Transcript Diabetes mellitus - Comenius University

Diabetes mellitus
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. MODYhereditary forms linked to mitochondrias, drug
induced DM - glucocorticoids, β-blockers,
thiazides)
Acute Complications of DM


diabetic ketoacidosis (typical for DM type
1, but can also occur at DM type 2)
hyperosmolar coma (typical for DM type
2)

hypoglycaemic coma
Chronic Complications of DM

diabetic macroangiopathy =
acceleration of atherosclerosis



diabetic microangiopathy = damage
of retinal and renal vessels
diabetic nephropathy
diabetic neuropathy = senzo-motoric
affection
Prevention of Complications


good long-term diabetes controll
complex treatment of concomitant
risk factors (hypertension, dyslipidemia,
obesity...)
DM type 1

most often among children

genetically determined (allele DQ8, DR3,4)
autoimune destruction of B-cells in
pancreas by Tc lymphocytes
absolute insufficiency of insulin
requires whole-life treatment with insulin



DM type 1 - Diagnosis

clinically: polyuria, polydypsia, loosing of
weight, acetone foetor ex ore

biochemically:
 fasting glycemia >7 mmol/l
 oGTT - glycemia 120 min. >11mmol/l
 C-peptide ↓ or 0
 urine: + ketonuria, glucose
DM type 1 - Treatment



nowadays exclusively only human
insulins
effort to imitate diurnal secretion of
insulin (basal + postprandial)
important education of parents and also
children (selfmonitoring, regimen
precaution)
Insulins According to Origin
1. Semisynthetic – from porcine insulin
by the change of AA (Insuman)
2. Prepared by recombinant
DNA method (Humulin - HM)
3. Insulin analogues (exchange, change of
sequence or type of AA) = better
pharmacocinetic
Insulins according to Length of
Action
A. Short acting:
 fast beginning of the effect
(15 - 30 min.)
 acting 3 - 6 hours
 water soluable
 s.c. or i.v. administration (acute
states require i.v. administration !!!)
Insulins according to Length of
Action
B. Intermediate acting (NPH) :
 slower beginning of the effect
(1 - 3 hours)
 acting 4 - 12 hours
 suspensions
 only s.c. administration (after i.v.
administration risk of embolisation !!)
Insulins according to Lenght of
Action
B. Insulins with prolonged action:
 slow beginning of the effect
(3 - 4 hours)
 acting 10 - 24 hours
 suspensions
 only s.c. administration
Insulin Analogues

Insulins lispro + aspart
 beginning of the effect till 15 min., lasts
shortly (cca 1 hour)
 possible to administer right before meal

Insulins glargine + detemir
 act 16 – 24 hours
 usually enough to administer one time
per day
Adverse Effects of Insulin




hypoglycemia: ↑ dose, insufficient
food income, interaction with alcohol
lipodystrophy: at human ins. rarely
weight gain: at ↑ daily doses of
insul. at DM type 2
local allergy: rarely
Insulin Regimens

the conventional regimen 1-2 s.c.
injections/day
 at DM type 2 after failure of treatment
with PAD or + PAD

intensified regimen (basal + bolus)
 standard at DM type 1
 at DM type 2 after failure of PAD
Intensified Regimen




the best imitation of physiologic insulin
secretion
Important is patient education (selfmonitoring)
most often 4-5 s.c. injections/day
intermediate ins. only at evening or in
morning – at evening (basal), short-acting
ins. before main meal morning-noon-evening
(bolus)
Insulin Pump




continual s.c. administration of insulin
only for good cooperating patients after
adequate education
the best compensation of diabetes
in case of combination with sensor to
monitor glycemia, automatic adjustment
of doses
Aplication Forms of Insulin





injection
insulin pens
ins. pump
inhaled insulin (powder)
peroral forms = in development
Indications of Insulin Therapy




DM type 1
DM type 2
 loss of PAD effectiveness
 surgery, intercurrent diseases
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
patient´s 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
Derivates of Sulfonylurea





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)

risk of hypoglycemia mainly glibenclamid,
less glipizid and gliklazid
Derivates of Meglitinide

short-lasting stimulation of insulin secretion =
influencing postprandial glycemia


taking before the main meal
metabolism in liver = possibility to give to
patients with renal insufficiency



mostly in combination with metformin
AE - hypoglycemia
repaglinid, nateglinid
Biguanines - Metformin




insulin sensitisers = increase sensitivity
of tissues to insulin, ↓ level of TAG,
anorectic and antabus effect
drug of the 1st choice in the treatment of
DM type 2
after treatment failure combination with
other PAD
AE - GIT intollerance, lactic acidosis (↑ risk
among alkoholitics and at chronic renal,
hepatal and respiratory diseases)
Thiazolidindions (Glitazons) –
Rosiglitazone, Pioglitazone



activators of nuclear receptor PPARy
(transkriptional factor) = increase sensitivity
of tissues to insulin, ↓ TAG, ↑ HDL
AE - ↑ weight (fat redistribution), fluid
retention = oedemas, heart failure, among
risk patients ↑ CV mortality !!
not the 1st choice, only in combination with
other PAD
Inhibitors of Intestine
Glukosidases (Akarbose)




inhibition of disacharidases in small
intestine = slowing down of composite
sacharides hydrolysis
influencing only postprandial glycemia
oft AE - flattulence, diarrhoea, stomach
pain
less used, only in combination
New Antidiabetics

on the ground of GLP-1 (glucagon-like
peptide 1)
= incretin, released in small intestine
after stimulation with food, degraded by
DPP-4 (dipeptidyl peptidáza 4)



 stimulates insulin secretion from B-cells
 decreases glucagon secretion
 has anorectic effect
low risk of hypoglycemia
don´t lead to weight gain
in combination with metformin
New Antidiabetics
1. Analogues of GLP-1 = liraglutid, exenatid
 s.c. aplication
2. Inhibitors of DPP-4 (gliptins) = sitagliptine
 p.o. aplication
AE - nasopharyngeal + urinary infections
DM Type 2 as the part of
Metabolic Syndrome

metabolic sy = ↑↑↑ CV risk
 insulin resistance (± DM type 2)
 abdominal obesity (weist circumference)
 hypertension
 dyslipidemia
 protrombotic state
 hyperuricaemia
DM Type 2 as the part of
Metabolic Syndrome
= need of complex therapy of all risk factors

hypertension - ACEI, Sartans, CaCB
(telmisartan = PPARy agonist)



protrombotic state - aspirin, clopidogrel
dyslipidemia - statins
obesity - diet, excercise, antiobesitic
drugs
Obesity

key etiologic factor of metabolic sy (ins.
resistance)

CV risk mainly abdominal obesity (weist
circumference > 102 cm men, > 88 cm
women)

without weight loss is good
compensation of DM type 2 almost
impossible !!!
Case



13 year old boy, last days is feeling more
tired, urinates several times per day also at
night, permanently feels thirst despite of
drinking more than 2 l fluids per day, fainted
at school, before cramp pain of stomach
Anamnesis: not seriously ill before, family
history without no remarkable
Objectively at admission: skin pale,
intensificated breathing, signs of dehydration,
foetor ex ore after fruit, BP: 90/60, P: 95/min.
Case
1. What is susspicious diagnosis?
2. What examinations would you
recommend ?
3. What is pseudoperitonitis diabetica?
4. Make pharmacoterapeutic plan