Download Diabetes Mellitus (DM) PHCL 442

Diabetes Mellitus (DM)
Part II
PHCL 442
Hadeel Al-Kofide MSc
1
Topics we will cover in DM
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Definition & Epidemiology
Carbohydrate metabolism
Classification
Signs & symptoms
Diagnosis
Long term complications
Monitoring parameter & test to Guide management
Principles of management:
 Part I: General principles
 Part II: a. Insulin & its clinical applications
b. Oral anti-diabetic agents
• Prevention & management of diabetes complications
Last
lecture
2
Principles of Management
Part II: A.Insulin & its Clinical
Applications
3
Clinical 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
4
Initiating Insulin Therapy
Clinical Situation
Insulin Dose
After calculating the total daily dose (TDD) of insulin:
Type 1 DM
1. Split the dose between the regular or short acting insulin &
1. Initial dose
0.5-0.8 U/kg
the intermediate or long acting insulin HOW? Either 50%
2. Honeymoon
phase
0.2-0.5
U/kg
each, or 70%
(the intermediate
or long
acting) & 30% (the
rapid orwith
short
actingduring
insulin) 1-1.5 U/kg
3. Patients
ketosis,
illnesses, during growth
2. Then it depends in which method of insulin delivery you
Typewill
2 DM
(insulin
resistance)
chose
e.g. insulin
pump, 0.7-1.5
MDI orU/kg
conventional method
5
Methods of Insulin Therapy
• Intensive insulin therapy (IIT):
 Insulin pump
 Multiple daily injections (MDI)
• Conventional method
• Example on different methods of insulin therapy
6
Methods of Insulin Therapy
Intensive 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
7
Methods of Insulin Therapy
Intensive 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
8
Methods of Insulin Therapy
Intensive Insulin Therapy
• Two major methods used to deliver IIT:
1. Insulin pump
2. MDI
9
Methods of Insulin Therapy
Intensive Insulin Therapy
Insulin pump:
• The most precise way to mimic normal insulin secretion
• Portable
• Delivers basal & bolus insulin doses
• New: Implantable insulin pumps
10
Methods of Insulin Therapy
Intensive 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
11
Methods of Insulin Therapy
Conventional Insulin Therapy
• Insulin is given twice daily
• It usually contains a mixture of intermediate acting & short
acting insulin
• Not commonly used now
12
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 1
AM
Why
we
Bedtime
Why
weneed
needan
a
intermediate
short
acting here?
--acting here?
PM
Lispro/NPH
Noon
Whywe
weneed
needan
a
Why
short
acting here?
intermediate
-- acting here?
To cover
lunch +
--To cover
breakfast
basal insulin
--
Lispro/NPH
--
Lispro/Lente
--
Lispro/Lente
--
Aspart/NPH
--
Aspart/NPH
--
Aspart/lente
--
Aspart/lente
--
Reg/NPH
Reg/Lente
Reg/NPH
Reg/Lente
To
Tocover
coversnack
dinner+
-basal insulin
13
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 1
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?
14
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 2
This method is used to
overcome disadvantages
of method 1
Bedtime
AM
Noon
PM
Reg/NPH
--
Reg
NPH
Reg/Lente
--
Reg
Lente
Lispro/NPH
--
Lispro
NPH
Lispro/Lente
--
Lispro
Lente
Aspart/NPH
--
Aspart
NPH
Aspart/Lente
--
Aspart
Lente
15
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 2
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
16
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 3
AM
Noon
PM
Bedtime
Reg
Reg
Reg
NPH
Reg
Reg
Reg
Lente
Reg
Reg
Reg
Glargine
Reg
Reg
Reg
Ultralente
17
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 3
• 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%
18
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 4
AM
Noon
PM
Bedtime
Lispro/NPH
Lispro
Lispro
NPH
Lispro/Lente
Lispro
Lispro
Lente
Aspart/NPH
Aspart
Aspart
NPH
Aspart/Lente
Aspart
Aspart
Lente
19
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 4
• 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%
20
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 5
AM
Noon
PM
Bedtime
Reg/Ultralente
Reg
Reg/Ultralente
--
Lente/Ultralente
Lispro
Lente/Ultralente
--
Aspart/Ultralente
Aspart
Aspart/Ultralente
--
21
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 5
• Why ultralente is given twice daily?
• If glargine replaces ultralente give it once daily
• The main disadvantage here is fasting hyperglycemia, why?
22
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 6
AM
Noon
PM
Bedtime
Reg/Ultralente
Reg
Reg
NPH
Lente/Ultralente
Lispro
Lente
NPH
Aspart/Ultralente
Aspart
Aspart
NPH
23
Methods of Insulin Therapy
Examples of Different Insulin Regimens
Method 6
• It overcomes the problems in method 5, why?
