This document summarizes chronic complications of diabetes mellitus, including macrovascular complications like coronary heart disease, stroke, and peripheral arterial disease, as well as microvascular complications like diabetic neuropathy, retinopathy, and nephropathy. It provides details on the pathogenesis, clinical presentation, diagnosis and management of peripheral diabetic neuropathy, noting that tight glycemic control through intensive insulin therapy can help prevent or delay the risk of developing diabetic complications.
The presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after exclusion of other causes is called diabetic peripheral neuropathy.
The diagnosis is principally a clinical one. Patients with type 1 diabetes for 5 or more years and all patients with type 2 diabetes should be assessed annually.Treatment goals include
good glycemic control,symptomatic treatment and halt progressive nerve damage.
Diabetic neuropathy is a major cause of neuropathy worldwide and may lead to amputations and incapacity. This study aimed at a detailed and updated review on diabetic neuropathy, focusing on its epidemiology, classification, clinical features, risk factor, diagnostic investigation and treatment. Dr. Siva Rami Reddy E "A Basic Review on Diabetic Neuropathy" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-2 , February 2019, URL: https://www.ijtsrd.com/papers/ijtsrd21391.pdf
Paper URL: https://www.ijtsrd.com/other-scientific-research-area/other/21391/a--basic-review-on-diabetic-neuropathy/dr-siva-rami-reddy-e
The presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after exclusion of other causes is called diabetic peripheral neuropathy.
The diagnosis is principally a clinical one. Patients with type 1 diabetes for 5 or more years and all patients with type 2 diabetes should be assessed annually.Treatment goals include
good glycemic control,symptomatic treatment and halt progressive nerve damage.
Diabetic neuropathy is a major cause of neuropathy worldwide and may lead to amputations and incapacity. This study aimed at a detailed and updated review on diabetic neuropathy, focusing on its epidemiology, classification, clinical features, risk factor, diagnostic investigation and treatment. Dr. Siva Rami Reddy E "A Basic Review on Diabetic Neuropathy" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-2 , February 2019, URL: https://www.ijtsrd.com/papers/ijtsrd21391.pdf
Paper URL: https://www.ijtsrd.com/other-scientific-research-area/other/21391/a--basic-review-on-diabetic-neuropathy/dr-siva-rami-reddy-e
Levelwise PageRank with Loop-Based Dead End Handling Strategy : SHORT REPORT ...Subhajit Sahu
Abstract — Levelwise PageRank is an alternative method of PageRank computation which decomposes the input graph into a directed acyclic block-graph of strongly connected components, and processes them in topological order, one level at a time. This enables calculation for ranks in a distributed fashion without per-iteration communication, unlike the standard method where all vertices are processed in each iteration. It however comes with a precondition of the absence of dead ends in the input graph. Here, the native non-distributed performance of Levelwise PageRank was compared against Monolithic PageRank on a CPU as well as a GPU. To ensure a fair comparison, Monolithic PageRank was also performed on a graph where vertices were split by components. Results indicate that Levelwise PageRank is about as fast as Monolithic PageRank on the CPU, but quite a bit slower on the GPU. Slowdown on the GPU is likely caused by a large submission of small workloads, and expected to be non-issue when the computation is performed on massive graphs.
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Techniques to optimize the pagerank algorithm usually fall in two categories. One is to try reducing the work per iteration, and the other is to try reducing the number of iterations. These goals are often at odds with one another. Skipping computation on vertices which have already converged has the potential to save iteration time. Skipping in-identical vertices, with the same in-links, helps reduce duplicate computations and thus could help reduce iteration time. Road networks often have chains which can be short-circuited before pagerank computation to improve performance. Final ranks of chain nodes can be easily calculated. This could reduce both the iteration time, and the number of iterations. If a graph has no dangling nodes, pagerank of each strongly connected component can be computed in topological order. This could help reduce the iteration time, no. of iterations, and also enable multi-iteration concurrency in pagerank computation. The combination of all of the above methods is the STICD algorithm. [sticd] For dynamic graphs, unchanged components whose ranks are unaffected can be skipped altogether.
