DETEKSI DINI KOMPLIKASI DIABETES MELITUS

Harsinen SanusiDivisi Endokrin dan Metabolik Bagian Penyakit Dalam FKUH

RS Wahidin sudirohusodoMakassar

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 ComplicationsHypoglicemiaDiabetic ketoacidosisHyperglycemic, Hyperosmolar,

nonketotic state• Chronic Complication

Greenspan’s Basic & Clinical Endocrinology 2007:722-5

Microangiopathy 1. Diabetic Retinopathy2. Diabetic Nephropathy3.Diabetic neuropathy

Chronic Complicationt

Macroangiopathy1.CVD2.Stroke3.Peripher Arteri Disease

Greenspan’s 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

• Coronary heart disease (CHD)• myocardial infarction• coronary atherosclerosis (angina)• heart failure

• Cerebrovascular arterial disease (stroke)

• Peripheral arterial disease• intermittent claudication• ischaemic foot ulcer

Diabetic macroangiopathy(cardiovascular disease - CVD)

UKPDS, DCCTRISIKO KOMPLIKASI

MENINGKAT APABILA KONTROL EUGLIKEMIK

JELEK

LESSONS FROM UKPDS:BETTER CONTROL MEANS FEWER COMPLICATIONS

LESSONS FROM UKPDS:BETTER CONTROL MEANS FEWER COMPLICATIONS

EVERY 1% reduction in A1C

Deaths from diabetes

Heart attacks

Microvascular complications

Peripheral vascular disorders

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

-37%

-43%

*p<0.0001

-14%

-21%

1%

Target Euglycemic ControllPARAMETER ADA-EASD AACE-ACE IDF PERKENI

FPG (mg/dL

70-130 <110 <100 <100

PPG (mg/dL)

<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):S11–S61. 2. AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007;13(suppl 1):3–68. 3. Rodbard HW et al. Endocr Pract. 2009;15(6):540–559. 4.

International Diabetes Federation. www.idf.org/webdata/docs/Guideline_PMG.pdf. Accessed September 2, 2010.

TARGETS

Type 2Diabetes

Multiple Defects in Type 2

Diabetes

Adverse Effectsof Therapy

Hyperglycemia

No Hypoglycemia

ImprovesGlycemicControl

Lowers HbA1c to normal levels

Decreases insulin resistance and hepatic glucose production

Increases or preserves

beta-cell mass

Does not cause weight gain

Does not cause edema or

congestive heart failure

Ophthalmopathy 25-30 X DR blind

Kidney 20-30 X CKD HDHeart 2-4 X CVD AMICerebral 2-4 X strokeNeuron 15-40 X parestesi,

amputation

Insulin resistance, DM and CVD–10 0 10 20

IGT Type 2 diabetes mellitus CVD

Diabetes duration (years)

CHD

Amputations

Blindness

Renal failure

Atherosclerosis Advance atherosclerosis

On-going Retinopathy metabolic Nephropathy

derangement Neuropathy

Hypertension

Insulin Resistance

HDL TG

Blood Presure Blood Glucose

Obesity

Macrovascular complications

Microvascular complications

---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

Proliferatif Retinopathy

Haemorhargic

Features

microaneurysms

Features

New vessels(also get tortuous vessels and haemorhages)

DIABETES RETINOPATHYPREVENTION 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;124:90–6

Diabetic Nephropathy

Definitions of urinary protein abnormalities

Spot collection(µg/mg

creatinine)

Timed collection(µg/min)

24-hour collection

(mg/24 hours)

Normal <30 <20 <30

Microalbuminuria(incipient nephropathy)

30–299 20–199 30–299

Macroproteinuria(clinical nephropathy)

≥300 ≥200 ≥300

American Diabetes Association. Diabetes Care 2004; 27:S79–S83

DIABETES NEPHROPATHYCharacteristics

• 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-stage renal disease (ESRD) usually follows.

