Diabetes

Mellitus
 What is diabetes?

▪ Diabetes mellitus (DM) is a chronic condition

that is characterised by raised blood glucose
levels (Hyperglycemia).
Regulation of Plasma Glucose Level
How Insuline Decrease Plasma
Glucose Level?
 Classification of DM

1. Type 1 DM

• It is due to insulin deficiency and is formerly known as.

• Type I

• Insulin Dependent DM (IDDM)

• Juvenile onset DM

2. Type 2 DM

• It is a combined insulin resistance and relative deficiency in insulin secretion and is frequently known as.

• Type II

• Noninsulin Dependent DM (NIDDM)

• Adult onset DM
3. Gestational Diabetes Mellitus (GDM):

➢ Gestational Diabetes Mellitus (GDM) developing during some cases of pregnancy

but usually disappears after pregnancy.

4. Other types:

➢ Secondary DM
 Etiology

1. Etiology of Type 1 Diabetes

2. Etiology of Type 2 Diabetes
 Characteristics Type 1 Type 2

% of diabetic pop 5-10% 90%

Usually > 40 + some obese
Age of onset Usually < 30 yr + some adults
children
Pancreatic function Usually none Insulin is low, normal or high

Defect in insulin secretion,

Pathogenesis Autoimmune process tissue resistance to insulin,
increased HGO

Family history Generally not strong Strong

Obesity Uncommon Common

History of ketoacidosis Often present Rare except in stress

moderate to severe symptoms: Mild symptoms: Polyuria and
Clinical presentation 3Ps, fatigue, wt loss and fatigue. Diagnosed on routine
ketoacidosis physical examination
Insulin, Diet Diet ,Exercise
Treatment Exercise Oral antidiabetics,Insulin
 Epidemiology
• Type 1 DM

– It is due to pancreatic islet β-cell destruction predominantly by an autoimmune

process.

– Usually develops in childhood or early adulthood

– It accounts for upto 10% of all DM cases

– Develops as a result of the exposure of a genetically susceptible individual to an

environmental agent
Type 2 DM

• It results from insulin resistance with a defect in compensatory insulin

secretion.

• Insulin may be low, normal or high!

• About 30% of the Type 2 DM patients are undiagnosed (they do

not know that they have the disease) because symptoms are mild.

• It accounts for up to 90% of all DM cases

 Risk Factors

• Type 1 DM

– Genetic predisposition

• In an individual with a genetic predisposition, an event such as virus or

toxin triggers autoimmune destruction of b-cells probably over a period of
several years.
 Risk Factors
• Type 2 DM

– Family History

– Obesity

– Habitual physical inactivity

– Previously identified impaired glucose tolerance

(IGT) or impaired fasting glucose (IFG)

– Hypertension

– Hyperlipidemia
 Carbohydrate Metabolism

• Carbohydrates are metabolized in the body to glucose.

• CNS uses glucose as its primary energy source. This is independent of

insulin.

• Glucose is taken by the muscle to produce energy (insulin required).

• Glucose is stored in the liver as glycogen and in adipose tissues as fat.

• Insulin is produced and stored by the β-cells of the pancreas

 Carbohydrate Metabolism (Cont’d)

– Postprandial glucose metabolism in normal individuals:

– After food is ingested, blood glucose concs rise and stimulate insulin release.

– Insulin action:

– glucose uptake by the tissues

– liver glycogen formation and glycogen

breakdown

– lipid synthesis and inhibits fatty acid

breakdown to ketone bodies

– Promotes protein synthesis

 Carbohydrate Metabolism (Cont’d)

• Fasting glucose metabolism in normal individuals:

– In the fasting state, insulin release is inhibited.

– Hormones that promote an increase in blood glucose are released:

• Glucagon, epinephrine, growth hormone, glucocorticoids, and thyroid hormones.

– Glycogenolysis

– Gluconeogenesis: AA are transported from muscle to liver and converted to glucose.

