Complications of Diabetes

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.


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
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
Type- I Diabetes Mellitus
T cell-mediated destruction of pancreatic -cells

Rapid onset, usually in childhood

Complete insulin deficiency

Absolute insulin requirement

Type- II Diabetes Mellitus
Pancreas doesnt 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

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


Salient Clinical Symptoms
Disease of mainly three Ps

Polydipsia- Excessive Thirst
Polyphagia- Excessive Hunger
Polyurea- Excessive Urination

Hyperglycemia
Tiredness
Loss of weight

Diabetes Mellitus - Complications
Complications of diabetes mellitus
Acute (Metabolic)
Chronic (Angiopathy)

Macro Vascular
Complications
Micro Vascular
Complications
Risk factors and complications
Microvascular disease
Eyes
Kidneys
Nerves
Macrovascular disease
Ischaemic heart disease
Strokes
Peripheral vascular
disease
Feet
Hypertension Hyperglycaemia
Dyslipidaemia
Coagulopathy
Smoking
Acute Complications
Diabetic Ketoacidosis (DKA)

Hyperosmolar non-ketomic
Coma (HONK)

Hypoglycemia

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
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
Microvascular Complications of Diabetes-1
Retinopathy: Damage to blood vessels in and around the
retina. It could occur with varying degrees of severity.

Normal ------------- Small hemorrhages --------- Large hemorrhage
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-2
Microvascular Complications of Diabetes-3
Neuropathy

Nerve fibres degenerate
Blood vessels supplying the nerves are grossly diseased


Mechanism of
Complications of Diabetes
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
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


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).

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.

23
Diabetes is Managed,
But it Does Not Go Away.
To maintain target
blood glucose
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
Management Of DM
Step 1: Diet and Exercise to achieve Euglycemia.
If Euglycemia not achieved; Follow Step 2.
Step 2: Monotherapy with:
Sulfonylurea
Bigunide
Glitazones
Meglitinides (Repaglinides)
Alpha-glucosidase
Step 3: Addition of second oral agent or Insulin.
Consider Insulin therapy in Type I DM always.


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