2013 6-19 DM, Pre-DM & MetS PSEM Weekend course bulacan insulin 101

Insulin 101:
Human vs Analogues:
Which, when, how
and to whom?
Jeremy F. Robles, MD, FPCP, FPSEM
5th Diabetes, Prediabetes and Metabolic Syndrome Weekend
Course (ENDOCRINE: ENhancing Diabetes Outpatient and
CRitical INitiativEs July 19, 2013 Malolos, Bulacan
Friday, July 19, 13

Case 1:
§Age: 52 years
§Duration of type 2 diabetes: 7 years
§FPG of 180 - 320 mg/dL in last 2
months
§Weight: 209 lbs (95 kg)
§BMI: 32 kg/m2
§Blood pressure: 135/85 mmHg
§Current treatment:
§Glimepiride 6 mg pre breakfast
§Metformin 1000 mg BID
Friday, July 19, 13

Lab Results:
§FPG: 190 mg/dl, HbA1C 10%
§2-hour PPG: 280 mg/dL
§Total cholesterol: 200 mg/dl,
Triglycerides: 180 mg/dL
§AST: 45 IU/L, ALT: 50 IU/L
§Urine microalbumin: 18 mg/24 hr
Friday, July 19, 13

1.) What would be your next step in managing this
patient?
A. Continue meds & monitor HbA1c again in 3 months
B. Add an additional oral agent (ex: TZD, DPP-4 inhib)
C. Add a basal insulin at bedtime
D. Begin a premixed insulin analogue therapy
E. Stop orals and start basal/bolus insulin therapy
Friday, July 19, 13

2.) What are the primary concerns that you should
address in
managing this patient?
A. Fear of guilt or failure
B. Fear of weight gain or hypoglycemia
C. Misconception of risks
D. Beliefs on treatment efficacy
E. Psychological barriers to insulin therapy
Friday, July 19, 13

Case 1:
§ Patient was started on biphasic human insulin given
twice a day 10 U AC breakfast and 5 U AC dinner
§ Metformin 1000mg BID was continued
§ She was started on rosuvastin 10 mg HS
§ She was seen by a dietician
§ Advised told to eat regularly with adequate servings
§ She monitored her blood sugar daily before meals
§ Patient came back for follow-up after 2 weeks
Succeeding follow-up showed improvement of
blood sugars as insulin dose was adjusted
Friday, July 19, 13

FF-up Lab Results after 3 months:
§FPG: 120 mg/dl
§Total cholesterol: 180 mg/dl
§Triglycerides: 120 mg/dL
§AST: 18 IU/L
§ALT: 18 IU/L
§HbA1c: 6.5 %
Initial Lab Results:
§FPG: 190 mg/dl, HbA1C 10%
§Total cholesterol: 200 mg/dl, Triglycerides: 180 mg/dL
§AST: 45 IU/L, ALT: 50 IU/L
Friday, July 19, 13

Daily Physiologic Insulin Secretion
• Human pancreas secretes about 30 U/day of insulin
• Fasting basal concentration of insulin of 10 U/mL
• Postprandial insulin rise within 8 to 10 minutes, peak by
30 - 45 minutes, then declines to baseline by 90 minutes
• Glucose is the most potent stimulant of insulin release
• Sustained hyperglycemia result in a reversible
desensitization of the cell response to glucose
Gardner DG & Shoback D .“Pancreatic Hormones & Diabetes Mellitus”
Greenspan’s Basic & Clinical Endocrinology 9th ed.. 2011.
Friday, July 19, 13

Physiologic Insulin Production
Basal insulin
• Nearly constant day-long insulin level
• Suppress hepatic glucose production overnight &
between meals
• Cover 50% of daily needs
Bolus insulin (mealtime)
• Immediate rise and sharp peak at 1 h
• Limit postmeal hyperglycemia
• Cover 10–20% of total daily insulin at each meal
Rosenstock J & Riddle M .“Insulin therapy in DM type 2”. The CADRE Handbook of Diabetes
Management. July 15, 2013. <http://cadre.emsix.com/handbooks/CADRE%20HB
%20ch09%20pg145-168.pdf>
Friday, July 19, 13

Beaser RS, et. al.“Insulin-Treated Type 2 Diabetes: Balancing Physiologic and Individual
Needs” Medscape. 30 June 2013. <http://www.medscape.org/viewarticle/544445>
Friday, July 19, 13