24
Testing Frequency
Ideally patients should test their blood glucose in the following
times:
• Before meals
• After meals
This means 8 times/day!!
• Bedtime
• At 2-3 am
25
Testing Frequency
But at least the patient should measure blood glucose in the
following times:
• Before meals
This means 4 times/day
• Bedtime
• At 2-3 am
3 times/week
• 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
26
Testing 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?
27
Interpreting 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 Dinner/bedtime
insulin
snack
28
Interpreting SMBG
Examples
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 preprandial 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)
Time
SMBG (mg/dl)
7 am
160-200
Noon
220-260
5 pm
130-180
11 pm
140-180
29
Interpreting SMBG
Examples
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?
30
Fasting Hyperglycemia
• Insufficient insulin dose
• Somogyi effect
• Dawn phenomenon
• Examples
31
Fasting Hyperglycemia
Insufficient 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
12 pm
5 pm
3 am
190
220
200
140
• Solution: increase the TDD of insulin
32
Fasting Hyperglycemia
Somogyi 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
12 pm
5 pm
3 am
190
120
100
80
33
Fasting Hyperglycemia
Somogyi 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
34
Fasting Hyperglycemia
Somogyi 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)
35
Fasting Hyperglycemia
Dawn 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
12 pm
5 pm
3 am
180
120
110
110
36
Fasting Hyperglycemia
Dawn 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
37
Fasting Hyperglycemia
Examples
• Example 1: Patient on NPH/Reg am & NPH/Reg pm
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 units
2. Give NPH at
bedtime
3. Give a snack
Solution:
Increase regular insulin
in breakfast
38
Fasting Hyperglycemia
Examples
• Example 2: Patient on NPH/Reg am & NPH/Reg pm
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 units
2. Decrease amount of
dinner or bedtime
snack
Solution:
1. May not need to do
anything, why?
2. Increase regular
insulin in breakfast39
Fasting Hyperglycemia
Examples
• Example 3: Patient on NPH/Reg am, Reg pm, & NPH bedtime
7 am
100
12 pm
60
5 pm
90
10 pm
100
3 am
110
Solution:
1. Snack at morning
2. Change from regular
to lispro
3. Decrease morning
dose of regular
insulin
Post-prandial
hypoglycemia
40
Supplemental 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
41
Supplemental 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)
42
Supplemental 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)
43
Supplemental Insulin
Compensatory insulin doses
• Example for algorithm for the previous patient:
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
44
Supplemental 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
45
Supplemental 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
46
Sliding 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
47
Sliding 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?
48
Sick 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
49
Principles of Management
Part II: B. Oral anti-diabetic agents
50
Oral Anti-Diabetic Agents
1. Alpha – glucosidase inhibitors
2. Biguanides
3. Non-sulfonylurea insulin secretagogues (Meglitindes)
4. Sulfonylureas
5. Thiazolidnediones
51
α – 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
52
α – 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
53
α – 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
54
α – Glucosidase Inhibitors
Drug interactions
• May decrease the bioavailability of digoxin
• Miglitol decreases the bioavailability of ranitidine &
propranolol
• Charcoal decreases the absorption of these drugs
55
α – 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)
56
Biguanides
• 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
57
Biguanides
Advantages
• Useful in obese patients because decreases insulin resistance
• Improves lipid profile
• Produces some weight loss
• No hypoglycemia
58
Biguanides
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
59
Biguanides
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
60
Biguanides
Drug interactions
• Cimetidin , nifedipine , furosemide – all can increase
metaformin levels
61
Biguanides
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
62
Non-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
63
Non-Sulfonylurea Insulin Secretagogues
Adverse effects
• Mild hypoglycemia
• Weight gain (mild)
64
Non-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
65
Non-Sulfonylurea Insulin Secretagogues
Drug interactions
• CYP450 3A4 Metabolism , so potential for interactions exist
66
Non-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
67
Non-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
68
Sulfonylureas
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
69
Sulfonylureas
Mechanism of action
• Stimulate insulin release from pancereatic beta cells
• Normalize hepatic glucose production & partially reverse
insulin resistance
70
Sulfonylureas
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)
