complications of diabetes mellitus

z
CHRONIC COMPLICATIONS
OF
DIABETES MELLITUS
By
DR M KRISHNA KUMAR
DNB RESIDENT
SSSGH,
Thursday,November15,2018
1krish

z
Chronic
complications
vascular
Micro vascular
Macro vascular
Non vascular
Gastroparesis,infections
Skin changes,
hearing loss etc
2krish

z
Micro vascular
• Eye disease
Retinopathy(proliferative/non
proliferative
• Macula edema
• NEUROPATHY
• sensory and motor
• mono and poly
• NEPHROPATHY
Macro vascular
• Coronary heart disease
• Peripheral arterial disease
• Cerebrovascular disease
other
• Gastrointestinal
• Genitourinary
• Dermatologic
• Infectious
• Cataracts
• Glaucoma
• Periodontal disease
• Hearing loss
3krish

z
Legacy effect or metabolic memory
 The positive impact of a period of improved glycemic
control on later disease has been termed as
 “legecy effect or metabolic memory”
4krish

z
5krish

zMechanisms
6
1. ↑ formation of advanced glycosylation end products
(AGEs)cross linking of protiens ,accelerated
atherosclerosis, glomerular dysfunction, and
altered extra cellular matrix composition
2. Hyperglycemia increases glucose metabolism via
sorbitol pathway by aldose reductase enzyme
3. Hyperglycemia  diacyl glycerolActivation of
protein kinase C (PKC). It alters transcription of
genes for fibronectin,type4 collagen,contractile
protiens,and extracellular matrix protiens in
endothelial cells and neurons
6krish

z
↑ intracellular glucose
Interaction of glucose with amino acids
via nonenzymatic glycosylation  Advanced glycosylation end products
↑ AGEs
• cross-link proteins eg.collagen
• accelerate atherosclerosis
• promote glomerular
dysfunction
• induce endothelial dysfunction
1. Hyperglycemia ↑ AGEs synthesis
7
7krish

z2. Hyperglycemia ↑ glucose metabolism via sorbitol
pathway
8
Intracellular glucose ↑ promotes conversion
to sorbitol
via aldose reductase
↑ Sorbitol
• alters redox potential
• ↑ cellular osmolality
• generates reactive O2 species
8krish

z
3. PKC Activation
Hyperglycemia  ↑ DAG formation  PKC activation
Effects of PKC activation :
•production of vascular endothelial growth factor(VEGF) 
neovascularization
 diabetic retinopathy
•↑ activity of vasoconstrictor & ↓ activity of vasodilator in
endothelial tissues
6
9krish

z
Mechanisms continued
hyperglycemia
Fructose-6-phosphate
O-linked glycosylation and proteoglycan production
Altered function by glycosylation of protiens
Such as endothelial nitric oxide synthase or by
changes in gene expression of TGF –beta or PAI-1
10krish

z
11krish

z
Diabetic retinopathy
 DM is the leading cause of blindness between the ages of
20-74 in US.
 Blindness is 25 times more common than non diabetics.
 Severe vision loss due to progressive DR and clinically
significant macular edema
 Diabetic retinopathy classified into 2 stages
1.non proliferative
2.proliferative
12krish

z
Non proliferative diabetic retinopathy
 Usually appears late in the 1st decade or early in the 2nd
decade.
 1.retinal vascular micro aneurysms
 2.blot hemorrhages
 3.cotton wool spots.
 4.changes in venous vessel caliber
 5.intra retinal microvascular abnormalities
 6.microaneurysms & hemorrhages
Mild form
severe
13krish

z
Pathophysiology
 Loss of retinal pericytes
 Increased retinal vascular permeability
 Alterations in retial blood flow
 Abnormal retinal vasculature
RETINAL ISCHEMIA
14krish

z
NEW CONCEPT in pathophysiology
 The pathology involves inflammatory process
in the retinal vacular unit,
 which consists of
 1.neurons
 2.glia
 3.astrocytes, muller cells
 4.specialized vasculature.
15krish

z
PROLIFERATIVE
DIABETIC RETINOPATHY
 HALL MARK—neovascularization in response to
retinal hypoxia.
This newly formed vessels appear near the optic nerve &
or macula rupture easily
Vitreous heamorrhages, fibrosis
Retinal detachment
16krish

