Complications of diabetes

1. Complications of Diabetes

2. What is Diabetes Mellitus?
Diabainein in greek refers - to pass through
Mel refers to- honey
Diabetes- “sweet urine”
Chronic metabolic disorder characterized-
persistent hyperglycemia, altered metabolism
of lipids, carbohydrates and proteins.

3. Diagnostic Criteria
American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S5-S10
FPG 2-h PPG (OGTT)
126
60
80
100
120
140
160
180
200
Plasma glucose
(mg/dL)
Normal
Diabetes
Mellitus
240
220
Diabetes
Mellitus
Normal
IGT
IGT
8

4. Etiological Classification
I. Type 1 diabetes - previously known as juvenile diabetes
insulin-dependent diabetes mellitus (IDDM)
II. Type 2 diabetes - previously known as adult-onset diabetes
non-insulin-dependent diabetes mellitus (NIDDM)
III. Gestational diabetes mellitus (GDM)
American Diabetes Association

5. Type- I Diabetes Mellitus
 T cell-mediated destruction of pancreatic ß-cells
 Rapid onset, usually in childhood
 Complete insulin deficiency
 Absolute insulin requirement

6. Type- II Diabetes Mellitus
 Pancreas doesn’t produce enough insulin or cells ignore it
(insulin resistance)
 Most people with diabetes have type 2 (85%), occurs after 40
years of age
 Associated with obesity & runs in families to some extent
 Lifestyle issues prominent

7. Gestational Diabetes Mellitus
(GDM)
 Any degree of glucose intolerance with onset during
pregnancy
 Return to normal glucose regulation after delivery is common
 Increased perinatal morbidity and mortality if untreated

8. Salient Clinical Symptoms
 Disease of mainly three P’s
Polydipsia- Excessive Thirst
Polyphagia- Excessive Hunger
Polyurea- Excessive Urination
 Hyperglycemia
 Tiredness
 Loss of weight

9. Diabetes Mellitus - Complications

10. Complications of diabetes mellitus
Acute (Metabolic) Chronic (Angiopathy)
Macro Vascular
Complications
Micro Vascular
Complications

11. Risk factors and complications
Microvascular disease
Eyes
Kidneys
Nerves
Macrovascular disease
Ischaemic heart disease
Strokes
Peripheral vascular
disease
Feet
HypertensionHyperglycaemia
Dyslipidaemia
Coagulopathy
Smoking

12. Acute Complications
 Diabetic Ketoacidosis
(DKA)
 Hyperosmolar non-ketomic
Coma (HONK)
Hypoglycemia

13. Metabolic injury to large vessels
Heart Brain Extremities
Coronary artery
disease
– Coronary
syndrome
– MI
– CHF
Cerebrovascular
disease
Peripheral vascular
disease
– Ulceration
– Gangrene
– Amputation
Biology of Macrovascular Injury

14. Hyperglycemia
Neuropathy
– Peripheral
– Autonomic
Kidney Nerves
Retinopathy
- Cataract
- Glaucoma
Nephropathy
– Microalbuminuria
– Gross albuminuria
Blindness Kidney failure Amputation
Death and/or disability
Eye
Biology of Microvascular Injury

15. • Main Risk Factors
Microvascular Complications of Diabetes

16. Microvascular Complications of Diabetes
Retinopathy: Damage to blood vessels in and around the
retina. It could occur with varying degrees of severity.
Normal ------------- Small hemorrhages --------- Large hemorrhage

17. Riabetic Retinopathy - Guideline

18. ACE/ARB and progression of diabetic
retinopathy

19. Nephropathy:
 Glomeruli are damaged in the
kidneys.
 Results in loss of protein
 DIAGNOSTIC VALUE-Normal
microalbumin level is 30mg/24 hours.
 May lead to kidney failure
Microvascular Complications of Diabetes

20. Microvascular Complications of Diabetes

21. Microvascular Complications of Diabetes
Neuropathy
 Nerve fibres degenerate
 Blood vessels supplying the nerves are ‘grossly diseased’
Classification:
• Symmetrical
• focal and multifocal (cranial, asymetrical lower limb, truncal,
limb mononeuropathy)
• Diabetic asymmetrical proximal motor neuropathy (hip, knee
back pain, loss of reflexes….)

22. Mechanism of
Complications of Diabetes

24. Mechanisms causing diabetic complications-1
Accumulation of Sorbitol
Polyol (Polyhydroxy alcohols) Pathway
 Sorbitol is formed from glucose catalyzed by aldose
reductase
 This pathway is activated in hyperglycemia
 Sorbitol does not cross cell membranes, accumulates
intracellularly and produces osmotic stress.
 Sorbitol normally helps in osmoregulation

25. Oxydative stress

26. Consequences of high Sorbitol concentration
• Osmotic damage to cells: caused by impermeable Sorbitol
intracellularly
• Reduction in nerve myoinositol: causes decrease activity of
Na/K ATP Pump- causes decreased nerve conduction
velocity
• Inhibition of nitric oxide (NO) production: results in
vasoconstriction and hypertension
• Increased production of free radicals: which cause oxidative
damage to tissue

27. Mechanisms causing diabetic complications-2
Glycation of Proteins
 Sugars in the blood and inside cells form chemical bonds to proteins and
to DNA by glycation or nonenzymatic glycosylation.
 Over time, the glycated proteins are chemically modified to become
molecular structures called Advanced Glycation Endproducts (AGEs).

28. Pathological Consequences
of Glycation of Proteins in Diabetics
 Crosslinking reduces the flexibility, elasticity and functionality of the
proteins.
 The chemical modifications of glycation and crosslinking can initiate
harmful inflammatory and autoimmune responses.
 Glycation has been found in connective tissue collagen, arterial collagen,
kidney glomerular basement membrane, eye lens crystallins, nerve myelin
proteins and in the circulating low-density lipoprotein (LDL) of the blood.

29. 29
Diabetes is Managed,
But it Does Not Go Away.
GOAL:
To maintain target
blood glucose

30. Management Of Diabetes Mellitus
The Fundamental Aim is - Glycemic Control
HbA1C < 7.0%
Pre-prandial PG 90 – 130 mg/dl
Postprandial PG < 180 mg/dl
Blood Pressure < 130/80 mmHg
Lipids - LDL < 100 mg/dl
Triglycerides < 150 mg/dl
HDL > 40 mg/dl

31. Management Of DM
• Step 1: Diet and Exercise to achieve Euglycemia.
If Euglycemia not achieved; Follow Step 2.
• Step 2: Bigunide
• Monotherapy with:
– Sulfonylurea or Meglitinides
– SGLT2
– DDP4 or GLP1
– TZD
– Alpha-glucosidase
– Insulin
• Step 3: Addition of oral agent or Insulin.
Consider Insulin therapy in Type I DM always.

32. THANK YOU