3. Biosynthesis
• produced in the beta cells of the pancreatic islets
• initially synthesized as a single-chain 86-amino-acid precursor
polypeptide, preproinsulin
• Subsequent proteolytic processing removes the aminoterminal
> proinsulin
• Cleavage of an internal 31-residue fragment from proinsulin,
generates
• C peptide and the A (21 amino acids) and B (30 amino
acids) chains of insulin
• The mature insulin molecule and C peptide
• stored and secreted from secretory granules in the beta cells
4. Secretion
Mechanisms of glucose-stimulated insulin secretion and abnormalities in diabetes
• Glucose regulate insulin secretion by the
pancreatic beta cell
• Glucose is transported by a glucose
transporter (GLUT1 in humans, GLUT2 in
rodents
• glucose metabolism by the beta cell
alters ion channel activity
• leading to insulin secretion
7. DEFENITION
• Diabetes mellitus (DM) refers to a group
of common metabolic disorders that
share the phenotype of hyperglycemia
• Distinct types of DM are caused by
genetics and environmental factors
• factors contributing to hyperglycemia
include :
• reduced insulin secretion
• decreased glucose utilization
• increased glucose production
• leading cause of end-stage renal
disease (ESRD), non- traumatic lower
extremity amputations, and adult
blindness
8. CLASSIFICATION
• DM is classified on the basis of the pathogenic process that leads to
hyperglycemia, as opposed to earlier criteria such as age of onset or type of
therapy
• The two broad categories of DM are designated type 1 and type 2
• Both preceded by a phase of abnormal glucose homeostasis
• Type 1 DM is the result of complete or near-total insulin defi
ciency
• Type 2 DM heterogeneous group characterized by variable degrees
• insulin resistance
• impaired insulin secretion
• increased glucose production
9. CLASSIFICATION
• Two features of the current
classification of DM diverge
• insulin-dependent
diabetes mellitus (IDDM)
• non-insulin-dependent
diabetes mellitus
(NIDDM)
• Type 2 DM eventually require
insulin treatmeant for control of
glycemia
• type 1 DM most commonly
develops before the age of 30,
an autoimmune beta cell
destruction
11. RISK FACTOR
• The overweight group (BMI > 23
kg/m2)
• Less physical activity
• Families with a history of
DM
• Newborn's weight > 4k
• Hypertension (>140/90)
• HDL <35mg/dl atau
trigliserida >250 mg/dl
• Usia > 45 tahun
• Polycystic ovary syndrome or
acanthosis nigricans
• History of cardiovascular disease
12. Etiologic Classification of Diabetes Mellitus
• Type 1 diabetes (beta cell destruction, usually leading to absolute insulin deficiency)
• Immune mediated
• Idiopathic
• Type 2 diabetes (insulin resistance with relative insulin deficiency to insulin secretory
defect)
• Other specific types of diabetes
• Genetic defects of beta cell function characterized by mutations in
• Hepatocyte nuclear transcription factor (HNF) 4α (MODY 1)
• Glucokinase (MODY 2)
• HNF-1α (MODY 3)
• Insulin promoter factor-1 (IPF-1; MODY 4)
• Genetic defects in insulin action
• Type A insulin resistance
13. Etiologic Classification of Diabetes Mellitus
• Diseases of the exocrine pancreas
• (pancreatitis, pancreatectomy,
neoplasia, cystic fibrosis,
hemochromatosis)
• Endocrinopathies
• (acromegaly, Cushing’s
syndrome, glucagonoma,
pheochromocytoma)
• Drug or chemical induced
• (glucocorticoids, vacor (a
rodenticide), pentamidine,
nicotinic acid)
• Gestational diabetes mellitus
(GDM)
15. Clinical Manifestation
Patients with diabetes mellitus most
commonly present with :
• increased thirst
• increased urination
• lack of energy and fatigue
• bacterial and fungal infections
• delayed wound healing
Some patients can also complain of
numbness or tingling in their hands or
feet or with blurred vision.
