Diabetes Mellitus

Definition
-is a multi-factorial disorder caused by diminished insulin action due to its decreased availability or effectiveness in varying combinations.
-or, is a syndrome of chronic hyperglycaemia due to relative insulin deficiency, resistance or both.

Reasons for increasing Prevalence:
1.rapid urbanization.
2.lack of exercise
3.mental stress
34.diet
5.undiagnosed gestational  DM.

6.obesity

Types:
(based on aetiology):

Type 1- immune mediated or idiopathic
Type 2-insulin resistance--->later--->insulin deficiency
Type 3-genetic syndromes
            -drug induced
            -hormonal(cushings, acromegaly,etc)
            -malnutrition related.
Type 4-gestational diabetes
            -Latent Autoimmune Diabetes of Adults(LADA)
            -Matured Onset Diabetes of Young(MODY)

Type 1 DM
-in younger
-lean
-seasonal incidence
-heredity-HLA-DR3 or DR4 in>90%
-Pathogenesis:
                   -autoimmune disease: islets cell autoantibodies, insulitis, association with other autoimmune disease diseases, immunosupression after diagnosis delays beta-cell destruction.
Clinical- insulin deficiency, may develop ketoacidosis, always need insulin
-Biochemical-eventual disappearance of C-peptide.

Diagnosis:

WHO(1999):

1.fasting plasma glucose >7.0mmol/l =126mg/dl
2.Random plasma glucose >11.1mmol/l =200mg/dl
*One abnormal laboratory value is diagnostic in symptomatic individuals; two are needed in asymptomatic people.

The glucose tolerance test is only required for borderline cases and for diagnosis of gestational diabetes.
The Glucose Tolerance Test-WHO:

Fasting:
         -normal: <7mmol/l
         -Imapaired glucose tolerance/IFG=6.1-6.9 mmol/l---introduced by ADA.
         -DM>7mmol/l
2 hours after glucose:
          -normal <7.8mmol/l
          -Impaired glucose tolerance=7.8-11.0mmol/l
          -DM= >11.1mmol/l

*Adult-75g of glucose in 300 ml water
*child-1.75g glucose/kg body.
*only fasting and 120 min sample are needed.

Screening For DM:
1.Population screening.
2.High risk screening:
                                -obese
                                -family history
                                -metabolic syndrome
                                -previous gestational diabetes
3.Opportunistic Screening:
                                 -sedentary occupation
                                 -Acanthosis Nigricans

Clinical Presentation:
1.Acute presentation:-with 2-6 weeks history.
-classic triad of:
                       1.polyuria-due to osmotic diuresis(blood glucose exceeds the renal threshold)
                       2.thirst-due to resulting loss of fluid and electrolytes.
                       3.weight loss-due to fluid depletion and accelerated fat and muscle breakdown secondary to insulin deficiency.
                      4.thin and nocturia

2.Subacute presentation: clinical onset may be over several months or years.-thirst, polyuria and weight loss are typically present.
-lack of energy
-visual blurring
-pruritus vulvae
-balanitis due to candida infection

3.Asymptomatic:
-gylcosuria or raised blood glucose detected on routine examination.

Ketoacidosis in Type 1 DM:
-seen in following circumstances:
                  -previously undiagnosed diabetes.
                  -interruption of insulin therapy.
                  -the stress of intercurrent illness.
HOW?
-rising blood glucose levels lead to osmotic diuresis, loss of fluid and electrolytes and dehydration.
-plasma osmolality rises and renal perfusion falls.
-In parallel, rapid lipolysis occurs, leading to elevated free fatty acids levels--->fatty acetyl-coA in hepatocytes.--->ketone bodies in mitochondria--->metabolic acidosis.

*SUMMARY:
Therefore hyperglycaemia results in osmotic diuresis, and hyperketonemia results in acidosis and vomiting. Renal hypoperfusion then occurs and a vicious cycle is established as the kidney becomes less able to compensate for the acidosis.

Symptoms Of Complications:
Macrovascular:
1.stroke is twice as likely.
2.MI is 3 or 5 times as likely, and women with DM lose their premenopausal protection from coronary artery disease.
3.amputation of a foot for gangrene is 50 times as likely.

-Atheroma in large and medium sized blodd vessels:
                                                                     -Macroangiopathy-CVD, IHD, PVD.

Dermopathy:
                 -carbuncles
                 -ulcers
                 -mucocutaneous candidasis

Microvascular:
-specific to DM
-all small vessels affected.
-But sites important in danger:
                          -retina
                          -renal glomerulus
                          -nerve sheaths
1.Diabetic retinopathy
2.Diabetic nephropathy
3.Diabetic Neuropathy.

Nephropathy:
                    -nodular glomerulosclerosis
                    -NS
                    -CRF
                    -Proteinuria
                    -Gen. atherosclerosis
                    -anaemia
Retinopathy:
                  -simple/background(microaneurysm-small red dots, exudate, blot eyes, cotton wool spots, tortuous veins)
                  -preliferative retinopathy(neurovasoulceration, vitrous haemorrhage)
                  -exudate retinopathy-macular oedema and macular exudates.


-Neuropathy
                   -peripheral neuropathy-seneory, motor or mixed(charkot's neuroarthropathy)
                   -Autonomic neuropathy
                                                     -postural hypotension
                                                     -impotent(erectile dysfunction)
                                                     -bladder retention
                                                     -bowel diarrhoea
                                                     -gut swelling.

*Cataract-snowflake in type 1 DM.

Management:
-Objectives: treat the symptoms, complications and normalize his life.

4 steps of approach:
1.life styles modification
2.drugs
3.discipline the patient
4.education