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Diabetes Complications

MUHAMMAD ZAMAN HABIB FINAL YEAR MBBS NISHTAR MEDICAL COLLEGE MULTAN

The Ticking Clock

Different Diabetes Complications


Macro vascular Micro vascular Neuropathy Infections

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

Macro vascular Complications

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

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:

Multiple Risk Factor Intervention Trial (MRFIT)

2-3 fold increase in clinically evident atherosclerotic disease in diabetics women diabetics=male diabetics in terms of CAD mortality

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 nondiabetic cohort

Risk Factor Clustering in Diabetes

Type 2 Diabetes at Diagnosis:

50% have hypertension 30% have dyslipidemia Prospective study Newly detected type 2 DM:

UKPDS:

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 CAD


DCCT trial:

UKPDS:

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

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 Hypertension
Mortality vs systolic blood pressure
70

Ten Year Mortality (per 1000)

60 50 40 30 20 10 0 110 120 130 140 150 160 Systolic Blood pressure (mmHg) 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 to nephropathy Activation of the RAAS

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

Goals of Treatment of Hypertension


Lower target for diabetic patients than nondiabetic patients:

130/85 vs. 140/90


UKPDS 38. BMJ 1998;317:703-713 HOT. Lancet 1998;351:1755-1762

Effect of Cholesterol
Serum cholesterol vs Mortality
Ten Year Mortality (per 1000)

70 60 50 40 30 20 10 0 4 5 6 7 s-Cholesterol (mmol/L)

Non-diabetic Diabetic

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) Background Pre-proliferative Proliferative Advanced diabetic eye disease Maculopathy 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 II u-albumin excretion < 30mg/24h Stage III Microalbuminuria (30 300 mg/24h)

Stages of DN (cont)
Stage IV Overt nephropathy (> 300mg/24h, positive u dipstick) Stage V ESRD characterized by blood urea and creatinine levels, hyperkalaemia and fluid overload

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 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

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 radiculoneuropathy)

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. Lipogram 3. ECG 4. Blood pressure 1-3 annually 4 every visit (quarterly)

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)

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

Screening for Nephropathy


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
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


Category
24h u collection (mg/24h) Timed collection (mg/min) Spot collection (mg/mg creat)

Normal

30 30 - 299

20 20 - 199

30 30 - 299

Microalbumi nuria Albuminuria Overt

300

200

300

Who to Screen For Microalbuminuria


Type 1 Diabetes Type 2 Diabetes

Begin with puberty Start screening at the Diagnosis of After 5 years diabetes duration of disease Should be done Should be done annually there after annually there after

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

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

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