DIABETES MELITUS

Yulianto Kusnadi
Agenda
• Anatomi dan fisiologi kelenjar pankreas
• Epidemiologi diabetes
• Definisi, klasifikasi, etiologi
• Gejala-gejala klinis diabetes
• Kriteria diagnosis dan faktor-faktor risiko
diabetes
• Manajemen diabetes
• Diabetes in specific condition
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

Alpha cell:
- Glucagon

Beta cell:
- Insulin

Delta cell: ?
Alpha cell > < Beta cell Contraregulatory
Glucagon > < Insulin hormone

Insulin  Gulcagon  Normoglycemia

Glucagon  Hyperglycemia
 Glukosa Insulin

Receptor Insulin

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

GLUT - 4 GLUT - 4
mRNA
PPRE

transcription
Sel Otot Dinding sel
Hyperglycemia

Diabetes
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
 Insulin Resistance

• A core defect in most T2DM patients

• Definition:
Impaired response to the physiological effects
of insulin, including those on glucose, lipid,
protein metabolism and vascular endothelial
function

Diab Care 1999;22:562

Diab Care 2000; 23(Suppl 1):54
 Glucose
Insulin

Insulin receptor

Auto phosphorilation
Serine phosphorilation

PPARg + RXR

mRNA
PPRE

transcription
Muscle cell Cell wall
 Insulin Resistance

Obesity is significantly associated with IR

due to:
- Sedentary
- Dietary factors
- Genetic factors

1
American Diabetes Association. Diabetes Care 1998
2
Beck-Nielsen et al. J Clin Invest 1994
3
Bloomgarden ZT Clin Ther 1996
 More than 80% of patients progressing to T2DM
are insulin resistant
Insulin sensitive;
low insulin secretion (16%)

Insulin resistant;
low insulin secretion (54%)
Insulin sensitive;
good insulin secretion
(1%)

83%
Insulin resistant;
good insulin secretion (29%)

Haffner SM, et al. Circulation 2000; 101:975–980.

Insulin Resistance Consequencies
• Decreased glucose uptake
• Increased lipolysis
• Increased hepatic glucose production
• Beta cell failure

Hyperglycemia
Pathogenesis of type 2 diabetes: the triumvirate
Pathogenesis of type 2 diabetes: the ominous octet
Adapted from DeFronzo RA. Diabetes. 1988;37:667-87.
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
Diagnosis Criteria
• Normal
- FBG: 70-99 mg/dL
- OGTT : 100-139 mg/dL
• Risk to diabetes (Prediabetes)
- IFG : 100-125 mg/dL
- IGT : 140-199 mg/dL
• Diabetes
- FBG: > 126 mg/dL
- OGTT : > 200 mg/dL
- RBG : > 200 mg/dL + classical symptoms
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,
triglyceride > 250 mg/dL
Diabetic Complications
Possible Pathogenesis of Diabetic
Complications

Overall Glycemic Control (HbA1c)

Hyperglycemic Fasting/Preprandial
"Peaks" glucose elevations

Acute toxicity Chronic toxicity

Tissue lesion

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

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

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

Retinopathy
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.

Konsensus PERKENI 2011

Indonesian Vildagliptin Product Information, 2007.

Diabetes and Pregnancy
• Pregnancy in diabetes
• Diabetes in pregnancy
Management of Hyperglycemia in
Pregnancy

• OAD?
- Limitation of study
• Insulin?
- Yes
Insulin use during pregnancy
• Insulin has been used in pregnancy since 1922
• It is essential for women with type 1 diabetes
• Insulin still widely considered the drug of
choice for women with either type 2 DM or
GDM who are not meeting treatment
goals with lifestyle modification and/or oral
glucoselowering
agents
Thank You