Diabetes Mellitus (DM) Part I PHCL 442 Hadeel Al-Kofide MSc 1
Jan 13, 2016
Diabetes Mellitus (DM)Part I
PHCL 442
Diabetes Mellitus (DM)Part I
PHCL 442
Hadeel Al-Kofide MSc
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Topics we will cover in DMTopics we will cover in DM
• Definition & Epidemiology• Carbohydrate metabolism• Classification• Signs & symptoms• Diagnosis• Long term complications• Monitoring parameter & test to Guide management• Principles of management:
Part I: General principlesPart II: a. Insulin & its clinical applications
b. Oral anti-diabetic agents• Prevention & management of diabetes complications
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Definition & EpidemiologyDefinition & Epidemiology
• A syndrome caused by relative or absolute lack of insulin
• Glucose intolerance & alteration in lipid metabolism
• Diabetes is the 6th leading cause of death in U.S
• Leading causes of blindness in adults aged 20-74
• Leading causes of end – stage renal disease
• The CDC has declared an epidemic of diabetes
3CDC: Center of Disease Control & Prevention
Carbohydrate MetabolismCarbohydrate Metabolism
• Homeostatic mechanisms maintain plasma glucose between 55 & 140 mg/dl
• A minimum concentration of 40 – 60 mg/dl needed for CNS (uses glucose as its primary energy source) & it is independent of insulin for glucose utilization
• Muscle & fat also used glucose as an energy source, but these tissues require insulin for glucose uptake
• When glucose concentration exceeds the reabsorptive capacity of the kidney (180 mg/dl)
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Carbohydrate MetabolismCarbohydrate Metabolism
Postprandial Metabolism
Insulin release (anabolism)
Glucose
Turns on
Glycogen
AA Protein
FFA TG
Fasting Metabolism
Counterregularty hormones releaseGluccagon
EpinephrineCortisol
Growith hormone
GlycogenolysisGluconeogensis
↑ Glucose
Shuts off
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Carbohydrate Metabolism & DMCarbohydrate Metabolism & DM
• Blood glucose concentration remain elevated after a meal with the absolute or relative lack of insulin
• Since glucose is inaccessible to cells fasting metabolism is triggered
• Further increase in glucose with glycogenolysis & gluconeogenesis
• Diabetes video
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ClassificationClassification
• Type I DM
• Type II DM
• Gestational DM
• Other specific types of diabetes due to other causes, e.g., genetic defects in cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis)
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Type I DMType I DM
• Known as ‘juvenile’, or Insulin-dependent DM (IDDM)
• Accounts for 5% - 10% of total diabetes cases
• Onset is between 8-14 yrs old usually presenting with ketosis
• Regarded as an auto-immune disease (Antibodies to islet cells &/or insulin)
• Gradual loss of beta cell function until no longer able to synthesize adequate insulin to control blood sugar
• Presenting symptoms are polydipsea, polyurea, polyphagia & weight loss
Classification
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Type I DMType I DM
• Patients are most often lean
• Patients must rely on exogenous sources of insulin
• Honey-moon phase:
After weeks of diagnosis patients have period of remission (decrease in blood glucose concentration)
Endogenous insulin secretion recovers temporarily
May last for weeks, months or a year
Continue on low dose insulin to prevent resistance & allergy
Classification
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Type II DMType II DM
• Formerly known as “adult-onset” or Non-insulin dependent diabetes mellitus (NIDDM)
• 90% of total cases
• Very strong genetic component
• 80% with Type 2 are obese
• Defect in insulin secretion:
Tissue resistance to insulin
Increase in hepatic glucose production
Classification
↑ Insulin↑ Glucose
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Type II DMType II DM
• Usually diagnosed through routine hospital visit
• Mild symptoms & gradual
• Weight loss is uncommon
• Treatment:
Exercise
Diet
Oral hypoglycemic agents
Last thing can add insulin
Classification
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Type II DMType II DM
• Risk factors for developing type II DM:
Genetic profile
Age
Race
Obesity
Physical inactivity
Classification
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Type II DMType II DM
• Usually associated with a variety of disorders:
Obesity
Atherosclerosis
Hyperlipidemia
Classification
Metabolic syndrome or syndrome X
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Gestational DM (GDM)Gestational DM (GDM)
• Affect around 7% of pregnancies
• Any carbohydrate intolerance with first recognition during pregnancy
• Risk on fetus:
Neonatal death
Macrosomia (infant weight > 9 pounds)
• Risk on mother:
Greater chance for cesarean section
HTN
Classification
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Signs & SymptomsSigns & Symptoms
• The 3 Ps
• Blurred vision
• Ketoacidosis
• Fatigue
• Weight loss
Type I DM:More common to see ketoacidosis &
weight loss
Type II DM:Usually mild symptoms & patient may
only complain of fatigue
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DiagnosisDiagnosis
• First look at S & S
• Fasting blood glucose
• Random blood glucose
• OGTT (oral glucose tolerance test)
• How to differ between type I & II DM?