As Europe's leading economic powerhouse and the fourth-largest hashtag#economy globally, Germany stands at the forefront of innovation and industrial might. Renowned for its precision engineering and high-tech sectors, Germany's economic structure is heavily supported by a robust service industry, accounting for approximately 68% of its GDP. This economic clout and strategic geopolitical stance position Germany as a focal point in the global cyber threat landscape.
In the face of escalating global tensions, particularly those emanating from geopolitical disputes with nations like hashtag#Russia and hashtag#China, hashtag#Germany has witnessed a significant uptick in targeted cyber operations. Our analysis indicates a marked increase in hashtag#cyberattack sophistication aimed at critical infrastructure and key industrial sectors. These attacks range from ransomware campaigns to hashtag#AdvancedPersistentThreats (hashtag#APTs), threatening national security and business integrity.
🔑 Key findings include:
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Our comprehensive report delves into these challenges, using a blend of open-source and proprietary data collection techniques. By monitoring activity on critical networks and analyzing attack patterns, our team provides a detailed overview of the threats facing German entities.
This report aims to equip stakeholders across public and private sectors with the knowledge to enhance their defensive strategies, reduce exposure to cyber risks, and reinforce Germany's resilience against cyber threats.
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Empowering the Data Analytics Ecosystem: A Laser Focus on Value
The data analytics ecosystem thrives when every component functions at its peak, unlocking the true potential of data. Here's a laser focus on key areas for an empowered ecosystem:
1. Democratize Access, Not Data:
Granular Access Controls: Provide users with self-service tools tailored to their specific needs, preventing data overload and misuse.
Data Catalogs: Implement robust data catalogs for easy discovery and understanding of available data sources.
2. Foster Collaboration with Clear Roles:
Data Mesh Architecture: Break down data silos by creating a distributed data ownership model with clear ownership and responsibilities.
Collaborative Workspaces: Utilize interactive platforms where data scientists, analysts, and domain experts can work seamlessly together.
3. Leverage Advanced Analytics Strategically:
AI-powered Automation: Automate repetitive tasks like data cleaning and feature engineering, freeing up data talent for higher-level analysis.
Right-Tool Selection: Strategically choose the most effective advanced analytics techniques (e.g., AI, ML) based on specific business problems.
4. Prioritize Data Quality with Automation:
Automated Data Validation: Implement automated data quality checks to identify and rectify errors at the source, minimizing downstream issues.
Data Lineage Tracking: Track the flow of data throughout the ecosystem, ensuring transparency and facilitating root cause analysis for errors.
5. Cultivate a Data-Driven Mindset:
Metrics-Driven Performance Management: Align KPIs and performance metrics with data-driven insights to ensure actionable decision making.
Data Storytelling Workshops: Equip stakeholders with the skills to translate complex data findings into compelling narratives that drive action.
Benefits of a Precise Ecosystem:
Sharpened Focus: Precise access and clear roles ensure everyone works with the most relevant data, maximizing efficiency.
Actionable Insights: Strategic analytics and automated quality checks lead to more reliable and actionable data insights.
Continuous Improvement: Data-driven performance management fosters a culture of learning and continuous improvement.
Sustainable Growth: Empowered by data, organizations can make informed decisions to drive sustainable growth and innovation.
By focusing on these precise actions, organizations can create an empowered data analytics ecosystem that delivers real value by driving data-driven decisions and maximizing the return on their data investment.
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4. In People with Diabetes Macrovascular
Complications Are Two Times Greater than
Microvascular Complications
20%
9%
0
5
10
15
20
25
Macrovascular complicationsMicrovascular complications
People
with
diabetes
developing
complications
within
9
years
of
diagnosis
(%)
Adapted from Turner R et al Ann Intern Med 1996;124:136-145.
5. Adapted from Alexander CM, Antonello S Pract Diabet 2002;21:21-28.
2/3 of People with Diabetes Die
of Macrovascular Diseases
67%
8. Does PAD differ in diabetic from
nondiabetic Subjects ?
• PAD is more common in Diabetes: 30% of
diabetic subjects older than 50 yrs have PAD.
• Occurs at a younger age
• Loss of female protection: A roughly equal
male-to-female ratio
10. • Diminished ability to establish collateral
circulation, especially around the knee.
