Diabetes Complication

Stroke
Diabetic
retinopathy 1.2- to 1.8-fold
increase in stroke3
Leading cause
of blindness
in working-age
adults1 Cardiovascular
disease
75% diabetic
patients
die from CV events4

Diabetic Diabetic
nephropathy neuropathy
Leading cause of Leading cause of
end-stage renal disease2 non-traumatic lower
extremity amputations5

1Fong DS, et al. Diabetes Care 2003;26 (Suppl. 1):S99S102. 2Molitch ME, et al. Diabetes Care 2003;26 (Suppl. 1):S94S98.
3Kannel WB, et al. Am Heart J 1990;120:672676. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997.
5Mayfield JA, et al. Diabetes Care 2003;26 (Suppl. 1):S78S79.
 Complication of insulin deficiency
Hyperglycemic emergencies
Diabetic ketoacidosis (DKA)
Hyperglycemic hyperosmolar nonketotic state (HHS)
Chronic complications
Neuropathy

Microangiopathy

Retinopathy
Nephropathy
Foot ischemia
Macroangiopathy Atherosclerosis
Risk of cardiovascular death in type 1 diabetics vs.
Nondiabetics : >5X higher in males, 7X higher in females
Complication of insulin excess

Hypoglycemia : Activation of the sympathetic

nervous system (diaphoresis, tremulousness
and tachycardia) and insufficient delivery of
oxygen to the brain (confusion, seizures and
unconsciousness
Diabetes Complications
Macro vascular
Micro vascular
Neuropathy
Infections
Mechanisms
Genetic susceptibility

*Repeated acute changes

in cellular metabolism

Hyperglycemia Tissue damage

**Cumulative long term

changes in stable
macromolecules

Independent accelerating factors

Macro vascular Complications
Macrovascular Complications(1)

Have a 2 to 6 times higher risk for development

of these complications than the general
population
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.
Macrovascular Complications(2)
Once clinical macro-vascular disease develops
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
Clinical manifestation :
Ischemic heart disease
Cerebrovascular disease
Peripheral vascular disease
 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
Risk of MI in Diabetes

Haffner, SM et al NEJM: 339: 229-234

Glycemic Control to Reduce CAD
DCCT trial:
UKPDS:
1441 patients, type 1 diabetes
3867 patients with newly
Randomized to intensive diagnosed type 2 DM
glycemic control vs.
Intensive vs.
conventional therapy
Conventional therapy
Monitored prospectively for 6.5
10 year follow-up
years
Microvascular endpoints
Results:
improved
Less retinopathy by 50%
Trend only towards
Macrovascular complications:
41% reduction (not statistically reduced incidence of MI (
significant) p=0.052)
-small number of events in
young patient cohort
 Effect of Hypertension

Mortality vs systolic blood pressure

70
Ten Year Mortality (per 1000)

60

50

40
Non-diabetic

30 Diabetic

20

10

0
110 120 130 140 150 160
Systolic Blood pressure
(mmHg)
Benefits of hypertension treatment
in DM

Treating hypertension can reduce the risk of:

Death 32%
Microvascular disease 37%
Stroke 44%
Heart failure 56%
Hypertension in Type 1 and 2 Diabetes
Type 1
Develop after several years of DM, ultimately affects ~30% of
patients
Secondary to nephropathy, activation of the RAAS
Type 2
Mostly present at diagnosis, affects at least 60% of patients
Hyperinsulinemia, secondary to insulin resistance
Activation of the sympathetic nervous system
Lower target for diabetic patients than non-
diabetic patients: 130/85

UKPDS 38. BMJ 1998;317:703-713

HOT. Lancet 1998;351:1755-1762
 Effect of Cholesterol

Serum cholesterol vs Mortality

Ten Year Mortality (per

70
60
50
1000)