• GDM diagnosis
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Type I & II DMType I & II DMCriteria for the diagnosis of diabetes
1FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h
OR
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Symptoms of hyperglycemia & a casual plasma glucose 200 mg/dl (11.1 mmol/l). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of hyperglycemia include polyuria, polydipsia, & unexplained weight loss
OR
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2-h plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water
Diagnosis
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Type I OR Type II DM?Type I OR Type II DM?
• Young (<30), lean & with S & S and high blood glucose usually type I
• Ketonuria strongly support the diagnosis of type I DM
• 8 – 45% of children diagnosed with DM have type II DM
• Obesity usually goes with type II DM
• In type II DM there is a strong family history
• C-peptide test: if (+) type II DM, if (-) type I DM Why?
Diagnosis
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GDMGDM
• Women at very high risk for GDM should be screened as soon as possible after the confirmation of pregnancy
• Criteria for very high risk are:
Severe obesity
History of GDM or delivery of large-for-gestational-age infant
Presence of glycosuria
Diagnosis of PCOS
Strong family history of type 2 diabetes
• If not found to have diabetes early in pregnancy, should undergo GDM testing at 24–28 weeks of gestation
Diagnosis
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GDMGDM
• Low risk status, which does not require GDM screening, is defined as women with all of the following characteristics:
Age 25 years
Weight normal before pregnancy
Member of an ethnic group with a low prevalence of DM
No known diabetes in first-degree relatives
No history of abnormal glucose tolerance
No history of poor obstetrical outcome
Diagnosis
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GDMGDM
• A diagnosis of GDM requires at least two of the following plasma glucose values:
Fasting: ≥95 mg/dl (≥ 5.3 mmol/l)
1 h: ≥ 180 mg/dl (≥ 10.0 mmol/l)
2 h: ≥ 155 mg/dl (≥ 8.6 mmol/l)
3 h: ≥ 140 mg/dl (≥ 7.8 mmol/l)
Diagnosis
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Long Term ComplicationsLong Term Complications
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Monitoring Parameter & Test to Guide Management
Monitoring Parameter & Test to Guide Management
• Urine ketone testing
• Plasma glucose
• Self monitoring blood glucose
• Glycosylated hemoglobin
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Urine Ketone TestingUrine Ketone Testing
• Type I DM & GDM
• May indicate ketoacidosis
• If blood glucose > 300 mg/dl or in acute illness must test for ketones
Monitoring
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Plasma GlucosePlasma Glucose
• Normal fasting blood glucose (FBG) 70 – 100 mg/dl
• FBG reflect hepatic glucose production (fasting state)
• Also can use random or postprandial blood glucose measurement
• To convert from mg/dl to mmol/L divide by 18
Monitoring
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Self Monitoring Blood GlucoseSelf Monitoring Blood Glucose
• SMBG is the day-to-day monitoring choice for all patients with DM
• Problem:
Expensive
Patient must understand how to use it
Monitoring
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Self Monitoring Blood GlucoseSelf Monitoring Blood Glucose
• Patients in whom SMBG is particularly valuable:
Type I DM: it helps patient to correlate between means, exercise & insulin dosing with blood glucose concentration
Pregnant: Infant morbidity & mortality is associated with mother’s glucose control
Patients having difficulty recognizing hypoglycemia
Patients on intensive insulin therapy: patients who are on multiple daily dosing of insulin or insulin pump
Monitoring
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Glycosylated HemoglobinGlycosylated Hemoglobin
• Non – enzymatic irreversible glycosylation of hemoglibine A circulating in blood, amount formed is related to degree of hyperglycemia
• Measures by % of hemoglobin
• It indicates glycemic control over 2-3 months
• Adjunct in assessing overall glycemic control
• In normal patients 4-6%
• A 1% change in the glycosylated hemoglobin can represent a 25-35 mg/dl change in the mean blood glucose
Monitoring