• Increased risk of progression from
intermittent claudication to critical limb
ischemia and gangrene.
12. Presentation of PAD
• One-half are
asymptomatic or
have atypical
symptoms,
• One-third have
claudication,
• The remainder
have more severe
forms of the
disease
13. Intermittent Claudication
• Intermittent claudication, defined as pain,
cramping, or aching in the calves, thighs, or
buttocks that appears reproducibly with
walking exercise and is relieved by rest.
• The history of PAD is characteristic and
consistently reproducible, and may alone be
diagnostic for many individuals.
14. Signs of PAD
Unlike other forms of
atherosclerotic disease, PAD is
easily diagnosed in the outpatient
clinic noninvasively.
15.
16. • The dorsalis pedis pulse is reported to be
absent in 8.1% of healthy individuals, and the
posterior tibial pulse is absent in 2.0%.
• Nevertheless, the absence of both pedal
pulses, when assessed by a person
experienced in this technique, strongly
suggests the presence of vascular disease
17. • Temperature
differences can
be reliably
assessed only
when limbs have
been exposed to
a constant room
temperature for
10-20 minutes.
18.
19. • Absence of hair growth, thin and shiny
skin, dystrophic toenails, and cool, dry,
fissured skin are signs of vascular
insufficiency and should be noted.
21. People with Diabetes Have MI Risk Levels
Comparable to People with Prior MI
20%
19%
0
5
10
15
20
25
Diabetes (no prior MI) Prior MI (no diabetes)
Incidence
of
fatal
or
nonfatal
MI
(%)
Patients with diabetes without previous MI have as high of a risk
of MI as nondiabetic patients with previous MI.
These data provide a rationale for treating cardiovascular risk
factors in diabetic patients as aggressively as in nondiabetic
patients with prior MI.
22. Poor prognosis following
a CV event
People with diabetes are up to two times
more likely to die than those without
diabetes after an MI.
32. Mononeuropathies
• Affect peroneal, median or ulnar nerves,
• tend to occur at sites of entrapment or external
compression.
• Peroneal nerve palsy is characterized by
weakness or paralysis of foot and toe extension
and foot eversion. Impaired sensation over the
dorsum of the foot and the lower anterior aspect
of the leg. The ankle reflex is preserved as is
foot inversion.
33. Cranial nerve palsies
• often affect III, VI, IV and rarely VII nerves.
• III nerve palsy is characterized by
• 1. Acute onset
• 2. Painful: severe pain around the eye.
• 3. Intact papillary reactions: pupilloconstrictor
fibres located peripherally so they are affected in
lesions that produce compression e.g.
aneurysm.
34. • 3rd nerve palsy :
Left ptosis and
diplopia.
• Intact pupillary
reactions are
characteristic
features of 3rd
nerve palsy in
diabetes.
35. Radiculopathy
• truncal neuropathy may yield sensory
manifestations ( band like or constricting
pain in thoracic root) or
• Motor manifestations (asymmetrical bulge
in abdominal wall).
36. • Bulging of the left
lower abdomenal wall
due to truncal
radiculopathy
37. Proximal motor neuropathy
(amyotrophy)
• More frequent in male type 2 diabetic
· Unilateral or asymmetrical bilateral
• Pain, wasting and weakness in proximal
muscles of the lower limbs.
• Often associated with polynuropathy and weight
loss.
• DD: Internal malignancy, chronic inflammatory
demyelinating polyneuropathy.
38. Entrapment Neuropathies
• 1-carpal tunnel syndrome: found in 5.8 % of
diabetic patients. It has a less favorable
outcome after surgical decompression, as
diabetes slows nerve regeneration.
• 2- Ulnar neuropathy at the elbow affect 2.1%
of diabetic patients
• 3- Peroneal neuropathy at the fibular head
affect 1.4–13% of diabetic patients.
• 4- Lateral cutaneous nerve of the thigh
(meralgia paresthetica) affect 0–1.0% of
diabetic patients.
