diabetes mellitus ( kuliah blok endokrin )
TRANSCRIPT
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Diabetes Mellitus tipe 1
Kuliah Blok Endokrin
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DM 1
• DM tipe 1 (Insulin-dependent diabetes mellitus = IDDM ) merupakan salah satu penyakit kronis pd anak yg sampai saat ini belum dpt disembuhkan
• Dengan kemajuan teknologi kedokteran dan tata laksana yg adekuat kualitas pend DM tipe 1 dapat sepadan dng anak normal
• DM1 sebagian besar pada anak , ttp akhir ini prevalensi DM tipe 2 pd anak meningkat
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• Diabetes mellitus tergantung insulin ( Insulin-dependent diabetes mellitus = IDDM ) tipe 1 , kelainan sistemik akibat terjadinya gangguan metabolisme glukosa yg ditandai oleh hiperglikemia kronik
• Disebabkan kerusakan sel B pankreas baik oleh proses autoimun maupun idiopatik , shg produksi insulin berkurang / berhenti
• Usia 5-6 th /11 th .• Laki : perempuan • Faktor genetik / kerentanan ( HLA )• Diperlukan faktor pemicu ( infeksi virus , toksin dll ) untuk
menimbulkan gejala klinis • Ras eropa• Komplikasi KAD lebih sering
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Normal Pancreatic Function
• Exocrine pancreas aids digestion– Bicarbonate– Lipase– Amylase– Proteases
• Endocrine pancreas (islets of Langerhans)– Beta cells secrete
insulin– Alpha cells secrete
glucagon – Other hormones
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Insulin Stimulates Cellular Glucose Uptake
LiverSkeletal Muscle
Adipocytes
Intestine & Pancreas
InsulinInsulin
Insulin
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Normal
LPL
Triglyceride
LipolysisGlycerol
Free fatty acids
Free fatty acids
Glucose
Synthesis
Insulin
Insulin
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Triglyceride
LPL
Type 1 Diabetes Mellitus
LipolysisGlycerol
Free fatty acids
Free fatty acids
Glucose
Synthesis
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Gambaran klinis
• Klasik :– paling sering dijumpai di klinik
• Silent diabetes : – diketahui karena skrining / penelitian atau
pemeriksaan khusus ok salah seorg kelurga penderita telah menderita DMT1
• Ketoasidosis diabetik ( KAD ) -> – 33 % penderita baru DMT1 didiagnosis dlm
bentuk KAD
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Klasik
• Polidipsi , poliuri , polifagi
• Dehidrasi
• Penurunan BB yg nyata ( 2-6 mg )
• Mudah lelah , irritable , penurunan prestasi sekolah
• Infeksi kulit berulang , kandidiasis ( pd wanita pubertas )
• Gagal tumbuh , kurus
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• Gejala paling awal IDDM adalah poliuria , meningkatnya rasa haus , polidipsia , polifagia
• Poliuria akibat diuresis osmotik yang terjadi sekunder akibat hiperglikemia dan glukosuria
• Hilangnya air di urine , osmolaritas ekstraselular meningkat , menyebabkan rasa haus dan polidipsi
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KAD
• Gejala klasik (Polidipsi , poliuri , polifagi ) yg cepat dlm beberapa hari
• Nyeri perut , muntah , berulang • Tanda dehidrasi sedang – berat ( mata cowong , bibir
dan mucosa kering , ekstremitas dingin , capilary refill > 4 detik ) , namun anak masih poliuria
• Sesak nafas , nafas cepat dan dalam ( Kussmaul ) disertai bau aseton
• Penurunan BB yg nyata dlm waktu cepat• Gangguan kesadaran • Renjatan ( tek darah menurun , takikardi )
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Patofisiologi KAD
• Kekurangan insulin -> gangguan metabolisme glukose -> glukosuria , metabolik asidosis -> ( kompensasi takipneu refleks respiratory alkalosis ) , dehidrasi , BB menurun
• Curigai KAD -> Anak anak , perubahan perilaku yg tiba tiba , takipneu , dehidrasi
• Segera periksa gula darah ( hiperglikemia ) , urin ( keton uria , glukosuria ) , serum elektrolit , blood gas ( metabolik asidosis )
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DM 2
• Poliuria , polidipsi , polifagi • Obesitas • Usia remaja / pubertas ( > 10 th ) • Perempuan > laki • Adanya keluarga DMT2• Penanda autoantibodi negatif • Kadar C-peptida normal atau tinggi • Ras atau etnik tertentu ( Pima- Indian , Arab ) • Hipertensi
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Pemeriksaan darah
• Diagnosia dapat dibuat dengan adanya temuan glukose dan keton pada urine
• Kadar glukosa darah sewaktu lebih 200 mg/dL (11,1 mmol )
• Pada penderita asimtomatis ditemukan kadar gula darah puasa lebih tinggi dari normal dan uji toleransi glukosa terganggu pd lebih dari satu kali pemeriksaan
