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259 Cards in this Set

  • Front
  • Back
What is the life expectancy in diabetic with ESRD
 3-4 years
How is risk of CVD increased in Diabetics
 2-6 times
What is the overall reduced life expectancy in diabetics
 7-10 years reduction
According to DCCT trial, which microvascular complications has greatest reduction following intensive control
 Retinopathy has greatest impact
 Followed by neuropathy and then nephropathy
Which type of cells in generally are affected by chronic hyperglycemia
 Cells that have intracellular hyperglycemia are affected like Endothelial cells
 These are cells which cannot downregulate glucose transport when exposed to extracellular hyperglycemia
What are the consequence of Endothelial cell dysfunction in Diabetics
…
Why is there increase GFR in early Diabetic nephropathy
 This is because of increase vasoconstriction of efferent arteriole
 This is because of 2 reason
o Endothelial cell dysfunction- leading to less NO
o Increased sensitivity to Angiotensin II
Narrowing of Blood vessels is common pathophysiological process affecting Diabetic microvascular disease. TRUE OR FALSE
 True
How does the narrowing of blood vessel take place
…
Which cells are destroyed in Diabetic Retinopathy
 Pericytes
 Endothelial cells
 Muller cells
 Ganglion cells
What is Hyperglycemic memory
 It is proved that a period of good glucose control reduce the risk of microvascular disease ins the subsequent periods of bad glycemic control and vice versa
Is there a genetic effect of susceptibility to microvascular complications
 Yes
PATHOPHYSIOLOGY OF MACROVASCULAR DISEASE
What are the special features of Diabetes and Macrovascular disease
 More Multivessal disease
 More rapidly progressive disease
 More number of diseased segments involved
Does insulin resistance itself confer a cardiovascular risk
 Yes. Even in Non Diabetic subjects
What is the characteristic Lipid profile pattern in Diabetic dyslipidemia
 High amount of Small dense LDL
 Low HDL
 High VLDL
 High TG
What are the two Pro atherogenic effects of Insulin
1. Increased PDGF- Increased Vascular smooth muscles
2. Increase vascular smooth muscle induced PAI- Platlet activator inhibitor (PAI-1)
There is selective insulin resistance in Arterial walls which enhance these effects of Insulin
Interestingly Hyperglycemia also produces the same effect !!
What is the anti-atherogenic effect of insulin
 Reduce production of Nitric Oxide
What is the Proatherogenic effect of Hyperglycemia
 Reduces Nitric oxide
Pearl
 Insulin and Hyperglycemia- Increase PDGF derived VSMC and PAI-1
 Insulin- Increases NO
 Hyperglycemia- Reduced NO
What are the two mechanisms of repair of blood supply in the body in case of ischemia
 Generation of collateral blood flow
 Regeneration of blood vessels
Which factor helps in regeneration of blood vessels
 Circulating endothelial progeniator cells released by bone marrow
What happens to this progenitor in Diabetics
 These cells are depleted in Diabetics
Which factor is critical response to acute ischemia which is depleted in diabetics
 Hypoxia Inducible factor 1 alpha (HIF-1alpha)
 This increases VEGF
Patients with Diabetes have reduced new vessel formation, yet they have Neovascularization in Retina ..why
 It is a difficult to explain Paradox
 Infact the bone marrow derived endothelial progenitor only takes part in the neovascularization in the Retina
 This is probably because retinal cells donot accumulate blood sugar and hence dono hae reduction of HIF 1alpha
HYPERGLYCEMIA INDUCED DAMAGE
Which are the 4 pathways which cause Hyperglycemia induced damage
1. Polyol Flux pathway
2. Hexosamine flux pathway
3. Increase protein Kinase C
4. Advanced glycosylated end product
What is the end product of Polyol Flux pathway
 Sorbitol
Is Sorbitol really responsible for the complications through Polyol flux pathway
 Probably not
So what is really responsible for damage in Polyol flux pathway
 Increase Polyol flux pathway reduced NADPH
 NADPH is required for Glutathione reactivation
 Absence of glutathione increase oxidative stress
Which is the enzyme involved in the Polyol flux pathway
 Aldose reductase which has low affinity for glucose
 So in normal person this pathway is not active
 In Hyperglycemia this pathway is active
Which is Aldose reductase inhibitor used in clinical practice
 Zenarestat (ZEN-A-RESTART)
Which microvascular complication is most greatly impacted by Zenarestat
 It benefits Diabetic neuropathy the most
 Less effect on Retinopathy and Nephropathy
Why was trial of Zenarestat discontinued
 Because it had higher dose dependent Renal toxicity
What are names of Rat models used in Obesity and Diabetes
 Zucker Rats
What is the earliest morphological change in Diabetic retinopathy
 Loss of Pericytes
Which are the 3 AGE precursors
1. Glyoxal
2. Methylglycoxal
3. 3 Deoxyglucasone
Increase of which factor is associated with increase vascular permiablity in diabetics
 VEGF
What is the mechanism of Hexosamine flux pathway
…
What is the rate limiting enzyme in Hexosamine pathway
 GFAT- Glucosamine- Fructose 6 phosphate aminodatransferase
How is protein Kinase C increased in Diabetics
 This is because of increase of intracellular second messenger DAG
Which forms of Protein kinase C are increased in Diabetics
 Protein Kinase C beta and Delta
Which is the common pathophysiological process linking the above four theories of Glycemic damage
 Production of Superoxide by mitochondria electron transport change
What produces AGE products- intracellular hyperglycemia or extracellular
 Intracellular hyperglycemia
what is importance of RAGE in Diabetes therapeutics
 Receptor of AGE – if inhibited reduced Atherosclerosis in Diabetes prone type 1 Diabetics