44. Pain and touch perception
• Pain perception is assessed by pin prick
testing. Pinprick should be delivered
once per second and not over the same
point. More rapid delivery of pinprick
produce summation of the effect and may
obscure sensory loss.
• Light touch is assessed by cotton wool .
48. • Percption of movement and position sense is tested
in the fingers and toes .
• In more severe cases, with loss of
proprioception, patients may demonstrate a
positive Romberg's sign.
• Examination of muscle status, tone, power: wasting
of small muscles of the hand and feet is common in
neuropathy often with minimal weakness.
• Ankle reflex often lost (reduced or absent in elderly).
50. Management of DPN
1. Primary prevention
2. Early detection and treatment
3. Disease modifying treatments
4. Symptomatic treatment of pain.
5. Protect a foot that lost its natural protective
mechanisms.
51. Management of DPN
1. Primary prevention
2. Early detection and treatment
3. Disease modifying treatments
4. Symptomatic treatment of pain.
5. Protect a foot that lost its natural protective
mechanisms.
52. • The DCCT and the UKPDS demonstrated that the
risk of neuropathy and other complications can
be dramatically reduced or delayed by
intensified glycemic control in patients with type
1 and 2 diabetes, respectively
53. Management of DPN
1. Primary prevention
2. Early detection and treatment
3. Disease modifying treatments
4. Symptomatic treatment of pain.
5. Protect a foot that lost its natural protective
mechanisms.
54. • The earlier the treatment of neuropathy the
better will be the response to therapy.
55. Management of DPN
1. Primary prevention
2. Early detection and treatment
3. Disease modifying treatments
4. Symptomatic treatment of pain.
5. Protect a foot that lost its natural protective
mechanisms.
56. Tight blood glucose control
• The stability rather than the actual level of
glycemic control may be more important in
relieving neuropathic pain especially in its early
stages.
57. Alpha Lipoic Acid
A meta analysis proved that treatment with alpha-
lipoic acid (600 mg/day i.v.) over 3 weeks is safe.
It significantly improves both positive neuropathic
symptoms and neuropathic deficits to a clinically
meaningful degree in diabetic patients with
symptomatic polyneuropathy.
Ziegler et al Diabet Med. 2004 Feb;21(2):114-21
ALADIN III Study
58. Benfotiamine
• A lipid-soluble derivative of thiamine.
• May reduce pain of PDN in a dose of 600 mg
per day (Stracke et al 2008).
• Prevent the Accumulation of
triosephosphates arising from high cytosolic
glucose concentrations via the reductive
pentosephosphate pathway.
59. PKC inhibitors {Ruboxistaurin (LY333531)}
•Therapy for diabetic macular oedema
and other diabetic angiopathies
including D retinopathy, D peripheral
neuropathy and D nephropathy.
• A phase III trial of the protein kinase C β
inhibitor ruboxistaurin has been
disappointing after encouraging data from
phase II studies were reported
60. Aldose reductase inhibitors (Epalrestat
and Ranirestat)
• Sorbitol pathway is involved in pathogenesis of
microvascular complications of diabetes.
• Aldose reductase inhibitors are effective in
experimental animals (Matsumoto et al 2009).
• Safety!!!!
61. Inhibitors of glycation (aminoguanidine)
• Studies of aminoguanidine have mainly focused
on nephropathy.
62. Management of DPN
1. Primary prevention
2. Early detection and treatment
3. Disease modifying treatments
4. Symptomatic treatment of pain.
5. Protect a foot that lost its natural protective
mechanisms.
63. NSAID Short courses may be used
Opioid analgesics Should be avoided. But
tramadol can be used for up to
6 months
SSRI Debate about their
effectiveness.
Carbamazepine More effective in lancinating
pain but it is a Toxic drug
64. Oxycarbazine More safe Derivative of
carbamazepine? Rapid titration of
the dose…. serious adverse events.
Mexiletine May induce serious arrhythmia
Capsaicin cream Helpful for superficial and localized
pain and in allodynia
Physiotherapeutic
modalities
Acupuncture, TENS, PENS, Static
magnetic field therapy, low-
intensive laser therapy,
monochromatic infrared light
65. Tricyclic antidepressants 1st line treatment, however, side effects are
frequent. The tricyclic antidepressants have
anticholinergic side effects.