• Kadar gula darah puasa >126 mg/dL ( puasa adalah tidak ada asupan kalori selama 8 jam )
• Kadar gula darah 2 jam pasca toleransi glukosa > 200 mg / dl ( 11.1 mmol / l )
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Clinical Chemistry
• Normal– Fasting blood glucose <
100 mg/dL
– Serum free fatty acids ~ 0.30 mM
– Serum triglyceride ~100 mg/dL
• Uncontrolled Type 1– Fasting blood glucose
up to 500 mg/dL
– Serum free fatty acids up to 2 mM
– Serum triglyceride > 1000 mg/dL
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Urine
• Diagnosia dapat dibuat dengan adanya temuan glukose dan keton pada urine
• Glukosuria : tidak spesifik , perlu dikonfirmasi dengan pemeriksaan gula darah
• Mikroalbuminuria merupakan tanda awal penyakit ginjal diabetik
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Lain-lain
• Kadar C peptida utk melihat fungsi sel B residu yi sel B yg masih memproduksi insulin , dpt digunakan apabila sulit membedakan DMT1 dan DMT2
• HbA1 : menilai pengendalian peny DM dng tujuan mencegah terjadinya komplikasi diabetes
• Autoantibodi ( CA, 1AA ) utk diagnosis pasti
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Putativetrigger
Circulating autoantibodies (ICA, GAD65)
Cellular autoimmunityCellular autoimmunity
Loss of first-phase insulin response (IVGTT)
Glucose intolerance (OGTT)
Clinicalonset—
only 10% of-cells remain
Time
-Cell mass 100%
“Pre”-diabetes
Geneticpredisposition
Insulitis-Cell injury
Eisenbarth GS. N Engl J Med. 1986;314:1360-1368
Diabetes
Natural History Of “Pre”–Type 1 Diabetes
14
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Progression to Type 1 DMProgression to Type 1 DM
Autoimmune destruction
“Diabetes threshold”
Honeymoon
100% Islet loss
Autoimmune markers (ICA, IAA, GAD)
Islet Cell Mass
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• Honey moon periode = fase remisi ( partial/ total ) akibat berfungsinya kembali jaringan residual pankreas shg pankreas mensekresikan kembali sisa insulin , fase ini akan berakhir apabila pankreas sdh menghabiskan seluruh sisa insulin
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Test toleransi glukosa
• Tidak diperlukan untuk mendiagnosis DM tipe 1 , ok gambaran klinis sudah khas
• Indikasi hanya pada kasus yang meragukan yang ditemukan gejala klnis yg khas untuk DM , namun pemeriksaan kadar glukosa tidak meyakinkan
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• Tujuan pengobatan adalah ( a) menjamin memberikan insulin dengan cara
yang cukup untuk mempertahakan kadar glukosa atau yang mendekati rentang normal dan
(b ) untuk menjamin terjadinya pertumbuhan dan perkembangan yang normal , untuk itu pasien harus :
• mematuhi diet yang mengandung jumlah KH yang cukup ,
• menghindari lemak berlebihan , harus olah raga untuk kebugaran tubuh , dan harus
• memantau respon gula darah terhadap terapi insulin
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Patient J.L., December 15, 1922
February 15, 1923
The Miracle of InsulinThe Miracle of Insulin
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Banting and BestBanting and Best
1923 Nobel Prize for 1923 Nobel Prize for discovery and use of discovery and use of insulin in the insulin in the treatment of IDDMtreatment of IDDM
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Insulin • Kerja pendek ( regular / soluble )
• Kerja cepat ( rapid acting ) – Aspart , glulisine , lispro
• Kerja pendek menengah / intermediate – Semilente – NPH – Lente
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Insulin
• Long acting / Insulin basal – Glargine – Determir
• Kerja panjang – Ultralente
• Insulin campuran – Cepat menengah– Pendek menengah
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Insulin and its action
Insulin type Onset (hr ) Peak (hr ) Duration (hr )
Shortacting
reguler
0,5 2-3 4-6
Short
Acting
< 0,5 1-2 2-3
Intermediat
Acting
2-4 4-8 12-18
Long acting 6-10 flat 18-24
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Insulin Preparations - USInsulin Preparations - US
• Novo NordiskNovo Nordisk– NovoLog (aspart) NovoLog (aspart)
short acting short acting – NovoLog Mix 70/30NovoLog Mix 70/30– NovolinNovolin R R– NovolinNovolin N N– NovolinNovolin 70/30 70/30
• Sanofi-AventisSanofi-Aventis– LantusLantus (glargine) , (glargine) ,
long acting long acting
• LillyLilly– Humalog (lispro) short Humalog (lispro) short
acting acting – Humalog Mix 75/25 Humalog Mix 75/25
