Pathology of Diabetes
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Transcript of Pathology of Diabetes
Always do your best. What you plant now, you will harvest later.
- - Og Mandino
CPC 3.2: Ms. ML, 18y, Thrush. Recurrent thrush*, boils*, tired*, Obese*, junk food, no exercise*, polyuria, polydipsia* , Abd. Striae*, Mom DM2*, smoker, social drinker. Dipstick: Nitrate +, WCC 3+, Blood 2+,
Prot. 2+, Glucose 2+ MSU: Ecoli >108, swab: Candida 4+, RBGL
35. ? Key points: ? Differential Diagnosis: Thrush, UTI, STI,
Pregn, DM
? Further questions:
CPC 3.1: Molly 15y.. Wee problem.
Molly is a 15 year old Y10 student comes to ED with her Aunty Ada, community health worker. Ada says Molly has ‘wee’ problem.
Molly : ‘I’m going to the toilet often to pass wee and it is sore and itchy afterwards’ ? Key points: ? Differential Diagnosis: ? Further questions ? DM type ? How to confirm Investigations? ? Complications Prognosis? ? Management
?Pathogenesis: “recurrent multisite infections”
1 2 3 4 5
4%9%
28%
59%
0%
1. Associated AIDS2. Hyperglycemia3. Ischemia4. Immunodeficien
cy5. Multifactorial
Specific features for diagnosis of DM2?
1 2 3 4 5
11% 11%
45%
4%
30%
1.On & off for long time.
2.Always drinking.3.Obesity.4.Recurrent boils.5.Mom has DM2
Miss ML: Most likely diagnosis:
1 2 3 4 5
21% 21%
0%
18%
39%1. DM Type 12. DM Type 23. MODY 14. MODY 25. LADA
?Pathogenesis: Whitish vaginal discharge.
1 2 3 4 5
0%7%
91%
0%2%
1. Proteinuria2. Bacterial
infection3. Glycosuria4. Trichomoniasis5. Candidiasis
“Nothing great in the world has ever been accomplished without passion”
- - CHRISTIAN FRIEDRICH HEBBEL
Most likely .. What type of DM ?
1.56 year male obese2.30 year female following
pregnancy3.8 year old boy, poor growth,
DKA.4.24 year female Cushing’s sy5.68 Year male following Ca.
pancreas.6.32 male, DM, BMI 18, Anti-
GAD +ve.7.34 year male, extensive
tuberculosis.8.12 year old female following
viral fever9.41y DM2, BMI 17.1, HbA1c
14.1, DKA10.15y male, BMI 16.2,
recurrent infect.
II NIDDMII GDMI IDDM
Sec IDDM
Sec IDDM
I LADASec
IDDMI IDDMLADAMODY
The foundation of lasting self-confidence and self esteem is
excellence, mastery of your work.
- Brian Tracy
Pathology of Diabetes
Dr. Venkatesh M. ShashidharAssoc. Prof. & Head of Pathology
What is Diabetes?
“….a wonderful but not very frequent affection among men, being a melting down of the flesh and limbs into urine…Life is short, offensive, and distressing, thirst unquenchable, death
inevitable…”
-- Aretaeus of Cappadocia (AD 81-3)
• 150 AD – Aretaeus, named "diabetes“ Greek word for "siphon”• 1788 – Cawley – damaged pancreas in DM.• 1921 – Banting & Best, Insulin
Introduction Diabetes mellitus (sweet urine) 3% of world population, 100m. Incidence increasing alarmingly (259m
2025) Most Common non communicable disease. High Morbidity & mortality. DM shortens life span by 15 years. Leading cause of blindness and Kidney
dis. Pacific Islands – leaders in DM &
Obesity…! Aus: 7th leading cause of death, 1M.. half
of whom may be unaware of their disease.
World Statistics:
Diabetes Mellitus - Definition
2nd Century, Greek physician, Aretus named Diabetes from diabainein, “to flow through or siphon & Mellitus meaning sweet/Honey.
* insipidus tasteless – dilute urine.