71
Sulfonylureas
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
72
Sulfonylureas
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
73
Sulfonylureas
Dosing & clinical application
• Adjunct to diet and exercise in type 2 patients
• Used in combination therapy with insulin, metformin,
thiazolidinediones or alpha – glucosidase inhibitors
74
Sulfonylureas
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
75
Sulfonylureas
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)
76
Sulfonylureas
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
77
Thiazolidinediones
• 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
78
Thiazolidinediones
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
79
Thiazolidinediones
Adverse effects
• Hematologic effects
 Decrease hemoglobin & hematocrit
• Cardiovascular effects
 Can cause edema
• Weight gain
 Fluid & fat accumulation
80
Thiazolidinediones
Contraindications & precautions
• Type 1 DM
• Hepatic disease
• Severe CHF
• History of hypersensitivity to TZD
81
Thiazolidinediones
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
82
Thiazolidinediones
Dosing & clinical application
• As an adjunct to diet and exercise
• In combination
• Dose:
• Rosiglitazone 4-8 mg/day
• Pioglitazone 15-30 mg/day
83
Pharmacological Effects of Anti-Diabetic
Agents
Therapeutic Class
Increases
peripheral
glucose
uptake
Decrease
hepatic
glucose
secretion
Increase
insulin
secretion
a-glucosidase
Delay
CHO
absorption
Target Organ
x
GIT
Biguanide
x
x
Liver &
intestine
Thiazolidinediones
x
x
Muscle,
adipose tissue
& liver
Sulfonylureas
x
x
Meglitinide
x
Islet cells of
pancreas
x
Islet cells of
pancreas
84
Combination Products
• Glucovance ® : glyburide / metformin
• Metaglip ® : glipizide / metformin
• Advadamet ® : rosiglitazone / metaformin
85
Type 2 DM Under Special Circumstance
Patients with decreased renal function:
• Consider: glipizide, glimerpiride, insulin, repaglinide,
thiazolidinediones
• Avoid: first generation SUs, glyburide, metformin, acarbose
86
Type 2 DM Under Special Circumstance
Patients with decreased hepatic function:
• Consider: insulin, repaglinide (cautious dosing), miglitol
• Avoid: thiazolidinediones, metformin, acarbose, glyburide,
first generation sulfonylurea
87
Type 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
88
Prevention & Management of
Diabetes Complications
89
Complication 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
90
Complication of DM
Goal
Endpoint
Assessment
Blood pressure
< 130/80 mmHg
Every visit
Lipid control
LDL < 70 mg/dl
TG < 150 mg/dl
HDL > 45 mg/dl
Yearly
Urine protein
Microalbuminuria
< 30 mg/24 hours
Yearly
91
Principles of Management
Treatment Algorithm for DM
92
1. Diagnose Your Patient
Criteria for the diagnosis of diabetes
1
FPG ≥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
93
2. Type 1 or Type 2
Type 1 DM
Type 2 DM
Young
Obese
PPPs
Strong family history
Thin
Fatigue
94
3. Set Your Goals
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)
95
4. Start Treatment for Type 1 DM
Chose your initial
dose 0.5 U/kg
70:30 or 50:50
Chose types of
insulin to
be used
Other things to remember
when
your dealing with a type
1 patient:
Honeymoon
Split the dose between
phase?
both insulin types
Remember you will need 1
Acute1.
illness?
short/regular acting
& 1 simogyi effect &
Fasting hyperglycemia
(including
intermediate/long acting
dawn phenomenon)
Tellguidelines
him the frequency
of
to
ADA
MDI is the
Remember
the
2.According
Insulin
sliding
scale
monitoring
the goals he has
method of&therapy
method of preferred
achieve
remember to see istoyour
calculation
3. But
Sick
day management patient is
welling to take MDI
(insulin
sensitivity
Supplemental insulin
factor)
doses if patient is not
meeting his goal
Chose the method
of insulin delivery
Educate your patient on
interpreting SBGM
96
5. Start Treatment for Type 2 DM
Life style
interventions
This includes diet &
exercise specially
for obese patients
Obese patient: metformin
Lean patient: sulfonylurea
Check HgbA1C
<7%
Continue on same mode
of therapy
>7%
Add metformin or
sulfonylurea
Check HgbA1C
If goals not achieved
switch to combination
97
5. Start Treatment for Type 2 DM
Use combination
of metformin
of the
followings:
• When prandial
rapid+ one
acting
insulin
is added,
• Rosiglitazone or pioglitazone
sulfonylureas or glinides should be DC
• Sulfonylurea
• Basal insulin (bedtime intermediate acting or bedtime or morning long-acting)
• Consider insulin as initial therapy (with lifestyle
modification) in patients with fasting glucose >250
<7%
mg/dL or HbA1C Continue
>10% oronthose
with ketonuria or
same mode
symptoms of hyperglycemia
of therapy
Check HgbA1C
• WhenAdd
initiating
start with
a bedtime dose of an
glitazoneinsulin,
or sulfonylurea
or insulin
intermediate-acting
or once-daily
Or intensify insulin
for those on long-acting
insulin
• Initiate with 0.2 units/kg
>7%
HgbA1C >7%
In
patients not
yet receiving
insulin,
add basal insulin or
• Monitor
HgbA1c
every
3 months
intensify insulin in those receiving insulin
98
6. Educate Your Patient
• Group discussion
99
Thank you
100