2. Topik Bahasan
• Definisi
• Etiologi
• Patofisiologi
• Deteksi/Pengukuran
• Zat-zat yang memiliki efek baik: Magnesium,
Leusin
• Resistensi Insulin Akut dan Surgical Diabetes
3. Definisi Resistensi Insulin
• Jumlah normal insulin tidak memadai untuk
menghasilkan respons insulin normal dari sel
lemak, sel otot dan sel hati. RI kronik sering
merupakan bagian dari Sindrom Metabolik.
Sel
lemak
Sel
otot
Sel
Hati
FFA plasma
Glukosa plasma
Glukosa plasma
4. Topik Bahasan
• Definisi
• Etiologi
• Patofisiologi
• Deteksi/Pengukuran
• Zat-zat yang memiliki efek baik: Magnesium,
Leusin
• Resistensi Insulin Akut dan Surgical Diabetes
6. Sebab-sebab lain
• Insulin eksogen: dulu pork insulin sering menghasilkan
pembentukan antibodi terhadap insulin. Sekarang tidak lagi
dg adanya insulin analogue
• Berkurangnya reseptor glukosa GLUT-4
pada membran sel
• faktor genetik
• Kurang aktivitas fisik (sedentary life style)
7. Topik Bahasan
• Definisi
• Etiologi
• Patofisiologi
• Deteksi/Pengukuran
• Zat-zat yang memiliki efek baik: Magnesium,
Leusin
• Resistensi Insulin Akut dan Surgical Diabetes
8. Progresi ke Diabetes
Genetik
Lingkungan
Imbang Energi Positif
Kurang aktifitas fisik
Resistensi Insulin & kegagalan sel
DM Tipe 2
9. Curigai Resistensi Insulin
• Body Mass Index* >25 (normal 18.5-24.9)
• IGT (impaired glucose tolerance test)
• Gula darah puasa 100mg/dl to 125mg/dl
• Lingkar pinggang > 94 cm
•Riwayat Keluarga DM tipe 2 diabetes,
Hipertensi
•atau arteriosclerosis
•Diabetes gestasional
•TD tinggi, Trigliserida tinggi, low HDL-C
•Acanthosis Nigricans
Catatan: Resistensi Insulin akut bisa terjadi pada trauma, stroke akut dan bedah mayor
10.
11. Beda Male obesity dan Female obesity
Visceral fat (central obesity) subcutaneous fat
Sel lemak viseral menghasilkan
sitokin pro-inflamatorik (TNF-Alfa,
Interleukin 1, Interleukin 6) yang meru
pakan hormon kontraregulatorik, melawan
efek insulin. Sitokin ini dinamakan juga
adipositokin.
Sel lemak subkutan tidak menghasilkan
sitokin pro-infamatorik
12. Metabolic Syndrome
Central obesity (defined as waist circumference ≥ 94cm for Europid men and ≥ 80cm
for Europid women, with ethnicity specific values for other groups)
plus any two of the following four factors:
• raised TG level: ≥ 150 mg/dL (1.7 mmol/L), or specific treatment for this
lipid abnormality
• reduced HDL cholesterol: < 40 mg/dL (1.03 mmol/L*) in males and < 50
mg/dL (1.29 mmol/L*) in females, or specific treatment for this lipid
abnormality
• raised blood pressure: systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg, or
treatment of previously diagnosed hypertension
• raised fasting plasma glucose (FPG) ≥ 100 mg/dL (5.6 mmol/L), or
previously diagnosed type 2 diabetes
If above 5.6 mmol/L or 100 mg/dL, OGTT is strongly recommended but is not
necessary to define presence of the syndrome.
The IDF (international Diabetic Federation)consensus worldwide definition of the metabolic
syndrome
13. Cut-off utk orang Asia berbeda
• Lingkar pinggang > 85 cm (laki) dan > 80 cm
(wanita)
• Waist-hip ratio (rasio lingar pinggang dan
pinggul) 0,9 dan 0,8 masing-masing untuk pria
dan wanita
Diduga karena proporsi lemak viseral pada orang asia lebih tinggi!!!
14. Topik Bahasan
• Definisi
• Etiologi
• Patofisiologi
• Deteksi/Pengukuran
• Zat-zat yang memiliki efek baik: Magnesium,
Leusin
• Resistensi Insulin Akut dan Surgical Diabetes
15. Deteksi/Pengukuran
(jarang di klinik, hanya utk penelitian)
1. HOMA (model homeostatik penilaian), dengan menggunakan rumus:
Io x Go
405
di mana
Io = kadar insulin puasa (μU / ml); Go Glukosa puasa (mg/dl)
nilai normal 100%
2. Rasio G / I . Rasio < 4,5 menunjukkan adanya IR
3. Insulin serum puasa (Io). Normal batas atas insulin serum puasa adalah 60
pmol / L atau 8,6 μU / ml. Konsentrasi di atas 20 μU / ml menegaskan
kehadiran IR
16. Topik Bahasan
• Definisi
• Etiologi
• Patofisiologi
• Deteksi/Pengukuran
• Zat-zat yang memiliki efek baik: Magnesium,
Leusin
• Resistensi Insulin Akut dan Surgical Diabetes
17. Mg++
• Kadar Mg intraselular yang kurang, seperti yang ditemukan
pada diabetes mellitus tipe 2 dan pada pasien hipertensi,
dapat mengakibatkan defek aktivitas tirosin kinase di
tingkat reseptor insulin dan konsentrasi kalsium intraseluler
yang berlebihan. Kedua kejadian ini bertanggung jawab
atas kerusakan dalam aksi insulin dan memburuknya
resistensi insulin dalam DM tipe 2 dan hipertensi.