RETINOPATHY
What is the most common cause of new onset blindness in Developed countries
 Diabetic neuropathy
How do you prevent Diabetic retinopathy
 There is no current means of preventing Retinopathy
Which Antihypertensive is known to prevent Diabetic retinopathy
 ACE and ARB are known to prevent Diabetic retinopathy
Which 3 agents are used / undergoing trial for treatment of DR
 PKC-beta
 VEGF inhibitor
 Corticosteroids
What is the 3 earliest pathological change in Diabetic Retinopathy
 Loss of Retinal pericytes, change in retinal vascularity and thickening of basement membrane
What produces microaneurysm
 Loss of retinal pericytes
 This results in outpouching of retinal blood vessels
 Which produces microaneurysm
Which 2 fundus changes are not distinguishable from each other
 Microaneurysm and Small hemorrhages look similar . Hence they are linked together
What produces retinal edema
 Loss of blood retinal barrier produces leakage of fluid which produces edema
What is the consequence Anterior segment neovascularization
 Anterior segment neovascularization leads to increase risk of Glaucoma
By what percentage does Intensive insulin therapy reduce the risk of Diabetic retinopathy
 Intensive insulin therapy reduces the risk of Diabetic retinopathy by 27%
Where do flame shaped and where do dot and blot hemorrhages appear
 Flame shaped hemorrhage are located in Inner retina close to vitreous
 Dot and Blot hemorrhages occur in Deeper retina
Where do Cotton wool spots appears
 Cotton wool spots appear because of Nerve layer infracts
What do Venous beading and venous caliber changes suggest
 Venous caliber changes suggests severe retinal hypoxia
What is ‘Featureless retina’
 Featureless retina is when retina is extensive vascular loss but Retina is free of proliferative changes
 Such retina is suggestive of extensive retinal hypoxia
Which are 3 causes of vision loss in Diabetic retinopathy
1. Diabetic macular edema
2. Persistent vitreous hemorrhage
3. Traction retinal detachment
Which is THE most common cause of vision loss in Diabetics
 Macular edema
Is Macular edema more common in type 1 or type 2 diabetics
 Macular edema is more common in type 2 Diabetics
Are terms like Preproliferative and Background retinopathy still used
 No
 These terms have been replaced
Diabetic macular edema falls in which group Non proliferative or proliferative
 It falls in either categories
What is the importance or DRS study
 It was the first multicentre trial that evaluated use of Panretinal photocoagulation in preventing vision loss in Diabetic retinopathy
What is ‘Neovascularization at Disc’ and what is ‘Neovascularization elsewhere’
 Neovascularization at disc refers to Neovascularization within 1500 um of the optic disc
 Neovascularization elsewhere refers to Neovascularization beyond 1500 um of the optic disc
Venous caliber abnormalities point to milder grades of NPDR or more severe grade of NPDR
 It refers to severe grades of NPDR
What is criteria for Clinically significant macular edema
 CSME refers to
o Hard exudates within 500 um of fovea
o Retinal thickening within 500 um of fovea
o Retinal thickening >1500 um within 500 um of Fovea
How does International classification of Diabetic retinopathy classify DR
 Mild , Moderate and severe NPDR
 PDR
What is Mild NPDR
 Microaneurysms only
What is Moderate NPDR
 Between mild and severe NPDR
What is severe NPDR
 4-2-1 Rule
 > 20 Hemorrhage in all 4 quadrants
 Venous beading in 2 or more quadrant
 IRMA in 1 or more qudranat
-----
Can CSME occur with normal vision
 Yes
What is the test required for diagnosis of CSME
 Flouroscein angiography
How is Diabetes macular edema classified
 Mild- Retinal thickening/hard exudate near posterior pole, far from centre
 Moderate- Retinal thickening approaching the centre but not involving the centre
 Severe- retinal thickening involving the centre
Which cranial nerves are associated with Diabetes
 Mononeuropathy of 3,4,6 may be associated with Diabetes
Amongst these CN, which is least commonly involved
 CN 4 is least commonly involved
Pearl: Isolated mononeuropathy of 3,4,6 cranial nerves should prompt the search for Diabetes
What are the causes of Optic disc pallor in Diabetes
 May occur after spontaneous remission of PDR or remission after laser photocoagulation
Is Open angle glaucoma more common in Diabetics
 Yes
 It is 1.4 times more common
IS Cataract more common in Diabetics
 Yes
 It is 1.6 times more common
What is the reason for fluctuation of vision in Diabetes
 It is because of osmotic lens swelling
Which is the dangerous infection of Diabetes which affects the orbit
 Mucormycosis
What is the treatment for CSME
 Focal / Grid laser photocoagulation
What is the indication for Panretinal photocoagulation
1. PDR
2. Severe NPDR
How frequently are DME followed up
 Every 3 months
How frequently are Severe NPDR followed up
 Every 4 months
How frequently are mild and moderate NPDR followed up
 Mild- every 8-12 months
 Moderate- every 4-8 months
 Severe- every 4 months

