CHRONIC COMPLICATIONS OF DIABETES MELLITUS

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1 CHRONIC COMPLICATIONS OF Microvascular complications: Diabetic retinopathy Diabetic nephropathy Diabetic neuropathy Macrovascular complications DIABETES MELLITUS Systemic atheroscerosis Mixted: diabetic foot

2 Pathogeny of chronic complications in diabetes mellitus Main factors: Genetic factors Duration of diabetes Metabolic control Pathogenic mechanisms: Glycosilation of proteins Poliol pathway activation Increased production of oxidative stress Haemorrheological disturbancies

3 Plasma glucose (mg/dl) CONTRIBUTIONS OF FASTING AND POST- PRANDIAL GLYCEMIA IN INCREASING HbA1c Uncontrolled Diabetes HbA 1c 8% Basal hyperglycaemia contributes ~2% Post-prandial hyperglycaemia contributes HbA 1c ~1% Post-prandial hyperglycaemia Fasting hyperglycaemia 0 6 B 12 L 18 D 24 6 Time of day (h) Normal HbA 1c ~5% B=breakfast; L=lunch; D=dinner. Adapted from Riddle MC. Diabetes Care. 1990;13:

4 Classification of diabetic retinopathy Non-proliferative DR:microaneurisms, hard exudates,microhaemorrhagies - Oftalmologic control in 1 year Diabetic maculopathy:macular oedema or ischaemical disorders -ophtalmologic control in 3-4 months Preproliferative DR: soft exudates,haemorrhagies Ophtalmologic cntrol in 2-3 months Proliferative retinopathy:capillary new vessels Ophtalmologic control in 2-3 months. Advanced eye disease:detached retina, rubeosis iridis,neovascular glaucoma

5 SCREENING OF DIABETIC RETINOPATHY TYPE OF DIABETES TYPE 1 TYPE 2 PREGNANCY FIRST EYE FUNDOSCOPY 3-5YEARS AFTER DIAGNOSIS AT FIRST DIAGNOSIS Preconception al and during pregnancy USUAL EXAMINATION EVERY YEAR EVERY YEAR

6 Main mechanisms of atherogenesis in diabetes Disturbancies in concentration,composition and lipoproteins Glycosilation end-products in plasma and arterial wall Oxidisation and glycosilatin of LDL Procoagulant status Insulinresistance and hyperinsulinism Muscle cell proliferation and foam cells in vascular wall

7 Mechanisms Contributing to Arterial Disease in Metabolic Syndrome and Type 2 Diabetes Adapted from Libby et al. Circulation. 2002;106:

8 Cardiac disturbancies in diabetes Genetic factor Age,sex Family history Hyperglycemia Macroangiopathy Autonomic cadiac neuropathy Abdominal obesity Arterial hypertension dyslipidemia Endothelial dysfunction Oxidative stress Microangiopathy Diabetic cardiomiopathy Procoagulant status insulinresistence Protein glycosilation

9 DIABETIC NEPHROPATHY

10 The evolution of glomerular filtrate and urinary albumin excretion

11 STAGE I RENAL HYPERFILTRATION AND HYPERTROPHY AT FIRST DIAGNOSIS OF DIABETES reversible % of GFR (>150 ml/min/1,73 m 2 ) After decreasing glycemia: 50% - GFR is normalising 50% - hiperfiltration microalbuminuria Intermitent microalbuminuria:increasing the glomeruli and kidneys Normal blood pressure

12 STAGE II SILENT, NORMOALBUMINURIC STAGE In first five years of diabetes Renal biopsy:thickening of basal membrane and mesangium GFR is increased ( %) UAER is normal normal BP

13 STAGE III EARLY NEPHROPATHY After 6-15years of diabetes The progression is stopped by a good metabolic control Persistent microalbuminuria ( mg/24 h) GFR is increased, but is decreasing with 3-5 ml/min/year Normal or little increased blood pressure ( with 3 mm Hg/year) Much more histological abnormalities +glomerular obstructions

14 STAGE IV CLINIC DIABETIC NEPHROPATHY After years of diabetes Clinic proteinuria (albuminuria > 300 mg/24 ore) GF progressivelly( 8-12 ml/min/year) 3 substages: - early(gf > 130 ml/min) - intermmediary (GF < 100 ml/min) - advanced (GF < 70 ml/min) BP ( with 5 mm Hg/year) Morphopatology:progressive glomerular sclerosis distruction of renal mass Good glycemic and BP control is delaying the progression of renal disease.

