diabetes mellitus kad

Ronald Chrisbianto Gani405090223

Faculty of Medicine 2009Tarumanagara University

ENDOCRINE SYSTEM BLOCK

CASE 1

DIABETES MELLITUS

DEFINISI

• Sindrom kronik gangguan metabolisme karbohidrat, protein, dan lemak akibat ketidak cukupan sekresi insulin atau resistensi insulin pada jaringan yang dituju

Dorland Medical Dictionary 29th Ed

EPIDEMIOLOGY

Harrison’s Principal of Medicine 18th Ed

TOP 10 COUNTRIES

• China• India• USA• Indonesia• Brazil

• Russia• Japan• Pakistan• Bangladesh• Nigeria

International Diabetes Federation 2011

Nelson’s Textbook of Pediatrics 19th Ed

CLASSIFICATION & ETIOLOGY• Type I Diabetes (beta cell destruction, usually

leading to absolute insulin deficiency)– Immune-mediated– Idiopathic

• Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly insulin secretory defect with insulin resistance)

• Gestational diabetes mellitus (GDM)

Harrison’s Principal of Medicine 18th Ed

Harrison’s Principal of Medicine 18th Ed

CLASSIFICATION

Harrison’s Principal of Medicine 18th Ed

CLASSIFICATION

Sherwood’s Human Physiology 7th Ed

CLASSIFICATION

Robbin’s Basic Pathology 8th Ed

DIAGNOSIS

Harrison’s Principal of Medicine 18th Ed

Diagnostic Criteria for Impaired Glucose Tolerance (IGT) and Diabetes Mellitus (DM)

IGT• Fasting Glucose 110-125

mg/dL (6,1-7,6mmol/L)• 2-hr plasma glucose during

OGTT <200mg/dL but <140mg/dL

DM• Symptoms of DM plus

random plasma glucose >= 200mg/dL or

• Fasting Plasma Glucose >= 126mg/dL or

• 2-hr plasma glucose during OGTT >= 200mg/dL

Nelson’s Textbook of Pediatrics 19th Ed

INSULIN SECRETION

Harrison’s Principal of Medicine 18th Ed

INSULIN ACTION

Harrison’s Principal of Medicine 18th Ed

TYPE I DIABETES

PATHOGENESIS OF TYPE I DIABETES

Nelson’s Textbook of Pediatrics 19th Ed

PATHOGENESIS OF TYPE I DIABETES

Harrison’s Principal of Medicine 18th Ed

PATHOPHYSIOLOGY

OF TYPE I DIABETES

Nelson’s Textbook of Pediatrics 19th Ed

Sherwood’s Human Physiology 7th Ed

CLINICAL MANIFESTATION

Classic Sign• Polyuria• Polydipsia• Polyphagia

Other• Nocturnal Enuresis• Monolial Vaginitis• Weight loss• Diminished subcutaneous

fat stores• Complications

Nelson’s Textbook of Pediatrics 19th Ed

TREATMENT

GOAL :Eliminate symptoms related to hyperglycemia (<200mg/dL)Reduce or eliminate complicationsAllow the patient to achieve as normal a lifestyle as possible

Harrison’s Principal of Medicine 18th Ed

NUTRITIONAL RECCOMENDATION

Harrison’s Principal of Medicine 18th Ed

EXERCISE

• Benefits :– Cardiovascular risk

reduction– BP reduction– Maintaining muscle mass– Body fat reduction– Weight loss– Lowering plasma glucose– Increasing insulin sensitivity

• Reccomended :– 150mins/week– Aerobic physical activity

• Caution– DM type I, pre-exercise

plasma glucose• Low ketone body

formation ketoacidosis• High hypoglycemia

Harrison’s Principal of Medicine 18th Ed

EXERCISE

• To avoid exercise related hypo-hyperglycemia– Monitor blood glucose before, during, after exercise– Delay if BG >250mg/dL or ketone is present– If BG <100mg/dL, ingest carbohydrate first– Decrease insulin dose before exercise and inject

insulin into non-exercising area– Learn individual glucose responses to different type

of exercise and increase food intake up to 24hr after exercise, depending on intensity and duration of exercise

Harrison’s Principal of Medicine 18th Ed

BLOOD GLUCOSE MONITORING

• Self-Monitoring Blood Glucose (SMBG)– Used to modify doses of insulin– Must be performed several times per day

• Current Continuous Glucose Monitoring System (CGMS)

• Ketones monitoring, especially when blood glucose is >300mg/dL, blood β-hydroxybutirate is preferred

• Long-term Glycemic Control– HbA1c / glycated hemoglobin : reflects alteration of

glycemic control over previous 2-3months

Harrison’s Principal of Medicine 18th Ed

BLOOD GLUCOSE MONITORING

• Mean Plasma Glucose based on HbA1c

• Reccomended to be performed at least twice a year

HbA1c Mean Plasma Glucose

6% 135mg/dL

7% 170mg/dL

8% 205mg/dL

(1% increase of HbA1c ~ 35mg/dL blood glucose increase)

Harrison’s Principal of Medicine 18th Ed

INSULIN

Harrison’s Principal of Medicine 18th Ed

CONTINUOUS SUBCUTANEOUS INSULIN INFUSION (CSII)

• Advantages– Multiple basal infusion rates can be programmed to

accomodate nocturnal vs daytime basal insulin requirement– Basal infusion rates can be altered during periods of exercise– Different waveforms of insulin infusion with meal related

bolus allow better matching of insulin depending meal composition

– Programmed algorithm consider prior insulin administration and blood glucose values in calculating insulin dose