Summary of follow up

 No DR- Every 12 month
 Mild NPDR- every 8-12 months
 Moderate NPDR- every 4-8 months
 Severe NPDR- every 4 months
 DME- every 3 months
How frequently are pregnant patients with DR followed up
 In each trimester – every 3 months
Which 2 conditions accelerate retinopathy
 Puberty and pregnancy
What is the treatment of cases of Proliferative retinopathy which cannot be treated with Photocoagulation
 Pars plana vitrectomy must be done
What is the method of choice for Diagnosing CSME
 OCT- optical coherence tomography
What is the role of Floroscein angiography in CSME
 Floroscein angiography is used once the diagnosis of CSME is established
 It is used for identifying lesions which which are close to macula which are contributing to macular thickening
 These lesions are identified and photocoagulated
Is there an effect of Pan retinal scatter photocoagulation on macular edema
 Yes, Pan retinal Scatter photocoagulation worsens macular edema
Why should patients with severe NPDR undergo focal photocoagulation even if they don’t have macular edema
 Because they may require scatter photocoagulation in future which can worsens macular edema
 So at present they are to undergo panretinal photocoagulation
Which is the novel therapy developed in treatment of Diabetic retinopathy
 Intraviterous injection of Anti- VEGF inhibitors are newer drugs developed in treatment of diabetic retinopathy
Which are the new anti VEGF inhibitors
 Bevacizumab
 Ranibizumab
Which other agent is used in treatment of DME
 Intraviteral injection of corticosteroids is used in treatment of DME
 Steroids help in reduction of Retinal thickning
What are the side effects of these steroid injections
 Increase of intraocular pressure and increase risk of cataract
What % of patients with Type 2 Diabetes are also hypertensive
 38-58% of patients with type 2 Diabetes are also hypertensive
What is the effect of concomitant hypertension on DR
 More severe grades of Retinopathy and more rapid progression of retinopathy
A patient has rapidly progressive retinopathy , apart from Hypertension what else should be considered
 The renal status of the patient should be considered
What is the relation of Hemoglobin with Retinopathy
 Low Hematocrit is associated with increased risk of progression of retinopathy
 Hence anemia in diabetics should be treated
What kind of hypogonadism is associated with Obesity – Hypo Hypo or Hyper hypo
 Hypo Hypo


