chronic complications of diabetes mellitus

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I- INTRODUCTION-DEFINITION :

Diabetes mellitus type it 1 or Type 2 is likely to cause the medium to long-term complications.

Chronic complications often life-threatening diabetic and involve important organs.

La microangiopathie: interesting small caliber vessels + hair: Specific complications D.S.. : eye, kidney, and neurological.

The macroangiopathie: Interestingly the vessels of medium and large caliber : Non-specific cardiovascular complications of D.S.

It is important to understand both current clinical axes:
– better detection
– prevention or early treatment

  • acute complications

– Coma keto-acidosis
– Coma hyperosmolaire
– Hypoglycémies

  • degenerative complications

* Microangiopathie
– retinopathy
– nephropathy
– neuropathy
* Macroangiopathie
– vascular risk factors
– Heart and Diabetes
– Peripheral arterial disease
– AVC
– diabetic foot
—> other complications
—> skin complications
—> infectious complications
—> musculoskeletal complications

II- EPIDEMIOLOGY :

– Diabetic retinopathy (RD) is the first cause of blindness 65 years in industrialized countries.
– Diabetes is the first cause of & rsquo; chronic renal failure.
– Amputation of a leg because of diabetes is practiced all 30 seconds.
– The cost of a transtibial amputation of 82 657 USD
– Finally 70 % of diabetics die of cardiovascular complications :
* 40 % by myocardial ischemia ;
* 25 % by stroke ;
* 5 % other vascular disorders.
So, Diabetes increases the risk of vascular disease 3 at 4 times compared to non-diabetic.

III- MICROANGIOPATHIE :

A- DEFINITION-EPIDEMIOLOGY :

BY microangiopathy means all lesions affecting the microcirculation ( terminal arterioles and capillary bed ) as opposed to macrovascular disease that affects the large arteries and medium caliber.

This is a disease of the small arteries arterioles =

It is a specific complication of diabetes: glycemic level 1,26 g / 1 defining diabetes corresponds to the threshold of appearance of lesions of the retinal microangiopathy in particular.

Microangiopathy is almost exclusively due to chronic hyperglycaemia. Its frequency in both types of diabetes is closely linked :

  • the disease duration of diabetes
  • the degree of glycemic control
  • Sometimes individual susceptibility (genetic)

—> RETINOPATHY : R & D affects about 40% diabetics, it is thein cause of acquired blindness in developed countries before the age of 65 years.

—> LA NEPHROPATHIE : The ND is a complication somewhat less common (30% of patients after 15 years of diabetes) but very serious consequences. Renal involvement is an important mortality factor diabetics, including cardiovascular.

—> NEUROPATHY : It is probably the most common complication, up & rsquo; to 50% diabetics to varying degrees, this is a complex disease involving disturbances both nerve fibers and microvessels (vasa nervosum) affecting the nervous system as well as the peripheral nerves the autonomic nervous system.

It plays a key role in the pathophysiology of diabetic foot.

B- PATHOPHYSIOLOGY :

  • The microvessels, arterioles, venules and in particular the capillary between them, are the site of exchange between blood and tissues.
  • Their integrity is necessary for the proper functioning of organs and tissues.
  • The Hyperglycemia is now recognized as the main cause of the microvascular complications of diabetes.
  • However, the mechanisms of glucose toxicity are not yet clearly determined.
  • Several hypotheses to explain the micro vx alterations Diabetes.
  • They probably involved competitions in the genesis of the disease.
  • The first hypothesis is concerned hemodynamics and physiology of the microcirculation and blood flow.

  • Beside 5 biochemical hypotheses were also proposed :

1- voice polyols
2- the path of & rsquo; hexosamine

=> accumulation of sorbitol and fructose,↑ of the intracellular osmotic pressure and accumulation of toxic free radicals

3- l & rsquo; PKC activation
4- formation of advanced glycation endproducts: by non-enzymatic glycosylation of proteins : Products half life
→ prolonged thickening of basement membranes.
5- oxidative stress : l & rsquo; auto-oxidation of glucose to & rsquo; origin of toxic hydroxyl radicals (OH−;H2O2 ... ..)

The polyol pathway and aldose reductase : In tissues where the penetration of glucose is independent of & rsquo; insulin, glucose s & rsquo; accumulates in excess in the cell (chronic hyperglycemia) and will be reduced to sorbitol in the & rsquo; influence & rsquo; the enzyme & rsquo; aldose reductase.. This accumulation was directly implicated in the genesis of diabetic cataracts and neuropathy in the peripheral. An accumulation of sorbitol was also evidenced in the retina and kidney, and its role in microangiopathy is likely.

– A decrease in the content myo-inositol (and NO also) at the retina, nerves, kidney glomeruli was also highlighted.

C- DIABETIC RETINOPATHY :

  • common complication
  • Leading cause of blindness in adults< 65 years in industrialized countries
  • 20 % DT 2 already have a DPR at diagnosis of diabetes
  • After 20 years of diabetes, DPR would be present at : 90 % DTI ; 60 % T2DM
  • It affects retinal capillaries in their wall is thickened and whose resistance is altered, responsible for the formation of micro aneurysms.
  • capillary leak syndrome responsible for intra retinal leakage of plasma (edema) or red blood cells (bleeding), and capillary responsible ischemia of the retina occlusion. This formidable ischemia will trigger the formation of neo vessels 'fragile'(RDP).
International Classification of Diabetic Retinopathy (AAO 2002)

macular edema : any retinal exudates or thickening at the posterior pole
OM minimum : retinal thickening or exudates away from the center of the macula
moderate OM : retinal thickening or exudates near the center of the macula, but did not reach
severe OM : retinal thickening or exudates reaching the center of the macula.

RISK FACTORS OF DEVELOPMENT OR WORSE :

  • glycemic
  • HTA
  • Pregnancy
  • Puberty
  • The presence of nephropathy
  • Cataract surgery
  • Too fast equilibration of glucose

COMPLICATIONS DE LA RD :

  • Intra vitreous hemorrhage
  • retinal detachment
  • neovascular glaucoma

THE SURVEILLANCE :

  • FO annuel, with tO, OF , Slit Lamp ; +/- Retinal fluorescein angiography,(visual loss late) ;Reinforced by stage of DR (each 06 months if moderate RDNP)
  • L’OCT (optical coherence tomography)Finds its main role in the diagnosis and monitoring of macular edema.

TREATMENT :

  • At all stages of R & D : Best glycemic, TA better balance
  • In advanced stages of R & D : Laser photocoagulation to reduce and prevent the néovscularisation (anti VEGF)
  • Surgery : vitrectomy in cases of hemorrhage.

PREVENTION :

  • glycemic
  • Control of hypertension and dyslipidemia.

D- DIABETIC KIDNEY :

  • Many stadiums have been described (especially DTI ++++)
  • History harder to describe in T2DM where T hypertension is often present before or early.
  • only concern 20 at 40 % DTI and 2 (genetic factors)
  • The leading cause of ESRD in industrialized countries.
  • 20,6 % dialysis patients are diabetics in France

– 14,8 % DT 2
– 4,8 % DT 1

  • the ND T2DM is a risk factor cvx (microalb= fr cvx).
  • Most of the time, it is easy to relate kidney abnormalities in diabetes :

– the presence of & rsquo; other complications of microangiopathy (RD+++).
– Negativity of immunological assessment.
– Sometimes, it is necessary to perform a renal biopsy.

Classification they Mogensen (See table) :
It describes the next evolution of the disease, a histologically and biological.
On distingue 5 stages & rsquo; evolution :
Stade In : Hyperfiltration glomérulaire.
The glomerular filtration rate is increased more than 20%.
nephromegaly.
Stade II : minimal histological lesions
– diffuse thickening of the basement membrane of the glomerular capillaries and mesangial nodular formations (glomerulosclerosis Kimmelstiel Wilson).
Stade III : Néphropathie fool;.
Onset of microalbuminuria (30-300mg/24h) and reduced glomerular filtration
This stage is where should focus therapeutic efforts, to prevent the & rsquo; further damage.
stage IV : nephropathy.
Development of & rsquo; permanent proteinuria (>0.3g/24h)
• concerns 30% patients
• nephrotic syndrome often unclean with hypertension and renal failure.
Stade V : kidney failure with anuria requiring the & rsquo; extrarenal treatment or transplantation.

Stages of diabetic nephropathy in accordance Mogensen

RISK FACTORS :

  • Ethnic
  • genetic
  • HTA
  • Tobacco
  • Dyslipidémie
  • Anemia
  • retinopathy
  • Food rich in protein

SURVEILLANCE :

screening = Search microalbuminuria

  • 1 once a year
  • On sample clock
  • On collection of urine 24 ++++ hours
  • In the absence of urinary tract infection ,disequilibrium ,fever or exercise.
  • Positive si 30-300mg/24 a 02 occasions.

– ASSESSING RENAL FUNCTION REGULAR

  • Plasma creatinine and measurement of creatinine clearance :

-Cockroft-Gault equation: overestimates EN obese and DT .
– MDRD (Modification of Diet in Renal Disease)+++++
More effective in diabetics or in case of obesity.

TREATMENT- PREVENTION :

  • Strict Balance Diabetes (HbAle < 6,5%,stages 1-111+++).
  • treatment renoprotective (IEC ou milk II) at the stage of low-dose or full microalbuminuria in case of hypertension (goal : 125/75).
  • restricted diet protein
  • Decrease salt intake : 5g/j
  • Screening and treatment of all other Fr cvx (smoking, obesity, hyperlipidemia, inactivity)
  • Avoid nephrotoxic drugs(AINS;aminosides) or PCI unless absolutely necessary.
  • Avoid aggravating factors of renal failure.

E- DIABETIC NEUROPATHY :

  • frequent common complication (5 at 60 %)
  • earliest complication
  • Interested :

– The peripheral nervous system
– The autonomic nervous system (autonomous)

  • ultimate stage :

– diabetic foot
– Charcot neuro-arthropathy

Contributing factors :

  • Of diabetes
  • glycemic
  • Age
  • male
  • Big size
  • Alcoholism, nutritional factors
  • PAD and chronic ischemia
  • Rapid change in glycemic

a) Peripheral neuropathy :

—> the polyneuropathy :

  • The most common form (80%)
  • bilaterally symmetrical lower limb
  • distal to start moving upwardly
  • secondarily affecting the upper limbs
  • usually predominantly sensory
  • Early involvement of the deep sensitivity and vibration
  • later thermoalgesic or epicritic, Deep tendon reflexes abolished in affected territories
  • L & rsquo; electromyogram to measure conduction velocity has little & rsquo; interest early, but can afford to follow & rsquo; evolution.

—> Mononeuropathies and multinévrites :

  • rare
  • must find another cause diabetes
  • are more common in elderly diabetic
  • various infringements:

– cruralgie
– oculomotor palsy (VI I III) with a vascular factor explaining their sudden onset
– proximal amyotrophy lower limb
– neuralgia of the ulnar, the median, intercostal

b) Autonomic neuropathy :

  • Cardiovascular associated neuropathy :

– From syndromes painless coronariens (myocardial ischemia painless IMS = +++)

– Hypotension orthostatique : NOT fall>20 and / or PAD>10 mmHg when switching lying / standing
– Tachycardia rest

  • The digestive neuropathy: consists in varying degrees:

– d & rsquo; a driving diarrhea
– d & rsquo; gastroparesis, with delayed gastric emptying.

  • l & rsquo; urological reached: with bladder weakness and post-void residual risks with d & rsquo; UTI.
  • l & rsquo; impotence is often multifactorial, with vascular factors and / or psychological associated

DIFFERENTIAL DIAGNOSIS :

  • NPD is a diagnosis of exclusion ++++
  • Metabolic (amylose, porphyrie… )
  • T oxic (alcohol, drug… )
  • paraneoplastic (bronchial K, gastric, lymphoma)
  • Carentielle (B6.B12…)
  • Inflammatory and infectious (Lyme… )
  • hereditary family
  • PAN, gammapathie monoclonal….