Daily Physiologic Insulin Secretion
Friday, July 19, 13

Therapeutic Options for DM type 2
Friday, July 19, 13

Houston we have a problem!
Friday, July 19, 13

Absolute Indications for Insulin Therapy
•All patients with type 1 diabetes
• Ketoacidosis or severe hyperglycemia (blood sugars over 500)
• Presence of serious infection (for example, pneumonia)
• Concurrent illness (such as heart attack)
• During and after major surgery
• During pregnancy
• Unable to control glycemic with 2 or 3 oral agents
•A1c over 10%
•A1c over 7.5 % plus fasting glucose over 250
Tanenberg R.“Insulin For Type 2 Diabetes: Who, When, And Why?”
Diabetes Health. 30 June 2013. <http://diabeteshealth.com/read/2009/03/20/5564/
insulin-for-type-2-diabetes-who-when-and-why/>
Friday, July 19, 13

Relative Indications for Insulin Therapy
• Patients who are underweight or losing weight without dieting
• Patients who have symptoms from blood sugars over 200
•Any patient who is hospitalized
• Patients on steroids (such as prednisone) for other disorders
• Onset of diabetes <30 yo, or a duration over ﬁfteen years
• Complications such as painful diabetic neuropathy
Tanenberg R.“Insulin For Type 2 Diabetes: Who, When, And Why?”
Diabetes Health. 30 June 2013. <http://diabeteshealth.com/read/2009/03/20/5564/
insulin-for-type-2-diabetes-who-when-and-why/>
Friday, July 19, 13

Barriers to Insulin Initiation
• Misconceptions & stigmas about insulin & complications
• Limitations of insulin formulations
• Complexity of insulin regimens
• Limited time and resources
• Skepticism that patients can reach glycemic targets
• Risk of hypoglycemia & Weight gain
• Misconceptions about insulin with atherogenesis
• Fear of needles
%20ch09%20pg145-168.pdf>
Friday, July 19, 13

Overcoming Major Barriers to Insulin Therapy
%20ch09%20pg145-168.pdf>
Barrier Effect of Insulin Therapy
Insulin resistance
Improves insulin sensitivity
by reducing glucotoxicity
Cardiovascluar risk
No evidence of atherosclerotic effects
Reduced cardiovascular risk factors
Weight gain Modest & avoidable
Hypoglycemia
Rarely causes severe events
when used properly
Friday, July 19, 13

Insulin preparations
%20ch09%20pg145-168.pdf>
Table Pharmacokinetics of Human Insulin
and Analogues
9-3
Onset of Peak Duration of
Action (h) Action (h)
Human insulin
Regular 0.5–1 h 2–4 6–8
NPH 2–4 h 4–10 12–20
Lente 2–4 h 4–10 12–20
Ultralente 4–6 h Unpredictable 18–20
Analogue
Lispro 5–15 min 1–2 4–5
Aspart 5–15 min 1–2 4–5
Glulisinea 5–15 min 1–2 4–5
Glargine 2–4 h Flat ~24
Detemira 2–3 h 6–10 16–22
The time course of action of any insulin may vary between individuals, or at
different times in the same individual. Consequently, the data presented
should be considered only as a general guideline.
a In development.Friday, July 19, 13

Human Classic vs Analog Insulin
%20ch09%20pg145-168.pdf>
Classic Analog
Cheaper better HbA1C control
Readily Available Lesser hypoglycemic risk
Regular
Aspart
Regular GlulisineRegular
Lispro
NPH
Glargine
NPH
Detemir
Friday, July 19, 13

Regular vs Rapid Acting Intermediate vs Long Acting
Human Classic vs Analog Insulin
Friday, July 19, 13

Insulin Pharmacodynamics
Tanyolac S.“Insulin - Pharmacology, Types of Regimens, and Adjustments”
Endotext. 30 June 2013. <http://www.endotext.org/diabetes/diabetes14/
diabetesframe14.html>
Insulin Onset Peak Duration Appearance
Regular 0.5 - 1 hr 2 - 4 hrs 5 - 8 hrs Clear
Lispro 0.25 hr 0.5 - 1.5 hrs 3 - 5 hrs Clear
Aspart 0.25 hr 1 - 3 hrs 3 - 5 hrs Clear
Glulisine 0.25 - 0.5 hrs 0.5 - 1 hr 4 hrs Clear
Friday, July 19, 13