DIABETIC NEPHROPATHY
Nephropathy is more common in type 1 or type 2 Diabetes
 It is more common in type 1
 However because of more number of Type 2- more patients of type 2 come in picture
What is the classical triad of Diabetic nephropathy
 Hypertension
 Proteinuria
 Renal impairment
Who described the 5 stages of Diabetic nephropathy
 Mogensen
Which are the 5 stages of Diabetic nephropathy
 Hyperfiltration
 Silent
 Microalbuminuria
 Macroalbuminuria
 Renal impairment
What is the cause of Hyperfilteration in the stage I of DN
 Because of concomitant renal hypertrophy
Is there glomerular or tubular hypertrophy in DN
 Both
Which factors are responsible for the hypertrophy
 GH
 TGF beta
What are the structural changes seen in the silent phase of DN
 Mesangial expansion
 Basement membrane thickening
Are there any markers that can identify the silent phase of the disease
 None have been validated
 Some approaches include
o Measurement of Albumin fragments (Ghost fragments) in urine
o Prorenin
o ACE genotype
o Modest raise in BP seen on ABPM
Define microalbuminuria in ug/min
 20-200 ug/min
When is the Urine albumin/creat sample taken
 Early morning Spot sample
Is regression of microalbuminuria possible
 Yes
 One study showered regression in 58% of patients
How frequently should urine albumin/creat ratio be done in Type 1 Diabetics
 Williams recommends twice annually !!
Is Pancreas-kidney transplant better than Kidney transplant alone
 Yes
 Pancreas-kidney transplant is better than kidney transplant alone
Does hyperfilteration occur in Type 2 Diabetes
 Yes
 Hyperfilteration also occurs in type 2 Diabetes but it is less common than Type 1 Diabetes
Is microalbuminuria specific for DN in type 2 Diabetes
 No
 There are other cause of Microalbuminuria as well in type 2 DM which include
o UTI
o Cardiac failure
o Enlarged prostrate
Can patients with Diabetes develop Renal impairment without proteinuria
 Yes


PATHOGENESIS OF DIABETIC NEPHROPATHY
Which factor plays a central role in Diabetic nephropathy
 Mitochondrial ROS plays a central role on Diabetic nephropathy
PATHOLOGY
What factor contributes to the Proteinuria in DN
 Podocyte dysfunction and apoptosis contributes to the proteinuria in DN
Are just the glomerular changes in Diabetes important
 No
 Recent studies have shown significant changes in the renal tubules as well
 It is called Diabetic Tubulopathy
Pearl: Loss of the Tubuloglomerular feedback drives the hyperfilteration seen in early phases of Diabetic nephropathy
Renal function detoriation has more to do with Glomerular or tubular dysfunction in DN
 It has more to do with Tubular rather than glomerular dysfunction \
Do patients with Diabetes have increase risk of Renal artery stenosis
 Yes
 Many are angiographically non significant
 However, if significant can lead to increase risk of Acute pulmonary edema
What type of RTA is common in diabetics
 Type IV RTA
 This increases risk of Severe hyperkalemia
What is Benfothiamine and what is its role
 Benfothiamine is a derivative of thiamine that reduces the reactive oxygen species
Which is more important for reducing microalbuminuria – Blood pressure or blood sugar
 Blood pressure
Which serum marker is a identifies patients who are normalalbuminuric having increased risk of Diabetic nephropathy
 Serum prorenin
Which is the drug of choice for BP reduction in Type 2 Diabetics with Albuminuria
 ARB
Which studies showed these benefits of ARB
 RENAAL – which invoved Losartan
 IDNT- Which involved Irbesartan
Is there any difference in use of ACEI vs ARB
 No
Which other drugs have been found to have additive renoprotective effect
 Alsikiren
 Eprelenone
Is there any benefit of Low protein diet
 Low protein diet 0.75 gram/kg found to have modest benefit in patients with DN
Which lipid lowering drug is found to reduce progression of Diabetic nephropathy
 Fenofibrate
is there any advantage of using EPO in patients with DN
 Role of EPO as renoprotective effect is controversial
Q . Which drug is PKC beta inhibitor ?

 Ruboxistaurin
 But It has failed to show any benefit in patients with DN
Which other drugs are tried in DN
 Sulodexide (SULO- DESK – SITE)
 Avosentan- endothelial receptor antagonist (AVO- SENTAN –A )


