DIABETES MELLITUS by dr aftab ahmed

DIABETES MELLITUS DR AFTAB AHMED RAJPUT FCPS PART 2 TRAINEE MEDICAL UNIT 2 PMCH,NAWAB SHAH

PRESENTATION OUTLINES
DM AND ITS CLASSIFICATION
PATHOPHYSIOLOGY OF DM
CLINICAL FEATURES OF DM
INVESTIGATIONS
DIAGNOSTIC CRITERIA FOR DM
MANAGEMENT OF DM

DIABETES MELITUS
… a metabolic disorder of multiple aetiology characterised by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both

CURRENT IMPACT OF DM
6 th leading cause of death by disease
Decreases life expectancy of middle-aged people by 5-10 years
2-4 x greater risk of death d/t heart disease
Compounding factors include: duration of disease, glycemic control, HTN, smoking, dyslipidemia, decreased activity, and obesity
Leading cause of blindness in 25-74 year olds
Leading cause of non-traumatic amputations
Responsible for 25-30% of all new dialysis patients

CLASSIFICATION OF DM
TRADITIONALY DM HAS BEEN DIVIDED INTO
PRIMARY DM
IN WHICH THERE IS DEFECT IN INSULIN PRODUCTION AND/OR ITS ACTION
2NDRY IN WHICH ANY DISEASE CAUSES EXTENSIVE DEMAGE OF PANCREATIC ISLET e.g,pancratitis,tumors,drugs,iron overload ,surgical removal of pancreatic substance and certain endocrinopathies that antagonize the action of insulin.

CLASSIFICATION
In 1997 AMERICAN DIABETES ASSOCIATION RECOMMENDED A NEW CLASSIFICATION BASED ON ETIOLOGY.
THERE IS NO DISTINCTION BETWEEN PRIMARY AND 2NDRY DM AND DESCRIPTION BASED ON AGE OF ONSET OR TYPE OF TREATMENT HAVE BEEN ELIMINATED.

CONTI……..
1. Type 1 diabetes (b-cell destruction, leads to absolute insulin deficiency) •Immune-mediated (TYPE 1A)
• Idiopathic (TYPE 1B)
2. Type 2 diabetes ( insulin resistance with relative insulin deficiency )
3. Genetic defects of b -cell function
• Maturity-onset diabetes of the young (MODY), caused by mutations in :
• Hepatocyte nuclear factor 4a [HNF-4a] (MODY1)
• Glucokinase (MODY2)
• Hepatocyte nuclear factor 1a [HNF-1a] (MODY3)
• Insulin promoter factor [IPF-1] (MODY4)
• Hepatocyte nuclear factor 1b [HNF-1b] (MODY5)
• Neurogenic differentiation factor 1 [Neuro D1] (MODY6)
• Mitochondrial DNA mutations

CONTI……
4. Genetic defects in insulin processing or insulin action
• Defects in proinsulin conversion
• Insulin gene mutations
• Insulin receptor mutations
5. Exocrine pancreatic defects
• Chronic pancreatitis
• Pancreatectomy
• Neoplasia
• Cystic fibrosis
• Hemachromatosis
• Fibrocalculous pancreatopathy
6. Endocrinopathies
Cushing syndrome
Hyperthyroidism
Pheochromocytoma
Glucagonoma
Acromegaly

CONTI……
7. Infections
Rubella
Cytomegalovirus
Coxsackie virus B
Epstein barr virus
8. Drugs
Glucocorticoids
interferon
Protease inhibitors
b-adrenergic agonists
Thiazides
Nicotinic acid
9. Genetic syndromes associated with diabetes
Down syndrome
Kleinfelter syndrome
Turner syndrome
10. Gestational diabetes mellitus

PATHOPHYSIOLOGGY OF DM
The pancreas functions as both an exocrine and an endocrine gland
Exocrine function is associated with the digestive system because it produces and secretes digestive enzymes
Endocrine Function: produces two important hormones in Islets of Langerhans, insulin and glucagon
They work together to maintain a steady level of glucose, or sugar, in the blood and to keep the body supplied with fuel to produce and maintain stores of energy.