short acting short acting – HumulinHumulin R R– HumulinHumulin N N– HumulinHumulin 70/30 70/30– HumulinHumulin 50/50 50/50
• Lente, Ultralente have Lente, Ultralente have been discontinuedbeen discontinued
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Treatment with InsulinTreatment with Insulin
• Total daily requirement:Total daily requirement:– 0.5/ 0,7 -1 unit/kg/day0.5/ 0,7 -1 unit/kg/day– 1.5 units/kg/day during puberty1.5 units/kg/day during puberty
• Typical RegimensTypical Regimens– NPH NPH ( intermediate acting )( intermediate acting ) and Regular and Regular
( ( short actingshort acting ) ) – Basal/BolusBasal/Bolus: glargine: glargine ( long acting ) ( long acting ) and and
Novolog/HumalogNovolog/Humalog ( short acting ) ( short acting )
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• Saat awal pengobatan insulin diberikan 3-4 kali injeksi ( kerja pendek ) , setelah diperoleh dosis optimal diusahakan utk memberi regimen insulin yg sesuai dng kondisi penderita
• Kebanyakan anak anak menerima pengobatan dengan injeksi insulin subkutan ( campuran sediaan insulin NPH / lente yg ber efek kerjanya sedang / intermediate dan insulin regular = larut yg efek kerjanya singkat / short ) , dua kali sehari
• Penyuntikan setiap hari di paha , lengan atas , sekitar umbilikus secara bergantian
• Dosis insulin harus disesuaikan pada masing-masing individu bergantung pada respons sebelumnya , dan pembatasan asupan makanan dan tingkat aktifitas ( latihan,sekolah ) , target metabolik , pendidikan , status sosial , dan keinginan keluarga
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Insulin DeliveryInsulin Delivery
• Vials and syringesVials and syringes
• PensPens
• Insulin pumpInsulin pump
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4:004:00
2525
5050
7575
8:008:00 12:0012:00 16:0016:00 20:00 20:00 24:0024:00 4:004:00
BreakfastBreakfast LunchLunch DinnerDinner
Pla
sma
insu
lin
(P
lasm
a in
suli
n (µ U
/ml)
U
/ml)
TimeTime
8:008:00
NPH and RegularNPH and Regular
RR RR
N N
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AM 2/3AM 2/3
PM 1/3PM 1/3
2/3 NPH2/3 NPH
1/3 Regular1/3 Regular
½ NPH (2/3)½ NPH (2/3)
½ Regular (1/3)½ Regular (1/3)
NPH and RegularNPH and Regular
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NPH and RegularNPH and Regular
• Regular insulin given 30 min prior to a Regular insulin given 30 min prior to a mealmeal
• NPH dose often given at bedtimeNPH dose often given at bedtime
• Prescribed amount of carbs at Prescribed amount of carbs at meals/snacksmeals/snacks
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NPH and RegularNPH and Regular
• AM blood glucoses AM blood glucoses → Evening NPH→ Evening NPH
• Lunch → AM RegularLunch → AM Regular
• Dinner → AM NPHDinner → AM NPH
• Bedtime → PM RegularBedtime → PM Regular
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4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:0012:008:00
Time
GlargineLong act
Lispro Lispro Lispro short act
Aspart Aspart Aspartor oror
Pla
sma
insu
lin
Basal/BolusBasal/Bolus
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Basal/BolusBasal/Bolus
• Basal: glargine, 50% total daily doseBasal: glargine, 50% total daily dose
• Bolus: NovoLog or Humalog Bolus: NovoLog or Humalog – Insulin to carbohydrate ratioInsulin to carbohydrate ratio– Correction Correction
BG – targetBG – targetCorrection factorCorrection factor
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Basal/BolusBasal/Bolus
• I:CHO = 450/total daily insulin dose = I:CHO = 450/total daily insulin dose = amount of carbs 1 units will coveramount of carbs 1 units will cover
• Correction Factor: “1700 rule” = Correction Factor: “1700 rule” = 1700/TDD1700/TDD
• Glargine can not be mixed with any Glargine can not be mixed with any other insulinsother insulins
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Basal/BolusBasal/Bolus
• Glargine dose limited by which blood Glargine dose limited by which blood sugar? sugar? – 2 AM and breakfast2 AM and breakfast
• Which blood sugar is affected by the Which blood sugar is affected by the I:CHO ratio?I:CHO ratio?– 2 hour post-prandial2 hour post-prandial
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NPH and RegularNPH and Regular
• AdvantagesAdvantages– 2-3 shots per day2-3 shots per day– ““Easier” – less carb counting and calculationsEasier” – less carb counting and calculations
• DisadvantagesDisadvantages– Strict dietary planStrict dietary plan– Less flexibleLess flexible– Less physiologicLess physiologic