DIABETIC NEUROPATHY

Pearl: Diabetic neuropathy can also in Impaired glucose tolerance as well as Metabolic syndrome without Overt Diabetes
It is the most common neuropathy worldwide
Classify diabetic neuropathy based on San Antonio classification
 Subclincial neuropathy
 Diffuse clinical neuropathy
o DSPN
o Autonomic neuropathy
 Focal syndromes
Which new diagnostic technique has become popular for diagnosis of Diabetic DSPN
 Skin biopsy
What is the advantage of skin biopsy
 It can diagnose small fibre neuropathy even If the NCV has still not picked up the neuropathy
Which marker is used for diagnosis of DSPN
 PSP 9.5 – Panaxonal marker protein gene product 9.5 is used for diagnosis of DSPN
What is the key measurement on nerve biopsy
 Intraepidermal nerve fibre density is the key measurement
Which loss is more prominent in NCV in patient with Diabetic neuropathy- Axonal or demyelinating
 Axonal
 Hence amplitude is reduced
Are changes in NCV more appropriate way of follow up of patients with DN
 No
 Changes in NCV are not a good way of following up a patient
 Change in NCV may not correlate with severity
What is the importance of Autonomic neuropathy on mortality
 Autonomic neuropathy is associated with increase risk of Cardiovasular mortality and MI
Define Diabetic neuropathy
the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes
Absence of symptoms means absence of neuropathy- True or false
 False
 Often neuropathy may be asymptomatic
What is the minimum thing required for diagnosis of Diabetic neuropathy
 Atleast 2 signs and symptoms are required for diagnosis of Diabetic neuropathy
Mononeuropathy are common in what profile of diabetics
 In older diabetics
What is the cause of mononeuropathy
 It is often due to vascular cause
what is the onset and course of neuropathy
 Hence often presents acutely and self resolves in 6-8 weeks
What is the main difference between Diabetic mononeuropathy and entrapment neuropathy
 Diabetic mononeuropathy is acute while entrapment neuropathy is slow and progressive
Which common nerves are involved in Diabetic Mononeuritis
 C3, C6, C7, median , ulnar , peroneal
Is carpal tunnel more common in diabetics
 Yes
 It is 3 times as common in diabetics as general population
 1/3rd diabetics have it !
What is the surgical treatment of CTS
 Sectioning of volar carpal ligament is the surgical treatment of CTS
DIFFUSE NEUROPATHIES
PROXIMAL MOTOR NEUROPATHIES (DIABETIC AMYOTROPHY)
Describe the clinical presentation of Diabetic amyotrophy
 Begins in elderly
 Start unilaterally as pain in the thighs or hips followed by buttocks
 This is followed by significant pain in the proximal limbs followed by weakness
 Associated with DSPN and Muscle fasciculation
 Later may spread bilaterally
Is diabetic amyotrophy due to Diabetes
 No
 It is now recognized that its cause is something else
 However it is more common in Diabetics
Which muscles are involved in Diabetic amyotrophy
 Iliopsoas
 Obutrator
 Adductor
Which muscles are spared in Diabetic amyotrophy
 Gluteus maximums , minimus and hamstrings
What does NCV show in such a patient
 Axonal loss
 Picture like Lumbosacaral plexopathy
A patient has similar picture but NCV shows demyelination, what is the diagnosis
 Than its more likely CIDP or MGUS or vasculitis rather than Diabetic amyotrophy
Is CIDP also more common in diabetics
 Yes
 Sharma et al found that CIDP is more common in Diabetics
Why is differentiation between CIDP and Diabetic amyotrophy important
 Because treatment is different
 CIDP responds well to IVIG while DA runs a progressive course
What are the clinical features of Spinal stenosis
 Claudciation and pain on walking downhill
 Relived by bending forward




DISTAL SYMMETRICAL POLYNEUROPATHY
Can DSPN have an acute onset
 Yes
 It could often be because of stress or treatment of hyperglycemia
Pearl: Treatment of Diabetes may often precipitate symptoms of DSPN
Is DSPN sensory or motor
 It can be both sensory and motor
 Can involve both large or small fibres
What are techniques for evaluating small fibre neuropathy
 Skin biopsy with staining for neuronal antigen PGP 9.5 – Method of choice
 Others are
o Corneal confocal microscopy
o Laser doppler flare reaction to cholinergic stimulation
o Sudomotor responses to cholingergic stimulation

--------------
PAIN IN DIABETIC NEUROPATHY

ACUTE PAINFUL NEUROPATHY
What is Insulin neuritis
 Acute (<6 months)
 Painful
 Small fibre neuropathy
 On starting of Insulin or SU
 Pain is more in night
 More in the feet
What is Diabetic Neuropathic cachexia
 Another painful small fibre neuropathy
 Associated with weight loss and depression
 More in males
 Responds to Symptomatic treatment
CHRONIC PAINFUL NEUROPATHY
What are features of chronic painful neuropathy
 Lasts for > 6months
 Patient develops tolerance to even narcotics
 Difficult to treat
Is loss of pain always a good sign
 Not necessarily
 Loss of pain may sometimes herald progression of neuropathy
What is difference between Hyperalgesia and Allodynia
 Hyperalgesia is increased pain on painful stimulus
 Allodynia is increased pain on stimulus that is generally not painful
Which fibres produce Hyperalgesia
 A – Delta and C fibres
Which fibres produce allodynia
 A beta
SMALL FIBRE NEUROPATHY
Which fibre produces pain in Small fibre neuropathy
 C fibres
How is clinical diagnosis of small fibre neuropathy done
 Using 1.0 gram Semmes- Weinstein filament
 Or use of Wartenberg wheel

