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…