Disorder of metabolism (Carb, Prot & Fat)
Absolute/Relative deficiency of insulin. Characterized by hyperglycemia. Polyuria, Polydypsia, Polyphagia.
Criteria for the Diagnosis of Diabetes
1. A random blood glucose concentration of 11mmol/L or higher, with classical signs and symptoms. or
2. A fasting glucose concentration of 7mmol/L or higher on more than one occasion. or
3. An abnormal oral glucose tolerance test (OGTT, done for borderline 5.5-6.9 mmol/L ), in which the glucose concentration is >11mmol/L at 2 hours after a standard carbohydrate load (75 gm of glucose).
Pancreas Normal Anatomy:
Normal Pancreas:
Normal Pancreas:
Islet of Langerhans (Endocrine Pancreas)Pancreatic acini (Exocrine Pancreas)
Duct
Normal Pancreatic Islet: (ipx stain)
α cells 20% (Glucagon) ß cells 70% (Insulin)
ßα
Other Cells in Islets: δ cells - Somatostatin
PP Cells - pancreatic polypeptideD1 cells – Vasoactive Intestinal PolypeptideEnterochromaffin – Seratonin.
Blood Glucose & HormonesHormones Insulin Glucortocoids Glucagon Growth Hormone Epinephrine
Action Glucose
Glucose
Glucose
Glucose
Glucose
Maintained within 3.5-5.5 mmol/l.
Insulin secretion:
Insulin - Anabolic Steroid
Transmembrane transport of glucose (Liver, muscle & adipose tissue. Maintain metabolism: Striated Muscle glucose uptake Adipose tissue lipogenesis Hepatic gluconeogenesis.
glycogen & gluco-neogenesis. lipolysis Lipogenesis. Protein & triglyceride synthesis Nucleic acid & Protein synthesis In DM Insulin glucose & catabolism
InsulinAnabolic Steroid
GLUT4*
only these tissue….!
DM2: Pathogenesis – 3 mechanism.
Insulin Requiring Cells Striated Muscle Liver Adipose Tissue
Intra cellular hypoglycemia Low glucose: Liver: Gluconeogenesis Adipose: Lipolysis FFAExtracellular hyperglycemia Vascular & tissue
damage…*
Non-Insulin Requiring Cells Blood Vessels Nerves & Brain Kidney, Eye Lens
Intracellular Hyperglycemia Glucose polymers “Polyol”
damageExcess glucose:Glucose Aldose reductase
Sorbitol (Polyol) Osmotic cell swelling and dysfunction.
DM2: Pathogenesis Liver & skeletal muscle insulin
resistance β-cell hypersecretion β-cell failure Lipotoxicity decreased incretin secretion increased glucagon secretion increased renal glucose re-absorption appetite dysregulation
New in DM Pathogenesis: Incretins. Insulin release through Incretins (from
intestine) in response to glucose intake. Glucagon-like Peptide-1 (GLP-1) Glucose-dependent Insulinotropic Polypeptide
(GIP) stimulate β cells (Insulin) & Inhibit α
(glucagon) Destroyed by dipeptidyl peptidase (DPP). Dysregulation in DM2 (early breakdown). Two new drugs, exenatide (GLP-1 mimetic)
and sitagliptin [DPP 4 inhibitor] – Approved for PBS.
http://www.medscape.com/infosite/dia/article-3 http://video.medscape.com/pi/editorial/cmecircle/
2004/3418/flash/beaser/index.html
Incretins: physiology
Diabetes Classification: (not a single disease)
Primary DM Type I – IDDM / Juvenile – 5-10%. Type II – NIDDM /Adult onset – 90-95%. MODY – 5% Maturity Onset Diabetes of Youth
Genetic, sub types MODY 1–6, LADA – Latent Autoimmune Diabetes in Adults
(LADA) Gestational Diabetes Mellitus. Other.
Secondary DM Excess hyperglycemic stimulus.
Cushings, Phaeochromocytoma, acromegaly, Steroid therapy.
Beta cell destruction: Pancreatitis/tumors/Hemochromatosis Infectious – congenital rubella, CMV, TB, Endocrinopathy, Downs Sy.
