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MUTJALLA KHUSHAB

(LCWU)

DIABETES MELLITUS

DIABETES MELLITUSDiabetes mellitus (DM) is a chronic

condition that is characterized by raised blood glucose levels (Hyperglycemia).

A metabolic disorder in which there is deficiency of insulin production or resistance of organs to the effect of insulin.

DIABETES MELLITUSDiabetes is a disorder of metabolism--the way our

bodies use digested food for growth and energy. Most of the food we eat is broken down into glucose,

the form of sugar in the blood. Glucose is the main source of fuel for the body.After digestion, glucose passes into the bloodstream,

where it is used by cells for growth and energy. For glucose to get into cells, insulin must be present. Insulin is a hormone produced by the pancreas, a

large gland behind the stomach.

DIABETES MELLITUSNORMAL: When non-diabetic people eat, the

pancreas automatically produces the right amount of insulin to move glucose from blood into our cells.

DIABETES MELLITUSDIABETES: In people with diabetes, when they eat,

the pancreas either produces little or no insulin, or the cells do not respond appropriately to the insulin that is produced (or both) => glucose builds up in the blood, overflows into the urine, and passes out of the body in urine => body loses its main source of fuel even though blood contains large amounts of glucose.

Long Term Complications Of Diabetes Mellitus

DiabetesDiabetes# 1 cause # 1 cause of new of new

BlindnessBlindness

# 1 cause of # 1 cause of Renal Renal failure failure

# 1 cause of # 1 cause of non-traumatic non-traumatic

AmputationAmputation

Life expectancy Life expectancy decreased 5decreased 5to 10 yrto 10 yr

CV Risk CV Risk increasedincreased2X to 2X to

4X fold4X fold

Nerve damage in Nerve damage in 60% to 70% of patients60% to 70% of patients

5th leading cause of death5th leading cause of death

Classification of diabetes mellitus

1. Primary Diabetes Mellitus2. Secondary Diabetes Mellitus

PRIMARY DIABETES MELLITUS

Insulin dependent diabetes mellitus (IDDM)

Non -insulin dependent diabetes mellitus (NIDDM)

SECONDARY DIABETES MELLITUS

Pancreatic diseases Pancreatitis Pancreactomy Cystic fibrosis

Endocrine diseases Acromegaly Thyrotoxicosis Pheochromocytoma Glucagonoma

SECONDARY DIABETES MELLITUS

Drug induced Corticosteroid therapy Thiazide diuretics Phenytoin

Associated with genetic syndromes Down’s syndrome Turner’s syndrome

Gestational diabetes Diabetes of pregnancy

PRIMARY DIABETES MELLITUS

1. TYPE 1 DM

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

Type I Insulin Dependent DM (IDDM) Juvenile onset DM

Usually manifests in childhood with a peak age at 10-13 years but it can present any age.

Etiology of type 1Genetic susceptibilityInheritancePancreatic pathologyImmunological factors.

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

Manifests usually above 30 years however can be diagnosed in children.

Maturity onset diabetes of youngIt is a rare variant of type 2 and is strongly

inherited . The disease should be suspected in young people with a typical family history and in whom other features of type 1 are lacking.

Etiology of type 2

Characteristics Type 1 Type 2

% of diabetic pop 5-10% 90%

Age of onset Usually < 30 yr + some adults

Usually > 40 + some obese children

Pancreatic function Usually none Insulin is low, normal or high

Pathogenesis Autoimmune process Defect in insulin secretion, tissue resistance to insulin,

Family history Generally not strong Strong

Obesity Uncommon Common

History of ketoacidosis Often present Rare except in stress

Clinical presentation moderate to severe symptoms: 3Ps, fatigue, wt loss and ketoacidosis

Mild symptoms: Polyuria and fatigue. Diagnosed on routine physicalexamination

Treatment Insulin, DietExercise

Diet ,ExerciseOral antidiabetics,Insulin

CLINICAL PRESENTATION TYPE 1 DM

- Polyuria- Polydipsia- Polyphagia- Weight loss- Weakness- Dry skin- Ketoacidosis

• TYPE 2 DM

- Patients can be asymptomatic

- Polyuria

- Polydipsia

- Polyphagia

- Fatigue

- Weight loss

- Most patients are discovered while performing urine glucose screening

PATHOPHYSIOLOGYTYPE 1 DM

Type 1 DM is characterized by an absolute deficiency of insulin due to immune- mediated destruction of the pancreatic -cells

In rare cases the -cell destruction is not due to immune mediated reaction (idiopathic type 1 DM)

PATHOPHYSIOLOGYTYPE 2 DM

Type 2 DM is characterized by the presence of both insulin resistance (tissue insensitivity) and some degree of insulin deficiency or - cell dysfunction

Type 2 DM occurs when a diabetogenic lifestyle (excessive calories, inadequate caloric expenditure and obesity) is superimposed upon a susceptible genotype.

