Diabetes Complications

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Diabetes Complications

• DG van Zyl

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The Ticking Clock
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Different Diabetes Complications

• Macro vascular
• Micro vascular
• Neuropathy
• Infections

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Mechanisms
Genetic susceptibility
Repeated acute changes in cellular metabolism
Hyperglycemia
Tissue damage
Cumulative long term changes in stable
macromolecules
Independent accelerating factors
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Mechanisms of Hyperglycaemia Induced Damage

• Increased Polyol - sorbitol Pathway flux
• Increased AGES formation
• Activation of protein kinase C
• Increased Hexosamine pathway flux

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Formation of AGEP
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Macro vascular Complications
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Macro-vascular Complications

• Ischemic heart disease
• Cerebrovascular disease
• Peripheral vascular disease
• Diabetic patients have a 2 to 6 times higher risk
  for
• development of these complications than the
• general population

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Macro-vascular Complications

• The major cardiovascular risk factors in the
  non-diabetic population (smoking, hypertension
  and hyperlipidemia) also operate in diabetes, but
  the risks are enhanced in the presence of
  diabetes.
• Overall life expectancy in diabetic patients is 7
  to 10 years shorter than non-diabetic people.

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Macro-vascular Disease

• Once clinical macro-vascular disease develops in
  diabetic patients they have a poorer prognosis
  for survival than normoglycemic patients with
  macrovascular disease
• The protective effect females have for the
  development of vascular disease are lost in
  diabetic females

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CAD Morbidity and Mortality in Type 2 DM

• Framingham Data 20 year follow-upAge 45-74
• 2-3 fold increase in clinically evident
  atherosclerotic disease in diabetics
• women diabeticsmale diabetics in terms of CAD
  mortality

• Multiple Risk Factor Intervention Trial (MRFIT)
• 5000 men with type 2 DM
• Followed for 12 years
• Men with type 2 DM had absolute risk of
  CAD-related death 3 times higher than
  non-diabetic cohort

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Risk Factor Clustering in Diabetes

• Type 2 Diabetes at Diagnosis
• 50 have hypertension
• 30 have dyslipidemia
• UKPDS
• Prospective study
• Newly detected type 2 DM
• 335 with CAD, 8 year follow-up
• Associated with elevated LDL-C, low levels of
  HDL-C, systolic hypertension

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Cardiovascular Death Rates MRFIT data
Stamler J., et al Diabetes Care 16 434-444
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Risk of MI in Diabetes
Haffner, SM et al NEJM 339 229-234
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Plasma Glucose as Independent Risk Factor
Andersson, DK et al. Diabetes Care 18 1534-1543
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Glycemic Control to Reduce CAD

• DCCT trial
• 1441 patients, type 1 diabetes
• Randomized to intensive glycemic control vs.
  conventional therapy
• Monitored prospectively for 6.5 years
• Results
• Less retinopathy by 50
• Macrovascular complications 41 reduction (not
  statistically significant)
• -small number of events in young patient cohort

• UKPDS
• 3867 patients with newly diagnosed type 2 DM
• Intensive vs. Conventional therapy
• 10 year follow-up
• Microvascular endpoints improved
• Trend only towards reduced incidence of MI (
  p0.052)

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Effect of Hypertension
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Why worry about Hypertension in Diabetic patients

• Treating hypertension can reduce the risk of
• Death 32
• Microvascular disease 37
• Stroke 44
• Heart failure 56
• UKPDS BMJ 1998317703 - 713

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Hypertension in Type 1 and 2 Diabetes

• Type 1
• Develop after several years of DM
• Ultimately affects 30 of patients

• Type 2
• Mostly present at diagnosis
• Affects at least 60 of patients

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Pathophysiology of hypertension

• Type 1 DM
• Secondary to
• nephropathy
• Activation of the
• RAAS

• Type 2 DM
• Hyperinsulinemia
• Secondary to insulin resistance
• Activation of the sympathetic nervous system

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Goals of Treatment of Hypertension

• Lower target for diabetic patients than
  non-diabetic patients
• 130/85 vs. 140/90
• UKPDS 38. BMJ 1998317703-713
• HOT. Lancet 19983511755-1762

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Effect of Cholesterol
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Dyslipidaemia in DM

• Most common abnormality is ? s HDL and ? s
  Triglyserides
• A low HDL is the most constant predictor of CV
  disease in DM
• Target lipid values LDL lt2.6 mmol/l, HDL gt1.15
  mmol/l, TG lt 2.5 mmol/l