Pancreatic Hormones
Insulin (beta cells)
stimulates the uptake of glucose by body cells thereby decreasing blood levels of glucose
Glucagon (alpha cells)
stimulates the breakdown of glycogen and the release of glucose, thereby increasing blood levels of glucose
Glucagon and insulin work together to regulate & maintain blood sugar levels
Glycogen
Polysaccharide consisting of numerous monosaccharide glucoses linked together. Stored as an energy source in liver & muscles

EFFECTS OF INSULIN

CONTIN…….
Type One Diabetes (10-15%)
results when the body’s immune system destroys its own beta cells in the pancreas. No insulin production is then possible.
Type Two Diabetes (85-90%) results from either
Insulin resistance (overweight people)
Inadequate insulin production (lean people)
A combination of both

Gestational Diabetes
Diabetes diagnosed during pregnancy
Increased health risk to mother and baby
May require insulin injections
Goes away after birth, but increased risk of developing Type 2 DM for mother and child

Pathophysiology of type 1 diabetes

Type One Diabetes
Usually under 30 yrs of age
Autoimmune disorder
Sudden onset of severe symptoms
Rapid weight loss
Total lack of insulin in the body
Insulin injections essential for life
Ketones produced
Genetic predisposition, though 80% have no relatives with the disease

Pathophysiology of type 2 diabetes

Type Two Diabetes
Usually over 40 yrs of age though the age of diagnosis is getting younger
Gradual onset with mild symptoms
Most produce a normal amount of insulin but it is unable to work properly due to insulin resistance
Many have complications at diagnosis

What is Insulin Resistance?
condition in which the body does not utilise insulin efficiently
Insulin resistance is the decreased response of the liver and peripheral tissues (muscle, fat) to insulin
Insulin resistance is a primary defect in the majority of patients with Type 2 diabetes

Insulin resistance syndrome (syndrome x,metabolic syndrome,REAVEN’S SYNDROME)
Metabolic syndrome is a name for a group of risk factors that occur together and increase the risk for CAD, STROKE, and type 2 diabetes
The two most important risk factors for metabolic syndrome are:
Extra weight around the middle and upper parts of the body (central obesity). The body may be described as "apple-shaped."
Insulin resistance, in which the body cannot use insulin effectively. Insulin is needed to help control the amount of sugar in the body. As a result, blood sugar and fat levels rise.
Other risk factors include:
Aging
Genes that make more likely to develop this condition
Hormone changes
Lack of exercise

metabolic syndrome is present if ONE have three or more of the following signs:
Blood pressure equal to or higher than 130/85 mmHg
Fasting blood sugar (glucose) equal to or higher than 100 mg/dL
Large waist circumference (length around the waist):
Men - 40 inches or more
Women - 35 inches or more
Low HDL cholesterol:
Men - under 40 mg/dL
Women - under 50 mg/dL
Triglycerides equal to or higher than 150 mg/dL

Tests that may be done to diagnose metabolic syndrome include:
Blood pressure measurement
Glucose test
HDL cholesterol level
LDL cholesterol level
Total cholesterol level
Triglyceride level

Type 2 Diabetes Risk Factors
Increasing age
Obesity – especially abdominal
Women with BMI > 35 compared to 22 have a 93 fold increased risk
Men with BMI > 35 have 40 fold increased risk
Physical inactivity
Family history
Ethnic background
High blood pressure
High Cholesterol
Previous gestational diabetes

Characteristics of Diabetes Type 1 Type 2
Usually under 30
Rapid onset
Normal or underweight
Little or no insulin
Ketosis common
Make up 15% of cases
Autoimmune plus environmental factors
Low familial factor
Treated with insulin, diet and exercise
Usually over 40
Gradual onset
80% are overweight
Most have insulin resistance
Ketosis rare
85% of diagnosed cases
Part of metabolic insulin resistance syndrome
Strongly hereditary
Diet & exercise, progressing to tablets, then insulin