LABORATORY TESTSFasting blood sugar :more than 126mg/dl

in diabetics.Random blood sugar: more than 200mg/dl

in diabetics.Glucose tolerance test:75 g of glucose in

250-300ml water.GTT is required if FBS is more than normal

but less than in diabetics range.(b/w 110-126mg/dl)

LABORATORY TESTSGlycosylated hemoglobin(hemoglobin A 1C)Serum fructosamineUrinanalysis to detect glucose in urineUrine for proteinuriaComplete blood countUrea , creatinine and electrolytesFasting serum cholesterol and triglycerides

LABORATORY TESTSGLYCOSYLATED 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 TESTS 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.

Acute complicationsHypoglycemiaDiabetes ketoacidosisNon-ketotic hyperosmolar coma

COMPLICATIONS OF DM

CHRONIC COMPLICATIONSMicrovascularRetinopathy (impaired vision)Nephropathy (renal failure)Peripheral neuropathy(sensory loss,motor

weakness)Autonomic neuropathy(postural hypotension)Foot disease (ulceration , infection)

CHRONIC COMPLICATIONSMacrovascularCoronary artery disease (angina, MI)Cerebral ischemia (stroke)Peripheral vascular disease.(claudication)Infections in diabetes:SkinUrinary tractLungs

COMPLICATIONS

HYPOGLYCEMIA: Imbalance b/w injected insulin and patients normal diet , activity and basal insulin requirement.

Causes: missed,delayed or inadequate meals.Unexpected or unusual exercisePoorly designed insulin regminMalabsorbtionEndocrine disoder

DIABETIC KETOACIDOSIS

Initial manifestation of type 1.Clinical featuresSymptoms: intense thirst , polyuria , nause ,

vomiting, abdominal pain (children)Signs: dry tounge , inelastic skin, sunken

eyes, rapid weak pulse, fruity breath odour of acetone, hypothermia, rapid weak pulse, hypotension.

NON KETOTIC HYPEROSMOLAR COMA

Severe hpoglycemia without significant ketosis. infection , myocardial infarcation , stroke are precipitating factors.

Clinical features: dehydration , stupor ,or coma. nausea vomiting and abdominal pain are less common because there is no acidosis.

Chronic microvascular complications

RETINOPATHY:There are two main categories of diabetic

retinopathy:Non- poliferative:Early stage of retinal involvementCharacterized by dot hemorrhages, exudates

and retinal edema.During this stage, the retinal capillaries leak

protiens, lipids or red cells into the retina.Common cause of visual impairment in type 2

patients.

CONT……Proliferative retinopathy:Involves the growth of new capillaries and

fibrous tissue within the retina.More common in type 1.

RETINOPATHY

NEPHROPATHYThe kidneys may be damaged by diabetes

in three main ways:Diabetic glomerulosclerosis:Thickening of the glomerular basement

membrane.Disruption of protein cross linkages that

makes the membrane as ineffective filter.Results in progressive loss of protein in

urine starting from microalbuminuria leading to proteinuria.

CONT…..Ischemic lesions:Characterized by hypertrophy and

hyalinization of the afferent and efferent arterioles.

Infective lesions:Infective lesions in kidneys occur as an

ascending infection due to bladder stasis that results from autonomic neuropathy.

NEPHROPATHY

NEUROPATHYHyperglycemia leads to increased

formation of sorbitol and fructose in schwann cells, accumulation of these sugars may disrupt the nerve function(causing delayed nerve conduction velocity) and nerve structure (causing segmental demyelination)

NEUROPATHY

DIABETIC FOOTNeuropathy : Necrosis occurs due to

prolonged pressure. Patient does not feel pain due to sensory neuropathy ,therefore if he/she gets injury, there is no feeling of pain resulting in negligence of wound care .This leads to tissue necrosis.

Ischemia: Ischemia occurs due to shunting of blood via peripheral arterio-venous anastomosis occuring in neuropathic feet, thereby reducing blood flow in the smallest vessels .Therefore there is reduced blood supply to the most peripheral tissues.

CONT…..Infection : Diabetic patient is more prone

to have skin infection and there is decreased ability of wound healing which leads to necrosis.

DIABETIC FOOT

COMMON SITES

PREVENTION………….

CARDIOVASCULAR DISODERSAtherosclerosis in large blood vessels.

