Natural History of Type 2 DM

Normal islet cell

Deposition of amyloid
in T2DM


metabolic.Insulin Insulin actions actions include include :: •• Ability Ability of of insulin insulin to to lower lower circulating circulating glucose glucose concentrations concentrations  Suppress Suppress glucose glucose production production :: liver liver  Stimulate Stimulate glucose glucose utilization utilization :: muscle muscle plus plus fat fat •• Additional Additional metabolic. vascular vascular & & mitogenic mitogenic actions actions .

1921) Marjorie .Frederick Banting and Charles Best (Toronto.

Oral Insulin . Actrapid. Insulin History 1869 Found “Islets of Langerhans” 1921 – 1983 Years of animals insulin 1983 – 1996 Years of highly synthetic purified Human Insulin ( Mixtard. Insulatard ) 1996 Years of Insulin Analogues Future ? Inhaled.

Sejarah Perkembangan insulin  1921 : penemuan insulin  s/d 1983 : era insulin hewan Menggunakan ekstrak pankreas hewan (sapi / babi)  1983 : era Human insulin Menggunakan rDNA manusia untuk menghasilkan insulin  1999 : era insulin modern (analog) dimulai Menggunakan teknologi bioengineering untuk memodifikasi rantai DNA human insulin untuk membuat insulin baru yang lebih baik dalam hal farmakologi Saccharomyces cerevisiae .

Disadvantage of Human Insulin Period of unwanted hyperglycemia Normal insulin secretion at mealtime Change in serum insulin Human insulin Period of unwanted hypoglycemia Baseline level Time (h) SC injection .

Structural Design Human InsulinNovoRapid (Insulin A mir (Insulin Detemir) C1 Asp 4 cha fatt ya (My in cid ri s Phe Gly tic Phe Arg ac Glu id) Tyr Thr Gly Pro Pro Cys Lys Thr Val B29 A21 Asn Cys Tyr Leu Gly Lys A1 Asn Tyr Ile Glu Leu Val Leu Ala Glu Gln Glu Gln Tyr Val Cys Leu Leu Cys Thr Ser Ile Cys Ser His Ser Gly Cys Leu B1 Phe Val Asn Gln His .

Structural Design Human Insulin Insulin Lispro (Humalog) Insulin glargine (Lantus ) Phe Gly Arg Phe Tyr Glu Thr Gly Pro Pro Cys Arg Lys Arg Thr Val B29 A21 Asn Cys Tyr Leu A1 Gly Asn Tyr Ile Glu Leu Gly Val Leu Ala Glu Gln Glu Gln Tyr Val Cys Leu Leu Cys Thr Ser Ile Cys Ser His Ser Gly Cys Leu B1 Phe Val Asn Gln His .

Change in serum insulin A More Physiologic Insulin Normal insulin secretion at mealtime Novorapid Baseline Level Time (h) SC injection .

NovoRapid NovoMix Makan Makan Makan Sebelum tidur Pagi Siang Malam . Insulin endogen Levemir ---.Profil Insulin Analog sangat mirip dengan Insulin Endogen ---.

New treatment paradigms for type 2 diabetes Stepwise treatment Diet/ Oral Oral Oral Insulin exercise monotherapy combination +/.insulin Early aggressive combination therapy .

Proactive management of glycaemia: early combination approach Diet and exercise OAD monotherapy 10 OAD combinations OADs uptitration HbA1c (%) 9 OAD + basal insulin OAD + multiple daily insulin injections 8 HbA1c = 7% 7 HbA1c = 6. . Int J Clin Pract 2000.5% 6 Duration of diabetes *OAD = oral anti-diabetic Del Prato S et al. 7: 625–31.

TIPE INSULIN Tipe Insulin Onset Peak/Puncak Duration Duration (Jam) (Jam) Efektif Maksimal Rapid Acting Human Lyspro 0.0 2–3 4–6 5–7 Intermediate Acting Human NPH 2–4 4 – 10 10 – 16 14 – 18 Human Lente 3–4 4 – 12 12 – 18 16 – 20 Long Acting Human Ultralente 6 – 10 14 – 24 18 – 20 20 .5 <5 4–5 Human Aspart <0.5 0.36 Insulin Glargine 2-4 Peakless 20 -24 Combinations Mixtard Novomix .5 – 2.25-0.5 – 1.20 1–3 3–5 Short Acting Human Regular 0.