Metabolic Syndrome (X) - IDF criteria
Central Obesity >90cm male, >80 fem – Asian, chinese,
Jap. >94cm male, >80 fem – Europ, Africa,
Arab. + Any two of the following.
Raised triglycerides >1.7mmol/l or treat. Reduled HDL-C <1.03mmol/l or treat. Hypertension 130/85 or treat. Fasting plasma glucose >5.6mmol/l or
DM2.
Australia prevalence 2005 – 30.7% 10 Year CVD risk - 23.4%
LADA: Late onset Autoimmune DM Features of both type 1 and type 2.
Younger, Rapid onset & progression to insulin dependency. Immune markers like type 1 diabetes, may lack ketoacidosis symptoms.
Incidence: - 6-10% (UK). Diagnosis: Elevated pancreatic
autoantibodies Risk factors: Metabolic Syndrome LADA + Metabolic syndrome = DM Type
1.5. Complications of both type 1 & 2.
(metabolic, Macro & Microangiopathy etc).
MODY: Maturity Onset Diabetes of Young.
5% of DM, Young*, non obese, insulin release defect*
Like DM2, non-ketotic hyperglycemia, no DM Antibodies.
Auto. Dom. - Monogenic – Genetic testing*.
Treatment is specific to type. Unline type 1 or 2
Also known as Type 1.5 (MODY + LADA)
Subtypes: 1,2,3,4,5,6 – type 3 & 2 common.
1,3,4,5,6 – Insulin transcription defect HNF.
Type 2 – Enzyme glucokinase, defective β cell response.
One machine can do the work of fifty ordinary men. No machine
can do the work of one extraordinary man.
- - Elbert Hubbard
Pathogenesis of Type I DM
Genetic HLA-DR3/4
EnvironmentViral infe..?
Insulin deficiency
Autoimmune InsulitisAb to ß cells/insulin
ß cell Destruction
Other Autoimmune disorders:• PS Glomerulonephritis• Graves, Hashimoto thyroiditis.• Rheumatic heart disease• SLE, Collagen vascular disease• Rheumatoid arthritis.
Secondary DMInflammation,
Tumor, InfectionTrauma
Pancreatitis
Antibodies:Islet cell Ab - ICA
Insulin Auto Ab - IAAGlut. Acid Decarb - GAD65
Insulitis – Type I
Lymphocytes.
DM1Course:
Progression of Type II
Years ..
Pathogenesis of Type II DM
Relative
Insulin Def.
ß cell Exhaustion
(IDDM)
Insulin Resistance:
Diabetes
Insulin Resistance:
JCU Research…!
DM2 Islets: Normal early amyloid late:
Normal.Loss of ß cells (only in late stage) replaced by Amyloid protein deposit (hyalinization).
Type-I Type-II
Less common (10%) Children < 25 Years Insulin- Dependent Duration: Weeks Acute Metabolic
complications Autoantibody: Yes Family History: No Insulin levels: low Islets: Insulitis 50% in twins
More common (90%) Adult >25 Years NIDDM* Months to years Chronic Vascular
complications. No Yes Normal or high * Normal / Exhaustion ~100% in twins
Type-I Type-II
Insulitis:Lymphocytic infiltrate within islets.
Islet Hyalinization:Central hyaline deposits replacing
dead beta cells(only in late stage…!)
Being a good human is maintaining complete harmony between thought, word and deed. Divergence between thought, word and deed is the cause of all our problems…!- BABA.
DM Complications: Glucose is highly reactive - damages
tissues. Glucose absorption, storage & use –
Timely Insulin release - critical. Diabetes is state of insulin deficiency. Absolute/Delayed/inappropriate insulin
response Glucose excess – Hyperglycemia. Neo-glucogenesis – Proteolysis, lipolysis Clinical symptoms & signs are mainly due
to complications. Complications:
Acute Metabolic & Chronic Vascular. Damage to BV, Kidney, CNS & immune system.
Diabetes Complications: Short term Complications: (metabolic)
Hypoglycemia Diabetic Ketoacidosis Non Ketotic hyperosmolar diabetic coma Lactic acidosis
Long term Complications: (Angiopathy) Microngiopathy - Retinopathy,
Nephropathy, Neurophathy, dermatopathy.
