micro macro complications of diabetes mellitus.pptx

pp about micro and macrovascular complications of dm2

1. C omplications of D iabetes Mellitus [Chronic] Dr. Md. Javed , MD Department of Medicine FHMC AGRA

2. Complications of Diabetes Mellitus Chronic complications Microvascular retinopathy Nephropathy neuropathy Macrovascular cerbrovascular, cardiovascular, peripheral vascular disease Acute complications diabetic ketoacidosis diabetic nonketotic, hyperosmolar com a hypoglycemia

3. Introduction Adults with diabetes have an annual mortality of 5.4% (double the rate for non-diabetic adults) L ife expectancy is decreased on average by 5-10 years Although the increased death rate is mainly due to cardiovascular disease , deaths from non-cardiovascular causes are also increased. A diagnosis of diabetes immediately increases the risk of developing various clinical complications that are largely irreversible and due to microvascular or macrovascular disease.

4. M ajor D etermining F actors Duration Glycemic Control Type 1 vs. Type 2 DM Complications

5. Y ears 350 300 250 200 150 100 50 Insulin Level Insulin Rasistance Beta- cell Deficiency 250 200 150 100 50 Relative beta- cell function (%) Fasting Glu cose Post prandial Glu cose Glu cose (mg/dl) Diagnosis Clinical Signs Ma crovascular Changes Obe sity IGT Di abetes Uncontrolled Hyperglycemia Prevention OAD Insulin -10 -5 0 5 10 15 20 25 30 Mic rovas cu l a r Changes D Kendall, R Bergenstal, International Diabetes Center Type 2 Diabetes is a Progressive Disease

6. 9.9 - 20.8 % of pts have retinopat hy Harris MI et al . Diab Care, 21: 1992. Hamman RF et al. Diabetes, 38: 1989 5 – 10 % protein u ri a Haffner SM et al. Diab Care, 12: 1989 At the diagnosis of T y p e 2 DM Type 2 DM Starts Years Before Diagnosis

7. Prevention is more rewarding than Management o f Complications

8. Microvascular Complications

9. Microvascular Complications Microvascular complications are specific to diabetes and do not occur without longstanding h yperglycaemia Both T1DM and T2DM are susceptible to microvascular complications The duration of diabetes and the quality of diabetic control are important determinants of m icrovascular disease

10. Microvascular C omplications A continuous relation exists between glycaemic control and the incidence and progression of microvascular complications. HTN and smoking also have an adverse effect on microvascular outcomes.

11. “ Tight Glycemic Control” reduces microvascular and macrovascular complications

12. Glycemic Control and Complications

13. Mortali ty (%) UK Prospective Study Group. yıl 40 1 2 3 4 5 6 7 8 9 20 30 10 convetional tight c ontrol Risk - reduction 32% P =0.019 Mortality due to Diabetes

14. Possible molecular mechanisms of diabetes-related complications. Harrison's Principles of Internal Medicine, 16th Edn

15. Consequences of hyperglycemia-induced activation of protein kinase C (PKC) Vascular Health and Risk Management 2007:3(6):823-832

16. Mechanisms of AGE Action

17. Pathophysiology of Mi crovascular D isease Structural changes thickening of the capillary basement membrane Functional changes increased capillary permeability increased blood flow and viscosity disturbed platelet function Chemical changes in basement membrane composition increased type IV collagen and its glycosylation products

18. Diabetic Retinopathy

19. Retinopathy Diabetic retinopathy is a progressive disorder It is the commonest cause of blindness in age 30-69 . Damage to the retina arises from a combination of microvascular leakage and microvascular occlusion A fifth of p ’ ts with newly discovered type 2 diabetes have retinopathy at the time of diagnosis.

20. Retinopathy In type 1 diabetes , vision threatening retinopathy almost never occurs in the first five years after diagnosis or before puberty. After 15 years , however, almost all type 1 diabetes and two thirds of type 2 diabetes have background retinopathy Vision threatening retinopathy is usually due to neovascularisation in type 1 diabetes and maculopathy in type 2 diabetes.

21. Retinopathy Depending on the relative contribution of leakage or capillary occlusion, maculopathy is divided into three types: exudative maculopathy (when hard exudates appear in the region of the macula), ischaemic maculopathy (characterised by a predominance of capillary occlusion which results in clusters of haemorrhages) edematous maculopathy (extensive leakage gives rise to macular e dema).

