Diabetes mellitus

Acute and chronic complications

Definition of diabetes mellitus

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia

resulting from defects in insulin secretion, insulin action, or both.

The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys,

nerves, heart, and blood vessels.

Classification of diabetic syndromes

Type 1 diabetes mellitus (10 %)autoimmune and idiopathic

IDDM, juvenile diabetes Type 2 diabetes mellitus (90 %)

NIDDM, adult type Other types of diabetes mellitus (rare, long

list) Gestational diabetes mellitus (temporary dg.)

And where is LADA and MODY ?impaired glucose toleranceand impaired fasting glucoseare RISK FACTORS

LADA latent autoimmune diabetes of adulthood late-onset autoimmune diabetes of adulthood slow onset type 1 diabetes, or type 1.5 (type one-and-a-half) diabetes

• slow-onset Type 1 autoimmune diabetes in adults

• age more than 35 years

MODY maturity onset diabetes of the young

• several hereditary forms of DM caused by autosomal dominant mutations of genes (MODY 1 – 9)

• early manifestation• positive familiar history• various types, most commonly acts like a very mild version of

type 1 DM

Other types of DM• genetic mutations• diseases of exocrine pancreas (chronic pancreatitis)• excessive secretion of insulin-antagonistic hormones

• induction of DM by drugs or chemicals (alloxan, streptozotocine)

• ...

Gestational DM• DM during pregnancy - resembles type 2 diabetes • about 2%–5% of all pregnancies, may improve or disappear after

delivery• about 20%–50% of affected women develop type 2 diabetes later in

life• untreated gestational diabetes - damage the health of the fetus -

macrosomia, congenital cardiac and central nervous system anomalies, skeletal muscle malformations, respiratory

infant syndrome...

Symptoms of diabetes mellitus

Basic Thirst Polyuria Weight loss Fatigue

Other Muscle cramps Obstipation Blurred vision Fungal and bacterial

infections

If you do not begin insulin therapy immediately

nausea, vomitus

abdominal pain dehydration Kussmaul breathing acetone smell of

breath ketones in blood, urine, acidosis

COMA DIABETICUM

Symptoms of DM

NOTHINGType 2 for long time (months, years)

Hypertension

Myocardial infarction, stroke with very bad prognosis

Microangiopathic complications (amputation)

Gestational diabetes mellitus

Screening!

Harmful both for baby and mother

Diagnostic criteria of DM

•symptoms of DM•casual glucose concentration > 11 mmol/l•fasting glycaemia > 7 mmol/l•glycaemia 2h after 75 g of glucose > 11 mmol/l

•symptoms of DM and 1 abnormal blood glucose•two abnormal BG values on 2 days

•fasting glycemia 5,6 – 6,99 = impaired fasting glycaemia, pre-diabetes•glycaemia in oGTT after 2 hod 7,8 – 11,0 = impaired glucose tolerance

Acute complications of DM

Diabetic hypoglycaemia

glycaemia lower than 3,5 mmol/lCause higher dose of insulin or PAD (sulfonylurea) inadequate food intake

Symptoms vegetative – sweating, palpitations, anxiety, shakiness, pallor neuroglycopenic – confusion, weakness, atypical

behaviour, impaired concentration, sleepeness, double vision, incoordination, dificulty speaking

other – hunger, nauzea and vomiting, headache

Hypoglycemia

Diabetic ketoacidosis

acute complication predominantly of type 1 DM inadequate or no therapy with insulin

Mechanism the absence of insulin release of free fatty acids from

adipose tissue converted in the liver into ketone bodies

(acetoacetate, acetone, -hydroxybutyrate) metabolic

acidosis diabetic coma

Diabetic ketoacidosis

Symptoms nausea, vomiting, abdominal pain polyuria, polydipsia, hyperglycemia, dehydratation hyperventilation (Kussmaul respiration) tachycardia, hypotension acetone smell of breath MAC – pH, AG

Nonketotic hyperosmolar state

nonketotic hyperglycemic hypeosmolar coma DM type 2

Mechanism hyperglycemia hyperosmolarity polyuria dehydratation the presence of some insulin inhibits lipolysis – no

ketoacidosis

Symptoms hyperglycemia, hyperosmolarity dehydratation – hypotension renal insuficiency, mental and neurologic signs,

trombosis coma, death

Lactate acidosis

diabetic pseudohypoxia increased lactate concentration

Symptoms dyspnea abdominal pain MAC (lactate acidosis) unconsciousness

Chronic microvascular complications of DM

The main mechanisms

Microangiopathy an angiopathy of small blood vessels hyperglycemia damage of endothelial cells, basement

membrane grow thicker and weaker

Polyol pathway sorbitol-aldose reductase pathway decrease of reduced NADPH and oxidized NAD+

diabetic pseudohypoxia

The main mechanisms

Glycation hyperglycemia higher non-enzymatic glucation of proteins Advanced Glycation End products (AGEs) are the result of a

chain of chemical reactions after an initial glycation reaction

Effect aging and some age-related chronic diseases in DM - increasing vascular permeability, inhibition of vascular

dilation by interfering with NO, oxidising LDL... they bind to receptors for AGE (RAGE on endothelial cells,

smooth muscle cells, cells of immune system) - contribute to age- and diabetes-related chronic complications

Diabetic retinopathy damage of the vessels of the retina the most frequent cause of blindness in developed countries

Mechanism endothelium damage, thickening of basal membrane changes of osmotic pressure, haemorrhage, microaneurysms, deposition of protein and lipid exsudates, oedema of macula

Other complications cataracta glaucoma disorders of refrakction and motility

Diabetic retinopathy

Diabetic nefropathy

angiopathy of capillaries in the kidney glomeruli ischemia

Symptoms microalbuminuria

(30 – 300 mg albumin/day) kidney failure oedema

Diabetic neuropathy

angiopathy of vasa nervorum (small blood vessels that supply nerves)

sensorimotor neuropathy sensitivity disorders – pain, heat, cold, pressure

vegetative neuropathy changes in sweating urogenital dysfunction gastroparesis, nausea, diarhea, constipation tachycardia, hypotonia

diabetic foot

Diabetic foot

ulcer,infection, gangrene...amputation

Diabetic foot

Risk factors

prevention

Chronic macrovascular complications of DM

Atherosclerosis ...one of the previous seminars...