SCREENING :

  • monofilament test +++
  • score DN4

TREATMENT :

  • glycemic +++
  • References treatment of pain and dysesthesia

– analgesics
– antiepileptic ( Tegretol®, Neurontin®, Lyrica® cymbalta…)
– antidepressants
– white B1B6
– BZD

  • Treatment of Gastroparesis : erythromycin (analogue GIP).
  • Screening and treatment of & rsquo; IMS +++.
  • Screening and treatment of urinary tract infections
  • Suggested treatments

– Inhibitors polyol pathway, PKC, antioxidants…. (disappointing results in humans)

IV- MACROANGIOPATHIE :

Atherosclerosis associated thickening of the wall of large arteries and blockage by atherosclerotic plaques

A- PATHOPHYSIOLOGY :

  • Diabetes is a major factor favoring lesions & rsquo; atherosclerosis :

– deleterious action of & rsquo; hyperglycemia on endothelial cells
– a role promoting on & rsquo; platelet aggregation
– an increase in LDL-cholesterol and triglycerides (elevated VLDL and decreased lipoprotein lipase activity ,small, dense LDL).

  • Diabetes is a risk factor Cvxaire.
  • Atherosclerosis associated thickening of the wall of large arteries and blockage by atherosclerotic plaques
  • An overall management of vascular risk is necessary with the reduction of other risk factors

cardiovascular risk factors :

A number of factors are likely to promote the emergence or worsening of atherosclerosis :
– Age of the diabetic patient of diabetes evolution Time ;
– Smoking ;
– Sedentary lifestyle ;
– HTA ;
– Dyslipidémie ;
– Microalbuminurie.

B- CORONARY HEART DISEASE :

  • Angina (angor) or & rsquo; myocardial infarction (IDM)
  • Often asymptomatic and painless , In 20 at 30% ischemia is silent, explained in part by the autonomic neuropathy.
  • more common (risk x 2 at 3 H, x 3 at 5 F), worse (mortality x 2 IDM)
  • We need to think systematically before the sudden onset of :

– Dyspnea effort
– Asthenia especially the effort digestive -Troubles or epigastric pain -Troubles heartbeat glycemic -Déséquilibre unexplained.
– can lead to heart failure

  • Impose a comprehensive treatment of risk factors (statins, aspirin, antihypertensive)
  • Impose a systematic screening:

– specialist consultation 1 times / year, with a resting ECG

  • Un ECG d&rsquo;effort, echocardiography, myocardial perfusion imaging and / or angiography (consensus)

C- The peripheral artery disease (AOMI) :

  • Stenosis or occlusion of the arteries in the lower limbs
  • Lesion often multiple and distal.
  • Touch 20 at 25% diabetic multiplying the risk of amputation 15.
  • Risk of acute or chronic ischemia, ulcerations, necrosis that will degenerate into gangrene -> amputation.
  • With 02 like lesions:

– Arteriosclerosis medical calcification = +++ —> arterial stiffness.
– atherosclerosis: more diffuse faster ;more severe with bilateral distal reached, tiered and often inaccessible to revascularization

  • Imposes & rsquo; auscultation of arterial routes, the peripheral pulse palpation, looking for intermittent claudication.
  • —> Role : inspection and patient education for feet, pay attention to mycoses, Screening and Prevention, vaccination (antitétanique).
  • Clinically rarely revealed by intermittent claudication due to the coexistence of neuropathy. The feet are blades, depilated, cold to the touch and a reduction or even abolition of distal pulses, but sometimes the presence of pulse does not eliminate the vascular damage due to autonomic neuropathy.
  • Clinically rarely revealed by intermittent claudication due to the coexistence of neuropathy.

ischemic foot :

  • cold feet
  • Pulse \ or = 0
  • limp intermittente???
  • depilation of the lower limbs
  • the raised member bleaching
  • cyanic coloring toes
  • muscle atrophy and fatty s / skin tissue
  • shiny skin
  • Onychodystrophie

