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. MODY-
hereditary 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