Introduction of DM

Diabetes Mellitus

Dr. BASIM AUDIB
Professor of Medicine
F.I.C.M.S,F.R.C.P (Edenbera)
SCE Diabetes and Endocrine (London)
Consultant of Medicine





• Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both.
• The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.
• The effects of diabetes mellitus include long–term damage, dysfunction and failure of various organs.
What is diabetes?

Diabetes mellitus may present with characteristic symptoms such as thirst, polyuria, blurring of vision, and weight loss.


In its most severe forms, ketoacidosis (DKA) (in type 1) or hyperosmolar hyperglycemic state (HHS) (in type 2) may develop and lead to stupor, coma and, in absence of effective treatment, death may occure.

Diabetes

• The long–term effects of diabetes mellitus include progressive development of the specific complications :
• 1- Retinopathy with potential blindness
• 2- Nephropathy that may lead to chronic kidney disease (CKD)
• 3- Neuropathy with risk of foot ulcers, amputation, Charcot joints
• 4- Autonomic dysfunction, including sexual dysfunction.
• People with diabetes are at increased risk of cardiovascular, peripheral vascular and cerebrovascular disease.
Diabetes Long-term Effects

Diabetes MellitusEtiology and Pathophysiology

Normal insulin metabolism
The insulin is Produced by the  cells in the islets of Langherans of the pancreas

Insulin Secretion

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Diabetes MellitusEtiology and Pathophysiology
Normal insulin metabolism
Promotes glucose transport from the bloodstream across the cell membrane to the cytoplasm of the cell


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Diabetes MellitusEtiology and Pathophysiology
 Insulin after a meal cause:
1- Stimulates storage of glucose as glycogen
2- Inhibits gluconeogenesis

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3- Enhances fat deposition in adipose tissue

4- Increases protein synthesis

1- Type 1 Diabetes Mellitus

2- Type 2 Diabetes Mellitus
3- Gestational Diabetes
4- LADA (latent autoimmune diabetes of adult)
5- MODY (maturity-onset diabetes of youth)
6- Secondary Diabetes Mellitus

Types of Diabetes

• Was previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes.
• Type 1 diabetes develops when the body’s immune system destroys pancreatic beta cells, the only cells in the body that make the hormone insulin regulates blood glucose.
• This form of diabetes usually occur in children and young adults, although disease onset can occur at any age.
• Type 1 diabetes may account for 5% - 10% of all diagnosed cases of diabetes.
• Risk factors for type 1 diabetes may include
• 1- Autoimmune
• 2- Genetic factors
• 3- Environmental factors
Type 1 diabetes


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Type 1 Diabetes MellitusEtiology and Pathophysiology
Progressive destruction of pancreatic  cells
Autoantibodies cause a reduction of 80% to 90% of normal  cell function before manifestations occur

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Type 1 Diabetes MellitusEtiology and Pathophysiology
Causes:
1- Autoimmune cause
• 2- Genetic predisposition
Related to human leukocyte antigens (HLA) : HLA DR4 and HLA DR3
• 3- Exposure to a virus : mumps, Coxackie B4, cytomeg., Epst.-Barr

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Type 1 Diabetes MellitusOnset of the Disease
Manifestations develop when the pancreas can no longer produce insulin
- Symptoms: Rapid in onset
- Present at Emergency Room with ketoacidosis in about 25% of cases at diagnosis

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Type 1 Diabetes Mellitusclassical manifestations :
1-Weight loss
2- Polydipsia
3- Polyuria
4- Polyphagia


• Was previously called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes.
• Type 2 diabetes may account for about 90% - 95% of all diagnosed cases of diabetes.
• It usually begins as insulin resistance, a disorder in which the cells do not use insulin properly. As the need for insulin rises, the pancreas gradually loses its ability to produce insulin.
• Type 2 diabetes is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity.
Type 2 diabetes

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Type 2 Diabetes Mellitus
Accounts for 90% -95% of patients with diabetes
Usually occurs in people over 40 years of age
80-90% of patients are overweight

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Type 2 Diabetes MellitusEtiology and Pathophysiology
Pancreas continues to produce some endogenous insulin
Insulin produced is either insufficient or poorly utilized by the tissues

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Type 2 Diabetes MellitusEtiology and Pathophysiology
Insulin resistance
Body tissues do not respond to insulin
Results in hyperglycemia


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Type 2 Diabetes MellitusOnset of Disease
Onset : Gradual
Person may go many months with undetected hyperglycemia

A form of diabetes that is diagnosed in some women during pregnancy.

During pregnancy, gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in the infant.
After pregnancy, 5% - 10% of women with gestational diabetes may develop type 2 diabetes.
Gestational diabetes

• Latent Autoimmune Diabetes in Adults (LADA) is a form of autoimmune ( like type 1 diabetes) which is diagnosed in individuals who are older than the usual age of onset of type 1 diabetes.
• Alternate terms that have been used for "LADA" include Late-onset Autoimmune Diabetes of Adulthood.
• Often, patients with LADA are mistakenly thought to have type 2 diabetes, based on their age at the time of diagnosis.
LADA

LADA (cont.)

About 80% of adults apparently with recently diagnosed Type 2 diabetes but with GAD auto-antibodies (i.e. LADA) progress to insulin requirement within 6 years.


LADA (cont.)

• MODY ( Maturity Onset Diabetes of the Young)

• MODY is an autosomal dominant mode of inheritance.

• Originally, diagnosis of MODY was based on

• absence of diabetic ketoacidosis in adolescents or young adults in conjunction with a family history of diabetes.
• However, genetic testing has shown that MODY can occur at any age and that a family history of diabetes is not always obvious.
MODY

Type Mutation % of total MODY

MODY 1 HNF-4α 5-10%
MODY 2 Glucokinase 30-70%
MODY 3 HNF-1α 30-70%
MODY 4 IPF less than 1%
MODY 5 HNF-1β
5 types of MODY

Secondary causes of Diabetes mellitus include:

1- Acromegaly
2- Cushing syndrome
3- Thyrotoxicosis
4- Pheochromocytoma
5- Chronic pancreatitis
6- Cancer
7- Drug induced hyperglycemia:
Beta-blockers
Corticosteroids
Thiazide Diuretics


Secondary DM

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