Responsible for high incidence of stroke and myocardial infarction.

MACROVASCULAR

Infections in diabetes

Skin :Staphylococcal infections (boils, abscesses)CandidiasisUrinary tract infections:urinary tract infectionsPerinephric abscessLungs:Staphylococcal and pneumococcal pneumoniatuberculosis

REASONThe reason why poor control predispose to

infection is that chemo taxis and phagocytosis by polymorph nuclear leukocytes is impaired at high blood glucose level……….

INFECTIONS IN DIABETES

SELF MONITORING TESTSELF-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.

TREATMENTDESIRED OUTCOME

• Relieve symptoms• Reduce mortality• Improve quality of life• Reduce the risk of microvascular and

macrovascular disease complications

TREATMENTHOW TO ACHIEVE THE GOALS ?Near normal glycemic control reduce the risk

of developing microvascular disease complications.

Control of the traditional CV risk factors such as smoking, management of dyslipidemia, intensive BP control and antiplatelet therapy

TREATMENT

There are three methods mainly:I. Diet aloneII. Diet and oral hypoglycemicsIII. Diet and insulin

About 60% of diabetic patients can be treated adequately by diet.

Balanced diet.calories

Daily intake requirements depends on age, sex, weight, activity, occupation and financial resources.

Diet

CONT…..An approximate calorie requirement of

various groups include:Obese middle aged or elderly patient with

mild diabetes 1000-1600 kcal/day.Elderly diabetic but not over weight 1400-

1800 kcal/day.Young active diabetic 1800 – 3000

kcal/day.

The daily intake of protein should be 60-110 grams. An adequate amount of proteins is required for the growth of children.

Proteins

Daily intake 100-300 grams.Starch form should be taken.Readily absorbed carbohydrates, such as

glucose and sucrose should be avoided, because they produce a sudden rise in blood glucose level.

Carbohydrates

SALT AND SWEETENERS

SALTDaily intake should not be more than 6 grams.

SWEETENERSNon nutritive sweeteners such as saccharin ,

aspartate makes food palpable without energy gain.

Present in beans, peas, fruits, and vegetables.

Cause 10% reduction in fasting blood sugar and LDL cholesterol.

DIETARY FIBERS

CONT…..Treatment of obese people with a diet low

in refined and higher in unrefined carbohydrate result in increased insulin sensitivity, which is associated with a rapid fall in the blood glucose concentrations.

Glucose, sucrose and foods high in sucrose/glucose ratio.

FOODS TO BE AVOIDED

FOODS WHICH CAN BE EATEN AS DESIRED

Green vegetables, meat extracts, tomato, lemon juice, tea and coffee.

General approachesDietary and exercise modificationMedicationsRegular complication monitoringSelf monitoring of blood glucoseControl of BP and lipid level

TREATMENT COMPLICATION MONITORINGAnnual eye examinationAnnual microalbuminuriaFeet examinationBP monitoringLipid profile

TREATMENT SELF-MONITORING OF BLOOD GLUCOSE

- Frequent self monitoring of blood glucose to achieve near normal level

- More intense insulin regimen require more frequent monitoring

TREATMENT NONPHARMACOLOGICAL THERAPYEXERCISE- Exercise improves insulin resistance

and achieving glycemic control.- Exercise should start slowly for

patients with limited activity.- Patients with CV diseases should be

evaluated before starting any exercise.

PHARMACOTHERAPYDrugs that primarily stimulate insulin

secretion by binding to the sulfonylurea receptor on the beta cells.

e.g SULFONYLUREASTolbutamide (1st generation)Glipizide (2nd generation)MEGLITINIDE ANALOGESD-PHENYLALANINE DERIVATIVE

Drugs that primarily lower glucose levels by their actions on the liver,muscles and adipose tissue.

MetforminsThiazolidinedionsDrugs that affect absorption of glucose.AcarboseMiglitol

INSULIN

INSULIN

- HYPOGLYCEMIA- Treatment:

- Patients should be aware of symptoms of hypoglycemia

- Oral administration of 10-15 gm glucose - IV dextrose in patients with lost consciousness- 1 gm glucagon IM if IV access is not available

- SKIN RASH AT INJECTION SITE- Treatment: Use more purified insulin

preparation

- LIPODYSTROPHIES (increase in fat mass) at injection site- Treatment: rotate the site of injection

ADVERSE EFFECTS

ROLE OF PHARMACIST:CaregiverDecision makerTeacherManagerLeaderLearner

LET FOOD BE YOUR MEDICINE,AND

MEDICINE YOUR FOOD

(HIPPOCRATES)