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, -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 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

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 peptidza 4)
stimulates insulin secretion from B-cells decreases glucagon secretion has anorectic effect low risk of hypoglycemia dont 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