z
Risk factors
1. Duration of DM
2. Degree of glycemic control
3. Hypertension
4. nephropathy
17krish

z
TREATMENT
 THE most effective therapy for DR is PREVENTION.
 by
 intensive glycemic and blood pressure control.
 Macular edema 1.focal laser photocoagulation
 2. anti VEGF ocular injections
 Proliferative DR pan retinal laser photocoagulation.
18krish

z
19krish

z
Diabetic nephropathy
 Is the leading cause of CKD,ESRD and CKD requiring renal
replacement therapy.
 Prognosis of diabetic patients on dialysis is poor
 Commonly associated with DIABETIC RETINOPATHY.
20krish

z
PATHOPHYSIOLOGY
the effects of soluble
factors(gf,angiotenisin2,endothelin,AGE
products)
hemodynamic alterations in the renal
microcirculation( glumerular
hyperperfusion or hyper filtration &
increased glomerular capillary pressure
Structural changes in the glomerulus
(increased extra celluar matrix
basement membrane thickening,
mesangial expansion , fibrosis)
21krish

z
Micro albuminuria(30-
299mg/24hr)
Macro
albumiburia(>300mg/24hr)
22krish

z
 Micro albuminuria is also a risk factor for CVD
 Once macro albuminuria is present there is
1.steady decline of GFR,
2.~50%of individuals reach ESRD in 7-10yrs
3.blood pressure rises slightly
4.the pathological changes are likely irreversible.
23krish

z
screeningThursday,November15,2018
24krish

z TREATMENT
 The optimal therapy for diabetic nephropathy is prevention by
control of glycemia.
 Interventions effective in slowing progression of albuminuria
include
1.improved glycemic control
2.strict blood pressure control
3.administrations of an ACE inhibitor or ARB
4.Dyslipidemia should also be treated.
25krish

zTreatment continued
 Sulfonylureas and metformin are contraindiacted in advanced
renal insufficiency.
 D.O.C are ARBs & or ACE inhibotors
then diuretics , CCBs or beta blockers should be used
 renal transplantation from a living related donor is the
preferered therapy,. But it requires chronic immunosuppression.
 Combined pancrease-kidney transplant normoglycemia and
freedom from dialysis.
26krish

z
27krish

z
DIABETIC NEUROPATHY
 IT occurs in~50% of individuals with long standing type 1 &
type 2 DM.
 IT may mainifest as
 1.polyneuropathy
 2.mononeuropathy
 3. autonamic neuropathy.
 Both myelinated and unmyelinated nerve fibers are lost.
28krish

z
Risk factors
1. Duration of diabetes
2. Poor Glycemic control
3. BMI
4. Smoking
5. CVD
6. Elevated triglycerides
7. Hypertension
29krish

z Poly neuropathy
 ~50% of patients are asymptomatic
 Most common form is distal symmetric polyneuropathy.
 Symptoms
1.sensation of numbness
2.tingling
3.sharpness or burninig that begins in the feet and
spreads proximally.
30krish

z
 Pain typicallly involves the lower extremeties
 More at rest and worsens at night.
 As DN progresses, the pain subsides and eventually
disappears, but sensory deficit in the lower extremities
persiists.
31krish

z Mono neuropathy
 def:dysfunction of isolated cranial cranial or peripheral nerve
 Less common
 C/F: pain and motor weakness in the distribution of a single nerve.
 3rd cranial nerve is most common diplopia.
 Clinically ptosis , opthalmoplegia with normal pupillary constriction
to light. Sometimes bells palsy also can notice.
 Peripheral mononeuropathies or mononeuropathy multiplex may
also occur.
32krish

z
AUTONOMIC NEUROPATHY
 IT involves multiple systems
 CVStachycardia,Orthostatic hypotension
 GIT & GUTgastroparesis and bladder emptying
 Hyperhydrosis of upper limbs
 Anhydrosis of lower limbs
anhydrosis of feet
promote dry skin with cracking
foot ulcers
Sympathetic system
dysfunction
33krish

z
It reduces counter regulatory hormone release
Inability to sense hypoglycemia appropriately
Risk of sevre hypoglycemia
34krish