Figure 1 WARTENBERG WHEEL
What are NCV changes in small fibre neuropathy
 Normal
How is diagnosis of Small fibre neuropathy confirmed
 Loss of cutenous nerve fibre that stain for PGP 9.5 on skin biopsy
What happens to reflexes and motor in Small fibre neuropathy
 They are normal
LARGE FIBRE NEUROPATHY

“Neuropathy of signs rather than symptoms”
Which are effect first – small fibre or large fibres
 Large because they are longer
Where to large fibres synapse
 In medulla
Which sensation are controlled by large fibres
 Vibration
 Position
 Cold thermal sensation
What are symptoms of large fibre neuropathy
 Sensation of walking on wool
CLINICAL PRESENTATION
Which is the first symptom of large fibre neuropathy
 Loss of vibration sensation
What are the signs or large fibre neuropathy
Sensory
 Loss of vibration
 Loss of Tendon reflex
 Sensory ataxia
 Loss of position sense
Motor

 Waddling gait
 Wasting of small muscles of foot
 Hammer toes
 Pes equinus


Figure 2 PES EQUINUS
Autonomic

 Hot foot- increase vascularity of feet
Which is sign of severe neuropathy
 Inabilty to stand on toes or feet – sign of severe neuropathy
Diagnosis and Differential Diagnosis of Peripheral Neuropathy
Name 3 questionnares developed for diabetic neuropathy
 Vinik
 Dyke
 Young
What frequency of tuning fork must you use for diagnosis of Diabetic neuropathy
 Tuning fork of 128 Hz
Can you use other tuning fork
 No
Name the tests for diagnosis of

 Small fibre neuropathy
 Large fibre neuropathy
 Autonomic neuropathy of foot
Answer
 Small fibre neuropathy – Skin biopsy and loss of PGP 9.5 staining nerve fibres
 Large fibre neuropathy - NCV / EMG
 Autonomic neuropathy of foot - QAFT- quantitative autonomic function test
Which is good clinical test for Entrapment neuropathy
 Tinel’s sign
Which is the questionnaire useful for screening patients with Diabetic neuropathy
 Michigan neuropathy screening instrument
What is the name of the severity grading used for diabetic neuropathy
 Dyck staging
Describe the Dyck staging
 N0- Ne neuropathy
 N1a- No signs or symptoms- but abnormalities on Testing
 N1b- No symptoms but neuropathy signs present
 N2a - Signs and symptoms present
 N2b- Above plus ankle dorsiflexor weakness
 N3- severe diabling neuropathy
Is QST useful for routine use
 AAN recommends QST mainly for clinical trials and does not recommend it for routine use

Peripheral Testing Devices
What does Semmes Weinstein filament test
 It tests pressure sensation
How much pressure is applied
 Enough pressure is applied to buckle the Filament
Which monofilament is most commonly used in clinical practice
 10 g monofilament
What is the 10 g monofilament called in clinical practice
 5.07 filament
Why is it called 5.07 filament
 The filaments are calibrated to exert a force that is 10 times the log of force applied on tip
 Hence 5.07 applies 10 g force on tip
How many sites on foot must be tested by monofilament
 There is no concensus
 But generally 4 sites are tested
Which are these 4 sites
 Hallux
 1st , 3rd and 5th metatarsal heads
What does monofilament testing actually predict
 It predicts the future risk of developing foot ulcers
Which monofilament is more sensitive and which is more specific
 1 g monofilament is more sensitive
 10 g monofilament is more specific
What is Rydel Seifer tuning fork
 It has optical illusion to allow assessor to determine intensity of residual vibration on scale of 0 to 8
What is principle of Corneal confocal microscopy
 Corenal confocal microscopy helps visualize unmyelinated axons In cornea
 These are lost early in Diabetic neuropathy and predict the development of Diabetic neuropathy