22. Classification of Diabetic Retinopathy Neovascularization (4 categories) – Nonproliferative (NPDR) 1. Early to moderate NPDR 2. Severe NPDR (preproliferative) – Proliferative (PDR) 1. Non-high-risk PDR 2. High-risk PDR

23. Non-Proliferative Diabetic Retinopathy

24. Severe NPDR (Pre-Proliferative)

25. Proliferative Diabetic Retinopathy

26. Retinal Neovascularization NVE vitreous hemorrhage

27. BDR with Clinically Significant Macular Edema (CSME)

28. Treatment of Diabetic Retinopathy (Systemic) Control Blood sugar Blood pressure Cholesterol Treat Heart failure Kidney failure Avoid smoking

29. Treatment of Diabetic Retinopathy (Ocular) Laser Focal for macular edema Pan-retinal for neovascularization Vitrectomy Medications

30. Laser Treatment for Diabetic Macular Edema

31. Vitrectomy Surgery

32. Diabetic Nephropathy

33. Diabetic Nephropathy Over 40% of new cases of end-stage renal disease (ESRD) are attributed to diabetes.

34. Nephropathy Diabetic nephropathy is characterised by proteinuria >300 mg/24 h , increased BP, and a progressive decline in renal function. I n the early stages , overt disease is preceded by a phase known as incipient nephropathy (or microalbuminuria) , in which the urine contains trace quantities of protein (not detectable by traditional dipstick testing). Microalbuminuria is defined as an albumin excretion rate of 3 0-300 mg/24 h and is highly predictive of overt diabetic nephropathy

35. Treatment of Diabetic Nephropathy Hypertension Control Goal: lower blood pressure to <1 40 / 90 mmHg Antihypertensive agents Angiotensin-converting enzyme (ACE) inhibitors captopril, enalapril, lisinopril, benazepril, fosinopril, ramipril, quinapril, perindopril, trandolapril, moexipril Angiotensin receptor blocker (ARB) therapy candesartan cilexetil, irbesartan, losartan potassium, telmisartan, valsartan, esprosartan Calcium channel blockers

36. Glycemic Control Preprandial blood glucose 8 0-1 2 0 mg/dl A1C < 6.5 % Postprandial blood glucose <1 4 0 mg/dl Self-monitoring of blood glucose (SMBG) Medical Nutrition Therapy Restrict dietary protein to RDA of 0.8 g/kg body weight per day Treatment of Diabetic Nephropathy

37. Treatment of End-Stage Renal Disease There are three primary treatment options for individuals who experience ESRD: 1. Hemodialysis 2. Peritoneal Dialysis 3. Kidney Transplantation

38. Diabetic Neuropathy

39. Diabetic Neuropathy About 60-70% of people with diabetes have mild to severe forms of nervous system damage, including: Impaired sensation or pain in the feet or hands Slowed digestion of food in the stomach Carpal tunnel syndrome Other nerve problems More than 60% of nontraumatic lower-limb amputations in the United States occur among people with diabetes.

40. Damage to nerve fibres and capillaries Symptoms depend on nerves involved Motor fibres → Muscular weakness Sensory fibres → Loss of sensation also prickling, tingling, aching and pain Autonomic fibres → loss of function functions not under conscious control such as digestion, bladder, genitals, cardiovascular. Diabetic Neuropathy

41. Other Consequences Diabetic foot (15% of all diabetics) Compression neuropathies eg carpal tunnel syndrome Risk factors Smoking, >40 years old, poor glucose control Affects Type 1 and Type 2 Diabetic Neuropathy

42. Classification of Diabetic Neuropathy Symmetric polyneuropathy Autonomic neuropathy Polyradiculopathy Mononeuropathy

43. Symmetric Polyneuropathy Most common form of diabetic neuropathy Affects distal lower extremities and hands ( “ stocking-glove ” sensory loss ) Symptoms/Signs Pain Paresthesia/dysesthesia Loss of vibratory sensation

44. Complications of Polyneuropathy Ulcers Charcot arthropathy Dislocation and stress fractures Amputation

45. Treatment of Symmetric Polyneuropathy Glucose control Pain control Alphalipoic acid Anticonvulsants (gabapentin, pregabalin) Tricyclic antidepressants Topical creams Foot care

46. Autonomic neuropathy Affects the autonomic nerves controlling internal organs Peripheral Genitourinary Gastrointestinal Cardiovascular Is classified as clinical or subclinical based on the presence or absence of symptoms

47. Peripheral Autonomic Dysfunction Contributes to the following symptoms/signs: Neuropathic arthropathy (Charcot foot) Aching, pulsation, tightness, cramping, dry skin, pruritus, edema, sweating abnormalities Weakening of the bones in the foot leading to fractures

48. Peripheral Autonomic Dysfunction Treatment Foot care/elevate feet when sitting Eliminate aggravating drugs ( tranquilizers, antidepressants, diuretics ) Reduce edema midodrine diuretics Support stockings Screen for CVD

49. Genitourinary Autonomic Neuropathy

50. Gastrointestinal Autonomic Neuropathy Symptoms/Signs Gastroparesis resulting in anorexia, nausea, vomiting, and early satiety Diabetic enteropathy resulting in diarrhea and constipation Treatment Other causes of gastroparesis or enteropathy should first be ruled out Gastroparesis - Small, frequent meals, m etoclopramide , erythromycin Enteropathy - loperamide , antibiotics, stool softeners or dietary fiber

51. Cardiovascular Autonomic Neuropathy Symptoms/Signs Exercise intolerance Postural hypotension Treatment Discontinue aggravating drugs Change posture (make postural changes slowly, elevate bed) Increase plasma volume

