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DM Definition, Prevalence
chronic metabolic disease caused by
absolute or relative insufficiency of
insulin (or their combination)
in the world approximately 270 million
diabetic patients
raising incidence, mainly DM type 2
Classification DM
DM type 1
DM type 2
Gestational DM
Other specific types of DM (e.g. MODY-
hereditary forms linked to mitochondrias, drug
induced DM - glucocorticoids, -blockers,
thiazides)
Acute Complications of DM
gestational DM
states after pancreatectomia, pankreatitis
Goals of DM Type 1 Therapy
prevention of chronic complications
by good diabetes compensation
long-term glycemia 7 mmol/l
HbA1c (glykosyled Hb) < 7%
keeping stabilized glycemia
without frequent
hypo-hyperglycemias
keeping the best possible quality of
patients lives
DM Type 2
insulin resistance at postreceptor level =
relative insulin deficiency, later also
absolute
the same CV risk as patients after MI !!!
marked therefore as also CV disease
frequently part of metabolic syndrome
DM Type 2 - Treatment
must be complex (hypertension,
dyslipidemia, obesity...)
important regimen precautions
loss of weight
reduction diet
physical activity
Peroral Antidiabetics
1. Stimulators of insulin secretion
a. derivates of sulfonylurea
b. derivates of meglitinides
2. Insulin sensitisers
a. biguanines
b. thiazolidindiones (glitazones)
3. Inhibitors of intestine glukosidases
4. New antidiabetics
Sulfonylurea Derivatives
stimulation of endogenous insulin secretion
effect depends on the functional B-cells of
pancr.
in monotherapy or in combination
binding to albumin > 90% = interactions !!!
AE - hypoglycemia (carefull, interactions with
NSA, alcohol, warfarin), weight gain
risk of hypoglycemia mainly glibenclamide,
less glipizide and gliklazide
Sulfonylurea Derivatives
effective only if functional beta-cells
ADRs:
hypoglycemia - mortality associated with treatment up to 10%!
stimulation of apetite - weight gain
Sulfonylurea Derivatives
block of ATP sensitive kallium channels
high affinity binding to SUR receptors depolarization - Ca2+ entry
insulin secretion
SU RECEPTOR
belongs to a family of transmembrane proteins a group of ABC
transporters (ATP-Binding Cassette transporter), is only a
regulator of ion channels
enzyme DPP-IV
(inactivates GLP-1) DPP-IV inhibitors (sitagliptin,
vildagliptin)
Glucagon like peptid (GLP-1) = insulinotropic peptide: