diabetes mellitus (dm) part ii phcl 442 hadeel al-kofide msc 1
TRANSCRIPT
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Diabetes Mellitus (DM)Part II
PHCL 442
Diabetes Mellitus (DM)Part II
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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Last lecture
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Principles of ManagementPart II: A.Insulin & its Clinical
Applications
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Clinical Applications of Insulin in DMClinical Applications of Insulin in DM
• Initiating insulin therapy
• Methods of insulin therapy
• Testing frequency
• Interpreting SMBG
• Fasting hyperglycemia
• Supplemental insulin doses
• Sliding scale
• Sick day management
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Initiating Insulin TherapyInitiating Insulin Therapy
Clinical Situation Insulin Dose
Type 1 DM
1. Initial dose 0.5-0.8 U/kg
2. Honeymoon phase 0.2-0.5 U/kg
3. Patients with ketosis, during illnesses, during growth
1-1.5 U/kg
Type 2 DM (insulin resistance) 0.7-1.5 U/kg
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After calculating the total daily dose (TDD) of insulin:
1.Split the dose between the regular or short acting insulin &
the intermediate or long acting insulin HOW? Either 50% each,
or 70% (the intermediate or long acting) & 30% (the rapid or
short acting insulin)
2.Then it depends in which method of insulin delivery you will
chose e.g. insulin pump, MDI or conventional method
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Methods of Insulin TherapyMethods of Insulin Therapy
• Intensive insulin therapy (IIT):
Insulin pump
Multiple daily injections (MDI)
• Conventional method
• Example on different methods of insulin therapy
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Intensive Insulin TherapyIntensive Insulin Therapy
Patient selection criteria:
1. Type 1 DM, healthy, >7 yr, highly motivated & compliant individuals, willing to test blood glucose 4 times/day
2. Diabetic women who plan to get pregnant
3. Pregnant diabetic patient
4. Patients poorly controlled on conventional therapy (including type 2)
5. Technical ability to test blood glucose
6. Intellectual ability to interpret blood glucose concentrations
7. Access to trained & skilled medical staff to direct treatment plan & provide supervision
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Methods of Insulin Therapy
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Intensive Insulin TherapyIntensive Insulin Therapy
When to avoid IIT?
1. Patient with counter-regulatory insufficiency
2. Type 1 DM for more tan 15 years (not all patients)
3. On beta-blockers
4. Autonomic, pituitary or adrenal insufficiency
5. Patients with coronary or cerebral vascular disease
6. Patients who are non-compliant, unable to measure blood glucose, or patients with psychiatric disorders
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Methods of Insulin Therapy
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Intensive Insulin TherapyIntensive Insulin Therapy
• Two major methods used to deliver IIT:
1. Insulin pump
2. MDI
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Methods of Insulin Therapy
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Intensive Insulin TherapyIntensive Insulin Therapy
Insulin pump:
• The most precise way to mimic normal insulin secretion
• Portable
• Delivers basal & bolus insulin doses
• New: Implantable insulin pumps
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Methods of Insulin Therapy
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Intensive Insulin TherapyIntensive Insulin Therapy
Multiple daily injections:
• It mimics the release of insulin from the pancreas
• Contains both basal & bolus insulin
• Insulin is given 3 times or more per day
• There are different methods to deliver MDI of insulin
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Methods of Insulin Therapy
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Conventional Insulin TherapyConventional Insulin Therapy
• Insulin is given twice daily
• It usually contains a mixture of intermediate acting & short acting insulin
• Not commonly used now
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Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
AM Noon PM Bedtime
Reg/NPH -- Reg/NPH --
Reg/Lente -- Reg/Lente --
Lispro/NPH -- Lispro/NPH --
Lispro/Lente -- Lispro/Lente --
Aspart/NPH -- Aspart/NPH --
Aspart/lente -- Aspart/lente --
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Method 1
Why we need a short acting here?
To cover breakfast
Why we need an intermediate acting here?
To cover lunch + basal insulin
Why we need a short acting here?
To cover dinner
Why we need an intermediate acting here?
To cover snack + basal insulin
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
Disadvantages:
• Peak of NPH will be between 2-4 am causing nocturnal hypoglycemia & morning hyperglycemia (rebound hyperglycemia)
• To overcome this problem: either decrease NPH dose, or give NPH at bedtime instead of pre-dinner, why?