52. Polyradiculopathy Lumbar polyradiculopathy (diabetic amyotrophy) Thigh pain followed by muscle weakness and atrophy Thoracic polyradiculopathy Severe pain on one or both sides of the abdomen, possibly in a band-like pattern Diabetic neuropathic cachexia Polyradiculopathy + peripheral neuropathy Associated with weight loss and depression

53. Mononeuropathy Peripheral mononeuropathy Single nerve damage due to compression or ischemia Occurs in wrist (carpal tunnel syndrome), elbow, or foot (unilateral foot drop) Symptoms/Signs numbness edema pain prickling

54. Cranial mononeuropathy Affects the 12 pairs of nerves that are connected with the brain and control sight, eye movement, hearing, and taste Symptoms/Signs unilateral pain near the affected eye paralysis of the eye muscle double vision Mononeuropathy multiplex Mononeuropathy

55. MACROVASCULAR COMPLICATIONS

56. Macrovascular C omplications Angina. Myocardial infarction. Transient ischaemic attacks. Cerebrovascular accident. Claudication lower limb. Neuropathy / infection.

57. Macrovascular C omplications Atherosclerotic disease accounts for most of the excess mortality in diabetes. In the UKPDS, fatal cardiovascular events were 70 times more common than deaths from microvascular complications. The relation between glucose concentrations and macrovascular events is less powerful than for microvascular disease; S moking, BP, proteinuria, and cholesterol concentration are more important risk factors for atheromatous large vessel disease in diabetes.

58. Macrovascular C omplications Hyperlipidaemia is no more common in well controlled type 1 diabetes than it is in the general population. In type 2 diabetes, total and LDL concentrations are also similar to those found in non-diabetic people, but type 2 diabetes is associated with a more atherogenic lipid profile, in particular low HDL and high small, dense, LDL particles.

59. Macrovascular C omplications HTN affects at least half of diabetes. In UKPDS, tight BP control (mean 144/82 mm Hg) achieved significant reductions in the risk of stroke (44%) , heart failure (56%) , and diabetes related deaths (32%) , as well as reductions in microvascular complications (for example, 34% reduction in progression of retinopathy). One third of p ’ ts required three or more antihypertensive drugs to maintain a target BP <150/85 mm Hg.

60. Unmodifiable R isk F actors Age >50 Gender Hereditary

61. Modifiable R isk F actors Smoking Inactivity Nutrition Obesity (BMI > 30) Excessive smoking & alcohol intake

62. Medical R isk F actors Hypertension (BP>130/80mmHg) High cholesterol Poor glycemic control (HbA1c>7%) Microalbuminuria

63. Coronary H eart D isease The incidence and severity of coronary heart disease events are higher in diabetes, and several clinical features are worth noting. The diabetes subgroups in the major secondary prevention studies of cholesterol reduction (Scandinavian simvastatin survival study (4S) and cholesterol and recurrent events (CARE) trial) show a beneficial effect of statins .

64. Peripheral V ascular D isease Atheromatous disease in the legs, as in the heart, tends to affect more distal vessels — for example, the tibial arteries — producing multiple, diffuse lesions that are less straightforward to bypass or dilate by angioplasty. Medial calcification of vessels ( M ö nckeberg's sclerosis ) is common

65. Stroke 85% of acute strokes are atherothrombotic, and the rest are haemorrhagic (10% primary ICH , 5% SAH ). The risk of atherothrombotic stroke is two to three times higher in diabetes, but the rates of haemorrhagic stroke and TIA are similar to those of the non-diabetic population. Diabetes are more prone to irreversible rather than reversible ischaemic brain damage, small lacunar infarcts are common.

66. Stroke Stroke p ’ ts with diabetes have a higher death rate and a poorer neurological outcome with more severe disability. Maintaining good glycaemic control immediately after a stroke is likely to improve outcome , but the long term survival is reduced because of a high rate of recurrence . Antihypertensive treatment is effective in preventing stroke.

67. Erectile D ysfunction A common complication of diabetes, occurring in up to half of men aged over 50 years (compared with 15-20% in age matched non-diabetic men), although the exact prevalance is unknown because of likely underreporting . Pathogenesis is multifactorial , with autonomic neuropathy , vascular insufficiency , and psychological factors contributing to the clinical picture. Sildenafil , Tadalafil , which is reported to have a 50-70% success rate in diabetes, is an important advance.

68. DIABETIC FOOT SYNDROME

69. Foot Problems and Diabetes Neuropathy Peripheral: loss of protective sensation Autonomic: loss of ability to sweat Motor: loss of structure/muscle tone Peripheral Vascular Disease Impaired circulation in legs and feet Increased incidence of inflammation and infection High risk of ulcers, gangrene and amputations when person also has neuropathy

70. Callus formation Subcutaneous hemorrhage Breakdown of skin Deep foot infection with osteomyelitis Illustration of ulcer due to repetitive stress

71. Diabetic Foot Ulcers

72. Diabetic foot ulcers

73. Diabetic Foot Ulcers

74. Diabetic foot ulcers

75. Prevention Foot exam by a health professional at every medical visit Comprehensive exam annually Vascular Musculoskeletal Skin and soft tissue Education

76. T h a n k Y o u !