysm
Exudative
Haemorhargic
Proliferatif Retinopathy

Features

microaneurysms

Features

New vessels
(also get tortuous
vessels and
haemorhages)

DIABETES RETINOPATHY
PREVENTION AND TREATMENT

Maintain tight glycaemic and


blood pressure, lipid, anemia
control
Regular eye examinations
Treat with laser photocoagulation
and vitreoretinal surgery
Klein et al. Ann Intern Med 1996;124:906

Diabetic
Nephropath
y

Definitions of urinary protein abnormalities

Normal
Microalbuminuria

Spot collection
(g/mg
creatinine)

Timed
collection
(g/min)

24-hour
collection
(mg/24 hours)

<30

<20

<30

30299

20199

30299

300

200

300

(incipient nephropathy)

Macroproteinuria
(clinical nephropathy)

American Diabetes Association. Diabetes Care 2004; 27:S79S83

DIABETES NEPHROPATHY
Characteristics

Persistent albuminuria
Diabetic retinopathy
Hypertension
Decline in kidney function

KIDNEY DISEASE
Useful proteins are lost in the
urine.
Get a condition known as
microalbuminuria.
There are several treatments at this
point that may keep the kidney
disease from getting worse.
When kidney disease is diagnosed
later, during macroalbuminuria, end-

UKPDS: Patient with survival


with time in year

Normal
urinary
albumin
secretion
Microalbuminur
ia

- 40%

Proteinuria

50%
(5-10 years)

20%
(20 year)

Death

End Stage
Renal
Disease
(ESRD)

DIABETIC NEPHROPATHY IS ASSOCIATED WITH


CARDIOVASCULAR MORTALITY IN TYPE 2 DM

Normal albumin excretion 1.4%


2.0%

Microalbuminuria

3.0%

Death

2.8%

Overt proteinuria

4.6%

2.3%
Elevated plasma creatinine or 19.2%
Renal replacement therapy
Adler et al. Kidney Int 2000;63:225-32

TREATING ALBUMINURIA
Use ACE-I or ARB in nonpregnant patiens
with micro- or macroalbuminuria
Reduce protein intake to 0.8-1.0
g/kgBW/day in DM & early CKD; 0.8
g/kgBW/day in later CKD
If ACE-Is /ARBs/diuretics are given, monitor
serum creatinine and potassium
When eGFR <60 ml/min/1.73m2, evaluate
for CKD complications
Diabetes Care. 2012

DIABETIC NEUROPATHY
Prevalence of DN approximately 50%
with a clinical course that paraleles the
duration and severity of hyperglicemia
Peripheral neuropathy is one of the most
common and disabling diabetic
complications.
Typical clinical manifestations: loss of
sensation in the feet, develop.ulcers,
deformations and gangrene
amputations

DIABETIC NEUROPATHY
Diabetic
neuropathy
:
diffuse,
symmetrical, predominantly sensory
peripheral
neuropathy,
often
associated
with
autonomic
dysfunction
The severity & duration of diabetes
etiological factors

Pathogenesis of Diabetic
Neuropathy

Risk factors:
Prodominace of men
Increasing age, height
Smoking
Microalbuminuria
Retinopati

Clinical manifestation diabetic


neuropathy

Painful diabetic neuropathy


Painless diabetic neuropathy
Patients with painful DN do
not usually develop foot
ulcers,
Patients with foot ulcers
painful symptom rare
Veves A etal.Diabetes care1993;1611871189

DIABETIC
AUTONOMIC
NEUROPATHY

Erection dysfunction
Gastropharesis
Incontinentia urinae
Atoni buli-buli
Diabetic diarrhae
Hyperhydrosis

OVERACTIVE BLADDER
Urgensi, frekuensi dan
inkontinensia
Tidak mengancam jiwa
Menurunkan kualitas hidup
PENGOBATAN:

antimuskarinik:
Solifenacin 5 mg, 10 mg
(vesicare)
Propiverine ( detrusitol)

ATONI BULI-BULI

Indwelling catheter
Penekanan

Erection Function Disorder


( Erection Dysfunction/Impotence )

MORTALITY IN TYPE 2 DM

Marble, Joslin Diabetes Center, Boston USA (1974)

CARDIO VASCULAR DISEASE


(CVD) IN TYPE 2 DIABETES
MELLITUS
2.5 x increase risk of stroke
2-4 X increase of
cardiovascular mortality
DM responsible for 25% of
cardiac surgeries

Framingham Heart
Study

Diabetes has been associated 2-4 X


CHD
Mortality rate CHD > non diabetic
patients
Cardiovascular mortality 2-3 X in DM
After 20 years of followup, CHD
mortality in diabetic patients 2 X non
diabetic males and 5 X greater in
females
Krolewski AS et al.Am J Med 1991;90(suppl
2A):56S-61S.