• can have modest hyperglycemia >
proceed to severe hyperglycemia or
ketoacidosis due to infection or stress
17. Pathophysiology
In T1DM
• cellular-mediated, autoimmune destruction of pancreatic beta cells
• Has a strong genetic predisposition
• The major histocompatibility complex (MHC) > reported for approximately 40
to 50% of the familial aggregation of T1DM
• The significant determinants > polymorphisms of class II MHC genes
encoding DQ and DR4-DQ8, with DR3-DQ2 > found in 90% of T1DM
patients
• destruction is generally rapid in children and faster in adults
• Autoantibodies against islet cells, insulin, glutamic acid decarboxylase-65
(GAD-65), and zinc transporter 8 (Zn T8) may be detected in the serum of
such patients
• These patients are generally not obese
18. Pathophysiology
In T1DM
• more prone to develop other autoimmune disorders such as Addison disease,
Graves disease, Hashimoto thyroiditis, and celiac disease
20. Diagnosis
Diabetes can be diagnosed either by the hemoglobin A1C criteria or plasma glucose
concentration (fasting or 2-hour plasma glucose)
• Fasting Plasma Glucose (FPG)
• A blood sample is taken after an 8 hour overnight fast
• fasting plasma glucose (FPG) level of more than 126 mg/dL (7.0 mm/L) >
consistent with the diagnosis
• Two-Hour Oral Glucose Tolerance Test (OGTT)
• measured before and 2 hours after the ingestion of 75 gm of glucose
• DM is diagnosed if the plasma glucose (PG) level in the 2-hour sample is
more than 200 mg/dL (11.1 mmol/L)
• atients need to consume a diet with at least 150 g per day of
carbohydrates for 3 to 5 days and not take any medications
21. Diagnosis
• Glycated Hemoglobin (Hb) A1C
• This test gives an average of
blood glucose over the last 2 to 3
months
• Hb A1C greater than 6.5% (48
mmol/mol) are diagnosed as
having DM
• Hb A1C is a convenient, rapid,
standardized test
• Hb A1C is costly and lower
sensitivity
• Anemia due to deficiency of
iron or vitamin B12 leads to
spurious elevation of Hb A1C
23. Differential Diagnosis
The list of differential diagnosis of diabetes mellitus consists of various conditions
that would exhibit similar signs and symptoms :
• Drug-induced signs and symptoms due to corticosteroids, neuroleptics,
pentamidine, etc.
• Genetic aberrations in beta-cell function and insulin action
• Metabolic syndrome (syndrome X)
• Infection
• Endocrinopathies such as acromegaly, Cushing disease, pheochromocytoma,
hypothyroidism, etc
• Complications of iron overload (hemochromatosis)
• Conditions affecting the exocrine part of the pancreas such as pancreatitis, cystic
fibrosis, etc.
25. Interaksi obat – tubuh
• Farmakokinetika (nasib obat dalam tubuh)
• Obat diberikan denga rute berbeda-beda
• Tempat kerja obat (target kerja obat)
• Absorbsi
• Distribusi
• Eleminasi
• Me
• Farmakodinamika (efek obat terhadap tubuh)
• obat harus berikatan dengan reseptor untuk menimbulkan efek
• Interaksi obat-reseptor
• Obat agonis/antagonis
• Lama kerja obat
27. Treatment / Management
• Principles of Management of type 2 DM
• Algorithm for Management of Type 2 DM Without Metabolic
Decompensation
• patient centered approach
• These considerations include the drug's effect on
cardiovascular and renal comorbidities, the effectiveness of
reducing blood glucose, the risk of hypoglycemia, the effect
on weight gain, the cost
31. Deterrence and Patient Education
• Patients must be educated about the importance of blood glucose
management to avoid complications associated with DM
• Stress must be given on lifestyle management, including diet control and
physical exercise
• Self-monitoring of blood glucose is an important means for their diabetes
management
• Healthcare professionals should educate patients about the symptoms of
hypoglycemia (such as tachycardia, sweating, confusion)
• Patients should be motivated to stop smoking
33. Complications
• uncontrolled diabetes mellitus can cause several complications, both acute
and chronic
• Diabetes mellitus is one of the leading causes of cardiovascular disease
(CVD), blindness, kidney failure, and amputation of lower limbs
• Acute complications include
• Hypoglycemia
• diabetic ketoacidosis
• hyperglycemic hyperosmolar state
• hyperglycaemic diabetic coma
• Chronic microvascular complications include
• nephropathy, neuropathy, and retinopathy
• Chronic macrovascular complications include :
• coronary artery disease (CAD), peripheral artery disease (PAD), and
cerebrovascular disease
36. Introduction
• Diabe(c Ketoacidosis is a medical emergency with a significant
morbidity and mortality
• It should be diagnosed promptly and managed intensively
• DKA is characterized by the triad of hyperglycemia, ketosis, and
acidosis
• DKA complicates mainly Type 1 diabetes
48. Prognosis
• DM is associated with increased atherosclerotic cardiovascular disease
(ASCVD)
• treating blood pressure, statin use, regular exercise, and smoking cessation
are of great importance in ameliorating risk
• The overall excess mortality in those with T2DM is around 15% higher
• The prevalence of vision-threatening diabetic retinopathy in the United
States is about 4.4% among adults with diabetes,
• hile it is 1% for end-stage renal disease
50. REFERENCES
1. Harrison's principles of internal medicine. (1998). New York
:McGraw-Hill, Health Professions Division,
2. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2
diabetes mellitus and its complications. Nat Rev Endocrinol. 2018
Feb;14(2):88-98.
3. Malek R, Hannat S, Nechadi A, Mekideche FZ, Kaabeche M. Diabetes and
Ramadan: A multicenter study in Algerian population. Diabetes Res Clin
Pract. 2019 Apr;150:322-330.
4. Hussain S, Chowdhury TA. The Impact of Comorbidities on the
Pharmacological Management of Type 2 Diabetes Mellitus. Drugs. 2019
Feb;79(3):231-242.
5. Martinez LC, Sherling D, Holley A. The Screening and Prevention of
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