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Method 1
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
AM Noon PM Bedtime
Reg/NPH -- Reg NPH
Reg/Lente -- Reg Lente
Lispro/NPH -- Lispro NPH
Lispro/Lente -- Lispro Lente
Aspart/NPH -- Aspart NPH
Aspart/Lente -- Aspart Lente
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Method 2 This method is used to overcome disadvantages
of method 1
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
How can method 2 overcome method 1 disadvantages?
• By shifting NPH or lente dose to bedtime the peak action will occur in early morning (5-7 am) when the patient is awake & ready to eat
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Method 2
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
AM Noon PM Bedtime
Reg Reg Reg NPH
Reg Reg Reg Lente
Reg Reg Reg Glargine
Reg Reg Reg Ultralente
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Method 3
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
• More flexibility in meals
• If regular insulin was replaced by lispro must add with it NPH, why?
• If glargine replaces either NPH or lente the dose should be decreased by 20%
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Method 3
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
AM Noon PM Bedtime
Lispro/NPH Lispro Lispro NPH
Lispro/Lente Lispro Lispro Lente
Aspart/NPH Aspart Aspart NPH
Aspart/Lente Aspart Aspart Lente
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Method 4
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
• The problem with lispro or aspart is post-prandial hyperglycemia due to short duration of action
• If glargine replaces either NPH or lente the dose should be decreased by 20%
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Method 4
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
AM Noon PM Bedtime
Reg/Ultralente Reg Reg/Ultralente --
Lente/Ultralente Lispro Lente/Ultralente --
Aspart/Ultralente Aspart Aspart/Ultralente --
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Method 5
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
• Why ultralente is given twice daily?
• If glargine replaces ultralente give it once daily
• The main disadvantage here is fasting hyperglycemia, why?
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Method 5
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
AM Noon PM Bedtime
Reg/Ultralente Reg Reg NPH
Lente/Ultralente Lispro Lente NPH
Aspart/Ultralente Aspart Aspart NPH
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Method 6
Methods of Insulin Therapy
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Examples of Different Insulin RegimensExamples of Different Insulin Regimens
• It overcomes the problems in method 5, why?
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Method 6
Methods of Insulin Therapy
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Testing FrequencyTesting Frequency
Ideally patients should test their blood glucose in the following times:
• Before meals
• After meals
• Bedtime
• At 2-3 am
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This means 8 times/day!!
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Testing FrequencyTesting Frequency
But at least the patient should measure blood glucose in the following times:
• Before meals
• Bedtime
• At 2-3 am
• Patients should evaluate blood glucose level when they are not feeling well, or in case of increased physical activity, large meal, final examinations or family crisis
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This means 4 times/day
3 times/week
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Testing FrequencyTesting Frequency
• Testing blood glucose at these times corresponds with the peak action of short & intermediate acting insulin administered at different times of the day
• This enables the clinician to evaluate the effect of various insulin components on meals & to identify nocturnal hypoglycemia
• GlucoWatch?
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Interpreting SMBGInterpreting SMBG
Test Time Target Insulin Dose Target Meal/Snack
Fasting (pre-breakfast) Pre-dinner/bedtime intermediate or long acting insulin
Bedtime snack
Pre-lunch Pre-breakfast regular insulin Breakfast
Pre-dinner Pre-breakfast intermediate acting insulin or pre-lunch regular acting insulin
Lunch
Bedtime Pre-dinner regular insulin Dinner
3 am Pre-dinner intermediate acting insulin
Dinner/bedtime snack
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Interpreting SMBGInterpreting SMBG
Case 1:
• J.F is a 20 year old female recently diagnosed with type I DM, she was prescribed NPH insulin twice daily: 16 units am & 8 units PM. Her initial goal of therapy was to achieve a pre-prandial blood glucose concentration <180 mg/dl. After being on this regimen for 1 week, trends in her blood glucose concentrations were: (occasional 3 am tests was 160 mg/dl)
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Examples
Time SMBG (mg/dl)
7 am 160-200
Noon 220-260
5 pm 130-180
11 pm 140-180
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Interpreting SMBGInterpreting SMBG
How to solve case 1?
• Increase TDD because her overall control is poor (increase dose to 0.6 U/kg)
• Split this dose to provide 2/3 in the morning & 1/3 at evening
• Add regular insulin to her regimen by 2:1 ratio, how?
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Examples
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Fasting HyperglycemiaFasting Hyperglycemia
• Insufficient insulin dose
• Somogyi effect
• Dawn phenomenon
• Examples
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Insufficient Insulin DoseInsufficient Insulin Dose
• In which there is at least 3 reading values of blood glucose are high
• The 3 am value must be high or normal (not low), why?
• Example:
7 am 190
12 pm 220
5 pm 200
3 am 140
• Solution: increase the TDD of insulin
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Fasting Hyperglycemia
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Somogyi EffectSomogyi Effect
• Also called rebound hyperglycemia; posthypoglycemic hyperglycemia
• Fasting hyperglycemia but normal blood glucose at bedtime, low at 3 am with symptoms of hypoglycemia (nightmares, sweating, hunger & morning headache)
• Example:
7 am 190
12 pm 120
5 pm 100
3 am 80
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Fasting Hyperglycemia
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Somogyi EffectSomogyi Effect
• It occurs after severe hypoglycemia & its 2nd to excessive increase in glucose production by the liver that is activated by counter regulatory hormones
• The evening dose of NPH is responsible for this effect
• It is the cause of morning hyperglycemia in >10% of diabetic patients
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Fasting Hyperglycemia
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Somogyi EffectSomogyi Effect
Solutions:
• Decrease NPH dose by 2-3 units, or
• Shift the pre-dinner NPH dose to bedtime (preferred than twice daily injection)
• Switch NPH to glargine, give it at bedtime & decrease the dose by 20% (remember glargine cannot be mixed with regular insulin)
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Fasting Hyperglycemia
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Dawn PhenomenonDawn Phenomenon
• A rise in blood glucose concentration that occurs between 4-8 am
• It is due to natural increase in growth hormone levels in the early morning (not rebound effect)
• Example:
7 am 180
12 pm 120
5 pm 110
3 am 110
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Fasting Hyperglycemia
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Dawn PhenomenonDawn Phenomenon
Solutions:
• Increase evening NPH by 1-2 units
• If patient on glargine switch to something with peak as NPH or lente
• Decrease bedtime snack
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Fasting Hyperglycemia
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ExamplesExamples
• Example 1: Patient on NPH/Reg am & NPH/Reg pm
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Fasting Hyperglycemia
7 am 160
12 pm 130
5 pm 90
10 pm 100
3 am 60
Somogyi effect
Solution:1.Decrease evening NPH by 1-2 units2.Give NPH at bedtime3.Give a snack
Solution:Increase regular insulin in breakfast
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ExamplesExamples
• Example 2: Patient on NPH/Reg am & NPH/Reg pm
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Fasting Hyperglycemia
7 am 160
12 pm 130
5 pm 90
10 pm 100
3 am 100
Down phenomenon
Solution:1.Increase evening NPH by 1-2 units2.Decrease amount of dinner or bedtime snack
Solution:1.May not need to do anything, why?2.Increase regular insulin in breakfast
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ExamplesExamples
• Example 3: Patient on NPH/Reg am, Reg pm, & NPH bedtime
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Fasting Hyperglycemia
7 am 100
12 pm 60
5 pm 90
10 pm 100
3 am 110
Post-prandial hypoglycemia
Solution:1.Snack at morning2.Change from regular to lispro3.Decrease morning dose of regular insulin
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Supplemental InsulinSupplemental Insulin
• After establishing the basic dose of insulin, each patient must be educated on supplemental insulin in case of increase or decrease in blood glucose level according to SMBG
• Two methods
1. Compensatory insulin doses
2. Anticipatory insulin doses
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Supplemental InsulinSupplemental Insulin
Compensatory insulin doses
• These doses are used to compensate for high blood glucose levels
• It assumes that there is no unusual changes in patient’s overall diet & exercise patterns
• Given as regular or short acting insulin (lispro & aspart are preferred due to shorter duration of action)
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Supplemental InsulinSupplemental Insulin
Compensatory insulin doses
• Usually for each 30-50 mg/dl elevation above the target level 1-2 units of supplemental insulin is required
• To be more accurate must determine the supplemental dose of insulin by using the sensitivity factor
• Sensitivity factor is determined by using the 1500 or 1800 rule
1500/TDD = sensitivity factor
• If TDD is 30: 1500/30 = 50 mg/dl (each unit of insulin will decrease blood glucose level by 50 mg/dl)
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Supplemental InsulinSupplemental Insulin
Compensatory insulin doses
• Example for algorithm for the previous patient:
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Blood glucose mg/dl Regular insulin
<80 1 unit less
80-120 Usual dose
120-170 1 unit extra
170-220 2 units extra
220-270 3 units extra
270-320 4 units extra
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Supplemental InsulinSupplemental Insulin
Compensatory insulin doses
• If the patient requires more than 4 units must seek medical advice
• Also in case of ketones in urine must go to hospital
• If supplemental doses of insulin are required for ≥3 days, insulin dose should be adjusted
• Example: if patients is usually taking lispro before meals and NPH at bedtime, and 3 days in a row he required 2 units of lispro before lunch, so increase lispro morning dose by 2 units
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Supplemental InsulinSupplemental Insulin
Anticipated insulin doses
• Prescribed in anticipation of an immediate event that is likely to alter a patient’s response to insulin
• This include an unusual large or small meal or exercise
• Increase lispro, aspart or regular insulin by 1 unit for each additional 15 g of carbohydrates
• Decrease lispro, aspart or regular insulin by 1 unit for smaller meals
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Sliding ScaleSliding Scale
• Algorithmic method for adjusting doses of short or regular acting insulin according to blood glucose test results
• Used for hospitalized patients in which their insulin requirements may vary significantly due to stress (infection, surgery or acute illnesses), inactivity or variable caloric intake
• Blood glucose levels are measured every 4 hours if given SC, & every hour if given IV
• Sliding scale should be individualized by using each patient sensitivity factor
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Sliding ScaleSliding Scale
• If sensitivity factor is not use the alternate method is for each 30-50 mg/dl elevation above the target level 1-2 units of insulin is given
• After sliding scale or upon hospital discharge what to do?
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Sick Day ManagementSick Day Management
1. Continue insulin even if food intake is decreased
2. Maintain fluid intake
3. Test blood glucose every 4 hours at a minimum
4. Test urine for ketones
5. Administer supplemental dose of insulin according to a prescribed algorithm (ex. 1-2 units for every 30-50 mg/dl over 120 mg/dl)
6. Seek medical attention if : Urine ketones, blood glucose > 300 mg/dl or mental status changes
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Principles of ManagementPart II: B. Oral anti-diabetic agents
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Oral Anti-Diabetic AgentsOral Anti-Diabetic Agents
1. Alpha – glucosidase inhibitors
2. Biguanides
3. Non-sulfonylurea insulin secretagogues (Meglitindes)
4. Sulfonylureas
5. Thiazolidnediones
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α – Glucosidase Inhibitorsα – Glucosidase Inhibitors
• Acarbose – precose® & Miglitol – Glyset ®
Mechanism of action
• Competitive reversible inhibition of intestinal α – glucosidase
• Delays glucose absorption & lower postprandial hyperglycemia
• Dose not enhance insulin secretion
• No effect on weight or lipids
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α – Glucosidase Inhibitorsα – Glucosidase Inhibitors
Adverse effects
• GI: flatulence, diarrhea & abdominal pain. Can decrease this side effect by slow titration in dose
• Elevated liver function test: monitor liver enzyme every 3 months for 1st year of therapy then periodically. Because miglitol is not metabolized through liver there is no liver toxicity
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α – Glucosidase Inhibitorsα – Glucosidase Inhibitors
Contraindications & precautions
• GI conditions: not recommended for patients with malabsorption, or inflammatory bowel disease
• Renal impairment: not studied in sever renal impairment so should be avoided
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α – Glucosidase Inhibitorsα – Glucosidase Inhibitors
Drug interactions
• May decrease the bioavailability of digoxin
• Miglitol decreases the bioavailability of ranitidine & propranolol
• Charcoal decreases the absorption of these drugs
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α – Glucosidase Inhibitorsα – Glucosidase Inhibitors
Dosing & clinical application
• As an adjunct to diet and exercise in type 2 diabetes
• In combination
• Titrate the dose:
25 mg QD with meal for first 7-14 days
25mg BID week 3-4
25mg TID week 5-12
50mg TID (max dose if wt < 60 kg)
100mg TID (max it wt > 60 kg)
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BiguanidesBiguanides
• Metformin ( Glucophage C. ®)
Mechanism of action
• Antihyperglycemic agent
• Improve insulin sensitivity (they do not stimulate insulin release from pancreas & they do not cause hypoglycemia)
• Increase tissue uptake & utilization of glucose by muscle
• Decrease hepatic production of glucose
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BiguanidesBiguanides
Advantages
• Useful in obese patients because decreases insulin resistance
• Improves lipid profile
• Produces some weight loss
• No hypoglycemia
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BiguanidesBiguanides
Adverse effects
• GI: diarrhea, abdominal discomfort, metallic taste, nausea & anorexia. Can decrease this side effect by slow titration in dose & by giving it with meals
• Lactic acidosis: it may decrease conversion of lactate to glucose & increase lactate production in gut & liver. Symptoms include weakness, malaise, myalgias, abdominal distress & heavy labored breathing
• Lactic acidosis only happen in patients with predisposing factors
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BiguanidesBiguanides
Contraindications & precautions (For lactic acidosis)
• Renal impairment (not recommended if CrCl <60 ml/min)
• Hepatic disease
• CHF
• Alcoholic
• Shock
• Dehydration
• Surgery
• Chronic metabolic acidosis or a history of lactic acidosis
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BiguanidesBiguanides
Drug interactions
• Cimetidin , nifedipine , furosemide – all can increase metaformin levels
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BiguanidesBiguanides
Dosing & clinical application
• As an adjunct to diet in type 2 patient that are uncontrolled
• In combination
• Initial dose is 500 mg po BID or 850mg Po QD, with meals to decrease side effects
• Titrate dose weekly and increase by 250-500mg
• Maximum dose 2550 mg OD or 850 mg TID
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Non-Sulfonylurea Insulin SecretagoguesNon-Sulfonylurea Insulin Secretagogues
• Meglitindes ( Repaglinide – Prandin ® and Netaglinide – Starlix ®)
Mechanism of action
• Stimulates release of insulin from the pancreatic beta cells (like sulfonyurea)
• The advantage over sulfonyurea is that they have rapid onset & shorter duration of action
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Non-Sulfonylurea Insulin SecretagoguesNon-Sulfonylurea Insulin Secretagogues
Adverse effects
• Mild hypoglycemia
• Weight gain (mild)
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Non-Sulfonylurea Insulin SecretagoguesNon-Sulfonylurea Insulin Secretagogues
Contraindications & precautions
• Not given in patients with no pancreas (or type 1)
• Caution in liver dysfunction
• No dose adjustment is required in renal impairment
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Non-Sulfonylurea Insulin SecretagoguesNon-Sulfonylurea Insulin Secretagogues
Drug interactions
• CYP450 3A4 Metabolism , so potential for interactions exist
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Non-Sulfonylurea Insulin SecretagoguesNon-Sulfonylurea Insulin Secretagogues
Dosing & clinical application
• As an adjunct to diet & exercise to patients with uncontrolled type 2 diabetes
• In combination (not with sulfonylurea, why?)
• Rapid Onset & short duration of action, so given with meals to enhance postprandial glucose utilization
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Non-Sulfonylurea Insulin SecretagoguesNon-Sulfonylurea Insulin Secretagogues
Dosing & clinical application
• If HgbAIC is < 8 % start 0.5 mg repaglinide or 60 mg netaglainide
• If HgbAIC is > 8 % start 1-2 mg or 120 mg netaglinide
• Adjust doses at weekly intervals
• Take 15-30 minutes prior to each meal
• Instruct patients who skip a meal to skip a dose
• Instruct patient who eat an extra meal to add a dose
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SulfonylureasSulfonylureas
First generation
• Acetohexamide, chlorpropamid, tolazamide, & tolbutamide
• Not used commonly today duo to increase adverse effects, active metabolites, some prolonged half lives , & increase drug interaction
Second generation
• Glyburide, glipizde, & glimepiride
• 100 times more potent than first generation
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SulfonylureasSulfonylureas
Mechanism of action
• Stimulate insulin release from pancereatic beta cells
• Normalize hepatic glucose production & partially reverse insulin resistance
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SulfonylureasSulfonylureas
Adverse effects
• Hypoglycemia & weight gain
Renal/hepatic insufficiency patients
Elderly or malnourished patients
Concurrent hypoglycemic drugs
• Hypothyroidism
• GI disturbances
• Hematologic
• Allergic skin reactions/photosensitivity
• Hepatotoxicity (Increase liver enzymes)
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SulfonylureasSulfonylureas
Contraindications & precautions
• Type 1 DM
• Pregnancy & breast-feeding except glyburide
• Documented hypersensitivity to sulfonylurea
• Severe hepatic or renal dysfunction
• Severe, acute intercurrent illness (e.g. infection or MI), surgery, or other stressful conditions
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SulfonylureasSulfonylureas
Drug interactions
• Increased hypoglycemic effect
• Warfarin, azole antifungals, gemfibrozil, clofibrate , sulfonamides, MAOIs, tricyclic antidepressant, alcohol, cimetidine, aspirin & concomitant agents for diabetes
• Decreased hypoglycemic effect
• beta – blockers, CCBs, cholestyramine, Glucocorticoides, phenytoin, oral contraceptives, rifampin, thiazides, niacin
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SulfonylureasSulfonylureas
Dosing & clinical application
• Adjunct to diet and exercise in type 2 patients
• Used in combination therapy with insulin, metformin, thiazolidinediones or alpha – glucosidase inhibitors
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SulfonylureasSulfonylureas
Dosing & clinical application
• Start at low end of the dosing range, especially in the elderly
• Increase dose every 1-2 weeks until maximum dosage
• Exceeding the maximum dosage increases side effects, but does not decrease blood glucose
• Use cautiously in patients with increase risk of hypoglycemia
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SulfonylureasSulfonylureas
Treatment failure
• 15 % will have primary failure (poor blood sugar control after a trial of 6-12 weeks on medication & diet)
• After 5 years, ~ 50 % may experience secondary failure (failure of medicine to work after initial good glycemic control)
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SulfonylureasSulfonylureas
Glipizde:
• Dose 10 mg/day (maximum 40 mg/day)
• If not respond to 10 mg/d give combination not increase dose
Glyburide:
• Maximum dose 20 mg/d (maximum effect occur at 10 mg/d)
• Advantage over others is that food does not delay extent of absorption (can be given without relation to meal)
Glimepiride :
• Has the advantage of once daily dosing
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ThiazolidinedionesThiazolidinediones
• Rosiglitazone – Avandia ® & Pioglitazone – Actos ®
Mechanism of action
• Improves cellular response to insulin W/O increasing pancreatic insulin secretion
• Decrease insulin resistance
• Decreases hepatic glucose production
• Results in reduction in exogenous insulin dosage when used in combination
• May have favorable effect on HDL
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ThiazolidinedionesThiazolidinediones
Adverse effects
• Hepatotoxicity
Troglitazone pulled from the market secondary to hepatic fatalities
Do not start therapy in patients with baseline LFTs> 2.5x
Check LFTs every 2 months for the first year
Monitor nausea vomiting, abdominal pain, fatigue, anorexia, dark urine
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ThiazolidinedionesThiazolidinediones
Adverse effects
• Hematologic effects
Decrease hemoglobin & hematocrit
• Cardiovascular effects
Can cause edema
• Weight gain
Fluid & fat accumulation
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ThiazolidinedionesThiazolidinediones
Contraindications & precautions
• Type 1 DM
• Hepatic disease
• Severe CHF
• History of hypersensitivity to TZD
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ThiazolidinedionesThiazolidinediones
Drug interactions
• Pioglitazone induces the hepatic enzyme CYP 3A4, may affect the following drugs: estrogen, cyclosporine, tacrolimus & HMG-CoA reductase inhibitors
• Rosiglitazone does not appear to inhibit any CYP enzymes
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ThiazolidinedionesThiazolidinediones
Dosing & clinical application
• As an adjunct to diet and exercise
• In combination
• Dose:
• Rosiglitazone 4-8 mg/day
• Pioglitazone 15-30 mg/day
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Pharmacological Effects of Anti-Diabetic Agents
Pharmacological Effects of Anti-Diabetic Agents
Therapeutic Class Increases peripheral glucose uptake
Decrease hepatic glucose secretion
Increase insulin secretion
Delay CHO absorption
Target Organ
a-glucosidase x GIT
Biguanide x x Liver & intestine
Thiazolidinediones x x Muscle, adipose tissue & liver
Sulfonylureas x x x Islet cells of pancreas
Meglitinide x Islet cells of pancreas
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Combination ProductsCombination Products
• Glucovance ® : glyburide / metformin
• Metaglip ® : glipizide / metformin
• Advadamet ® : rosiglitazone / metaformin
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Type 2 DM Under Special CircumstanceType 2 DM Under Special Circumstance
Patients with decreased renal function:
• Consider: glipizide, glimerpiride, insulin, repaglinide, thiazolidinediones
• Avoid: first generation SUs, glyburide, metformin, acarbose
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Type 2 DM Under Special CircumstanceType 2 DM Under Special Circumstance
Patients with decreased hepatic function:
• Consider: insulin, repaglinide (cautious dosing), miglitol
• Avoid: thiazolidinediones, metformin, acarbose, glyburide, first generation sulfonylurea
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Type 2 DM Under Special CircumstanceType 2 DM Under Special Circumstance
Obese patients:
• Consider: metformin, acarbose, miglitol
• Avoid: SUs, insulin (unless you are at the end stage of disease), repaglinide, thiazolidinediones
Patients experiencing hypoglycemia due to irregular eating patterns
• Avoid: insulin & long acting SUs
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Prevention & Management of Diabetes Complications
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Complication of DMComplication of DM
• CVD
1. Hypertension/blood pressure control
2. Dyslipidemia/lipid management
3. Antiplatelet agents
4. Smoking cessation
5. CHD screening and treatment
• Nephropathy
• Retinopathy screening & treatment
• Neuropathy screening & treatment
• Foot care
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Complication of DMComplication of DM
Goal Endpoint Assessment
Blood pressure < 130/80 mmHg Every visit
Lipid control LDL < 70 mg/dlTG < 150 mg/dlHDL > 45 mg/dl
Yearly
Urine protein Microalbuminuria< 30 mg/24 hours
Yearly
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Principles of ManagementTreatment Algorithm for DM
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1. Diagnose Your Patient1. Diagnose Your Patient
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Criteria 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
2
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
3
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
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2. Type 1 or Type 22. Type 1 or Type 2
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3. Set Your Goals3. Set Your Goals
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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)
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4. Start Treatment for Type 1 DM4. Start Treatment for Type 1 DM
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Chose your initial dose 0.5
U/kg Chose types of insulin to be used
Honeymoon phase?
Acute illness?Remember you will need 1
short/regular acting & 1 intermediate/long acting
Split the dose between both insulin types
70:30 or 50:50
Chose the method of insulin delivery
According to ADA guidelines MDI is the preferred method of therapy
But remember to see is your patient is welling to take MDI
Educate your patient on interpreting SBGM
Tell him the frequency of monitoring & the goals he has
to achieve
Supplemental insulin doses if patient is not
meeting his goal
Remember the method of calculation
(insulin sensitivity
factor)
Other things to remember when your dealing with a type 1 patient:
1.Fasting hyperglycemia (including simogyi effect & dawn phenomenon)
2.Insulin sliding scale
3.Sick day management
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5. Start Treatment for Type 2 DM5. Start Treatment for Type 2 DM
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Life style interventions
Check HgbA1C
This includes diet & exercise specially for obese patients
>7%Add metformin or
sulfonylurea
Obese patient: metforminLean patient: sulfonylurea
If goals not achieved switch to combination
<7%Continue on same mode
of therapy
Check HgbA1C
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5. Start Treatment for Type 2 DM5. Start Treatment for Type 2 DM
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Use combination of metformin + one of the followings: • Rosiglitazone or pioglitazone • Sulfonylurea• Basal insulin (bedtime intermediate acting or bedtime or morning long-acting)
>7%
Check HgbA1C
<7%Continue on same mode
of therapy
Add glitazone or sulfonylurea or insulinOr intensify insulin for those on insulin
HgbA1C >7%In patients not yet receiving insulin, add basal insulin or
intensify insulin in those receiving insulin
• When prandial rapid acting insulin is added, sulfonylureas or glinides should be DC
• Consider insulin as initial therapy (with lifestyle modification) in patients with fasting glucose >250 mg/dL or HbA1C >10% or those with ketonuria or symptoms of hyperglycemia
• When initiating insulin, start with a bedtime dose of an intermediate-acting or once-daily long-acting
• Initiate with 0.2 units/kg
• Monitor HgbA1c every 3 months
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6. Educate Your Patient6. Educate Your Patient
• Group discussion
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Thank youThank you
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