Figure 3 CONFOCAL MICROSCOPY

MANAGEMENT
Diabetes affects- Amplitude or velocity on NCV
 It mainly affects the amplitude
Is there benefit of Glycemic control on preventing progession of diabetic neuropathy
 Yes
What is the mechanism of action of Aldose reductase inhibitors
 Aldose reductase inhibitors reduce the flux of flux of glucose to polyol pathway
Name some Aldose reductase inhibitors
 Tolrestat
 Zenarestat
 Zopolrestat
How does Alpha Lipoic acid act
 It’s a cofactor for pyruvate dehydrogenase complex
 Its helps in replenishing thiol group and acts as a redox modulating agent
 Its basically an antioxidant
Which essential fatty acid is used in treatment of diabetic neuropathy
 Gamma linoleic acid (γ-linolenic acid)
Name a PKC-Beta inhibitor
 Ruboxistaurin
-------
When is IVIG used in treatment of diabetic neuropathy
 It is used when anti-neuronal antibodies are positive
PAIN CONTROL
What is type of Pain in C fibre pain
 Burining , lacinating pain with parastheesia and hyperalgesias
Which drug is useful for C fibre pain
 Clonidine or Capsaicin cream
 C fibre pain is because of small unmyelinated fibres
 There is a cross sensitivity between pain and sympathetic fibres , hence clonidine is useful
 Clonidine can also be applied locally
How can Capsaicin cream be made at home
 It can be made my putting 1-3 teaspoons of Ceynne pepper in Cold cream and applying to the affected part
 The affected part is then wrapped with Cellophane paper
 There is initial exacerbation of pain followed by reduction of pain in 2-3 weeks by depletion of substance P in the umyleinated fibres that cause pain
What type of Pain is found because of A-delta fibres
 It is a more deep seated , gnawing pain
 It does not respond to above measures
Which agents are used for A delta pain
 Continous insulin infusion
o Patient responds within 48 hrs
 Nerve blocking agents- local or systemic Lidocaine or Mexiletine
 Opioids like Tramadol
 Dextrometorphan- NMDA receptor blocker
 TCA- Amitryptiline and Nortryptiline
 SSRI
 Anticonvulsants
What is advantage of Nortryptiline over Amitryptiline
 It has lesser sedation compared to Amitryptiline
 Brand is NOTRI 25 mg HS
Which SSRI is found to be best
 Paroxetine (PARI- CR 12.5 mg HS )
What is the dose of Duloxetine used in Diabetic neuropathy
 60-120 mg
in which patients Duloxetine must be avoided
 Must be avoided in patients with Bipolar tendencies , as it increases risk of Sucidal ideation
What is mechanism of Action of Pregabalin
 It is GABA analogue
What is minimum dose useful for Pregabalin
 It is 150 mg – can go upto 600 mg
Is phenytoin useful in diabetic neuropathy
 No
 Studies have shown it not be beneficial
What is the major problem with use of Phenytoin in diabetes
 Phenytoin in Diabetes suppresses insulin secreation and can hence increase the risk of precipitating hyperosmolar diabetic coma
What is the advantages of Gabapentin over other drugs
 It is known to improve Mood and improve sleep
What is the disadvantage of Gabapentin
 It is not found useful in all trials
 Effective Dose required is higher – 1800-3000 mg
 And associated with weight gain
Can Lamotrigine be used in management of painful neuropathy
 Yes
Which anticonvulsant has anti-diabetes properties and is known to help increase the intraepidermal nerve fibre density
 Topiramate
What are other benefits of Topiramate use in Diabetes
 Also reduces blood pressure and has favourable effect on lipids
TOPIRAMATE- NEXTOP- 25 MG AT BEDTIME
Williams recommends which drug as first line in treatment of painful diabetic neuropathy
 TCA





IMP PARA
Which are some of the newer technologies used in treatment of Neuropathy
 Trancutenous electric nerve stimulation
 Static magnetic field therapy
 Infrared light
Which other hormone is found to be useful in painful diabetic neuropathy
 Calcitonin given in dose of 100 IU for 2 weeks often caused complete resolution of painful diabetes neuropathy
PATIENTS WITH LARGE FIBRE NEUROPATHY HAVE HIGHER TENDENCY TO FALL

Q . What is the recommended physical thing in Large fibre neuropathy ?