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Glycosylated HemoglobinGlycosylated Hemoglobin
Hgb A1C 5% 6% 7% 8% 9% 10% 11% 12%
Average Blood glucose in mg/dl
90 120 150 180 210 240 270 300
Monitoring
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Glycosylated HemoglobinGlycosylated Hemoglobin
• Advantages:
No need any special patient preparations (e.g. fasting)
Not subject to acute changes in insulin dosing, exercise or diet
• It does not replace the daily monitoring of blood glucose, because daily monitoring is required to adjust acute changes in glucose level and according to it plan meals & insulin dosing
Monitoring
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Glycemic Goals According to ADAGlycemic Goals According to ADA
A1C < 7%
Preprandial plasma glucose 70–130 mg/dl (3.9–7.2 mmol/l)
Peak postprandial plasma glucose
<180 mg/dl (<10.0 mmol/l)
Monitoring
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Principles of ManagementPart I: General Principles
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General PrinciplesGeneral Principles
• Goals of therapy
• Components of therapy
• Non-pharmacological therapy
• Patient education
• Prevent & treatment of complications
• Role of pharmacists in diabetes management
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Goals of TherapyGoals of Therapy
• Keep patient asymptomatic
• Prevent long term complications
• Maintain patient near euglycemia
• Achieve & maintain an appropriate body weight
• Maintain normal growth & development in children
• Enhance patient & self reliance in management of the disease
• Eliminate or minimize all cardiovascular risk factors
General Principles
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Components of TherapyComponents of TherapyGeneral Principles
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Non-Pharmacological TherapyNon-Pharmacological Therapy
• Diet:
Moderate caloric restriction
Moderate weight loss
Protein: 10 – 20% of daily caloric intake
< 10 % saturated fats and < 10 % polyunsaturated fats
< 300 mg cholesterol
20-35 gm fiber
• Exercise
General Principles
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Patient EducationPatient Education
• Educate the patient and family about disease & treatment
• Instruct how to use insulin
• Instruct patient on method of glycemic control
• Set realistic goals
• Formulate a plan for achieving glycemic control
• Obtain agreement with the patient regarding goals & treatment & provide supportive follow up
General Principles
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Prevent & Treatment of Complications
Prevent & Treatment of Complications
• Foot care
• Annual eye exam
• Nephropathy
• Cardiovascular risk factors
General Principles
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Role of PharmacistsRole of Pharmacists
• Pivotal role in the overall management of the diabetic patient
• Obtain patient history & pertinent information
Record & review all medication including OTCs & herbal
Monitor patient’s adherence to their therapy
Counsel on disease state, HBGM, injections, oral medications
• Assess outcomes
• Collaborate with other healthcare professionals
• Documentation is key
General Principles
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Principles of ManagementPart II: A.Insulin & its Clinical
Applications
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InsulinInsulin
• Immunogenicity
• Uses
• Insulin Types & Their Physical Properties
• Review of newer agents
• Factor Altering Insulin Action
• Stability
• Complications of Insulin Therapy
• Application on insulin in clinical practice
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InsulinInsulin
• A hormone secreted from the pancreatic β cell in response to glucose & other stimulants like amino acids
• Made up of 2 polypeptide chains which are connected by 2 disulfide bonds
Insulin
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ImmunogenicityImmunogenicity
• Now impurities are rare & most patients use human insulin (less hypersensitivity)
• Species source is now the primary immunogenic component
• Beef > Pork > human
Insulin
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UsesUses
• Type 1 diabetes
• Type2 diabetes (if nothing works)
• Pregnant diabetic patient
• Hyperkalemia
Insulin