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Basal/BolusBasal/Bolus
• AdvantagesAdvantages– More physiologicMore physiologic– More flexibleMore flexible– Less hypoglycemiaLess hypoglycemia
• DisadvantagesDisadvantages– More labor-intensive (CHO counting, More labor-intensive (CHO counting,
insulin calculations)insulin calculations)– At least 4 injections per dayAt least 4 injections per day
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Efek somogyi & efek subuh
• Mengakibatikan hiperglikemia pada pagi hari , namun memerlukan penanganan yang berbeda
• Efek somogyi terjadi sebagai kompensasi terhadap hipoglikemia pd malam hari yg terjadi sebelumnya ( rebound effect ) , akibat pemberian insulin yg berlebihan – Shg perlu penambahan makanan kecil sebelum tidur
atau pengurangan dosis insulin malam hari • Efek subuh ( dawn effect ) terjadi akibat kerja
hormon kontra insulin pd malam hari – Memerlukan penambahan dosis insulin malam hari
untuk menghindari hiperglikemia pagi hari
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4:004:00
2525
5050
7575
8:008:00 12:0012:00 16:0016:00 20:00 20:00 24:0024:00 4:004:00
BreakfastBreakfast LunchLunch DinnerDinner
Pla
sma
insu
lin
(P
lasm
a in
suli
n (µ U
/ml)
U
/ml)
TimeTime
8:008:00
Physiological Serum Insulin Physiological Serum Insulin Secretion ProfileSecretion Profile
Dawn Dawn phenomenonphenomenon
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• Pengaturan makan : • Anak yang menderita IDDM harus memantau
diet untuk me minimal kan akan kebutuhan dosis injeksi insulin harian
• Kebutuhan kalori sama dengan anak non diabetik : ( 1000 kalori + ( usia tahun ) x 100 ) kalori perhari
• Sebaiknya 60-65% KH , < 30% lemak , 25% protein
• Untuk mempertahankan kontrol kadar glukosa perlu makan dan kudapan beberapa kali setiap harinya
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• Olah raga tidak memperbaiki kontrol metabolik ,
membantu peningkatan jati diri , mempertahankan BB ideal , meningkatkan kapasitas jantung , mengurangi komplikasi jangka panjang , shg dpt mengurangi kebutuhan insulin
• Diperhatikan pemantauan terhadap kemungkinan hipoglikemia sehingga perlu menyesuaikan dosis insulin
• Jenis : pemanasan 10 menit , latihan aerobik 20 menit ( berjalan , bersepeda ) , paling sedikit 3 kali seminggu
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Edukasi
• Pendidikan harus dilakukan secara terus menerus dan bertahap sesuai tingkatan pengetahuan serta status sosial pend / keluarga
• Pengetahuan dasar ttg DM tipe 1, pengaturan makanan , insulin ( jenis , cara pemberian , efek samping ) dan pertolongan pertama kedaruratan medik akibat DM tipe 1 ( hipoglikemia , pemberian insulin pada saat sakit )
• Penderita dan keluarganya diperkenalkan dng keluarga DM tipe 1 ( perkemahan ) atau diperkenalkan dengan sumber informasi ttg DM tipe 1
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Aspek psikososial
• Efek pada keluarga : – Perasaan duka cita , marah , menolak ,
depresi , resolusi , penerimaaan – Masalah Biaya
• Efek pada anak : – Fluktuasi gula darah menyebabkan
perubahan mood dan tingkah laku , kegelisahan , irritabel , gangguan konsentrasi
– Sedih , anxietas , menarik diri , depresi dan ketergantungan , motivasi , karier
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• Komplikasi dapat terjadi seperti hipoglikemia , ketoasidosis diabetik ( Diabetic Ketoacidosis = DKA ) , retinopati , nefropati
• DKA ok tidak patuh jadwal dng suntikan , pemberian insulin dihentikan ok tidak makan/ minum , kasus baru . Perlu insulin kerja pendek ( short acting ) : Humulin , actrapid
• Hipoglikemia merupakan komplikasi tersering dapat disebabkan oleh sehabis latihan , lupa atau terlambat makan , atau pemberian insulin yang berlebihan / tidak tepat
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Hipoglikemia
• Ringan , sedang , berat• Ringan : Lapar , tremor , mudah goyah , pucat ,
ansietas , berkeringat , palpitasi , takikardi , penurunan konsentrasi , kognitiv
• Sedang : sakit kepala , sakit perut , perub tingkah laku , agresiv , gangg visus , bingung , ngantuk, lemah , kesulitan bicara , takhikardi , pucat, berkeringat , dilatasi pupil
• Berat : disorientasi berat, penururnan kesadaran , koma , kejang
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Terapi
• Ringan : Sari buah , limun manis , anggur manis , makanan ringan , memajukan jadwal makan dlm 15-30 mnt .