Gabapentin Effective and safe drug in a dose of 1800 mg
/day (gradual increase of the dose every
3days)
Pregabalin Analog of gamma aminobutyric acid, has
anticonvulsant, analgesic, and anxiolytic
properties . The greatest effect was observed
in patients treated with 600 mg/day
(Freeman et al 2008)
SNRI (Dual selective
serotonin noradrenaline
reuptake inhibitor)
It relieves pain by increasing the synaptic
availability of 5-HT and noradrenaline in the
descending pathways that inhibit pain
impulses.
66. Management of DPN
1. Primary prevention
2. Early detection and treatment
3. Disease modifying treatments
4. Symptomatic treatment of pain.
5. Protect a foot that lost its natural protective
mechanisms.
67. The neuropathic foot does not ulcerate
spontaneously
It is the combination of neuropathy with either:
Extrinsic factors (e.g., ill-fitting shoe gear or
foreign body in shoe)
Intrinsic factors (e.g., high foot pressures or
plantar callus) that results in ulceration.
69. • Diabetic retinopathy is the commonest
cause of blindness worldwide.
• Diabetic retinopathy increases with the
duration of diabetes.
• Progression of retinopathy often
accelerated with poor control of diabetes
and blood pressure.
• Asymptomatic until become advanced, so
fundus examination should be routinely
done at least annually.
70. Background diabetic retinopathy
• The first sign is the development of
microaneurysms (small red dots).
• Superficial haemorrhages
• Cotton wool spots are micro-infarcts within
the retina.
• Hard exudates (exudation of plasma rich
in lipids and protein)
71. Proliferative retinopathy
• Proliferative retinopathy is preceded by the
widespread development of capillary non-
perfusion. This ischaemia induces new
blood vessels to grow.
• New vessels do not give rise to any
symptoms.
• New vessels are prone to bleed,
particularly if there is vitreous traction.
72. • Small haemorrhages give rise to the
preretinal haemorrhage with further
bleeding or traction, the blood seeps into
the vitreous with the consequent loss of
vision.
• Once new vessels have developed this is
an indication for laser therapy.
73. Diabetic eye diseases
1. Diabetic retinopathy
2. Cataract which develops earlier in diabetes than
in the general population.
3. Error of refraction due to fluctuations in blood
sugar leading to osmotic changes within the lens.
4. Ocular Nerve palsies: The sixth and the third
nerve are the most commonly affected. These
nerve palsies usually recover spontaneously
within a period of 3–6 months
75. Renal affection in Diabetes
Increased risk of:
• Renal atherosclerosis
• Urinary tract infections, papillary necrosis
• Glomerular lesions, e.g. from basement
membrane thickening and
glomerulosclerosis.
76. Diabetic nephropathy
• Approximately 40% of patients with type 1 and
20% with type 2 diabetes develop nephropathy.
• Some centres have reported a falling incidence
rate of diabetic nephropathy in type 1 diabetes.
This may reflect good-quality local care for
diabetes
77. • Diabetic nephropathy is the most common
cause of chronic kidney failure and end-
stage kidney disease in the United States.
78. Pathophysiology
• The earliest functional abnormality in the
diabetic kidney is renal hypertrophy
associated with a raised glomerular
filtration rate.
• As the kidney becomes damaged by
diabetes, the afferent arteriole becomes
vasodilated to a greater extent than the
efferent glomerular arteriole. This
increases the intraglomerular filtration
pressure.
79. • This increased intraglomerular pressure
leads to increased shearing forces locally
which are thought to contribute to
mesangial cell hypertrophy and increased
secretion of extracellular mesangial matrix
material.
• This process eventually leads to
glomerular sclerosis.
80. • The initial structural lesion in the
glomerulus is thickening of the basement
membrane.
• Associated changes result in disruption of
the protein cross-linkages which normally
make the membrane an effective filter. In
consequence, there is a progressive leak
of large molecules (particularly protein)
into the urine.