 Patients should undergo strength training to improve muscle strength in large fibre neuropathy
How do you assess the efficacy of the strength training in diabetic large fibre neuropathy
 By asking patient to do a backward tandem walking
AUTONOMIC NEUROPATHY
What pupillary abnormality is seen in Diabetic autonomic neuropathy
 Argyl Robertson pupil
 Increased diameter of Dark adapted pupil
Autonomic neuropathy is a late sign of diabetic neuropathy , TRUE OR FALSE
 False
 It can often occur early
What are the effects of Autonomic neuropathy on blood pressure
 Patient may have paradoxical supine or nocturnal hypertension
Amongst complications of Diabetes, which is the greatest predictor of Mortality and CV risk
 Autonomic neuropathy
Amongst test for autonomic neuropathy, which one should be done definitely
 Cardiac autonomic testing must be done
 Other are not required routinely
 Also if cardiac autonomic testing is normal, then Autonomic neuropathy can actually be ruled out
DIAGNOSTIC TESTS FOR CARDIAC AUTONOMIC NEUROPATHY
What is first thing done for diagnosis of Cardiac autonomic neuropathy
 Resting heart rate is first checked
 HR >100 is abnormal
Describe heart rate change on standing
 Normally on standing there is initial reflex tachycardia followed by bradycardia
 The RR interval at beats 30 and beat 15 are taken
 Ratio of RR at 30:15 > 1.03 is normal
How to perform the test for Valsalva variability and its interpretation
 During ECG recording patient is asked to blow in to Sphygmonamometer with pressure at 40 mm Hg
 There is initially tachycardia during strain and overshoot bradycardia later
 The ratio of longest RR to shortest RR >1.2 – which is normal
How is systolic BP during standing done and interpreted
 BP is taken in supine position
 Patient is asked to stand for 2 min
 Systolic BP is taken again
o Fall by <10 mm Hg- normal
o 10-30 mm Hg – borderline
o >30 mm Hg- abnormal
What is importance of QTc interval for autonomic testing
 QTc >440 ms suggest autonomic dysfunction
What is effect of isometric hand grip and Diastolic BP
 Patient is asked to squeeze handgrip dynamometer for 5 min
 The diastolic pressure in other arm raised by >16 mm Hg


MANAGEMENT OF AUTONOMIC NEUROPATHY
What dietery advice would you give patient with Diabetic gastropathy
 Small frequent meals
 Less fat in diet
Which antibiotic is used in Diabetic gastroparesis
 Erythromycin
How frequent is ED in Diabetic males
 Present in 50-75%
What are indirect evidence that ED in diabetes is because of Autonomic dysfunction
 Loss of Ankle jerks and reduction in Vibration sense over great toe often accompanies ED because of autonomic dysfunction in Diabetics
What is importance of Penile – Brachial index
 Penile brachial index <0.7 suggest vascular insufficiency of the penis
Which investigation would help differentiate psychogenic from organic ED
 Nocturnal penile tumescence (NPT)
Name 3 drugs used in treatment of Orthostatic hypotension
 Fludrocortisone
 Octerotide
 Clonidine
What is the endocrine side effect of Levosulfide
 Galactorrhea
What is diabetic Cystopathy
 Loss of bladder sensation due to diabetes
 The bladder are often full and upto umbilicus yet the patient has no bladder sensation
 It often produces overflow incontinence and increases UTI risk
Which maneuver helps empty the bladder in patients with Cystopathy
 Crede’s maneuver
Which drug is used in treatment of Diabetic cystopathy
 Bethanecol
 Parasympethomimetic

DRUG: BETHACOL 25 MG TID
What Typical sweating abnormality is seen in Diabetics
 Gustatory sweating esp. in upper body is very typical
 It is treated with topical glycopyrrolate
What happens to sweating in lower body
 Anhidrosis is more common in lower body
 This leads to cracks and fissures in Diabetic foot
What is Hypoglycemic unawareness
 Lack of Cathecholamine response to neuroglycopenia is known as Hypoglycemic unawareness
What happens to Glucagon response in Type 1 Diabetics
 Glucagon response in type 1 Diabetics, reduces after 1-5 years and is almost absent after 15-30 years

CORONARY ARTERY DISEASE

Effect of Diabetes on Risk of Coronary Heart Disease



Depression of myocardial GLUT4 levels in the setting of diabetes and ischemia inhibits glucose entry and glycolysis in the heart. As a result, intracellular metabolism shifts from glycolysis to FFA oxidation, thereby suppressing glycolytic ATP generation, a major source of energy under anaerobic (i.e., ischemic) conditions.869 The production of oxygen free radicals can also be enhanced in this situation, further depressing myocardial contractile function.


The Diabetic Foot (See separate notes)