Regular vs Rapid Acting Insulin
• Regular Acting Insulin
• appears 30 after injection, regular schedule
• used when the insulin requirement is changing rapidly
• action prolonged with larger doses
• immediate effect if given IV
• Rapid Acting Insulin
• duration of action remains at 4 hrs irrespective of dosage
• quickly dissociate into monomers & absorbed rapidly
• superior control over post-prandial hyperglycemia
Friday, July 19, 13

7:00am 7:00pmnoon midnight 7:00am
Breakfast Lunch Supper
Physiologic insulin secretion
Classic Insulin
Friday, July 19, 13

Analog Insulin / Rapid Acting
Classic Insulin
Friday, July 19, 13

Analog Insulin / Rapid Acting
Friday, July 19, 13

NPH 1 - 2 hr 4 - 10 hrs 14 hrs Cloudy
Detemir 3 - 4 hrs 6 - 8 hrs 20 - 24 hrs Clear
Glargine 1.5 hrs ﬂat 24 hrs Clear
Friday, July 19, 13

Intermediate vs Long Acting Insulin
• Intermediate Acting Insulin
• delayed onset of action, requires 2 injections daily
• Long Acting Insulin
• no pronounced peak, less nocturnal hypoglycemia
• given once or twice a day
• glargine (acidic) cannot be mixed with other insulins
• detemir lower within-subject pharmacodynamic
variability compared to NPH insulin and insulin glargine
Friday, July 19, 13

Classic Insulin (NPH)
Friday, July 19, 13

Analog Insulin (Detemir, Glargine)
Classic Insulin (NPH)
Friday, July 19, 13

Analog Insulin (Detemir, Glargine)
Friday, July 19, 13

Split Mixed vs Premixed
• Split Mixed Insulin
• Given before breakfast and dinner
• Intermediate + regular/rapid
• Can adjust each component (Flexible)
• Premixed Insulin
• Given before breakfast and dinner
• Intermediate + regular/rapid
• Fixed dose, cannot adjust components
Friday, July 19, 13

Classic 70/30 0.5 - 1 hr 3 - 6 hrs 14 hrs Cloudy
Aspart Mix
(70/30)
0.1 - 0.2 hr 1 - 4 hrs 18 - 24 hrs Cloudy
Lispro Mix
(75/25)
0.25 - 0.5 hr 0.5 - 2.5 hrs 14 - 24 hrs Cloudy
Lispro Mix
(50/50)
0.25 - 0.5 hr 0.5 - 3 hrs 14 - 24 hrs Cloudy
Friday, July 19, 13

Analog Insulin
Classic Insulin
Friday, July 19, 13

Analog Insulin
Friday, July 19, 13

Basal - Bolus Insulin Strategy
Prandial Insulin
Basal Insulin
Friday, July 19, 13

Insulin Regimens for Diabetes Mellitus Type 2
McGill JB.“Diabetes Mellitus Type 2”.
Endocrinology Subspecialty Consult 2nd ed. 2009.
Regimen
Oral
Agents
Insulin
Type
Starting
Dose
Basal + Oral
(starting regimens)
continue all oral agents,
TZD submaximal
Intermediate /
Long acting
0.1 - 0.2 U/kg at
bedtime till FBS at
target
Premixed (Patients
with regular meal schedule)
continue insulin
sensitizers
70/30 NPH/regular;
Humalog mix 75/25;
Novomix 70/30
0.1 U/kg am & pm,
increase until glucose
nears target
Multiple Daily
(Irregular meal schedule/
needs tighter control)
continue insulin
sensitizers, discontinue
secretagogues
Basal: glargine or detemir/
NPH OD or BID
Premeal: rapid or regular
0.5 - 2 U/kg/day, 50%
basal, 50% divided
pre-meals
Continuous
Infusion
sensitizers may still be
useful
Lispro,Aspart, Glulisine 0.5 - 2 U/kg/day
Friday, July 19, 13

Basal - Oral Strategy
Basal Insulin
Friday, July 19, 13

Goals of Insulin Therapy
ADA Standards of Care 2013
Blood Glucose Level
Preprandial Plasma Glucose 70 - 130 mg/dl
Postprandial Plasma Glucose < 180 mg/dl
HbA1c < 7 %
Friday, July 19, 13

Factors Affecting Insulin Absorption
• Exercise of injected area
• Local massage
•Temperature
• Site of injection
• Lipohypertrophy
• Jet injectors
• Insulin mixtures
• Insulin dose
• Physical status
(soluble vs. suspension)
* The abdomen is the preferred site of injection because it
is the least susceptible to factors affecting insulin absorption.
Variability is correlated to blood ﬂow at the injection sites.
Friday, July 19, 13