Macroangiopathy – Atherosclerosis.
Pathogenesis of complications: Insulin dependant tissue: Striated muscle, adipose tissue & Liver.
Low glucose inside cell decreased cell metabolism.
High glucose outside Glycosylation damage (AGE), cross linking, trap plasma
proteins, LDL, cholesterol, - *
Insulin independent tissue:BV, nerve, (kidney, eye, CNS)
Excess glucose Sorbitol, Polyol osmotic damage*
Excess glucose Diacylglycerol (DAG) Activation of Protein Kinase C angiogenesis, BM matrix.
DM:Complications:
The best gift of Nature to man is the briefness of his life…!
Latin quote
Microangiopathy Pathogenesis:
Chronic Hyperglycemia. Glycosylation of basement
membrane proteins Leaky blood vessels.
Deposition of proteins, matrix, LDL. Narrow, thick, fragile, Leaky BV.
Ischemia, defective inflammation. Leakage – edema, Proteinuria (kidney) Micro Aneurysms (retina) Atherosclerosis.
Diabetic Microangiopathy
Normal
Diabetic
Glucose Glycosylation BM damage leak ‘AGE’ deposition
Neuropathy Sensory Motor (myelin) Peripheral Neuropathy
Bilateral, symmetric Progressive, irreversible Paraesthesia, pain,
muscle atrophy Visceral neuropathy
Cranial nerve – diplopia, Bells palsy
GIT- constipation, diarrhoea
CVS – orthostatic hypotension
DM-Neuropathy – Myelin stain
Myelin loss in nerve
Normal
Neuropathic ulcer
Etiology: peripheral sensory
neuropathy, Trauma & deformity.
Factors: Ischemia, callus
formation, and edema.
Neuropathic ulcers
FEATURES:Painless, surrounded by callus At pressure points. associated with good foot pulsesMay not be associated with gangrene
Nephropathy
Nodular Glomerulo Sclerosis.
Common morbidity & mortality.
Deposition of ‘AGE’ Advanced Glycosylation End-products as nodules.
Nephrotic syndromePyelonephritisEnd stage renal failure
Diabetic Nephropathy
Microangiopathy, atherosclerosis & infections:
Diffuse or nodular diabetic glomerulosclerosis (Kimmelstiel Wilson Sy)
Renal arteriolosclerosis & atherosclerosis
Necrotizing renal papillitis. Pyelonephritis. End stage kidney.
Nodular Glomerulosclerosis – KW
Diabetic Glomerulosclerosis
B
A
A: Nodular glomerulosclerosis. B: Hyaline Arteriolosclerosis.
What is the pathogenesis?
DM Kidney: advanced (KW Lesion)
B
A
DM Kidney: thickening of BM (PCT)
PCT
DCT
PCT: Proximal Convoluted Tubule, DCT: Distal Convoluted Tubule
Gross : Diabetic kidney
Nephropathy – Progression:
Nephropathy Classes: I - IV
DM with Infarction:
Papillary necrosis
Retinopathy: Non Proliferative
Microaneurysms, Dots & blots Hard and soft
exudates Cotton wool –
infarcts Macular edema.
Proliferative. Neovascularization Large hemorrhages Retinal
detachment.
Non Proliferative RetinopathyVenous dilation and small red dots posterior retinal pole - capillary micro-aneurysms.
Dot and blot retinal hemorrhages and deep-lying edema and lipid exudates impair macular function.
Cotton-wool spots (soft exudates) - microinfarcts due to ischemia. They are white and obscure underlying vessels. Hard exudates are caused by chronic edema. They are yellow and generally deep to retinal vessels.
Late generalized diminution of vision due to ischemia and macular edema - common cause of visual defect (best detected by fluorescein angiography)
Proliferative RetinopathyNeovascularization – new capillaries grow into the vitreous cavity.
hemorrhages may lead to sudden severe loss of vision.
In advanced disease, neovascular membranes can occur, resulting in a traction & retinal detachment. Leading to permanent blindness.