40 Non-diabetic
30 Diabetic
20
10
0
4 5 6 7
s-Cholesterol (mmol/L)
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
Retinopathy (stages)
Background
Pre-proliferative
Proliferative
Advanced diabetic eye disease
Maculopathy
Glaucoma
Cataracts
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
Pre-Proliferative Retinopathy

Rapid increase in
amount of micro
aneurisms
Multiple hemorrhages
Cotton wool spots
(>5)
Venous beading,
looping and Proliferative retinopathy
duplication
Proliferative Retinopathy

New vessels (on disc,

elsewhere)
Fibrous proliferation
(on disc, elsewhere)
Hemorrhages
(preretinal, vitreous)

Panretinal photo-coagulation
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 II : u-albumin excretion < 30mg/24h
Stage III : Microalbuminuria (30 300 mg/24h)
Stage IV : Overt nephropathy (> 300mg/24h,
positive u dipstick)
Stage V : ESRD characterized by blood urea
and creatinine levels, hyperkalaemia
and fluid overload
Screening for Nephropathy
Type 1 Diabetes : begin with puberty, after 5 years
duration of disease
Type 2 Diabetes : start screening at the diagnosis of
diabetes
Annually, do one of the following:
u Albumin:Creatinine ratio (spot sample)
24h u Albumin excretion rate
Early morning Albumin concentration (spot sample)
Dipstick for Microalbuminuria
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

Microalbuminuria is an indication for screening

for possible vascular disease and aggressive
intervention to reduce all cardiovascular risk
factors
Screening Tests for Microalbuminuria
Spot
24h u Timed
Category collection
collection collection
(mg/mg
(mg/24h) (mg/min)
creat)

Normal 30 20 30

Microalbum
30 - 299 20 - 199 30 - 299
inuria

Albuminuri
300 200 300
a Overt
 Management of Nephropathy

Improvement of glycemic control

Treatment of hypertension
Treatment with angiotensin converting enzyme
(ACE) inhibitors or angiotensin II receptor
antagonis (AIIRA)
Restriction of dietary intake of protein
Once persistent elevation in u-Albumin is found
refer to a Internist or Nephrologist
Diabetic Neuropathy
Sensorimotor neuropathy (acute/chronic)
Autonomic neuropathy
Mononeuropathy
Spontaneous
Entrapment
External 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

Symptomatic Subclinical abnormalities

Postural hypotension Abnormal pupillary reflexes
Gastroparesis Esophageal dysfunction
Diabetic diarrhea Abnormal cardiovascular
Neuropathic bladder reflexes
Erectile dysfunction Blunted counter-regulatory
Neuropathic edema responses to hypoglycemia
Charcot arthropathy Increased peripheral blood
flow
Gustatatory sweating
 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
Mononeuropathies
Cranial nerve palsies (most common are n. IV,VI,VII)
Proximal Motor Neuropathy
Amyotrophy most common proximal neuropathy,
affects the Quadriceps muscles with weakness and
atrophy (synonym: Diabetic Femoral radiculo-
neuropathy)
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
Using of the Monofilament
Management of Neuropathy
Burning pain TADs / Capsaicin
Lancinating pain Anticonvulsants / TAD /
Capsaicin
Painful cramps Quinidine sulphate
Restless legs - Clonazepam
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 Necrotizing fasciitis

pneumonia
Invasive otitis externa
Acute bacterial
cystitis Rhinocerebral
mucormycosis
Acute pyelonephritis
Emphysematous Emphysematous
pyelonephritis cholecystitis
Perinephric abscess
Fungal cystitis
Acute Complications of Diabetes

DKA

HHNK

Hypoglycemia

44
 Diabetic Keto-Acidosis
Diabetic Ketoacidosis
Most serious complication in Type 1 diabetes
Precipitating Causes
Not enough insulin
Skipping insulin
Stress, trauma
Insulin resistance