15 STAGE V CHRONIC RENAL FAILURE After years of diabetes Proteinuria Urinary ureea<10g/24h GF < 10 ml/min BP Morphopatology: severe glomerular occlusions and lesion

16 V. SCREENING FOR MICROALBUMINURIA Every year : At puberty or 5 years of type 1 diabetes At first diagnosis of type 2 diabetes

17 Optimal treatment of arterial hypertension in diabetic patient Intensive glycemic control Intensive treatment to decrease cadiovascular risk Optimising lifestyle HbA 1c <7% Glucose (mg/dl): Preprandial Postprandial <180 Dyslipidemia: Statines Hypertension : 2 classes of drugs Microalbuminuria: ACE or ARB Aspirin CHD: ACE, -blockers CVD/risc: ACE Diet Physical exercise Smoking cessation Weight control ADA. Diabetes Care. 2005;28(suppl 1):S1-79.

18 Hyperglycemia polyol pathway Intracellular hyperosmolarity Decreasing intracellular myoinositol Decreasing activity decreasing axonal flow decreased phosphoinositol Na + /K + ATP-ase Axonal demyelinisation

19 CLASSIFICATION AND STAGING of DIABETIC NEUROPATHY Subclinical neuropathy Abnormal Electrodiagnostic Tests ADA: Consensus San Antonio 1.decreased nerve conduction velocity 2.decreased amplitude of evoked muscle or nerve action potential Abnormal Quantitative Sensory Testing 1.vibratory/tactile 2.thermal 3.others Abnormal Autonomic Function Tests 1.Diminished sinus arrhythmia 2.Diminished sudomotor function 3.Increased pupillary latency

20 Clinical neuropathy Diffuse neuropathy 1.distal symmetric sensorimotor polyneuropathy -primarly small-fiber neuropathy -primarly large fiber neuropathy - mixed 2.autonomic neuropathy a.abnormal pupillary function b.sudomotor dysfunction c.genito-urinary autonomic neuropathy -bladder dysfunction -sexual dysfunction d.gastro-intestinal autonomic neuropathy -gastric atony -gallbladder atony -diabetic diarrhea -hypoglycemia unawareness

21 Clinical neuropathy e.cardiovascular autonomic neuropathy f.hypoglycemia unawareness Focal Neuropathy 1.Mononeuropathy 2.Mononeuripathy multiplex 3.Plexopathy 4.Radiculopathy 5.Cranial neuropathy

22 AUTONOMIC NEUROPATHY Cardiovascular -tachycardia, exercise intolerance -cardiac denervation -orthostatic hypotension Gastrointestinal -esophageal dysfunction -gastroparesis -diarrhea -constipation -fecal incontinence Genitourinary - erectile dysfunction - retrograde ejaculation -cystopathy -neurogenic bladder Neurovascular -heat intolerance -gustatory sweating -dry skin -impaired skin blood flow Pupillary Decreased diameter of dark adapted pupil

23 Clinical manifestations of cardiac autonomic neuropathy Exercise intolerance Impairment of exercise tolerance Reduced response to heart rate and blood pressure Decreased cardiac output Decreased ejection fraction Systolic dysfunction Decrease in diastolic filling Intraoperative cardiovascular lability Increased necessity for vasopresor support Excessive vasodilation with anesthesia due to loss of normal vasoconstrictor response and tachycardia Orthostatic hypotension Dizziness Weakness Fatigue Visual blurring Neck pain Sylent myocardial ischemia Decreased perception of anginal pain, often accompanied by unexplained fatigue, confusion, tiredness, edema, hemoptysis, nausea, vomiting, diaphoresis, arrhytmias, cough or dyspnea