CLINICAL FEATURES OF DM
Diabetes Mellitus Type 1
Clinical Manifestations:
Polyuria – increased urine
Polydipsia – increased thirst
Polyphagia – increased hunger
3 ‘Ps”
Weight loss
Fatigue
Nausea, vomiting
Ketoacidosis may be a presenting sign

Usually develop symptoms over a short period of time, and the condition is often diagnosed in an emergency setting
In addition to high glucose levels, acutely ill type 1 diabetics have high levels of ketones.
As cells cannot get glucose, they burn fats as an alternate energy source
Ketones are produced by the breakdown of fat and muscle, and are toxic at high levels
Ketones in the blood cause a condition called "acidosis” or “ketoacidosis" (low blood pH)
Urine testing detects ketones in the urine
Blood glucose levels are also high.

Type 2 Clinical Manifestations:
Polydipsia – increased thirst
Polyuria – increased urine
Polyphagia – increased hunger
Fatigue
Blurred vision
Slow healing infections
Impotence in men

INVESTIGATION AND LABORATORY FINDINGS
URINALYSIS
BLOOD TESTING PROCEDURES
LIPOPROTEIN ABNORMALITIES IN DIABETES

URINALYSIS
Urine glucose
Ketones
Protein(microalbuminia)

Blood tests
BLOOD GLUCOSE
GLYCELATED HAEMOGLOBIN (HBA1C)
BLOOD LIPIDS(TOTAL CHOLESTROL,LDL,HDL,TRIGLYCERIDE)

Other test
Routine blood count and coagulation screen
Arterial blood gases an any emergency like diabetic ketoacidosis
Serum electrolyte and urea-creatinine
Lipid profile
Liver function test
Chest x ray
ECG

DIAGNOSTIC CRITERIA FOR DM
Blood glucose levels - venous samples
1 sample is diagnostic if symptoms are present; 2 samples if asymtomatic :
Fasting plasma glucose of > 7.0mmols(126MG/DL)
Random plasma glucose of > 11.1mmols ( 200MG/DL)
Plasma glucose of > 11.1(mmols (200MG/DL)2 hours after an oral glucose tolerance test (OGTT

GTT
Venous Plasma
Fasting >126MG/DL DIABETES
Fasting 110MG/DL TO< 126MG/DL Impaired Fasting Glycaemia
2 hour level > 200MG/DL DIABETES
2 hour 140MG/DL –200MG/DL Impaired Glucose Tolerance

Impaired Fasting Glucose (IFG)
Fasting plasma glucose > (100MG/DL)and (120) mmol/l
Intermediate state between normal glucose tolerance and diabetes
Present in 5% of the population and increasing with age
Has greater risk CVD

Impaired Glucose Tolerance (IGT)
Fasting plasma glucose < 126MG/DLand OGTT 2 hour value >140MG/DL but <200MG/DL
Intermediate state between normal glucose tolerance and diabetes
Individuals often manifest hyperglycaemia only when challenged with oral glucose in an OGTT
2-5% of people with IGT progress to diabetes per year
IGT associated with increase risk of developing cardiovascular disease

MANAGEMENT OF DM

Cornerstones of Diabetes Management
Healthy eating
Exercise
Monitoring
Medication/Insulin
Health Care Team

Management of Diabetes
Type One: Insulin + Healthy Eating + Exercise
Type Two :
Healthy eating + exercise
then Healthy eating + exercise + tablets
then Healthy eating + exercise + tablets + insulin

Diabetes Mellitus
Role of Diet in Diabetic Management
A. Goals for diabetic therapy include
1. Maintain as near-normal blood glucose levels as possible with balance of food with medications
2. Obtain optimal serum lipid levels
3. Provide adequate calories to attain or maintain reasonable weight