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Micro vascular Complications
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Eye Complications

• Cataracts
• Non enzymatic glycation of lens protein and
  subsequent cross linking
• Sorbitol accumulation could also lead to osmotic
  swelling of the lens but evidence of involvement
  in cataract formation is less strong

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Eye Complications

• Retinopathy (stages)
• Background
• Pre-proliferative
• Proliferative
• Advanced diabetic eye disease
• Maculopathy
• Glaucoma

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Diabetic Retinopathy (DR)

• DR is the leading cause of blindness in the
  working population of the Western world
• The prevalence increase with the duration of the
  disease (few within 5 years, 80 100 will have
  some form of DR after 20 years)
• Maculopathy is most common in type 2 patients and
  can cause severe visual loss

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Background Retinopathy

• Micro aneurisms
• Scattered exudates
• Hemorrhages(flame shaped, Dot and Blot)
• Cotton wool spots (lt5)
• Venous dilatations

Background retinopathy
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Background retinopathy
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Pre-Proliferative Retinopathy

• Rapid increase in amount of micro aneurisms
• Multiple hemorrhages
• Cotton wool spots (gt5)
• Venous beading, looping and duplication

Proliferative retinopathy
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Proliferative Retinopathy

• New vessels (on disc, elsewhere)
• Fibrous proliferation (on disc, elsewhere)
• Hemorrhages (preretinal, vitreous)

Panretinal photo-coagulation
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Proliferative retinopathy
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Vitreous Bleeding
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Rubeosis Iridis
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Advanced Diabetic Eye Disease

• Retinal detachment with or without retinal tears
• Rubeosis iridis
• Neovascular glaucoma

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Maculopathy

• Macular edema (focal or diffuse)
• Ischaemic maculopathy

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Maculopathy
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Diabetic Nephropathy (DN)

• Diabetes has become the most common cause of end
  stage renal failure in the US and Europe
• About 20 30 of patients with diabetes develop
  evidence of nephropathy
• The prevalence of DN is higher in Black Americans
  than in Whites (Figures for South Africa is not
  available)

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Stages of Diabetic Nephropathy
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Stages of DN

• Stage I
• ? glomerular filtration and kidney hypertrophy
• Stage II
• u-albumin excretion lt 30mg/24h
• Stage III
• Microalbuminuria (30 300 mg/24h)

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Stages of DN (cont)

• Stage IV
• Overt nephropathy (gt 300mg/24h, positive u
  dipstick)
• Stage V
• ESRD characterized by ? blood urea and
  creatinine levels, hyperkalaemia and fluid
  overload

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Diabetic Neuropathy

• Sensorimotor neuropathy (acute/chronic)
• Autonomic neuropathy
• Mononeuropathy
• Spontaneous
• Entrapment
• External pressure palsies
• Proximal motor neuropathy

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Sensorimotor Neuropathy

• Patients may be asymptomatic / complain of
  numbness, paresthesias, allodynia or pain
• Feet are mostly affected, hands are seldom
  affected
• In Diabetic patients sensory neuropathy usually
  predominates

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Complications of Sensorimotor neuropathy

• Ulceration (painless)
• Neuropathic edema
• Charcot arthropathy
• Callosities

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Autonomic Neuropathy

• Symptomatic
• Postural hypotension
• Gastroparesis
• Diabetic diarrhea
• Neuropathic bladder
• Erectile dysfunction
• Neuropathic edema
• Charcot arthropathy
• Gustatatory sweating

• Subclinical abnormalities
• Abnormal pupillary reflexes
• Esophageal dysfunction
• Abnormal cardiovascular reflexes
• Blunted counter-regulatory responses to
  hypoglycemia
• Increased peripheral blood flow

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Mononeuropathies

• Cranial nerve palsies (most common are n.
  IV,VI,VII)
• Truncal neuropathy (rare)

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Entrapment Neuropathies

• Carpal tunnel syndrome (median nerve)
• Ulnar compression syndrome
• Meralgia paresthetica (lat cut nerve to the
  thigh)
• Lat Popliteal nerve compression (drop foot)
• All the above are more common in diabetic
  patients

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Proximal Motor Neuropathy

• Amyotrophy most common proximal neuropathy,
  affects the Quadriceps muscles with weakness and
  atrophy
• (synonym Diabetic Femoral radiculo-neuropathy)