Diabetic Foot

Risk Factors

Peripheral nerve
disorder
Peripheral arterial
disease
Foot deformity
Trauma or amputation

Treatment
priority

Control of insulin resistance:


Glucose control as
near to normal as hyperinsulinemia, obesity, glucose
intolerance, dyslipidemia, hypertens
reasonably
procoagulant state
possible

Microvascul
ar

Macrovascular

Summary of recommendations for


adults with diabetes (IDF 2007)

Glycemic control
A1C < 6.0%
Preprandial plasma glucose90-100 mg/dl
Postprandial plasma glucose < 140 mg/dl

Blood pressure<130/80 mg/dl


Lipids
LDL.. <100mg/dl
Triglicerides<100mg/dl
HDL >40mg/dl

The Good News


By managing the ABCs of
diabetes, people with
diabetes can reduce their risk
for heart disease and stroke.

A stands for A1C


B stands for Blood
pressure
C stands for Cholesterol
5

The cornerstone of preventing or delaying the


progression of macrovascular complications of
diabetes

Aggressive management of hypertension


and cholesterol. ACE inhibitors have
proven effective in managing
hypertension and avoiding other
complications of diabetes
Statins the first-line agents in the
management of dyslipidemia.
Lifestyle modification strategies and
AntiplateletJournal
therapy
also
remain22, 135-148
of Pharmacy
Practice.2009.
essential.

PREVENTION PROGRESSION OF
ATHEROSCLEROSIS IN TYPE 2 DM

kman JA. JAMA. 2002;287:2570-2581

Beware of Your Blood


Pressure
High blood pressure raises your
risk for heart attack, stroke, eye
problems and kidney disease.
Get your blood pressure
checked at every visit.

Target BP = less than


130/80
8

KOMPLIKASI AKUT
HIPOGLIKEMIA
HIPERGLIKEMIA
KETOASIDOSIS DIABETIK
HIPEROSMOLER NON KETOTIK
ASIDOSIS LAKTAT

HIPOGLIKEMIA
Definisi : Fluktuasi kadar glukosa darah
turun dibawah limit terendah untuk
fisiologis normal
(Hipoglikemia : GDS < 50 mg%)

Etiologi :
Hipoglikemia eksogen insulin, anti
diabetik oral, alkohol, obat2
lain:salisilat, beta bloker dll
Hipoglikemia endogen insulinoma
Hipoglikemia fungsional H. alimenter,
ggn hati berat, aktifitas otot lama,

Symptoms and Sign of


Hypoglycemia
Hypoglycaemia
Signs

Symptoms
Neuroglycopenic

Pallor
Diaphoresis

Cognitive
impairments
Behavioural changes
Psychomotor
abnormalities
Seizure
Coma

Cryer PE. Diabetes. 2008;57:3169-76.

Neurogenic

Adrenergic:
palpitations,
tremor, and
anxiety/arousal
Cholinergic: sweating,
hunger, and paresthesia

Oral Hypoglycemic Agents (OHA)


(classified by risk of
hypoglycaemia)
Low risk

High risk

Insulin

Metformin

Sulfonylureas

-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.