z
Treatment
 Risk factors should be treated
 Avoidance of neurotoxins( alcohol), smoking
 Supplementation with vitamins
 Pts should check their feet daily and take precautions to
prevent calluses or ulcerations.
 Chronic, painful DNduloxetine ,amiptrityline,gabapentine
 Orthostatic hypotensionfludrocorticosone,midodrine, clonidine
1.adequate salt intake,
2.avoidance of dehydration and diuretics
3.lower extremity support hose
35krish

z
36krish

z
Clinical features in GIT
 Affects the motility and function of both sysytems
 Mc is delayed gastric emptying (gastroparesis) and constipation or
diarrhoea.
 Gastroparesis manifests as
1.anorexia, nausea and vomiting
2.early satiety and abdomial bloating.
 Nocturnal diarrhea,alternating with constipation is MC in type 1 dm.
 Esophageal dysfunction .
37krish

z
Clinical features in genitourinary system
 Cystopathy and female sexual dysfunction like reduced
sexual desire, dyspareunia, reduced vaginal lubrication.
Inability to sense a full bladder and
failure to void completely
As bladder contractality worsens,
bladder capacity & post voidal increase
Urinary hesitancy,decreased voiding
frequency, incontinence,
Recurrent urinary tract infections
38krish

z
 Diagnostic evaluation includes cystometry and urodynamic
studies.
 Erectile dysfunction and retrograde ejaculation are very
common in DM.
 May be one of the earliest signs of diabetic neuropathy.
39krish

z treatment
 Smaller , more frequent meals that are easier to
digest(Liquid diet)
 Low fat and fiber
 Gastric electric stimulatory devices are availble but not
approved.
 5-phosphodiesterase inhibitors erectile dysfunction
 Vaginal lubricants, treatment of vaginal infections , and
systemic or local estrogen replacement may helpful in
cure of sexual dysfunction in females
40krish

z
41krish

z
Risk factors
 Dyslipidemia,
 hypertension
 obesity,
 Reduced physical activity
 Cigarette smoking
 Micro & macro albuminuria,
 Raised serum creatinine
 Abnormal platelet function and endothelial dysfunction
42krish

z
 The Framingham Heart study revealed a marked increase
in PAD, coronary artery disease,MI,CHF risk increse from
1 to 5 fold in DM.
 Prognosis is poor in DM
 Higher rates of restenosis ,lower long term patency and
survival rates of stents .
43krish

z
treatment
 Strict glycemic control
 ACE inhibitor ( ARB),
 A statin
 Acetylsalicylic acid(aspirin).
44krish

z
45krish

z
 Hyper triglyceridemia
 Reduced HDL
 Increased LDL.
LDL are more atherogenic because they are more easily
glycated and susceptible to oxidation
46krish

z
47krish

z
treatment
 HMG-CoA reductase inhibitorsfor lowering LDL
 HMG-CoA reductase inhibitor and a fibrate or another lipid
lowering agent (ezetimibe, niacin) may be consider.
 Nicotinic acid raises HDL
48krish

z
49krish

z DM is the leading cause of non traumatic lower extremity
amputation.
 Disordered proprioception abnormal weight bearing
while walking  subsequent formation of callus or
ulceration.
 Motor and sensory neuropathy abnormal foot
mechanics structural changes in the foot.
like hammer toe,claw toe deformity, prominent metatrsal
heads, charcot joint.
 Autonomic neuropathy anhidrosis & altered superficial
blood flow in the foot drying of the skin and fissure
formation.
50krish

z
Risk factors
1. Male sex
2. Diabetes for >10years
3. Peripheral neuropathy
4. Abnormal structcure of foot
5. PAD
6. Smoking
7. H/O previous ulcers or amputation,
8. visual impairment
9. Poor glycemic control
51krish

z
Prevention
 Careful selection of footwear
 Daily inspection of the feet
 Daily foot hygiene to keep the skin clean &moist
 Avoidance of self treatment of foot abnormalities and high
risk behaviour ( eg: walking bare foot)
 Prompt consultation with a health care provider if an
abnormality arises.
52krish

z
krish
53

z
treatment
 Proper antibiotics
 If need surgical debridement or
revascularization are indicated
 Regular follow up.
54krish

z
55krish

complications of diabetes mellitus

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to complications of diabetes mellitus

Similar to complications of diabetes mellitus (20)

Recently uploaded

Recently uploaded (20)

complications of diabetes mellitus