Diabetes Mellitus
B. Diet Composition
1. Carbohydrates: 60 – 70% of daily diet
Carbohydrates convert quickly to sugars
Advice patient to consume a similar amount of carbs at each meal
Medications can work on a consistent glucose response from foods
2. Protein: 15 – 20% of daily diet
3. Fats: No more than 10% of total calories from saturated fats

Diabetes Mellitus
4. Fiber: 20 to 35 grams/day; promotes intestinal motility and gives feeling of fullness
5. Sodium: recommended intake 1000 mg per 1000 kcal
6. Sweeteners approved by FDA instead of refined sugars
7. Limited use of alcohol: potential hypoglycemic effect of insulin and oral hypoglycemics

Exercise & Weight Loss
Benefits of a 10kg weight loss
Fall of 50% in fasting glucose
Fall of 10% total cholesterol
Fall of 15% LDL
Fall of 30% triglycerides
Rise of 8% HDL
Fall of 10 mmHg systolic, 20 mmHg diastolic
SIGN guidelines

Oral Hypoglycemics

Oral Hypoglycemics
All taken orally in the form of tablets.
Pts with type 2 diabetes have two physiological defects:
Abnormal insulin secretion
Resistance to insulin action in target tissues associated with decreased number of insulin receptors

Oral Anti-Diabetic Agents Sulfonylureas Drugs other than Sulfonylurea

Sulfonylureas (Oral Hypoglycemic drugs) Tolbutamide Acetohexamide Tolazamide Chlorpropamide Glipizide Glyburide (Glibenclamide) Glimepiride Short acting First generation Intermediate acting Long acting Long acting Short acting Second generation

FIRST GENERATION SULPHONYLUREA COMPOUNDS * Good for pts with renal impairment ** Pts with renal impairment can expect long t1/2 Tolbutamid short-acting Acetohexamide intermediate-acting Tolazamide intermediate-acting Chlorpropamide long- acting Absorption Well Well Slow Well Metabolism Yes Yes Yes Yes Metabolites Inactive * Active +++ ** Active ++ ** Inactive ** Half-life 4 - 5 hrs 6 – 8 hrs 7 hrs 24 – 40 hrs Duration of action Short (6 – 8 hrs) Intermediate (12 – 20 hrs) Intermediate (12 – 18 hrs) Long ( 20 – 60 hrs) Excretion Urine Urine Urine Urine

SECOND GENERATION SULPHONYLUREA COMPOUNDS Glipizide Short- acting Glibenclamide (Glyburide) Long-acting Glimepiride Long-acting Absorption Well Well Well Metabolism Yes Yes Yes Metabolites Inactive Inactive Inactive Half-life 3 – 4 hrs Less than 3 hrs 5 - 9 hrs Duration of action 10 – 16 hrs 12 – 24 hrs 12 – 24 hrs Excretion Urine Urine Urine

MECHANISM OF ACTION OF SULPHONYLUREAS 1) Release of insulin from β-cells 2) Reduction of serum glucagon concentration 3) Potentiation of insulin action on target tissues

SIDE EFFECTS OF SULPHONYLUREAS 1) Nausea, vomiting, abdominal pain, diarrhea 2) Hypoglycaemia 3) Dilutional hyponatraemia & water intoxication (Chlorpropamide) 4) Weight gain

CONTRAINDICATIONS OF SULPHONYLUREAS 1) Type 1 DM ( insulin dependent) 2) Parenchymal disease of the liver or kidney 3) Pregnancy, lactation 4) Major stress

Drugs other than Sulfonylurea Metformin Biguanides α-Glucosidase Inhibitors Thiazolidinediones Acarbose Rosiglitazone Pioglitazone Repaglinide Nateglinide Meglitinides

MEGLITINIDES e.g. Repaglinide, Nateglinide PHARMACOKINETICS Taken orally Rapidly absorbed ( Peak approx. 1hr ) Metabolized by liver t 1/2 = 1 hr Duration of action 4-5 hr

MEGLITINIDES (Contd.) MECHANISM OF ACTION Bind to the same K ATP Channel as do Sulfonylureas, to cause insulin release from β-cells.