Criteria for
Hypoglycemia
Mild
hypoglycemia

Still can help


themselves

Severe
hypoglycemia

Need help from


others

Does not depend on low blood


glucose level

HIPOGLIKEMIA
Gambaran klinis : Bervariasi, tidak
adaa korelasi gejala klinik dan gula darah.
Gejala parasimpatik:
Lapar, mual, tekanan darah turun
Gejala simpatik:
Pucat, palpitasi, keringatan, rasa lapar, gelisah,
anxiety
Gejala neuroglikopenik:
Lemah, lesu, iritabel, skt kepala, konsentrasi
menurun, somnolen, ggn pglihatan, gejala
psikiatri,, kejang2, koma

HIPOGLIKEMIA
Diagnosis :
GD plasma < 70 mg %
Riwayat DM tlh dpt obat
hipoglikemik
Trias Whipple
Keluhan dan tanda klinis
hipoglikemia
Kadar glukose plasma <50 mg/dl
Keluhan menghilang dgn
pemberian

HIPOGLIKEMIA
Pengobatan:
Sadar :
Tablet glukosa 30 gr, sirup, air gula, kuekue manis, Fruktosa murni dilarang
Stop obat hipoglikemik. Periksa GDS
Koma :
Dextrose 40 % 50 ml, ulangi setiap 10-20
mnt sp pasien`sadar
Infus dextrose 10%, 6 jam perkolf;
dipertahankan sp GDS normal atau
meningkat sdkt
Glukagon 1 mg IM, madu, kortisol

Management

Severe
hypoglycemia

Mild hypoglycemia
Drink sugar solution or
glucose tab
15-20 gr,
Wait for 20 min
Re-check blood glucose
If blood glucose is not 18
mg/dl,
Re-administered glucose
solution

IV glucose 10-25 gram


1-3
min
Or glucagon 1 mg IM/SC

HIPOGLIKEMIA
Pengobatan:
Respons cepat (5-20 mnt),
kecuali hipoglikemia lama
kecuali sdh trjd ggn otak
organik, walaupun GDS 200
mg/dl
Bila tidak ada repons
hidrokortison 100mg / 4 jam
dilanjtkan tiap 12 jam untuk

Unawareness
Hypoglycemia
In elderly
people receiving insulin or
sulphonylureas, the symptoms of
hypoglycemia most commonly recognized
are not specific in nature:

* Transient cerebral ischemia


* Vertebrobasilar insufficiency
* Vasovagal attacks
* Cardiac dysarhythmia
McAulay V, et al. Diabet Med. 2001;18:690-705.

PENCEGAHAN
Edukasi ps DM yg dpt insulin
dosis insulin tepat, kurangi dosis
insulin bl kurang makan, olahraga,
operasi, melahirkan
Dosis ADO mulai dosis kecil,
ditingkatkan bertahap
Waspada pada orang tua dan DM
dgn CKD

summary

Complication of T2DM : Acute and


Chronic
Chronic complication:
Micro and
Macroangiopathy
Macroangiopathy = atherosclerosis
Type 2 DM = CHD equivalent
Poor glycemic control increases the
risk for CVD

Summary
Macroangipathy and microangipathy are chronic
complication in type 2 DM and can occur earlier
before diagnosis.
Holistic management of type 2 DM such as blood
pressure control, blood glucose control and other
comorbidity can reduce the chronic complication.
Hypoglycemia can be caused by OHAs,
esp.insulin secretagogue group.
Be aware for unawareness hypoglycemia in
elderly diabetic patient.

Thank you for your


attention

Kasuistik
Seorang wanita 55 tahun datang dengan keluhan
gatalgatal, cepat lelah, berat badan menurun ,
b.a.k. 2-3 kali permalam. Baru mengetahui
Diabetes
Pemeriksaan fisis: berat badan 67 kg, tinggi
badan 155 cm, Tensi 140/90 mmHg.pemeriksaan
fisis lain-lain normal semua.
Laboratorium:GDS 250 mg/dL
Apa yang perlu lagi ditanyakan pada anamnesis?
Pemeriksaan fisis apa yang perlu disimpulkan
Bagaimana cara mengetahui gizi?

Diagnosis :
Kriteria diagnosis :
Pemeriksaan laboratorium yang diperlukan:
Comorbidity pasien ini:
Kapan dikatakan dislipidemia pada DM?
Bila ureum, creatinine diperiksa rumus apa
yang dipakai untuk menentukan fungsi ginjal
Pemeriksaan untuk mengetahui neuropati
perifer
Pemeriksaan apa untuk mengetahui
neuropati otonom
Apa yang harus diketahui pada jantung
pasien ini.

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