LOs

ALBERT
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Diabetes melitus (DM) = suatu kelompok peny metabolik dgn
karakteristik hiperglikemia yg tjd krn kelainan sekresi insulin, kerja
insulin atau kedua-duanya
ACUTE DISORDERS RELATED TO SEVERE
HYPERGLYCEMIA
• Diabetic ketoacidosis (DKA)
• Ketones, hallmark of type 1 DM
• Hyperglycemic hyperosmolar state (HHS)
• type 2 DM
DIABETIC KETOACIDOSIS
• Pathophysiology
• DKA results from relative or absolute insulin deficiency combined with
counterregulatory hormone excess (glucagon, catecholamines,
cortisol, and growth hormone)
• Promotes gluconeogenesis, glycogenolysis & ketone body formation in
the liver
• Ketosis results from a marked increase in free fatty acid release from
adipocytes, with a resulting shift toward ketone body synthesis in the
liver
• Reduced insulin levels, in combination with elevations in catecholamines
and growth hormone, increase lipolysis and the release of free fatty acids
• Normally, these free fatty acids are converted to triglycerides or very-low-
density lipoprotein (VLDL) in the liver
• Hyperglucagonemia alters hepatic metabolism to favor ketone body
formation, through activation of the enzyme carnitine
palmitoyltransferase I (regulating fatty acid transport to mitochondria)
where beta oxidation and conversion to ketone bodies occur
• As bicarbonate stores are depleted, metabolic acidosis ensues. Increased
lactic acid production also contributes to the acidosis.
HYPERGLYCEMIC HYPEROSMOLAR STATE
Clinical features
• an elderly individual with type 2 DM, with a several-week history of polyuria,
weight loss, and diminished oral intake that culminates in mental confusion,
lethargy, or coma
• Physical exam: dehydration. hyperosmolality and reveals hypotension,
tachycardia, and altered mental status

• HHS is often precipitated by a serious, concurrent illness such as myocardial

infarction or stroke. Sepsis, pneumonia, and other serious infections are frequent
precipitants.
• In addition, a debilitating condition (prior stroke or dementia) or social situation
that compromises water intake usually contributes to the development of the
disorder
Pathophysiology
• Relative insulin deficiency and inadequate fluid intake are the
underlying causes of HHS.
• Insulin deficiency increases hepatic glucose production (through
glycogenolysis and gluconeogenesis) and impairs glucose utilization in
skeletal muscle
• Hyperglycemia -> osmotic diuresis -> intravascular volume depletion,
which is exacerbated by inadequate fluid replacement
HYPOGLYCEMIA
HIPOGLIKEMIA
• ↓ kadar glukosa darah < 60 mg/dl
• ! Penurunan kesadaran pada penyandang DM
• Paling sering disebabkan oleh penggunaan sulfonilurea dan insulin
• Hipoglikemia e.c. sulfonilurea → dapat berlangsung lama
• Pengawasan (24 – 72 jam) sampai seluruh obat diekskresi dan waktu kerja
obat habis
• Hipoglikemia pada usia lanjut → harus dihindari
• Dampaknya yang fatal; terjadi kemunduran mental bermakna; perbaikan
kesadaran sering lebih lambat; perlu pengawasan lebih lama

Perkumpulan Endokrinologi Indonesia. Konsensus

pengendalian dan pencegahan diabetes mellitus tipe 2 di
indonesia 2011. Jakarta: PB PERKENI; 2011.
GEJALA HIPOGLIKEMIA
• Gejala adrenergik (biasanya muncul pertama kali; karena aktivitas
SSO) → berdebar-debar, banyak keringat, gemetar, rasa lapar, tremor
• Gejala neuro-glikopenik (karena berkurangnya aktivitas SSP) →
pusing, gelisah, sakit kepala, penglihatan kabur, kelelahan, konfusio,
kesadaran menurun s/d koma

Perkumpulan Endokrinologi Indonesia. Konsensus pengendalian dan pencegahan

diabetes mellitus tipe 2 di indonesia 2011. Jakarta: PB PERKENI; 2011.
Vojvodic M, Young A, editors. Toronto notes 2014. Toronto: Toronto Notes for
Medical Students Inc.; 2014.
GEJALA HIPOGLIKEMIA
• Whipple’s triad :
• Glukosa serum < 45 mg/dl (pada pria) atau < 40 mg/dl (pada wanita)
• Gejala neuro-glikopenik
• Perbaikan yang cepat setelah pemberian glukosa

Vojvodic M, Young A, editors. Toronto notes 2014. Toronto:

Toronto Notes for Medical Students Inc.; 2014.
 TANDA-TANDA HIPOGLIKEMIA
• Stadium parasimpatik → lapar, mual, tekanan darah ↓
• Stadium gangguan otak ringan → lemah, lesu, sulit bicara, kesulitan
menghitung sederhana
• Stadium simpatik → keringat dingin pada muka terutama di hidung,
bibir atau tangan; berdebar-debar
• Stadium gangguan otak berat → koma (tidak sadar) dengan atau
tanpa kejang