Panretinal photocoagulation may diminish or eliminate proliferative retinopathy
Normal Retina
Diabetic Retinopathy
Diabetic Retinopathy
Fluorescein angiogram of the eye of a diabetic patient. Note the numerous, small, dot-like capillary microaneurysms.
Diabetic Retinopathy
Pre retinal Hemorrhage - detachment
You must learn to distinguish between good and bad, truth and untruth. You must use your education for the
purpose of serving community. - Sai - Summer Showers, 1973.
Macroangiopathy Atherosclerosis
Dyslipidemia HDL Non-Enzymatic Glycosylation Platelet Adhesiveness
Thromboxane A2
Prostacyclin Endothelial damage
Atherosclerosis MI, CVA, Gangrene of Leg (PVD), Renal
Insufficiency
Atherosclerosis:
Fungal infections: Candidiasis
Macrosomia
With Polycythemia
Blood vessel calcification:
In digital arteries in DM
Amputated Toe
Calcified BV
Cataract – Sorbitol.. Polyol..osmotic..
Lens epithelium (Insulin independent) is exposed to Hyperglycaemia, excessive flux of glucose to sorbitol by the polyol pathway. The accumulation of intracellular sorbitol exerts osmoprotection and prevents cell shrinkage. The excessive accumulation of sorbitol, causes an increased osmotic load within the lens causing swelling, fibre breakdown, and opacification (the osmotic hypothesis). Other mechanisms, including glycation and oxidative stress, may also be responsible for lens opacification.
Acanthosis Nigricans
Insulin resistance…
ComplicationsSummary:
Pathogenesis of Infections in DM:
Multifactorial: Impaired inflammation – BV
thickening – Decreased immune function: WBC,
chemical mediator glycosylation. Glycosylation of immune mediators.
Abs. Tissue damage: Ischemia &
infarctions. Decreased metabolism – low
immunity. Increased glucose (alone is not the cause*)
Laboratory Diagnosis: Urine glucose - dip-stick –Screening Fasting > 7mmol, Random >11mmol If Fasting level is 5.5 to 7 OGTT HbA1c - for follow-up, not for
diagnosis Fructosamine – similar to HbA1c -
long term maintenance. Antibodies – Type-1 Gene testing: MODY
“It's not that I'm so smart, it's just that I stay with problems longer”…!
--Albert Einstein
CPC-3.2– END–DM2 Pathology – Major Core Learning Issues:
Pathology of Diabetes Overview & Classification. Pathological basis of clinical features.
Details of Type 1 & 2 (Etiology, pathogenesis, morphology, clinical features)
Complications of Diabetes: Micro & Macroangiopathy. Retinopathy, nephropathy, neuropathy, dermatopathy.. etc.. &
Metabolic complications (ketoacidosis, coma etc) Laboratory diagnosis of diabetes. (GTT, HBA1c, etc)
Pathology – Minor CLI: Metabolic Syndrome (Syndrome X). MODY, LADA, Gestational, childhood type 2, Secondary diabetes, Bronze diabetes. Hyperglycemia Syndromes: Cushings, drugs, etc. Hypoglycemia syndromes, Insulinoma. New research & developments
Case 1 A 29y woman BMI = 33 kg/m2.
complains of declining visual acuity since 6 months. Fundoscopic examination shows peripheral retinal microaneurysms. Urinalysis reveals 3+ proteinuria and 3+ glucosuria. Serum albumin is low & cholesterol is high.
These clinicopathologic findings are best explained by which of the following pathologic mechanisms of disease
Pathologic mechanism?
1 2 3 4 5
0% 2%
14%
81%
2%
1. Anti-insulin antibodies.2. Increased insulin uptake.3. Irregular insulin secretion.4. Peripheral insulin resistance.5. Serum Anti GAD-67
antibodies.
DM– Pancreatic Islet- ? Feature shown by arrow?
A. B. C. D. E.
3%5%
3%
10%
79%
A. Β cell exhaution.B. Amyloid depositsC. Lymphocytic InsulitisD. Pancreatic acinusE. Chronic Pancreatitis
50y, male DM2, kidney biopsy. Likely nature of feature shown by arrow?
