Diabetes Complications
DG van Zyl
The Ticking Clock
Different Diabetes Complications
Macro vascular Micro vascular Neuropathy Infections
Mechanisms
Hyperglycemia Tissue damage
*Repeated acute changes in cellular metabolism
**Cumulative long term changes in stable macromolecules
Genetic susceptibility
Independent accelerating factors
Macro vascular Complications
Macro-vascular Complications
Ischemic heart disease Cerebrovascular disease Peripheral vascular disease
Diabetic patients have a 2 to 6 times higher risk fordevelopment of these complications than thegeneral population
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.
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
CAD Morbidity and Mortality in Type 2 DM Framingham Data: 20
year follow-up:Age 45-74: 2-3 fold increase in
clinically evident atherosclerotic disease in diabetics
women diabetics=male 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
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
Cardiovascular Death Rates: MRFIT data
Stamler J., et al Diabetes Care: 16: 434-444
Risk of MI in Diabetes
Haffner, SM et al NEJM: 339: 229-234
Plasma Glucose as Independent Risk Factor
Andersson, DK et al. Diabetes Care 18: 1534-1543
Glycemic Control to Reduce CADDCCT 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 ( p=0.052)
Effect of HypertensionMortality vs systolic blood pressure
0
10
20
30
40
50
60
70
110 120 130 140 150 160
Systolic Blood pressure (mmHg)
Ten
Year
Mor
talit
y (p
er 1
000)
Non-diabetic
Diabetic
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 1998;317:703 - 713
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
Pathophysiology of hypertension
Type 1 DM
Secondary tonephropathy
Activation of the RAAS
Type 2 DM
HyperinsulinemiaSecondary to insulin
resistanceActivation of the
sympathetic nervous system
Goals of Treatment of Hypertension
Lower target for diabetic patients than non-diabetic patients:
130/85 vs. 140/90
UKPDS 38. BMJ 1998;317:703-713HOT. Lancet 1998;351:1755-1762
Effect of Cholesterol
Serum cholesterol vs Mortality
010203040506070
4 5 6 7
s-Cholesterol (mmol/L)
Ten
Year
Mor
talit
y (p
er
1000
) Non-diabeticDiabetic
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 <2.6 mmol/l, HDL >1.15 mmol/l, TG < 2.5 mmol/l
Micro vascular Complications
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
Eye Complications
Retinopathy (stages)BackgroundPre-proliferativeProliferativeAdvanced diabetic eye diseaseMaculopathy
Glaucoma
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
Background Retinopathy
Micro aneurisms Scattered exudates Hemorrhages(flame
shaped, Dot and Blot) Cotton wool spots
(<5) Venous dilatations
Background retinopathy
Background retinopathy
Pre-Proliferative Retinopathy Rapid increase in
amount of micro aneurisms
Multiple hemorrhages Cotton wool spots
(>5) Venous beading,
looping and duplication
Proliferative retinopathy
Proliferative Retinopathy
New vessels (on disc, elsewhere)
Fibrous proliferation (on disc, elsewhere)
Hemorrhages (preretinal, vitreous)
Panretinal photo-coagulation
Proliferative retinopathy
Vitreous Bleeding
Rubeosis Iridis
Advanced Diabetic Eye Disease
Retinal detachment with or without retinal tears
Rubeosis iridis Neovascular
glaucoma
Maculopathy
Macular edema (focal or diffuse)
Ischaemic maculopathy
Maculopathy
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)
Stages of Diabetic Nephropathy
Stages of DN
Stage I glomerular filtration and kidney hypertrophy
Stage IIu-albumin excretion < 30mg/24h
Stage IIIMicroalbuminuria (30 – 300 mg/24h)
Stages of DN (cont)
Stage IVOvert nephropathy (> 300mg/24h, positive u dipstick)
Stage VESRD characterized by blood urea and creatinine levels, hyperkalaemia and fluid overload
Diabetic Neuropathy
Sensorimotor neuropathy (acute/chronic)Autonomic neuropathyMononeuropathy
SpontaneousEntrapmentExternal pressure palsies
Proximal motor neuropathy
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
Complications of Sensorimotor neuropathy
Ulceration (painless) Neuropathic edema Charcot arthropathy Callosities
Autonomic Neuropathy
SymptomaticPostural hypotensionGastroparesisDiabetic diarrheaNeuropathic bladderErectile dysfunctionNeuropathic edemaCharcot arthropathyGustatatory sweating
Subclinical abnormalitiesAbnormal pupillary reflexesEsophageal dysfunctionAbnormal cardiovascular
reflexesBlunted counter-regulatory
responses to hypoglycemia
Increased peripheral blood flow
Mononeuropathies
Cranial nerve palsies (most common are n. IV,VI,VII)
Truncal neuropathy (rare)
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
Proximal Motor Neuropathy
Amyotrophy – most common proximal neuropathy, affects the Quadriceps muscles with weakness and atrophy(synonym: Diabetic Femoral radiculo-neuropathy)
Diabetic Amyotrophy
Thoracoabdominal Radiculopathy
Sudomotor Dysautonomia
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
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
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
Infections (cont)
Several aspects of immunity are altered in patients with diabetes
There is evidence that improving glycemic control patients improves immune function
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
Rhino-Cerebral Mucormycosis
Screening and Management Strategy for Diabetes
Complications
Screening for Macrovascular Complications
1. Examine pulses and for cardiovascular disease
2. Lipogram3. ECG4. Blood pressure 1-3 annually4 every visit (quarterly)
Screening for Eye disease
AnnuallyVisual acuity (corrected with pinhole or
lenses)Careful eye examination (noting the clarity
of the lens and any retinal changes (Ophthalmoscopy through dilated pupils)
Screening for Eye disease
When to refer?Severe non-proliferative/proliferative retinopathyMacular edema or exudates in close proximity to
the maculaCataractUnexplained reduction in visual acuity
Screening for Nephropathy
AnnuallyDo one of the following:
u Albumin:Creatinine ratio (spot sample)24h u Albumin excretion rateEarly 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
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
Screening Tests for Microalbuminuria
Category24h u
collection(mg/24h)
Timed collection(mg/min)
Spot collection(mg/mg creat)
Normal 30 20 30
Microalbuminuria 30 - 299 20 - 199 30 - 299
Albuminuria Overt 300 200 300
Who to Screen For Microalbuminuria
Type 1 DiabetesBegin with pubertyAfter 5 years
duration of diseaseShould be done
annually there after
Type 2 DiabetesStart screening at
the Diagnosis of diabetes
Should be done annually there after
Management of Nephropathy
Improvement of glycemic control Treatment of hypertension Treatment with angiotensin converting
enzyme inhibitors Restriction of dietary intake of proteinOnce persistent elevation in u-Albumin isfound refer to a Internist or Nephrologist
Screening for Neuropathy 128 Hz tuning fork for
testing of vibration perception
10g Semmers monofilament
The main reason is toidentify patients at riskfor development ofdiabetic foot
Using of the Monofilament
Management of Neuropathy
Burning pain – TADs / Capsaicin Lancinating pain – Anticonvulsants / TAD /
Capsaicin Painful cramps – Quinidine sulphate Restless legs - Clonazepam
Do’s 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
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