Diabetes therapy

Diabetes

 Diabetes is a chronic disease that occurs either when the pancreas does not
produce enough insulin or when the body cannot effectively use the insulin
it produces.
 Hyperglycemia, or raised blood sugar, is a common effect of uncontrolled
diabetes and over time leads to serious damage to many of the body's
systems.

Blood glucose level regulation

Glucagon Insulin
GH
CA
Cortisol
Types

• Type I • Gestational
• Type II
Symptoms and complications
Clinical presentation
Symptoms of Hypoglycemia in DM
Diagnosis

 Hg A1c: 6.5% or >

 FBS: 126 mg/dl, 7 mmol/L or >
 OGTT: 75g anhydr. glu. solution → 2hrs → BS: 200 mg/dl, 11.1 mmol/L or >
 Random BS test: 200 mg/dl, 11.1 mmol/L or >
Glucose transport

Insulin secretion
Mechanism of action

TK
Physiological effect
 Liver: Inhib. catabolic and activate the anabolic

• Glycogenolysis • Glycogenosis
• Conversion of FA & AA to ketone body • TG & VLDL
• Conversion of AA to glu.

 Muscle: ↑ protein & glycogen synth.

• ↑ AA transport • ↑ glu. Transport

• ↑ ribosomal protein synth. • Induce glycogen synthase and inhi. phosphorylase

 Adipose tissue: ↑ TG storage

• Induce and activation of LPL

• Esterification of FA
• Inhib. IC lipase
DM therapy
S.E

1. Hypoglycemia
Insulin and derivatives
• Cc : 100 U/ml ; 1U ~ 0.035mg

• Recombinant human active insulin, porcine (1AA), bovine (3AA)

Kin.
Insulin admin.
Consequence of long-term insulin therapy
 Absorption is depend on:

• Insulin source
• Additives
• Site of injection
• Blood flow of the area (exercise, body temp.)

But insulin analogues retain

their kinetic profile at all sites
of inj.
Non-pharmacological treatment
 Risk factors of T2DM

• Overweight
• Genetic background
• Race (Spanish, Afro-American, Indian, Asian)
• Age (above 40)
• ↓ glu. tolerance
• Hypertension
• Hyperlipidemia
• Alcoholism
• Smoking
• Gestational DM
• PCOS
Treatment of T2DM

• Non-pharmaco.
- Diet
- W. loss
- Exercise

• Pharmaco.
- OADs
- OADs + insulin

• Treatment of complications
Pharmaco. Therapy
OADs activity
Sulfonylureas

M. A:
Sulfonylurea Receptor
Kin.:
Meglitinides (glinides)
S.E :
Biguanides

M.A : insulin sensitizer

S.E :
Thiazolidindiones , glitazones

M.A :
PPARγ agonist → insulin responsive gene activator
S.E :
α-Glycosidase inhibitors

M.A :
S.E :

GI discomfort, flatulence, bloating, diarrhea

Dosage :

• Start with very low dose

• With the 1st bite of meal
• Increase gradually
DPP-4 inhibitors

M.A :
GLP-1 agonists
Liraglutide
Dose response effect of GLP-1
SGLT-2 inhibitors (Sodium-glucose cotransporter 2)
Monitoring

Therapy
Hb-A1c :
- Gold standard
- Follow long term glycemic control
- Pervious 3 months ˂ 7%

Complications

- Eye
- Blood pressure
- Feet
- UA
- Plasma lipids