A. B. C. D. E.
14%
82%
2%2%0%
A. Amyloid protein.B. AGE proteinC. Basement mem protein.D. Fibrinoid necrosis.E. Inflammatory cells.
47y F, DM2 - foot ulcer: ? Diagnosis
1 2 3 4 5
0%
61%
2%
22%
15%
A. Fungal infectionB. Neuropathic ulcerC. Venous ulcerD. Arterial ulcerE. Atypical TB in AIDS
Thickening of small BV in this patient is most likely related which pathologic mechansim?
1 2 3 4 5
8% 8%
73%
4%8%
1. Glycosylation of hemoglobin.2. Inadequate inflammtion resp.3. Insulin resistance in tissues.4. Increased Atherosclersis.5. Microvascular disease.
57y M, DM2: Gross Kidney- arrow ? feature
1 2 3 4 5
4%0% 0%
13%
83%
A. Benign nephrosclerosis.B. GlomerulonephritisC. Papillary necrosisD. Nodular
glomerulosclerosisE. Renal artery
Atherosclerosis
DM– Pancreatic Islet- ? Feature shown by arrow?
A. B. C. D. E.
0%
11%
0%0%
89%
A. Β cell exhaution.B. Amyloid depositsC. Lymphocytic InsulitisD. Pancreatic acinusE. Chronic Pancreatitis
47y F, DM2 – Kidney- arrow ? feature
1 2 3 4 5
6%
81%
0%
10%
2%
A. Nodular glomerulosclerosis.
B. ArtereolosclerosisC. AtherosclerosisD. AGE depositionE. Diffuse glomerulosclerosis
DM Kidney.Microscopy. ? Feature Arrow B
1 2 3 4 5
20%
74%
0%0%6%
B
A
A. Nodular sclerosisB. ArtereolosclerosisC. Diffuse sclerosisD. PyelonephritisE. Abscess
formation
DM Kidney.Microscopy. ? Feature Arrow A
1 2 3 4 5
43%
4%
10%8%
35%
B
AA. Nodular sclerosisB. ArtereolosclerosisC. Diffuse sclerosisD. PyelonephritisE. Abscess
formation
57y M, DM2 – Kidney- arrow ? feature
1 2 3 4 5
30%
4%
18%18%
30%
A. Dot hemorrhageB. Hard exudateC. Soft cotton wool exudateD. NeovascularizationE. Micro Aneurysm
57y M, DM2 – Eye ? Pathogenesis
1 2 3 4 5
3%
15%
3%
74%
5%
A. AGE depositionB. GlycosylationC. Collagen depositionD. Osmotic Polyol damageE. Artereolosclerosis
47y F, DM2 - foot ulcer: ? Diagnosis
1 2 3 4 5
0%
97%
0%0%3%
A. Fungal infectionB. Neuropathic ulcerC. Venous ulcerD. Arterial ulcerE. Atypical TB in AIDS
56y Fem, Anterior wall MI. 3+ proteinuria & FBG 19mmol/L. Image shows her pancreas. What complication she may develop?
A. B. C. D. E.
8%
42%
0%
44%
6%
A. Gall stones.B. Chronic
pancreatitis.C. Uric acid stones.D. Gangrene of foot.E. Pancreatic
carcinoma
A. B. C. D. E.
0%
65%
9%
24%
2%
A 65y man, BMI 40, peripheral neuropathy, retinopathy and abdominal aortic aneurysm is now developing renal failure. His FBS is 18.3 mmol/L, microscopic examination of his renal biopsy. What is the microscopic feature shown ?
1. What is the chemical nature of nodular deposit within glomerulus?2. Briefly describe steps in the Pathogenesis of nodular glomerulosclerosis?3. What other renal pathology are commonly seen in diabetic patients?
A. Renal papillary necrosis.B. Nodular
glomerulosclerosis.C. Hyaline artereolosclerosis.D. Atrophy + Amyloid
deposition.E. Diffuse glomerular
sclerosis.