Indications of Insulin Treatment Indication for the use of insulin in Type 2 DM •• In In severe severe metabolic metabolic decompensation decompensation •• Ketoacidosis Ketoacidosis •• Hyperosmolar Hyperosmolar non non ketotic ketotic coma coma •• Lactic Lactic acidosis acidosis •• Severe Severe stress stress :: Systemic Systemic infection infection Major Major surgery surgery •• Weight Weight loss loss within within aa short short period period of of time time •• Pregnancy Pregnancy ifif diet diet does does not not succeed succeed toto control control glycemia glycemia •• OHA OHA failure failure or or contra-indication contra-indication ofof OHA OHA .

with natural secretory pattern Biguanide Plus Insulin Reduces hepatic insulin resistance May achieve better control with less insulin Can reduce weight gain Alpha Glucosidase Inhibitor Plus Insulin Reduces posotprandial glucose level Thiazolidinedione Plus Insulin Reduces peripheral insulin resistance Reduces insulin requirement Must balance TZD and insulin carefully to minimize weight gain .Combination Therapy in T2DM: Insulin Plus Oral Hypoglycemic Agents Insulin Plus Sulphonylurea .BIDS Some insulin is endogenous.

patients patients continue continue the the oral oral drugs drugs •• less less // minimal minimal education education is is needed needed •• treatment treatment can can bebe started started inin an an •• outpatients-setting outpatients-setting •• better better compliance.Benefits Benefits of of Insulin Insulin and and Oral Oral Agents Agents Combination Combination •• Improves Improves glycemic glycemic control control Treats Treats multiple multiple physiologic physiologic abnormalities abnormalities •• Less Less insulin insulin is is needed needed to to achieve achieve good good glycemic glycemic control control •• Reduces Reduces potensial potensial for for weight weight gain gain •• Patients: Patients: •• more more practical practical and and less less frightening frightening •• improved improved psychological psychological acceptance. compliance. and and cost cost may may be be less less . acceptance.

http://www.aace.5% Fasting Gluc <100 <110 90-130 <110 80-110 PP (2h) Gluc <140 <155 <180 <140 80-145 * Realistic Target: Lowest A1c possible without unacceptable adverse effects  IDF = International Diabetes Federation  ADA = American Diabetes Association.49:1711-21.pdf . 3.5% <7% <6. Glycemic Control: Recommended goals Measurement Normal IDF1 ADA/EASD2 AACE3 PERKENI A1c* <6% <6. Nathan DM et 2.  AACE = American Association of Clinical Endocrinology 1. Global guideline for type 2 diabetes clinical guidelines taskforce (Brussels: IDF.5% <6. Diabetologia 2006.

When to Start Insulin Therapy ? .

insulin can be initiated earlier. as soon as is required. Insulin can be initiated anytime • Traditionally. insulin had been reserved as the last line of therapy • Considering the benefits of normal glycemic status. + + 3 OAD Inadequate + Lifestyle 1 OAD 2 OAD Initiate Insulin Indication: Permanent Not permanent T1DM Infection OAD failure Pregnancy OAD Contra Indication Hospitalized Diabetic Ketoacidosis Perioperative .

How to Start Insulin Therapy ? .

premix insulin (NovoMix) . If Fasting and Post Prandial are elevated : . If Fasting BG is elevated. If Prandial BG is elevated. start for basal insulin with long acting insulin (Levemir) 2.1.Oral agent with basal insulin .basal/bolus as in multiple daily injection (MDI) . start for prandial /bolus insulin with rapid acting insulin (NovoRapid) 3.

first Continue oral agent SMBG is important Basal Insulin (Levemir) Prandial Insulin (NovoRapid) . Treatment Based on Type of Hyperglycemia BASAL – PRANDIAL CONCEPT Fasting Hyperglycemia Prandial Treat fasting hyperglyc.


The Novo Syringe 1925 – First home use syringe .



Insulin Injection Development 1989 1920s 1925 1960 From syringes to safe and convenient portable 1985pens with insulin cartridges More insulin pen introductions in the 1990’s .


Suntikan pada Daerah gluteus .

Daerah pantat ( gluteus ) .Lokasi penyuntikan : 1. Abdomen (kec. Paha atas bagian depan 3. 2 inci dari pusat) 4. Lengan atas bagian luar 2.

Cara mengkocok Insulin sebelum injeksi .

Teknik Injeksi Insulin pada Lengan atas bagian luar .

Contoh cara penyuntikan pada abdomen .

5 mm 6 mm needle 8 mm 12 mm needle . NovoFine 6 mm – safe and effective deposition 2.

! It hurts ! Expensive ! Drug addiction ? .Kendala dalam terapi Insulin I don’t want it.