• Disadvantages : require very frequent interaction with helath proffesional and alteration of device can be fatal

Harrison’s Principal of Medicine 18th Ed

INSULIN REGIMENT

Harrison’s Principal of Medicine 18th Ed

OTHER AGENTS THAT IMPROVE GLUCOSE CONTROL

• Pramlintide – Analogue of amylin (peptide cosecreted with insulin)– Injected before meal– Slows gastric emptying– Supress glucagon– Does not alter insulin level– Side effect : nausea and vomiting

(dose-dependent) – Influence absorbtion of other medication

Harrison’s Principal of Medicine 18th Ed

PREVENTION

• Many prevention has been performed and success in animals, but no satisfactory results in human

TYPE II DIABETES

RISK FACTOR

Individual with high risk is recommended to do a screening test

PATHOGENESIS

OFTYPE II

DIABETESMELLITUS

MECHANISM OFINSULIN

RESISTANCE

PATHOPHYSIOLOGY

• Metabolic Abnormalities– Abnormal Muscle and

Fat Metabolism– Impaired insulin

secretion– Increased Hepatic

Glucose and Lipid Production

TREATMENT

TREATMENT

ONGOING CARE

ANTIDIABETIC AGENT

ANTIDIABETIC AGENT

INSULIN SECRETAGOGUE

ANTIHIPERGLYCEMIC ORAL• Insulin Sensitizing

– Biguanid• Contoh : metformin• Meningkatkan pemakaian

glukosa oleh sel dan menstimulasi produksi GLP-1menekan fungsi sel alfa

• DOC pd awal pengelolaan diabetes

• Bisa diberikan monoterapi atau kombinasi dg SU / insulin

• ES: asidosis laktat• KI : gangguan ginjal, hati,

infeksi beratm, gangguan jantung, anemia (gangguan vit B12)

– Glitazone• Agonist PPAR• Merangsang ekspresi bbrp

protein u/ memperbaiki sensitivitas insulin

• Rosiglitazone : meningkatkan LDL dan HDL

• Pioglitazon : menurunkan TG meningkatkan HDL

• Monoterapi, atau kombinasi dg metformin dan sekretagok

• ES: BB ↑, ISPA, sakit kepala, anemia dilusional

• KI : dihentikan jk kenaikan ALT / AST 3x BANN, hati2 pd NYHA kelas 3 dan 4

ANTIHYPERGLICEMIC ORAL

• Sekretagok Insulin– Sulfonilurea

• Merangsang sel B pankreas melepas insuli

• SU gen I : acetohexamide, tolbutamide

• SU gen II : glibenclamide• SU gen III : glimepiride• Kombinasi dg insulin• ES: Hipoglikemik, BB ↑,

gangguan pencernaan, fotosensitivitas, gangguan enzim hati, flushing

• KI : DM tipe I, hamil, menyusui

– Glinid• Mirip SU, masa kerja pendek• Obat prandial (2-3x/day)

• Penghambat Alfa Glukosidase

• Menghambat kerja enzim alfa glukosidase penurunan penyerapan glukosa, menurunkan hiperglikemia postprandial

• Mek kerja : memperlambat pemecahan dan penyerapan karbohidrat kompleks

• ES: metrorismus, flatulence, diare

• KI : IBS, sirosis, gangguan ginjal

ANTIHYPERGLYCEMIC ORAL

• Incretin– Penghambat DPP-IV• Memperpanjang masa kerja GLP-1 (menekan kerja sel

alfa dan menghambat pengsongan lambung)• Sitagliptin dan vildaglitin• ES: nasofaringitis, resiko infeksi sal kemih, sakit kepala

KETOASIDOSIS DIABETIC AND HYPERGLYCEMIC HYPEROSMOLAR STATE

DKA & HHS

CLINICAL MANIFESTATION

MANAGEMENT

DIABETIC RETINOPATHY

DIABETIC RETINOPATHY

• Leading causes for blindness in US

• Risk for blind diabetic : non diabetic = 25 : 1

• Classified into : – Proliferative– Non-Proliferative

• Treatment : prophilactic photocoagulation, proliferative : panretinal laser

DIABETIC NEPHROPATHY

SCREENING DIAGNOSIS

INTERVENTION

• Normalization of hyperglycemia• Strict blood pressure control• Administration of ACE inhibitor or ARB, if not

possible, CCB, B-Blocker, or diuretic• Dyslipidemia should be treated• Nephrologist consult if GFR <60mL/min

DAFTAR PUSTAKA

• Fauci AS, Braunwald E, Kasper DL, Longo DL, Jameson JL, et al, editors. Harrison’s Principle of Internal Medicine. 18th ed. USA : McGraw Hill Medical, 2011

• Sudoyo AW, Setiyohadi B, Alwi I, Simadibrata M, Setiadi S, et al, editors. Buku Ajar Ilmu Penyakit Dalam 5th ed. Jakarta : Pusat Penerbitan Ilmu Penyakit Dalam FKUI, 2006

• Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease 7th ed. Philadelphia : Elsevier Saunders 2005

• Kliegman, Behrman, Jenson, Stanton ; 2007 ; NELSON TEXTBOOK OF PEDIATRICS 18th Edition Volume II ; Philadelphia : Sunders Elsevier