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Diabetic Amyotrophy
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Thoracoabdominal Radiculopathy
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Sudomotor Dysautonomia
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Summary

• Diabetic neuropathy is a common complication, and
  result in significant morbidity
• Diabetic neuropathy present in numerous ways
• Hyperglycemia is the cause of diabetic neuropathy

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Summary (cont)

• Diabetic neuropathy have bad consequences
• Diabetic neuropathy can be prevented in only one
  way
• Once diabetic neuropathy is present it can only
  be managed symptomatically
• Early diagnosis and aggressive management can
  prevent progression

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Infections

• The association between diabetes and increased
  susceptibility to infection in general is not
  supported by strong evidence
• However, many specific infections are more common
  in diabetic patients and some occur almost
  exclusively in them
• Other infections occur with increased severity
  and are associated with an increased risk of
  complications

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Infections (cont)

• Several aspects of immunity are altered in
  patients with diabetes
• There is evidence that improving glycemic control
  patients improves immune function

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Specific Infections

• Community acquired pneumonia
• Acute bacterial cystitis
• Acute pyelonephritis
• Emphysematous pyelonephritis
• Perinephric abscess
• Fungal cystitis

• Necrotizing fasciitis
• Invasive otitis externa
• Rhinocerebral mucormycosis
• Emphysematous cholecystitis

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Rhino-Cerebral Mucormycosis
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Screening and Management Strategy for Diabetes
Complications
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Screening for Macrovascular Complications

• 1. Examine pulses and for cardiovascular disease
• 2. Lipogram
• 3. ECG
• 4. Blood pressure
• 1-3 annually
• 4 every visit (quarterly)

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Screening for Eye disease

• Annually
• Visual acuity (corrected with pinhole or lenses)
• Careful eye examination (noting the clarity of
  the lens and any retinal changes (Ophthalmoscopy
  through dilated pupils)

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Screening for Eye disease

• When to refer?
• Severe non-proliferative/proliferative
  retinopathy
• Macular edema or exudates in close proximity to
  the macula
• Cataract
• Unexplained reduction in visual acuity

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Screening for Nephropathy

• Annually
• Do one of the following
• u AlbuminCreatinine ratio (spot sample)
• 24h u Albumin excretion rate
• Early morning Albumin concentration
• (spot sample)
• Dipstick for Microalbuminuria
• If positive the test must be repeated twice in
  the ensuing 3 months. Microalbuminuria with
  incipient nephropathy is diagnosed if 2 or more
  of the tests are within the microalbumin range

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Microalbuminuria

• Increased risk for overt nephropathy
• Increased cardiovascular mortality
• Increased risk of Retinopathy
• Increased all-cause mortality
• Thus
• Microalbuminuria is an indication for
  screening for possible vascular disease and
  aggressive intervention to reduce all
  cardiovascular risk factors

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Screening Tests for Microalbuminuria
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Who to Screen For Microalbuminuria

• Type 1 Diabetes
• Begin with puberty
• After 5 years duration of disease
• Should be done annually there after

• Type 2 Diabetes
• Start screening at the Diagnosis of diabetes
• Should be done annually there after

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Management of Nephropathy

• Improvement of glycemic control
• Treatment of hypertension
• Treatment with angiotensin converting enzyme
  inhibitors
• Restriction of dietary intake of protein
• Once persistent elevation in u-Albumin is
• found refer to a Internist or Nephrologist

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Screening for Neuropathy

• 128 Hz tuning fork for testing of vibration
  perception
• 10g Semmers monofilament
• The main reason is to
• identify patients at risk
• for development of
• diabetic foot

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Using of the Monofilament
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Management of Neuropathy

• Burning pain TADs / Capsaicin
• Lancinating pain Anticonvulsants / TAD /
  Capsaicin
• Painful cramps Quinidine sulphate
• Restless legs - Clonazepam

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Dos and Don'ts of foot care

• Patient should
• check feet daily
• Wash feet daily
• Keep toenails short
• Protect feet
• Always wear shoes
• Look inside shoes before putting them on
• Always wear socks
• Break in new shoes gradually

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Conclusion

• This is just an outline of the major diabetic
  complications, and doesn't aim to be
  comprehensive
• All complications are preventable with good
  glycaemic control
• The progression of most complications can be
  halted if detected early and appropriate therapy
  instituted