Insulin Administration
• Syringes
•Available in 1-mL, 0.5-mL, and 0.3-mL sizes
• 30- to 31-gauge needles reduced the pain
• Needle length short (8 mm) and long (12.7 mm)
• Long needles for obese reduce absorption variability
• Insulin Pens
• Eliminate the need to carry vials and syringes
• Cartridges are available for reusable pens
• 31 gauge needles (4, 5, 8 and 12 mm long) painless
• angle of entry (subcutaneous)
Friday, July 19, 13

Insulin Storage
• All insulins have an expiration date which is labeled on
directly on the product applies when they are unopened and
refrigerated.
• Insulin should not be frozen or stored in a temp > 30°C.
• Insulin vial in use may be kept at room temperature, below
30°C for a month.
• Insulin cartridges, disposable pens & other delivery devices
can have different storage recommendations for room
temperature. Once opened, insulin cartridges and pens should
not be refrigerated.
Friday, July 19, 13

Adverse Effects
• Most signiﬁcant adverse effect of insulin is hypoglycemia
• Patients should be aware of hypoglycemia & its treatment
•Weight gain is another signiﬁcant side effect of insulin therapy.
• Less weight gain is encountered with long-acting insulin
•True allergic reactions and cutaneous reactions are rare.
•Avoid lipohypertrophy by rotating injection sights
Friday, July 19, 13

Case 2:
§Age: 40 years
§Duration of type 2 diabetes: 3 years
§FPG of 230 mg/dL over the past mo.
§Weight: 200 lbs (92 kg)
§BMI: 30 kg/m2
§Blood pressure: 140/80 mmHg
§Current treatment:
Intermediate insulin N BID
15 units sc before BF
5 units sc before dinner
Friday, July 19, 13

Lab Results:
§FPG: 162 mg/dl
§AST: 90 IU/L
§ALT: 50 IU/L
§HbA1c: >12 %
Friday, July 19, 13

1.) What would be your next step in managing this
patient?
A. Continue meds & monitor HbA1c again in 3 months
B. Add an additional oral agent (ex: TZD, DPP-4 inhib)
C. Add a basal insulin at bedtime
D. Begin a premixed insulin analogue therapy
E. Start basal/bolus insulin therapy
Friday, July 19, 13

Case 2:
§Patient was started on Basal-Bolus regimen
§Glargine 20 units sc before breakfast
§Glulisine 4 units before meals (skip am if no BF)
§Started on metformin 500 TID PC & Fenofibrate 160 mg
§He was asked to control his diet and refrain from drinking
softdrinks
§He borrowed his neighbors glucometer to monitor his
sugar at pre breakfast and 2 hours after lunch every
other day
§Patient came back for follow-up after 2 weeks
Succeeding ff -up showed improvement of
blood sugars as insulin dose was adjusted
Friday, July 19, 13

FF-up Lab Results after 3 months:
§FPG: 101 mg/dl
§AST: 15 IU/L
§ALT: 18 IU/L
§HbA1c: 6.2 %
Initial Lab Results:
§FPG: 162 mg/dl
§AST: 90 IU/L
§ALT: 50 IU/L
§HbA1c: >12 %
Friday, July 19, 13

2013 AACE Guidelines for Diabetes Management
Friday, July 19, 13

Sumary
• Good glycemic control decreases risk of microvascular disease
• Oral agents less effective as beta cell function further decline,
consider insulin therapy in patients with uncontrolled
hyperglycemia especially with mutilple oral medications
• Choosing the appropriate insulin regimen for your patient
• Less aggressive control for older patients
• Monitor the blood sugar closely & follow up patients regularly
Friday, July 19, 13

Magandang umaga po sa
inyong lahat . . .
Huwag po tayo matakot
sa insulin.
Friday, July 19, 13

2013 6-19 DM, Pre-DM & MetS PSEM Weekend course bulacan insulin 101

Recommended

Recommended

More Related Content

Viewers also liked

Viewers also liked (12)

More from Jeremy F. Robles MD, FPCP, FPSEM

More from Jeremy F. Robles MD, FPCP, FPSEM (10)

Recently uploaded

Recently uploaded (20)

2013 6-19 DM, Pre-DM & MetS PSEM Weekend course bulacan insulin 101