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Types of InsulinTypes of Insulin
• Rapid acting (ultra-short acting) insulin
Insulin lispro, aspart & glulisine
• Short acting insulin
• Intermediate acting insulin
NPH, lente & NPL
• Long acting insulin:
Ultralent, glargine & detemir
• Premixed
Insulin
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Types of InsulinTypes of InsulinInsulin Onset Peak Duration Appearance
Short acting Lispro (Humalog)Aspart ( Novolog)Glulisine(Apidra)Regular
15 min5-15 min15-20 min30-60 min
30-90 min1-3 hrs0.5-2hrs2-4 hrs
3-4 hrs3-5 hrs
5-7 hrs
ClearClear
Clear
Intermediate acting
NPHLente
1-1.5 hrs1-3 hrs
4-12 hrs6-14 hrs
24 hrs24 hrs
CloudyCloudy
Long acting UltralenteGlargine (lantus)detemir (Levemir)
6 hrs1.5 hrs1-3 hrs
18-24 hrsFlat
36 hrs24 hrs24 hrs
CloudyClear
Insulin
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Types of InsulinTypes of InsulinInsulin
Available insulin pre-Mixtures Brand Names
NPH/Regular mixture (70/30 %)Humulin 70 / 30Novolin 70/30
NPH/ RegularMixture ( 50/50 %) Humulin 50/50
NPL/Lispro mixture ( 75 / 25 %) Humalog 75/25
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Review of Newer AgentsReview of Newer Agents
• Lispro , aspart or glulisine insulin: more closely simulates physiologic insulin secretion relative to meals
• Advantages :
Decreases post-prandial hypoglycemia
Fewer overall occurrence of hypoglycemia, less nocturnal hypoglycemia
Greater flexibility
Insulin
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Review of Newer AgentsReview of Newer Agents
• Disadvantages:
Risk of hypoglycemia if no meal within 15 minutes of dose
Will need to combine with a longer acting insulin for optimal BS Control
If mixed with another insulin give immediately after mixing
Hyperglycemia / ketosis may occur more rapidly if insulin delivery is interrupted
Insulin
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Review of Newer AgentsReview of Newer Agents
• Insulin glulisine:
• When used in a pump, do not mix insulin glulisine with other insulins or with a diluent
• If glulisine is mixed with NPH human insulin, draw the glulisine into the syringe first. Make injection immediately after mixing
• Do not mix glulisine with insulin preparations other than NPH
Insulin
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Review of Newer AgentsReview of Newer Agents
• Glargine & Detimir insulin:
• Advantages:
Provided 24 hour coverage with a constant absorption pattern & no pronounced peak
May be beneficial in patients suffering from nocturnal hypoglycemic episodes
• Disadvantages:
Can Not be mixed with any other insulin
Cost
Insulin
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Factor Altering Insulin ActionFactor Altering Insulin Action
• Route of administration
• Site of injection
• Temperature
• Exercises / massage
• Preparation / mixtures
• Dose
• Patient compliance
• Patient errors
• Irregular diet & excesses
• Renal function
• Stress
• Drugs
Insulin
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StabilityStability
• Stable at room temperature for one month
• Refrigerate vials not in use & do NOT freeze
• Opened insulin vials in refrigerator discarded after 90 days
• Insulin prefilled syringes is stable for 28 days refrigerated
• Mixture stability
Regular / NPH
Regular / Lente or Ultralente
Lispro / NPH or Lentre or Ultralente
Glarginel/all other insulins
Insulin
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Complications of Insulin TherapyComplications of Insulin Therapy
1. Hypoglycemia
• Causes:
Increase insulin dosage
Decrease caloric intake
Increased muscle utilization
Excessive alcohol
Insulin
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Complications of Insulin TherapyComplications of Insulin Therapy
• Signs / symptoms
Termors, tachycardia, diaphorersis, confusion slurred speech, drowsiness, etc
Beta- Blockers can decrease responsiveness to hypoglycemia due to blocking sympathetic warning symptoms
• Treatment
15 –30 gm carbohydrate follow with complex carbohydrate
Glucagon for severe patients
Insulin
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Complications of Insulin TherapyComplications of Insulin Therapy
2. Lipohypertrophy
3. Lipoatrophy
4. Allergic reactions
5. Weight gain
Insulin
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Thank youThank you
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