Ketosis
Dehydration
Electrolyte imbalance
45
 Polyuria
Symptoms of DKA
Somnolence
Abdominal pain Tachycardia
Anorexia Thirst
Dehydration Visual
Fuity breath disturbances
Kussmauls Warm, dry skin
Change LOC Weakness
Hypotension Wt. loss
N&V
46
Assessment DKA
Hyperglycemia Rehydrate
Hyperosmolality Reverse shock
Dehydration Give Potassium
Electrolyte Corret pH
imbalances Give insulin
Metabolic acidosis
Hypoglycemia
Fluid overload

47
Treatment principle
IV Fluids
Potassium Replacement
Correct pH
Give Regular Insulin only
Initial bolus IV (0.15u/kg)
Then Regular Insulin IV drip

48
 HHNK
Hyperglycemic Hyperosmolar Noketotic
Syndrome

Most commonly occurs in older adults

with Type II diabetes
Always look for precipitating factors
Factors Associated with HHNK : Drugs,
procedures, chronic illness, acute illness

49
 Four Major Clinical Features
Severe hyperglycemia
No or slight ketosis
Profound dehydration
Hyperosmolality
Treatment
Similar to DKA
More agresive fluid replacement
Find underlying cause

50
Hypoglycemia
Also known as insulin reaction or hypoglycemic
reaction
Risk Factors
Overdose of insulin
Omitting a meal
Overexertion
Nausea and vomiting
Alcohol intake

51
Symptoms of Hypoglycemia

Adrenergic Neuroglycopenic
Shakiness Headache
Irritability Mental illness
Nervousness Inability to concentrate
Tachycardia Slurred speech
Tremor Blurred vision
Hunger Confusion
Diaphoresis Irrational behavior
Pallor Lethargy
Paresthesias LOC, coma, seizure
52
Interventions

Mild
carbohydrate 10-15 gram
Moderate
20-30 gram of carbs
Glucagon, 1 mg SC or IM
Severe
50% dextrose 25 g IV
Glucagon 1 mg IM or IV

53
 Retinopathy
microaneurysms cluster at macula->terminal
vessels obstructed->ischemia->new vessel
proliferation
Nephropathy-leads to hypertension. Assoc
with the highest mortality.
Cardiovascular disease- silent ischemia
Peripheral neuropathy- numbness and tingling
progressing to total insensitivity
Stiff joint syndrome- prayer sign and atlanto-
occipital joint involvement
 Autonomic nervous system dysfunction
-orthostatic hypotension, resting tachycardia, absent
beat-to-beat variation
-hypogylcemic unawareness
-gastroparesis occurs in 20-30%
DKA
Insulin transfers glucose and amino acids into
the cells.
Hyperglycemia->osmotic diuresis-
>dehydration->acidosis. Also, a build up of
amino acids in the blood->lipolysis->free fatty
acids->converted to ketone bodies in the liver
Results in a intravascular fluid volume deficit of
5-8 liters, potassium deficit of 200-400 mEq,
and NaCl deficit of 350-600 mEq
Treatment of DKA
Intubate for CNS depression
Regular insulin 10 units IVP followed by 5-10
units/hr IV
Normal saline 5-10 ml/kg/hr IV
Add 5% glucose when serum blood sugar<250
mg/dl
Potassium 0.3-0.5 mEq/kg/hr IV
Monitor blood sugar, potassium, arterial pH and
urine ketones hourly
Identify cause (sepsis, MI, compliance)
HYPEROSMOLAR, HYPERGLYCEMIC
NONKETOTIC COMA

-elderly, insulin deficiency, renal insufficiency, thirst

deficiency
-sepsis, hyperalimentation or drugs (corticosteriods)
-glucose >600 mg/dl
-osmotic diuresis->hypokalemia and dehydration
-serum osmolarity >350 mOsm/L
-pH >7.3
-hypovolemia (severe, up to 25% total body water)
-patients are insulin deficient but liver insulin levels
sufficient for metabolism of free fatty acids->no ketosis
-coma due to shrinkage of brain cells
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
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