MEGLITINIDES (Contd.) CLINICAL USE Approved as monotherapy and in combination with metformin in type 2 diabetes Taken before each meal, 3 times / day Does not offer any advantage over sulfonylureas; Advantage: Pts. allergic to sulfur or sulfonylurea SIDE EFFECTS: Hypoglycemia Wt gain ( less than SUs ) Caution in pts with renal & hepatic impairement.

BIGUANIDES e.g. Metformin PHARMACOKINETICS Given orally Not bind to plasma proteins Not metabolized Excreted unchanged in urine t 1/2 2 hr

BIGUANIDES (Contd.) MECHANISM OF ACTION 1. Increase peripheral glucose utilization 2. Inhibits gluconeogenesis 3. Impaired absorption of glucose from the gut

Advantages of Metformin over SUs
Does not cause hypoglycemia
Does not result in wt gain
( Ideal for obese pts )

BIGUANIDES (Contd.) SIDE EFFECTS 1. Metallic taste in the mouth 2. Gastrointestinal (anorexia, nausea, vomiting, diarrhea, abdominal discomfort) 3. Vitamin B 12 deficiency (prolonged use) 4. Lactic acidosis ( rare – 01/ 30,000-exclusive in renal & hepatic failure)

1. Hepatic impairment 2. Renal impairment 3. Alcoholism 4. Heart failure BIGUANIDES (Contd.) CONTRAINDICATIONS

Obese patients with type 11 diabetes
2. Alone or in combination with sulfonylureas
BIGUANIDES (Contd.) INDICATIONS

α-GLUCOSIDASE INHIBITORS e.g. Acarbose PHARMACOKINETICS Given orally Not absorbed from intestine except small amount t 1/2 3 - 7 hr Excreted with stool

MECHANISM OF ACTION Inhibits intestinal alpha-glucosidases and delays carbohydrate absorption, reducing postprandial increase in blood glucose α-GLUCOSIDASE INHIBITORS (Contd.)

SIDE EFFECTS Flatulence Loose stool or diarrhea Abdominal pain Alone does not cause hypoglycemia α-GLUCOSIDASE INHIBITORS (Contd.)

INDICATIONS Patients with Type 11 inadequately controlled by diet with or without other agents( SU, Metformin) Can be combined with insulin may be helpful in obese Type 11 patients (similar to metformin) α-GLUCOSIDASE INHIBITORS (Contd.)

THIAZOLIDINEDIONE DERIVATIVES New class of oral antidiabetics e.g.: Rosiglitazone Pioglitazone

PHARMACOKINETICS
99% absorbed
Metabolized by liver
99% of drug binds to plasma proteins
Half-life 3 – 4 h
Eliminated via the urine 64% and feces 23%
THIAZOLIDINEDIONE DERIVATIVES (Contd.)

MECHANISM OF ACTION
Increase target tissue sensitivity to insulin by:
reducing hepatic glucose output & increase glucose uptake & oxidation in muscles & adipose tissues.
They do not cause hypoglycemia (similar to metformin and acarbose ) .

ADVERSE EFFECTS
Mild to moderate edema
Wt gain
Headache
Myalgia
Hepatotoxicity

INDICATIONS Type 11 diabetes alone or in combination with metformin or sulfonylurea or insulin in patients resistant to insulin treatment. THIAZOLIDINEDIONE DERIVATIVES (Contd.)