SCREENING :

  • Physical examination:pulse ++
  • The measurement of the index of systolic pressure or IPS ++++ and classify ischemia, (See table)
  • Doppler ultrasound of the lower limbs
  • TcPO2(and<30mmHg critical ischemia) or trans-cutaneous pressure 02
  • Angio-scanner des MI
  • Prevention : FDR cardiovascular
Clinical interpretation of the extent of the & rsquo; IPS

D- STROKE (AVC) :

  • Stenosis or occlusion of cerebral arteries designed with risk & rsquo; stroke, transient ischemic attacks (AIT), vascular dementia.
  • Touch 2 at 3 Once more the man and 3 at 5 times more women compared to non-diabetic
  • Imposes & rsquo; auscultation of arterial routes, looking for a neurological deficit
  • Doppler screening trunks supra aortic regularly
  • Prevention: Control of Cardiovascular FDR

E- HYPERTENSION (HTA) :

  • More than 60 % type diabetes 2 are hypertensive after 45 years.
  • Note the pejorative role on blood pressure of a syndrome of apnea sum which is common in overweight context of diabetes Type 2.
  • Hypertension is seen in the type of diabetes 1 if diabétique.Tandis nephropathy than in T2DM is often due to nephroureterectomy angiosclerose
  • Hypertension is a major risk factor for cardiovascular events.
  • But it also constitutes an aggravating factor microangiopathy.
  • The treatment often requires associations ,inhibitors of angiotensin converting enzyme (IEC) and receptor antagonists of angiotensin II(ARAII) are privileged.

V- PREVENTION Macroangiopathy :

Preventing macrovascular involves standardizing cardiovascular risk factors :

  • Have better glycemic control
  • Regular physical activity tailored to the patient
  • Reducing alcohol
  • Stopping tobacco intoxication
  • Treatment of hypertension
  • Treatment of dyslipidemia. The objective is to limit all cardiovascular risk in diabetic Goals:
  • HTA < 130/85
  • LDL dyslipidemia based on risk factors
  • smoking = 0
  • HbAlc diabetes < 7 %
  • Overload weight and obesity 4 limit the weight gain

WE- THE DIABETIC FOOT :

SEE TD

VII- OTHER COMPLICATIONS :

A- INFECTIOUS COMPLICATIONS :

bacterial: lung, ORL, urinary, mucocutaneous, genital
Need to update the tetanus vaccination
viral : importance of preventive measures (flu shot)
fungal, especially genital and / or digestive
Urinary tract infections

  • mostly unrealized
  • favored by the & rsquo; age, diabetes duration, l & rsquo; hyperglycemia
  • are systematically search
  • can be in & rsquo; origin & rsquo; glycemic control
  • sometimes evolve as part of & rsquo; an atonic bladder with bladder residue postvoid.
  • may be complicated form:

– acute pyelonephritis
– papillary necrosis
– d & rsquo; kidney failure

B- THE SKIN COMPLICATIONS :

Are mostly of staphylococcal infectious nature favored by more frequent nasal carriage (folliculites, furoncles) sometimes Candida (vulvaire pruritus and vulvar vaginitis, balanite, stomatitis, onyxis). Increased frequency of & rsquo; erysipelas (staphylococci or streptococci) sometimes associated with phlebitis are sometimes relatively specific:

  • Necrobiosis lipoic at the pre-tibial region
  • granuloma annulare
  • Bullose diabetic treatment Complications:
  • Allergy (urticaria or localized reactions)
  • Lipodystrophies :

Atrophic related to the nature of the & rsquo; insulin
Hypertrophic related to poor d & rsquo technique, injection

C- THE COMPLICATIONS OSTEOARTICULAR :

– Some are more common in diabetics: Capsulitis of the shoulder ;
Carpal tunnel syndrome ;Dupuytren's Contracture ; Osteo arthritis of the foot or Charcot foot.

Course of Dr A. ZAIOUA – Faculty of Constantine