A. B. C. D. E.
0%
16%
0%
43%41%
A 47 year old man, Hypertensive & DM2 since 6 years for checkup. Complains of his vision as spectacles recently made does not seem to help. Image shows his fundoscopy. What is the most likely diagnosis ?
1. Retinopathy – Differences between Hypertensive & Diabetic retinopathy?2. Briefly describe steps in the Pathogenesis of diabetic retinopathy?3. Differentiate soft & hard exudates, dots & blots, proliferative & non-
proliferative.?
A. Normal fundus.B. Mild Hypertensive
retinopathy.C. Non proliferative
retinopathy.D. Proliferative retinopathy.E. Retinal detachment.
A. B. C. D. E.
27%
7%
36%
2%
27%
A 65y man, BMI 40, Diabetes since 18 years. His FBS is 18.3 mmol/L, is now developing hypertension since 3 years (BP 186/98 mm of Hg) . Image shows microscopic appearance of his renal biopsy. What microscopic feature shows pathogenesis of high blood pressure?
1. What is the pathogenesis of feature A (hyperplastic arterosclerosis) in the image?
2. Briefly describe feature B and its clinical presentation?3. What is seen in the interstitium of this kidney? Pathogenesis? Clinical
feature?
A. Hyperplastic artereosclerosis B. Protein cast within tubule.C. Artereolosclerosis.D. Nodular glomerulosclerosis.E. Both A & C.
A. B. C. D. E.
70%
5%
23%
2%0%
A 42 year female presents with recent onset polyuria, polydypsia and decreasing vision. HbA1c was 16.1%. She is chronic alcoholic with past history of jaundice. Image shows her pancreatic biopsy compared with normal. What is the most likely diagnosis ?
1. Briefly describe features of LADA?2. What further investigations can be done to confirm the diagnosis?3. List & briefly describe other types of Diabetes ?
Normal Patient
A. Secondary diabetes.B. Late onset Type 2
diabetes.C. Chronic cholecystitis.D. Cushing’s syndrome.E. Type 1 diabetes.
A. B. C. D. E.
38%
54%
0%
8%
0%
70y man brought from nursing home with progressive confused & disoriented status since 2 weeks. Not eating or drinking well. On steroid therapy for COPD.What is the most likely diagnosis ?
1. List & briefly discuss common metabolic complications of Diabetes?2. ?3. ?
A. Diabetic ketoacidosis.B. Non-ketotic hyperosmolar
coma.C. Diabetic lactic acidosis.D. Respiratory acidosis.E. Diabetic nephropathy.
Lab tests:
The most splendid achievement of all is the constant striving to
surpass yourself and to be worthy of your own approval.
- - Denis Waitley
Label the diagram.1.2.3.4.5.
Hard/waxy dep
Optic discMaculaBlot hemCotton wool / soft dep.
Label the diagram.
1.2.3.4.
Capillary
Nodule – AGE
Bowman cap.
Hyaline arteriolo sclerosis in arteriole.
Diabetic Retinopathy
Cotton wool
Dot hemBlot hemNeovascul. Cotton wool
Neuropathic Arthropathy: Charcot’s foot.
Acute, swollen, red, warm Minimal or no pain. No or minimal h/o trauma. Pathogenesis:
Neuropathyosteoporosis# Chronic - Foot deformity.
Normal Charcot
DM Amyotrophy - Painful muscle wasting
Pain & weakness of lower limb muscles.
Neuropathy. Muscle wasting. Minimal sensory
loss. Loss of knee reflex. Inflammation in
spinal cord.
Chronic Polyneuropathy
Pathophysiology: (unknown)
Polyol Sorbitol damage.
Ishcemic injuty. Impaired Nerve growth
factor. Autoimmune damage.
Claw foot – Dermopathy & Neuropathy
Diabetic Amyotrophy
Painful, proximal Asymmetrical, motor neuropathy.
Poor diabetic control – hyperglycemia – AGE.
Occlusion of capillaries of proximal lumbar plexus nerve damage. (no myelin degeneration*)
It is multiple mononeuropathy
Your life should rest on morality and truth. Base your life on truth & love for all.
- Sai - Summer Showers, 1973
Money and goes but morality comes and grows.
