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DIABETES MELLITUS

Yulianto Kusnadi
Endocrine organs – endocrine glands

• Brain
- Anterior pituitary gland (ACTH), TSH, LH, FSH, GH, PRL
- Posterior pituitary gland (ADH, oxytocin)
- Hypothalamus (Releasing and inhibitory factors that that
regulate secretion of the anterior pituitary hormones
- Pineal gland (melatonin)

• In the periphery
- Thyroid gland (thyroid hormones)
- Parathyroid gland (parathyroid hormone [PTH])
- Adrenal gland (corticosteroids, epinephrine)
- Ovaries and testis (sex steroids)
- Pancreas (insulin, glucagon and somatostatin)
Anatomy of Pancreas
Anatomy of Pancreas
Sejarah Diabetes Melitus (DM)
• Pertama kali diketahui di Mesir (1500 SM),
Yunani, India dan Cina
• Asal kata :
Diabere (tabung)
 mengalirkan daging dan tungkai
yang meleleh ke urine
Mellitus (madu)
 urine digelimangi madu dan gula
• Diabetes melitus  kencing manis
Top 10 countries for numbers of people aged 20–79 years with
diabetes in 2010 and 2030

Shaw JE, et al. Diabetes Research and Clinical Practice. 2010;87:4-14.


Indonesia

Prevalence of IGT, DDM, UDDM and Total DM in Urban


Indonesia, Riskesdas 2007

Mihardja L et al. Acta Med Indones-Indones J Intern Med. 2009;41(4):169-74.


Definition

•Diabetes mellitus is a group of metabolic


diseases characterized by hyperglycemia
resulting from defects in insulin secretion,
insulin action, or both

American Diabetes Association, 2012


Classification of DM

• Type 1 DM
• Type 2 DM (80-90%)
• Other types of DM
• Gestational DM
Etiology of diabetes
• Type 1 DM:
- Genetic
- Autoimmune

• Type 2 DM
- Genetic
- Lifestyle
Glukosa
Insulin

Receptor Insulin

GLUT - 4
Auto phosphorilation
Prot Tyrosine phosphorilation
GLUT 4 Kinase B
Phosphoinositide IRS
p110 p85
Dependent-Kinase
GLUT - 4 Atypical Phosphoisnositide-3
PK C Kinase
PPARg + RXR

GLUT - 4 GLUT - 4
mRNA
PPRE

transcription
Muscle cell Cell wall
Glukosa
Insulin

Receptor Insulin

Auto phosphorilation
Serine phosphorilation

PPARg + RXR

mRNA
PPRE

transcription
Muscle cell Cell wall
Pathogenesis of type 2 diabetes
Pathogenesis of type 2 diabetes: the ominous octet
Adapted from DeFronzo RA. Diabetes. 1988;37:667-87.
Consequencies of insulin resistance:
1. Hyperglycemia
2. Glucosuria
3. Loss of energy
4. Lipolysis
Signs and Symptoms
of Diabetes
Polyphagia, polydipsi

Colo-colo
Polyuria
Weight loss
Fatique
Neuropathic symptoms
Itching
Visual disturbance
Wounds
Giant baby (> 4 kg)
Libido , ED
Diagnostic criteria of DM
• Random BG > 200 mg/dL + Classical symptoms
• Fasting BG > 126 mg/dL
• OGTT > 200 mg/dl
(75-g OGTT)
• HbA1C > 6,5%
Risk factors of DM
• Age > 30 y.o.
• BW > 110% ideal BW
• Hypertension (BP > 140/90 mmHg)
• Family history of DM
• Recurrent stillbirth, giant baby
• HDL-cholesterol < 35 mg/dL,
trygliceride > 250 mg/dL
Diabetic Complications
Possible Pathogenesis of Diabetic Complications

Overall Glycemic Control (HbA1c)

Hyperglycemic "Peaks" Fasting/Preprandial glucose


elevations

Acute toxicity Chronic toxicity

Tissue lesion

Complications
Diabetic complication
Acute:
1. Diabetic ketoacidosis
2. Hyperosmolar Hyperglycemia
State
3. Hypoglicemia

Chronic:
1. Angiopathy
Macro: stroke, CAD, Diabetic foot
Micro: retinopathy, nephropathy

2. Neuropathy
Peripher: pain, paresthesia,
numbness
Autonom: ED, CDM, gastropathy
Normal

Retinopathy
Katarak
Treatment Modalities
Summary of glucose-lowering interventions
Intervention Expt. decreased in Advantages Disadvantages
A1C (%)
Lifestyle 1.0-2.0 Broad benefits Insufficient for most within first year

Metformin 1.0-2.0 Weight neutral GI side effects, contraindicated with renal


insufficiency

Insulin 1.5-3.5 No dose limit, rapidly effective, 1-4 injections daily, monitoring, weight gain,
improved lipid profile hypoglycemia, analogues are expensive

Sulfonylurea 1.0-2.0 Rapidly effective Weight gain, hypoglycemia (especially with


glibenclamide or chlorpropamide)

TZD 0.5-1.4 Improved lipid profile Fluid retention, CHF, weight gain, bone fractures,
(pioglitazone), potential expensive, potential increase in MI (rosiglitazone)
decrease in MI (pioglitazone)
GLP-1 agonist 0.5-1.0 Weight loss Two injections daily, frequent GI side effects, long-
term safety not established, expensive

Acarbose 0.5-0.8 Weight neutral Frequent GI side effects, three times/day dosing,
expensive

Glinide 0.5-1.5 Rapidly effective Weight gain, three times/day


dosing, hypoglycemia,
expensive
Pramlintide 0.5-1.0 Weight loss Three injections daily, frequent GI side effects,
long-term safety not established, expensive

DPP-4 inhibitor 0.5-0.8 Weight neutral Long-term safety not established, expensive

Nathan DM, et al. Diabetes Care. 2008;31:1-11.


ADA/EASD ALGORITHM FOR THE MANAGEMENT OF
TYPE 2 DIABETES (2009)
Tier 1: well-validated therapies
Lifestyle + Metformin Lifestyle + Metformin
At diagnosis: + Basal insulin + Intensive insulin
Lifestyle + Metformin
Lifestyle + Metformin
+ Sulfonylureas
STEP 1 STEP 2 STEP 3

Tier 2: Less well validated therapies

Lifestyle + Metformin
Lifestyle + metformin
+ Pioglitazone
+ Pioglitazone
No hypoglycaemia
Oedema/CHF + Sulfonylurea
Lifestyle + metformin
Bone loss
Lifestyle + metformin
+ GLP-1 agonist + Basal insulin
No hypoglycaemia
Weight loss
Nausea/vomiting

Nathan DM, et al. Diabetes Care. 2009;32(1):193-203.


Konsensus PERKENI 2011

Indonesian Vildagliptin Product Information, 2007.

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