DIABETES MELLITUS (DM)

 DM is a metabolic disorders characterized by

hyperglycemia because of resistance to the action
of insulin, insufficient insulin secretion, or both,
associated with abnormalities in carbohydrate,
fat, and protein metabolism and results in
chronic complications including microvascular,
macrovascular, and neuropathic disorders
( Dipiro et al, 2008)
DM  ENDOCRINOLOGY DESEASE
 Endocrine :
1. Glandula Suprarenalis (a. korteks & a. medula)
2. Paratiroid hormon
3. Tiroid
4. Reproduction Hormon
5. Hipofisis/ Glandula pituitari (GH, LH, ACTH,
dll)
6. Pankreas
PANKREAS : 4 CELLS

 A cell  synthesis dan secreting glucagon, GLP-1

dan GLP-2
 B cell  synthesis insulin, amyllin, GABA
(GABA can inhibits the release of glucagon)
 D cell  produce somatostatin

 F cell ( pancreatic polypeptide / PP)

HOMEWORK PLEASE..............
Hormon Action
A. Insulin 1. Can reduce blood glucose
by...........................
2. Can increasing in lipogenesis by.............
3. For synthesis protein ( A & K)

Stimulate by increase of blood glucose, ACTH,

glukagon,.......................
Inhibits by somatostatin
B. Glukagon …………
C. Somatostatis ………………….
D. PP
E. amyllin
F. adiponectine
G. GLP
TYPE OF DM
 DM type 1  results from autoimmune destruction of
the β cells of the pancreas  deficiency insulin absolut
 DM type 2  resistance to the action of insulin,
insufficient insulin secretion, or both
 DM Gestational  pregnancy (hormonal ) what
hormon??? how???
 Other type  Genetic, drug induce, sindrom of desease
( pancreatitis, acromegaly, etc)

 What kind of drug that induced DM?

CRITERIA FOR THE DIAGNOSIS OF DM

 Symptoms of diabetes  Polyuria, Polydipsia,

Polyphagia and weight loss
 Plus one or two part of
 Casual plasma glucose concentration (GDA) ≥ 200 mg/dL
(11.1 mmol/L)
or
 Fasting plasma glucose (GDP) ≥126 mg/dL (7.0 mmol/L)
or
 2-Hour postload glucose (GD2PP) ≥ 200 mg/dL (11.1 mmol/L)
during an OGTT

 GDA : Gula Darah Acak

 GDP : Gula Darah Puasa
 GD2PP : Gula Darah Post Prandial
 OGTT (TTGO) : Tes Toleransi Glukosa Oral
PATOPHYSIOLOGY
DEFECT OF INSULIN SECRETION
 Normally, The β cell pancreas is able to adjust its secretion of
insulin and Amylin to maintain normal glucose tolerance .
 Insulin lowers blood glucose by a variety of mechanisms including:
(a) stimulation of tissue glucose uptake,
(b) suppression of glucose production by the liver,
(c) and suppression of free fatty acid release from fat cells  The
suppression of free fatty acids plays an important role in glucose
homeostasis.
 Amylin, a glucoregulatory peptide hormone cosecreted with
insulin, plays a role in lowering blood glucose by slowing gastric
emptying, suppressing glucagon output from pancreatic α cells,
and increasing satiety
 Insulin is increased about 73% in proportion to the severity of the
insulin resistance, and glucose tolerance remains normal.
 In the type 2 diabetic patient, decreased postprandial insulin
secretion is caused by both impaired pancreatic β-cell
function and a reduced stimulus for insulin secretion from
gut hormones ( incretin effect is blunted with the increase in
insulin secretion to only 50% ).
 LANJUTAN PATOFISIOLOGI
INSULIN RESISTANCE
 Weight gain leads to insulin resistance and a progressive loss of insulin
sensitivity when the BMI increased from 18 kg/m2 to 38 kg/m2.
 The increase in insulin resistance with weight gain is directly related to the
amount of visceral adipose tissue (VAT) refers to fat cells located within the
abdominal cavity and includes omental, mesenteric, retroperitoneal, and
perinephric adipose tissue.
 This fat tissue has been shown to have a higher rate of lipolysis than
subcutaneous fat, resulting in an increase in FFA production (released into
the portal circulation and drain into the liver  stimulate the production of
very low density lipoproteins (VLDL) and decrease insulin sensitivity in
peripheral tissues.
 VAT also produces a number of cytokines that cause insulin resistance with
weight gain is directly related to the amount of visceral adipose tissue
resistance.
 These factors drain into the portal circulation and reduce insulin sensitivity in
peripheral tissues
 The fat cell also has the capability of producing at least one hormone that
improves insulin sensitivity: adiponectin decreasing amounts as an
individual becomes more obese.
 In animal models, adiponectin decreases hepatic glucose production
and increases fatty acid oxidation in muscle
ABNORMALITIES METABOLISME
 Carbohidrat metabolisme in Normally : Insuline have
effect in
 increasing ( glycogenesis, glycolysis) ;
 decreasing ( glycogenolisis & glukoneogenesis)
 Protein metabolisme in normally  Insuline have effect
in
 increasing protein synthesis ;
 decreasing proteolysis
 Lipid Metabolisme in normally: Insuline have effect in

 normal lipolysis on diet; Lipogenesis

 decreasing Ketogenesis
In DM  increasing fat catabolisme  release asetil Co
A >> is not accomodate in Krebs Cycle  keton bodies
(ketoacidosis)
SYMPTOM OF DM (HIPERGLIKEMI)
 Polyuri
 Polidipsi

 Polifagi

How could those things happen?

( Greene and harris, 2008)

PERKENI
 INSULIN
Insulin diperlukan pada keadaan :
 HbA1c > 9% dengan kondisi dekompensasi metabolik

 Penurunan berat badan yang cepat

 Hiperglikemia berat yang disertai ketosis

 Krisis Hiperglikemia

 Gagal dengan kombinasi OHO dosis optimal

 Stres berat (infeksi sistemik, operasi besar, infark

miokard akut, stroke)
 Kehamilan dengan DM/Diabetes melitus gestasional yang
tidak terkendali dengan perencanaan makan
 Gangguan fungsi ginjal atau hati yang
berat
 Kontraindikasi dan atau alergi terhadap OHO

 Kondisi perioperatif sesuai dengan indikasi

JENIS DAN LAMA KERJA INSULIN

Berdasarkan lama kerja, insulin dibagi

menjadi 5 jenis :
 Insulin kerja cepat (Rapid-acting insulin)

 Insulin kerja pendek (Short-acting insulin)

 Insulin kerja menengah (Intermediateacting insulin)

 Insulin kerja panjang (Long-acting insulin)

 Insulin kerja ultra panjang (Ultra longacting insulin)

Insulin campuran tetap, kerja pendek dengan menengah

dan kerja cepat dengan menengah (Premixed insulin)
FARMAKOKINETIK INSULIN EKSOGEN BERDASARKAN WAKTU KERJA
(TIME COURSE OF ACTION)
COMPLICATION OF DM
ACUTE COMPLICATIONS
CHRONIC COMPLICATIONS