• Sebaliknya, pemberian Mg setiap hari ke pasien DM tipe 2,
memulihkan kadar Mg intraselular. Ini berkontribusi
meningkatkan ambilan glukosa yang dimediasi insulin.
• Manfaat suplemen Mg harian pada pasien T2DM lebih
lanjut didukung oleh penelitian epidemiologi yang
menunjukkan bahwa asupan Mg harian tinggi memiliki nilai
prediktif menurunkan insiden DM tipe 2
18. Leucine
Asupan Leusin bersama glukosa akan
secara sintergis merangsang sekresi
insulin dan merendahkan gula darah
Metabolism. 2008 Dec;57(12):1747-52.
19. Topik Bahasan
• Definisi
• Etiologi
• Patofisiologi
• Deteksi/Pengukuran
• Zat-zat yang memiliki efek baik: Magnesium,
Leusin
• Resistensi Insulin Akut dan Surgical Diabetes
20. Resistensi Insulin Akut
• Resistensi insulin yang terjadi pada penyakit
kronis, seperti diabetes tipe 2, obesitas dan
hipertensi, biasanya memakan waktu berbulan-bulan,
bertahun-tahun atau bahkan puluhan
tahun untuk berkembang.
• Hiperglikemia dan resistensi insulin pada pasien
sakit kritis ditandai dengan onset cepat,
berkembang dalam hitungan menit, jam atau
hari, dan dengan demikian disebut resistensi
insulin akut.
23. (1,2) (3) (4,5)
Glucose containing
maintenance solution
Pre
operative
Intra-operative
Post-operative
Preop nutrition or
Carbohydrate
Load 800 ml + 200 ml
Intraop isotonic
crystalloid
> 12-14 ml/kg/hr
Postop Maintenance
fluid
< 30 ml/kg/24 hr; Na+
60-100 mEq
or
preop
glucose
prevents/mi
nimizes post
op insulin
resistance
1. Nygren J. Best Practice & Research Clinical Anaesthesiology Vol. 20, No. 3, pp. 429e438, 2006
2. Fearon KCH. Enhanced recovery after surgery: A consensus review of clinical care for patients undergoing colonic resection Clinical
Nutrition (2005) 24, 466–477
3. Futier E et al. Conservative vs Restrictive Individualized Goal-Directed Fluid Replacement Strategy in Major Abdominal Surgery. Arch Surg.
2010;145(12):1193-1200
4. Lobo DN et al.Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection. Lancet 2002 May
25.359(5320):1792-3
5. Brandtsruo B. Fluid therapy for the surgical patient. Best Practice & Research Clinical Anaesthesiology Vol. 20, No. 2, pp. 265–283, 2006
Editor's Notes
Metabolism. 2008 Dec;57(12):1747-52.
Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose.
Kalogeropoulou D, Lafave L, Schweim K, Gannon MC, Nuttall FQ.
Source
Endocrine, Metabolism and Nutrition Section, VA Medical Center, Minneapolis, MN 55417, USA.
Abstract
Our laboratory is interested in the metabolic effects of ingested proteins. As part of this research, we currently are investigating the metabolic effects of ingested individual amino acids. The objective of the current study was to determine whether leucine stimulates insulin and/or glucagon secretion and whether, when it is ingested with glucose, it modifies the glucose, insulin, or glucagon response. Thirteen healthy subjects (6 men and 7 women) were studied on 4 different occasions. Subjects were admitted to the special diagnostic and treatment unit after a 12-hour fast. They received test meals at 8:00 am. On the first occasion, they received water only. Thereafter, they received 25 g glucose or 1 mmol/kg lean body mass leucine or 1 mmol/kg lean body mass leucine plus 25 g glucose in random order. Serum leucine, glucose, insulin, glucagon, and alpha-amino nitrogen concentrations were measured at various times during a 2.5-hour period after ingestion of the test meal. The amount of leucine provided was equivalent to that present in a high-protein meal, that is, that approximately present in a 350-g steak. After leucine ingestion, the leucine concentration increased 7-fold; and the alpha-amino nitrogen concentration increased by 16%. Ingested leucine did not affect the serum glucose concentration. When leucine was ingested with glucose, it reduced the 2.5-hour glucose area response by 50%. Leucine, when ingested alone, increased the serum insulin area response modestly. However, it increased the insulin area response to glucose by an additional 66%; that is, it almost doubled the response. Ingested leucine stimulated an increase in glucagon. Ingested glucose decreased it. When ingested together, the net effect was essentially no change in glucagon area. In summary, leucine at a dose equivalent to that present in a high-protein meal, had little effect on serum glucose or insulin concentrations but did increase the glucagon concentration. When leucine was ingested with glucose, it attenuated the serum glucose response and strongly stimulated additional insulin secretion. Leucine also attenuated the decrease in glucagon expected when glucose alone is ingested. The data suggest that a rise in glucose concentration is necessary for leucine to stimulate significant insulin secretion. This in turn reduces the glucose response to ingested glucose.