81. Stages of Diabetic nephropathy
1. Elevated glomerular filtration rate with
enlarged kidneys
2. Intermittent Microalbuminuria
3. Microalbuminuria
4. Proteinuria and Nephrotic syndrome.
5. ESRD
82. Early Detection of Diabetic Nephropathy
• Clinical features are usually absent until
advanced chronic kidney disease
develops.
• Therefore, we should evaluate urinary
albumin excretion (microalbuminuria)
annually in all subjects with diabetes.
83. Definitions
• In healthy individuals, urinary albumin
excretion is less than 30 mg per day.
• Microalbuminuria is defined as urinary
albumin excretion 30 -300mg/day or
albumin:creatinine ratio (ACR) greater
than 2.5 mg/mmol (men) or 3.5 mg/mmol
(women).
• Macroalbuminuria is defined as urinary
albumin excretion >300mg/day
84. DD
Other renal disease should be suspected:
• In the absence of progressive retinopathy
• If proteinuria develops suddenly
• If significant haematuria is present
85. Management
• Primary prevention
• Optimal control of blood glucose and blood pressure.
– The Diabetes Control and Complications Trial (DCCT) found that
a reduction in mean HbA1c from 9.0% to 7.3% in people with
type 1 diabetes was associated with a 39% reduction in
microalbuminuria and 54% reduction in proteinuria over 6.5
years.
– The United Kingdom Prospective Diabetes Study (UKPDS) also
showed that a reduction in blood pressure from 154/87 to 144/82
mm Hg was associated with an absolute risk reduction of
developing microalbuminuria of 8% over 6 years in patients with
type 2 diabetes
86. Microalbuminuria and proteinuria
• Ensure good blood glucose control (HbA1c below 6.5-
7.5%, according to the individual's target).
• ACE inhibitors should be started and titrated to full dose
in all adults with confirmed nephropathy (including those
with microalbuminuria alone) and type 1 diabetes.
• If ACE inhibitors are not tolerated, angiotensin ll receptor
antagonists should be substituted but combination
therapy with both ACE inhibitors and angiotensin ll
receptor antagonists is not recommended at present.
• ACE inhibitor and angiotensin ll receptor antagonists
should be used with caution in those with:
– Peripheral vascular disease or known renovascular disease
– Raised serum creatinine
87. • Measure, assess and manage
Cardiovascular risk factors aggressively
(smoking, glucose, raised lipids, high
blood pressure).
• Blood pressure should be maintained
below 130/80 mm Hg by addition of other
antihypertensive drugs if necessary.
88. • Avoid high protein intake.
• Avoid taking Contrast agents containing
Iodine and NSAIDs.
91. The term diabetic foot indicate any foot
pathology that results directly from diabetes
or its long-term complications
92. The WHO definition of the diabetic foot
• The foot of a diabetic patient that has the potential risk of
pathologic consequences including infection, ulceration
and or destruction of deep tissues associated with
neurologic abnormalities, various degrees of peripheral
vascular disease and/or metabolic complications of
diabetes in the lower limb
93. • Diabetic gangrene doesn’t occur suddenly
but is preceded by several stages
96. The high risk foot
The high risk foot is the foot that has developed one or more
of the following risk factors for ulceration:
Neuropathy
Ischaemia
Deformity
Trauma
Callus.
Nail pathology
97. The National Institute of Health and Clinical
Excellence defines low-risk patients as those with
normal sensation and palpable pulses
The low risk foot
98. key educational elements for diabetic
patients at low
risk of complication
Foot care education in patients with diabetes at low risk of
complications: a consensus statement. Diabet. Med. 28, 162–
167 (2011)
99. • Control: control blood glucose levels
• Annual: attend your annual foot screening
examination.
• Report: report any changes in your feet
immediately to your healthcare
professional.
• Engage: engage in a simple daily foot care
routine by washing and drying between
your toes,moisturizing and checking for
abnormalities.
CARE
100. • In order to prevent amputation, we should
diagnose and treat any mild foot pathology
before its progression into advanced foot
pathology.
102. What can be done to prevent the development of
advanced foot pathology?
• Regular inspection and examination of the foot.
• Identification of the foot at risk.
• Education of patient, family and healthcare
providers.
• Appropriate footwear.
• Treatment of non ulcerative pathology