DPP-4 Inhibitor
Inhibits the dipeptidyl-peptidase 4 enzyme
Enhances the incretin hormones
GLP-1 (Glucagon-like peptide 1)
GIP (glucose-dependent insulinotropic polypeptide)

Incretin Hormones
Stimulate insulin response from beta cells in a glucose-dependent manner
Inhibit gastric emptying
Reduces food intake and body weight
Inhibit glucagon secretion from alpha cells in a glucose-dependent manner

DPP-4 Inhibitor
Available product: Januvia (Sitagliptin)
Once daily dosing
Indicated for use with metformin or thiazolidinedione
Dosing adjustment for renal impairment
Adverse effects: Diarrhea, upper respiratory infection
Expensive

INSULIN THERAPHY

Diabetes Mellitus
Medications
A. Insulin
1. Sources: standard practice is use of human insulin prepared by alteration of pork insulin or recombinant DNA therapy
2. Clients who need insulin as therapy:
a. All type 1 diabetics since their bodies essentially no longer produce insulin
b. Some Type 2 diabetics, if oral medications are not adequate for control (both oral medications and insulin may be needed)
c. Diabetics enduring stressor situations such as surgery, corticosteroid therapy, infections, treatment for DKA
d. Women with gestational diabetes who are not adequately controlled with diet
e. Some clients receiving high caloric feedings including tube feedings or parenteral nutrition

Insulin Degradation
Hydrolysis of the disulfide linkage between A&B chains.
60% liver, 40% kidney(endogenous insulin)
60% kidney,40% liver (exogenous insulin)
Half-Life 5-7min (endogenous insulin)
Delayed-release form( injected one)
Category B ( not teratogenic)
Usual places for injection: upper arm, front& side parts of the thighs& the abdomen.
Not to inject in the same place ( rotate)
Should be stored in refrigerator& warm up to room temp before use.
Must be used within 30 days.

TYPES OF INSULIN PREPARATIONS 1. Ultra-short-acting 2. Short-acting (Regular) 3. Intermediate-acting 4. Long-acting

3. Intermediate - acting insulins e.g. isophane (NPH) Turbid suspension Injected S.C.(Only) Onset of action 1 - 2 hr Peak serum level 5 - 7 hr Duration of action 13 - 18 hr Insulin mixtures 75/25 70/30 50/50 ( NPH / Regular )

3. Intermediate - acting insulins (contd.) Lente insulin Turbid suspension Mixture of 30% semilente insulin 70% ultralente insulin Injected S.C. (only) Onset of action 1 - 3 hr Peak serum level 4 - 8 hr Duration of action 13 - 20 hr

3. Intermediate - acting insulins (contd.) Lente and NPH insulins Are roughly equivalent in biological effects. They are usually given once or twice a day. N.B: They are not used during emergencies (e.g. diabetic ketoacidosis).

4. Long – acting insulins e.g.Insulin glargine Onset of action 2 hr Absorbed less rapidly than NPH&Lente insulins. Duration of action upto 24 hr Designed to overcome the deficiencies of intermediate acting insulins Advantages over intermediate-acting insulins: Constant circulating insulin over 24hr with no pronounced peak. More safe than NPH&Lente insulins due to reduced risk of hypoglycemia(esp.nocturnal hypoglycemia). Clear solution that does not require resuspention before administration.

Methods of Adminisration
Insulin Syringes
Pre-filled insulin pens
External insulin pump
Under Clinical Trials
Oral tablets
Inhaled aerosol
Intranasal, Transdermal
Insulin Jet injectors
Ultrasound pulses

COMPLICATIONS OF INSULIN THERAPY 1. Severe Hypoglycemia (< 50 mg/dl )– Life threatening Overdose of insulin Excessive (unusual) physical exercise A meal is missed 2. Weight gain 3. Local or systemic allergic reactions (rare) 4. Lipodystrophy at injection sites 5. Insulin resistance 6. Hypokalemia

DIABETES MELLITUS by dr aftab ahmed

by aaiman46

Accessibilité

Catégories

Détails de l'import

Droits d'utilisation

Statistiques

DIABETES MELLITUS by dr aftab ahmed Presentation Transcript