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
5th Diabetes, Prediabetes and Metabolic Syndrome Weekend Course (ENDOCRINE: ENhancing Diabetes Outpatient and CRitical INitiativEs July 19, 2013 Malolos, Bulacan
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Insul in 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
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
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
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
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
• 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>
• 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/>
• 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/>
• 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
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>
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>
Barrier Effect of Insulin Therapy
Insulin resistance Improves insulin sensitivity by reducing glucotoxicity
Cardiovascluar risk No evidence of atherosclerotic effectsReduced cardiovascular risk factors
Weight gain Modest & avoidable
Hypoglycemia Rarely causes severe events when used properly
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>
153Insulin Therapy in Type 2 Diabetes
Table Pharmacokinetics of Human Insulinand Analogues
9-3
Onset of Peak Duration of Action (h) Action (h)
Human insulinRegular 0.5–1 h 2–4 6–8NPH 2–4 h 4–10 12–20Lente 2–4 h 4–10 12–20Ultralente 4–6 h Unpredictable 18–20
AnalogueLispro 5–15 min 1–2 4–5Aspart 5–15 min 1–2 4–5Glulisinea 5–15 min 1–2 4–5Glargine 2–4 h Flat ~24Detemira 2–3 h 6–10 16–22
The time course of action of any insulin may vary between individuals, or atdifferent times in the same individual. Consequently, the data presentedshould be considered only as a general guideline.a In development.Source: Refs. 13, 23, 27, 32.
tributing to an increased risk of hypoglycemia, especially at night.Another lente formulation, ultralente, has a more gradual and latepeak with longer duration of action than NPH or lente, but itseffects are similarly erratic and unpredictable.
Long-acting insulin analogues: glargine and detemirInsulin glargine is the first insulin analogue with a prolongedduration of action (Table 9-3, Fig. 9-3, Fig. 9-4). Changes in theamino acid sequence of human insulin produce a shift in the iso-electric point, which results in a clear preparation that is solubleonly at acidic pH 4. In subcutaneous tissues, which have a neutralpH, the reduced solubility of glargine stabilizes the hexamericform of insulin and delays dissociation into dimers and monomersand subsequent absorption into the systemic circulation. Consis-
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>
Tanyolac S. “Insulin - Pharmacology, Types of Regimens, and Adjustments” Endotext. 30 June 2013. <http://www.endotext.org/diabetes/diabetes14/diabetesframe14.html>
• 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 hyperglycemiaGardner DG & Shoback D . “Pancreatic Hormones & Diabetes Mellitus” Greenspan’s Basic & Clinical Endocrinology 9th ed.. 2011.
Friday, July 19, 13
Insulin Pharmacodynamics
7:00am 7:00pmnoon midnight 7:00am
Breakfast Lunch Supper
Physiologic insulin secretion
Classic Insulin
Friday, July 19, 13
Insulin Pharmacodynamics
7:00am 7:00pmnoon midnight 7:00am
Breakfast Lunch Supper
Physiologic insulin secretion
Classic Insulin
Friday, July 19, 13
Insulin Pharmacodynamics
7:00am 7:00pmnoon midnight 7:00am
Breakfast Lunch Supper
Physiologic insulin secretion
Analog Insulin / Rapid Acting
Classic Insulin
Friday, July 19, 13
Insulin Pharmacodynamics
7:00am 7:00pmnoon midnight 7:00am
Breakfast Lunch Supper
Physiologic insulin secretion
Analog Insulin / Rapid Acting
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>
Tanyolac S. “Insulin - Pharmacology, Types of Regimens, and Adjustments” Endotext. 30 June 2013. <http://www.endotext.org/diabetes/diabetes14/diabetesframe14.html>
* 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.
Tanyolac S. “Insulin - Pharmacology, Types of Regimens, and Adjustments” Endotext. 30 June 2013. <http://www.endotext.org/diabetes/diabetes14/diabetesframe14.html>
• 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)
• 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.
Tanyolac S. “Insulin - Pharmacology, Types of Regimens, and Adjustments” Endotext. 30 June 2013. <http://www.endotext.org/diabetes/diabetes14/diabetesframe14.html>
• 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
Tanyolac S. “Insulin - Pharmacology, Types of Regimens, and Adjustments” Endotext. 30 June 2013. <http://www.endotext.org/diabetes/diabetes14/diabetesframe14.html>
• 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