– TG are broken down into free FAs as an alternative fuel source.

 Pathophysiology

• Type 1 DM

– Type 1 DM is characterized by an absolute deficiency of insulin due

to immune- mediated destruction of the pancreatic b-cells

– In rare cases the b-cell destruction is not due to immune mediated

reaction (idiopathic type 1 DM)
 Pathophysiology

• Type 1 DM

▪ There are four stages in the development of Type 1 DM:

1. Preclinical period with positive b-cell antibodies

2. Hyperglycemia when 80-90% of the

β- cells are destroyed.

3. Transient remission (honeymoon phase).

4. Establishment of the disease

 Pathophysiology

Birth Time (years)

 Pathophysiology

• Type 2 DM

– Type 2 DM is characterized by the presence of both insulin resistance

(tissue insensitivity) and some degree of insulin deficiency or b- cell
dysfunction

– Type 2 DM occurs when a diabetogenic lifestyle (excessive calories,

inadequate caloric expenditure and obesity) is superimposed upon a
susceptible genotype
 Pathophysiology

300
250
200
150
Glucose 100
50
mg/dL 0

Fasting blood glucose

• Type 2 DM
Relative
Post-meal glucose

250
200
b- cell 150
Function 100
b-cell failure
50
% 0

Years of diabetes
 Laboratory Tests

1. Glucosuria

2. Ketonuria
• To detect glucose in urine by a paper strip
– To detect ketonbodies in urine by a paper strip
• Semi-quantitative • Semi-quantitative

• Normal kidney threshold for glucose is essential

 Laboratory Tests (Cont’d)

3. Fasting blood glucose

• Glucose blood concentration in samples obtained after at least 8 hours of

the last meal 4. Random Blood glucose

– Glucose blood concentration in samples obtained at any time

regardless the time of the last meal
 Laboratory Tests (Cont’d)

5. Glucose tolerance test

• 75 gm of glucose are given to the patient with 300 ml of water after an overnight fast

• Blood samples are drawn 1, 2, and 3 hours after taking the glucose

• This is a more accurate test for glucose utilization if the fasting glucose is borderline
 Laboratory Tests (Cont’d)

6. Glycosylated hemoglobin (HbA1C)

– HbA1C is formed by condensation of glucose with free amino groups of the globin component of
hemoglobin

– Normally it comprises 4-6% of the total hemoglobin.

– Increase in the glucose blood concentration increases the glycated hemoglobin fraction.

– HbA1C reflects the glycemic state during the preceding 8-12 weeks.
 Laboratory Findings (Cont’d)

7. Serum Fructosamine

• Formed by glycosylation of serum protein (mainly albumin)

• Since serum albumin has shorter half life than hemoglobin, serum fructosamine
reflects the glycemic state in the preceding 2 weeks

• Normal is 1.5 - 2.4 mmole/L when serum albumin is 5 gm/dL.

 Self Monitoring Test

• Self-monitoring of blood glucose

– Extremely useful for outpatient monitoring specially for patients who need
tight control for their glycemic state.

– A portable battery operated device that measures the color intensity

produced from adding a drop of blood to a glucose oxidase paper strip.

– e.g. One Touch, Accu-Chek, DEX, Prestige and Precision.

 Diagnostic Criteria

• Any one test should be confirmed with a second test, most often fasting plasma glucose
(FPG).

• This criteria for diagnosis should be confirmed by repeating the test on a different day.
 Clinical Presentation

• Type 1 DM • Type 2 DM
- Patients can be asymptomatic
- Polyuria - Polyuria
- - Polydipsia
Polydipsia
- Polyphagia
- Polyphagia
- Fatigue
- Weight loss - Weight loss
- Weakness - Most patients are discovered while performing
- Dry skin urine glucose screening
- Ketoacidosis
 Treatment

General approaches

- Medications
- Dietary and exercise modification
- Regular complication monitoring
- Self monitoring of blood glucose
- Control of BP and lipid level