Case 2 – 58y Fem Asymptomatic. She has a BMI of 29 and is on enalapril for
hypertension. She has no symptoms of diabetes. A fasting glucose is 6.5mmol/L. Mother had DM type2.
Should she be tested for DM? Indications? Yes. (IGTT, IFG, Aboriginals, High risk immig,
Obese fem+, cardiac event, >45y+ BMI>30, FH of DM2 or HPTN).
Diagnosis? next investigation for this patient?
IFG, oGTT (FG 5.5-7, RG 7-11 mmol/L) How do you manage a IGT patient? Advice about Diet & excercise.
CPC-3.2– KFP Questions: DM – Definition, epidemiology Type I,II, NIDDM, IDDM, GDM, MODY. Etiology, Risk factors Pathogenesis of Clinical features –
PPP Complications
Acute – metabolic – ketoacidosis, coma Chronic – vascular – Micro/Macro
Glycosylation, AGE, Polyols Lab Diagnosis – FBS, GTT, KFT, Lipids.
Summary Abnormal metabolic state characterised by
glucose intolerance due to inadequate insulin action.
Type I (juvenile onset) Autoimmune destruction of β-cells (Genetic + ? Virus + Autoimmunity); insulin-dependent – Treat by Insulin.
Type II (maturity onset) - defective insulin action – peripheral resistance to insulin. treatment by life style change & oral hypoglycaemic agents.
Complications: accelerated atherosclerosis, susceptibility to infections, and microangiopathy (retinopathy, neuropathy, dermatopathy, nephrophathy)
Points to remember/review:
Diabetes is a state of hyper ketabolism. Increased fat & protein breakdown, wt loss. Blood vessel damage – arteriosclerosis is
central to chronic complications. Increased Infections – why?. Glucose control is critical * why? Hypoglycemia is more dangerous. Not hyper FBS, GTT & HbA1C – interpretation.
Questions.. How – Ketoacidosis? How – hypoglycemia ? Macro Angiopathy ? – (atherosclerosis) Micro Angiopathy “Pathy”
(arteriolosclerosis) Retinopathy – types, morphology, Nephropathy – types, morphology. Dermatopathy – morphology. Diabetic Amyotrophy - What is Diabetes insipidus ?
56y woman, nocturia 56y Fem, 3/12 nocturia excessive thirst and
polyuria(1-4 times) disturbing her sleep. Recently noticed blurring of vision, & tingling
sensation in her toes on both sides. Weight 94kg & height 1.71m. BMI 32.
Hypertensive for several years. Mother diabetic type2. Glucometer capillary BS is 15mmol/L.
What further Investigations? Ans: Twice..Lab RBS/FBS, GTT. Why not HbA1c for diagnosis? 60% of new diabetics have normal HbA1c. What other investigations should be done? Retina, urine, Lipid profile, Cardiac exam.
It is a matter of great satisfaction if you are educated on the right lines, become an example to others and accept positions of responsibility. In all these things, always
keep “Truth & Love for all” as your goal.Then only you will get the Grace of God….!
- Sai - Summer Showers, 1973.
Site of action of Anti DM drugs:
Metabolic (short term) complications:
Diagnostic criteria for DM, IFG, and IGT
DECODE: increased 2-hour glucose is associated with increased mortality rate (adjusted for age, center, and
gender).
Cumulative incidence of diabetes mellitus (based on American Diabetes Association criteria) according to study group in the
DPP.
* The incidence of diabetes differed significantly among the 3 groups (p <0.001 for each comparison. Reprinted with permission from Knowler et al.13
Endocrinology Other : (Brief notes)
Tumours – adenomas of endocrine gl. Cushings disease. Pheochromocytoma. Zollinger Ellison syndrome. MEN Syndromes – MEN type 1 & 2.
Diabetic Retinopathy
Neovascularization Cotton wool spots
Diabetic Retinopathy
Advanced fibrous plaques
Diabetic Retinopathy - Proliferative
Diabetic Retinopathy - Proliferative
Normal Retina:
Progression of Type I
DM - Clinical Examination:
Daily changes in hormone…