Soegondo S, Soewondo P, Subekti I, editors. Penatalaksanaan

diabetes melitus terpadu. Ed 2. Jakarta: Pusat Diabetes dan
Lipid RSUPN Cipto Mangunkusumo; 2009.
4 theories on how hyperglycemia might lead to the chronic
complications include the following pathways:
• Increased intracellular glucose leads to the formation of advanced
glycosylation end products, which bind to a cell surface receptor via
the nonenzymatic glycosylation of intra and extracellular protein,
leading to cross linking of protein
• Hyperglycemia increases glucose metabolism via the sorbitol pathway
related to the enzyme aldose reductase
• Hyperglycemia increases the formation of diacylglycerol, leading to
activation of protein kinase C
• Hyperglycemia increases the flux through the hexosamine pathway
OPHTHALMOLOGIC COMPLICATIONS OF
DIABETES MELLITUS
Diabetic retinopathy is classified into two stages:
• nonproliferative
• (marked by retinal vascular microaneurysms, blot hemorrhages & cotton-
wool spots)
• loss of retinal pericytes, increased retinal vascular permeability, alterations in
retinal blood flow, and abnormal retinal microvasculature -> ischemia
• Proliferative
• (marked by the appearance of neovascularization)
• The most effective therapy for diabetic retinopathy is prevention
• Intensive glycemic and blood pressure control will delay the
development

• Individuals with known retinopathy may be candidates for

prophylactic laser photocoagulation
• Proliferative retinopathy is usually treated with panretinal laser
photocoagulation, whereas macular edema is treated with focal laser
photocoagulation and anti–vascular endothelial growth factor
therapy (ocular injection)
NEFROPATI DIABETIK
• Ditandai dengan adanya mikroalbuniuria (30 mg/hari atau 20 µg/mnt)
tanpa adanya ggn ginjal, disertai dgn peningkatan tekanan darah ->
menurunnya filtrasi glomerulus -> gagal ginjal tahap akhir

Patogenesis
• Glomerulosklerosis
• Hiperfiltrasi di glomerulus, hipertrofi glomerulus, peningkatan ekskresi
albumin urin, peningkatan ketebalan membran basal, ekspansi mesangial
dgn penimbunan protein-protein MES spt kolagen, fibronektin, dan
laminin.
• Nefropati diabetik lbh lanjut ditandai dgn proteinuria, penurunan fs ginjal,
penurunan bersihan kreatinin, glomerulosklerosis dan fibrosis interstisial
NEUROPATI
• Komplikasi yang tersering dan terpenting → neuropati perifer berupa
hilangnya sensasi distal (distal symmetric neuropathy) → berisiko ↑
untuk terjadi ulkus kaki dan amputasi
• Gejala yang sering dirasakan → kaki terasa terbakar dan bergetar
sendiri, lebih terasa sakit di malam hari
• Setelah diagnosis DM ditegakkan → setiap pasien perlu dilakukan
skrining untuk mendeteksi adanya polineuropati distal dengan
pemeriksaan neurologi sederhana (dengan monofilamen 10 gram
sedikitnya tiap tahun)
• Apabila terdapat polineuropati distal → perawatan kaki yang
memadai akan ↓ risiko amputasi
• Untuk << rasa sakit → duloxetine, antidepresan trisiklik, atau
gabapentin
• Semua penyandang DM yang disertai neuropati perifer → harus
diberikan edukasi perawatan kaki → << risiko ulkus kaki.
Penatalaksanaan penyulit ini → diperlukan kerja sama dengan
bidang/disiplin ilmu lain
KARDIOMIOPATI
• Kelainan kardiovaskular yg tjd pd pasien DM, ditandai dgn dilatasi &
hipertrofi miokardium, penurunan fs sistolik & diastolik dr ventrikel kiri
serta proses tjdnya tdk berhubungan dgn penyebab umumm dr penyakit
jantung.

Mekanisme tjdnya ggn kontraksi miokardium antara lain disebabkan krn:

• Ggn homeostasis kalsium
• Aktivasi sistem renin angiotensin
• Peningkatan stres oksidatif
• Perubahan substrat metabolisme
• Disfungsi mitokondria
Gejala dan tanda:
• Hipertrofi ventrikel kiri
• Disfungsi diastolik
• Disfungsi sistolik
Diagnosis
• Ekokardiografi
• Cardiac MRI
• Cardiac biomarkers
• Tatalaksana
• Kendali glikemik
• Beta blocker
• Ace inhibitor
• Angiotensin II receptor antagonist
• Ca2+ channel antagonist
• Statin
• Thiazolelidindione
• PARP Inhibitors (Poly Adenosine
Diphosphate Ribose Polymerase)