UKPDS: Patient with survival with time in year

Normal urinary albumin

secretion

Proteinuria

End Stage Renal Disease (ESRD)

Death

Microalbuminuria

50% (5-10 years)

20%(20 year)

- 40%

DIABETIC NEPHROPATHY IS ASSOCIATED WITH CARDIOVASCULAR MORTALITY IN TYPE 2 DM

Normal albumin excretion

Overt proteinuria

Microalbuminuria

Elevated plasma creatinine orRenal replacement therapy

2.0%

1.4%

2.8%

2.3%

4.6%

3.0%

19.2%

Death

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

• 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

DIABETIC NEUROPATHY

Pathogenesis of Diabetic Neuropathy

Risk factors:Prodominace of menIncreasing age, heightSmokingMicroalbuminuriaRetinopati

Clinical manifestation diabetic neuropathy

• Painful diabetic neuropathyPainless diabetic neuropathy

• Patients with painful DN do not usually develop foot ulcers,

• Patients with foot ulcers painful symptom rare

Veves A etal.Diabetes care1993;1611871-189

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 hidupPENGOBATAN:

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

ATONI BULI-BULI

• Indwelling catheter• Penekanan

Erection Function Disorder( Erection Dysfunction/Impotence )

53,2%

12,9%8,9%

1,0% 1,0%

10,8%6,2%

0,0%

10,0%

20,0%

30,0%

40,0%

50,0%

60,0%

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 FootRisk Factors Peripheral nerve disorderPeripheral arterial diseaseFoot deformityTrauma or amputation historyUnfit shoesInfection

Treatment priority

Glucose control as near to normal as reasonably

possible

Microvascular

Control of insulin resistance: hyperinsulinemia, obesity, glucose

intolerance, dyslipidemia, hypertension, procoagulant state

Macrovascular

Summary of recommendations for adults with diabetes (IDF 2007)

• Glycemic controlA1C …………………………………< 6.0%Preprandial plasma glucose……90-100 mg/dlPostprandial plasma glucose… < 140 mg/dl

• Blood pressure………<130/80 mg/dl

• Lipids LDL…………………………….. <100mg/dl

Triglicerides……………………<100mg/dlHDL……………………………… >40mg/dl

The Good News…

5

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

A stands for A1CB stands for Blood pressureC stands for Cholesterol

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 • Antiplatelet therapy also remain essential.

Journal of Pharmacy Practice.2009. 22, 135-148

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

PREVENTION PROGRESSION OF ATHEROSCLEROSIS IN TYPE 2 DM

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 DIABETIKHIPEROSMOLER NON KETOTIK ASIDOSIS LAKTAT

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 dllHipoglikemia endogen insulinomaHipoglikemia fungsional H. alimenter, ggn hati berat, aktifitas otot lama,

HIPOGLIKEMIA

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

SymptomsSigns

Hypoglycaemia

Pallor Diaphoresis

Neuro-glycopenic

Cognitive impairmentsBehavioural changesPsychomotor abnormalitiesSeizureComa

Neurogenic

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

Symptoms and Sign of Hypoglycemia

High risk Low risk

Insulin Metformin

Sulfonylureas 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.

Oral Hypoglycemic Agents (OHA) (classified by risk of hypoglycaemia)

Criteria for Hypoglycemia

Still can help themselves

Severe hypoglycemia

Need help from others

Mild hypoglycemia

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 hipoglikemikTrias Whipple

• Keluhan dan tanda klinis hipoglikemia• Kadar glukose plasma <50 mg/dl• Keluhan menghilang dgn pemberian glukose

HIPOGLIKEMIA Pengobatan:Sadar :

Tablet glukosa 30 gr, sirup, air gula, kue-kue manis, Fruktosa murni dilarang Stop obat hipoglikemik. Periksa GDS

Koma : Dextrose 40 % 50 ml, ulangi setiap 10-20 mnt sp pasien`sadarInfus dextrose 10%, 6 jam perkolf; dipertahankan sp GDS normal atau meningkat sdkt

Glukagon 1 mg IM, madu, kortisol

Management

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

Severe hypoglycemia

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 mengurangi edema otak

In elderly people receiving insulin or sulphonylureas, the symptoms of hypoglycemia most commonly

recognized are not specific in nature:

McAulay V, et al. Diabet Med. 2001;18:690-705.

* Transient cerebral ischemia* Vertebrobasilar insufficiency

* Vasovagal attacks* Cardiac dysarhythmia

Unawareness Hypoglycemia

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.