• Sedang : 10 – 20 gram gula , snack • Berat : injeksi glukagon (Sc, IM atau IV ) 0, 5mg
( kurang 5 th ) , 1 mg ( lbh 5 th ) , bisa diulangi lagi , atau dekstrose 10% IV dosis 2 mL/kgBB ( di RS )
• ( pencegahan : konsumsi makanan malam hari KH yg lambat dicerna spt susu , roti , pisang apel , harus bawa permen atau tablet glikosa )
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Indikasi rawat inap
• Penderita baru ( < 2 th ) yg memulai terapi insulin
• KAD
• Dehidrasi sedang – berat
• Persiapan operasi dng anestesi umum
• Hipoglikemia berat
• Tidak bisa rawat jalan
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Insulin Pump CandidatesInsulin Pump Candidates
• Highly motivatedHighly motivated
• Willing to perform frequent blood Willing to perform frequent blood glucose monitoringglucose monitoring
• Good control on basal/bolus regimenGood control on basal/bolus regimen
• Proficient at carbohydrate countingProficient at carbohydrate counting
• Proficient at adjusting insulin doses Proficient at adjusting insulin doses with I:CHO and correction factorwith I:CHO and correction factor
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Insulin PumpInsulin Pump
• Only NovoLog or Humalog insulinOnly NovoLog or Humalog insulin
• Hourly basal rate: Hourly basal rate: 1.1. 80% of total daily insulin dose80% of total daily insulin dose
2.2. Divided by 2Divided by 2
3.3. Divide by 24Divide by 24
• Same I:CHO and correction factorSame I:CHO and correction factor
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Insulin PumpInsulin Pump• AdvantagesAdvantages
– Mimics physiologic pancreatic secretionMimics physiologic pancreatic secretion– LifestyleLifestyle– Accurate dosingAccurate dosing– Less hypoglycemiaLess hypoglycemia
• DisadvantagesDisadvantages– No depot to protect from DKANo depot to protect from DKA– Labor intensiveLabor intensive– ExpensiveExpensive
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Jason JohnsonJason Johnson
Detroit Tigers Detroit Tigers PitcherPitcher
Type 1 diabetes Type 1 diabetes diagnosed age 11diagnosed age 11
Wears insulin pump Wears insulin pump on fieldon field
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New Directions: Inhaled InsulinNew Directions: Inhaled Insulin
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Halle BerryHalle Berry
ActressActress
Type 1 diabetesType 1 diabetes
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Nicole JohnsonNicole Johnson
Miss America 1999Miss America 1999
Type 1 diabetesType 1 diabetes
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Gary Hall Jr.Gary Hall Jr.
Olympic swimming Olympic swimming medalistmedalist
Type 1 diabetesType 1 diabetes
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Case
• 13 yearsi old girl is brought to the emergency departement by her parents because they think she has been “ acting strangely “ and “ breathing too fast “ for the past several days . She has not been “ herself “ recently and has complained of fatique , abdominal pain , and increased thirst . Parents think that she is acting out , because she is upset about being prevented from attending the yunior high dance . The emergency departement physican thinks that is appropriate the rule out diabetes
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Questions
• A. what question should the physician ask to clarify the diagnosis and plan evaluation
• B. what finding on physical examination are consistent with DKA ?
• C. why does the emergency departement physician suspect DKA in this patient ?
• D, what laboratory test should be ordered for this patient ?
• E. How will the physician differentiate type 1 diabetes from type 2 diabetes ?
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KEPUSTAKAAN
• PEDOMAN Klinis Pediatri , editor M. william Schwartz , Penerbit Buku Kedokteran EGC
• Konsensus Nasional Pengelolaan Diabeter Mellitus tipe 1 , UKK Endokrinologi anak dan remaja Ikatan Dokter Anak Indonesia , World Diabetic Foundation 2009
• Pedoman pelayanan medis IDAI 2010