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Insulins in Type 2 Diabetes
          Mellitus

 Dr. Sharat S. Kolke MD, DNB
When
Why
How?
Serum Insulin level




                                      Endogenous insulin




                         Time (hrs)


Dynamic nature of normal endogenous insulin secretion.
Main components are basal insulin and postprandial
insulin.
β cell function at diagnosis and later……
Insulin over the ages….

1922 – Insulin discovered by Banting and Best
1923 – Insulin commercially available
1930s to 1940s – PZI, NPH and lente insulin
1960s to 1970s – Purified animal insulin
1980s – Human insulin by r DNA technology
2000 – Insulin analogues
Onset of        Peak (h)        Duration of
               Action (h)                      Action (h)


                    Human insulin
                   0.5-1             2-4           6-10
 Regular


 NPH               1-3               5-7          10-20

 Lente®            1-3               4-8          10-20

 Ultralente®       2-4         Unpredictable      16-20

                           Analogs
  Lispro       5 min-15 min           1            4-5
(Humalog®)
  Aspart       5 min-15 min           1            4-5
(Novolog®)
  Glargine         1-2               Flat          ~24
(Lantus®)
Serum Insulin level



                                       Endogenous insulin




                          Time (hrs)


Dynamic nature of normal endogenous insulin secretion.
Main components are basal insulin and postprandial
insulin.
Split self mixed


Insulin treatment Regimens   Split pre mixed


                              Basal bolus
Split self mixed


Effective for helping patients achieve glycemic control

Problems with mixing technique

Inaccurate dosing ratios

Reducing the effectiveness of the short-acting insulin.
Self pre-mixed


The benefits of premixed insulin formulations
(such as a human insulin 30/70 mixed suspension)

1.   reduced errors
2.   and improved dosing accuracy
3.   the convenience of using a single vial.
Applying the Basal/Bolus Insulin Concept
 Basal insulin
• Nearly constant day-long insulin level
• Suppress hepatic glucose production between meals
and overnight
• Cover 50% of daily needs


 Bolus insulin (mealtime)
• Immediate rise and sharp peak at 1 hour
• Limit postmeal hyperglycemia
• Cover 10% to 20% of total daily insulin requirement at each
  meal


Ideally, each component should come from a different insulin,
with a specific profile
Barriers             Reassurances with Insulin Therapy
Insulin resistance   Improves insulin sensitivity by reducing
                        glucotoxicity

Cardiovascular       No evidence of atherosclerotic effects
   (CV) risk

                     May reduce CV risk


Weight gain          Modest


Hypoglycemia         Rarely causes severe events
Practical guidelines – Combination regimens
Average patient
 Early combination of insulin secretagogue and insulin sensitizer
 Most simple and cost-effective
   –Start low-dose, once-daily sulfonylurea with increasing doses of
   Metformin
   –Full-dose sulfonylurea in combination with maximally tolerated
   Metformin



For marked insulin resistance
 Combination of Metformin + Glitazone


If target HbA1c <7% not achieved
 Try triple oral therapy
        or
 Add evening basal insulin while continuing oral therapy
Practical guidelines – Starting Basal Insulin …

Continue oral agent(s) at same dosage (eventually
  reduce)
Add single, evening insulin dose (around 10 units)
  Glargine (bedtime or anytime?)
  NPH (bedtime)


Adjust dose according to fasting blood glucose
  (FBG) monitoring
Increase insulin dose weekly as needed
  Increase by 2 units if FBG >120 mg/dL
  Increase by 4 units if FBG >140 mg/dL
  Increase by 6 units if FBG >180 mg/dL
Practical guidelines – Advancing to Basal Bolus insulin


  Indicated when FBG acceptable but
    HbA1c >7%
   and/or
    SBGM before dinner >160-180 mg/dL


  Insulin options
     To glargine, add mealtime lispro or aspart
     To bedtime NPH, add morning NPH and mealtime lispro or
    aspart


  Oral agent options
     Continue sulfonylurea for endogenous secretion?
     Continue metformin for weight control?
     Continue glitazone for glycemic stability?
Are Analogues better?
What are the different analogues
                  available?

             Insulin Lispro (Humalog)
           Insulin Aspart (Novorapid R)
             Insulin Glargine (Lantus)
             Insulin Detemir (Levemir)



    How do they differ from conventional
                 insulin?
  The main difference is usually in the ‘time
  action profile’. This means the new insulin
either works faster and for shorter periods or
 have a more prolonged course of action for
               twenty four hours.
What are the potential benefits? 
• Timing of injections – can be injected immediately
before meals

• Risk of hypoglycaemia may be less particularly
nocturnal hypoglycaemia

• Compliance may be improved with use of once daily
long acting analogues

• The need for snacks between meals may be reduced
with short acting analogues

• Some advantages in terms of weight gain
Are analogues more effective than
      conventional insulin?

      The advantage in terms of improved
      glycaemic control is not that great.
      It is possible to achieve equally good
      control using conventional insulin.




      Are they safe to use during Pregnancy?

These drugs have not as yet been licensed for use in pregnancy
In conclusion…..

 Strict glycemic control is the only to prevent
 chronic complications.
 Strict glycemic control without hypoglycemia.

 Insulin regimens that closely mimic physiologic insulin
 secretory patterns must be used.
 The older conventional insulin products do not have
 time-action profiles that closely mimic normal secretory
 patterns.
 Analogues offer the physician the ability
 to closely approximate endogenous insulin secretory
 patterns.

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Insulins in type 2 diabetes mellitus

  • 1. Insulins in Type 2 Diabetes Mellitus Dr. Sharat S. Kolke MD, DNB
  • 3. Serum Insulin level Endogenous insulin Time (hrs) Dynamic nature of normal endogenous insulin secretion. Main components are basal insulin and postprandial insulin.
  • 4. β cell function at diagnosis and later……
  • 5.
  • 6. Insulin over the ages…. 1922 – Insulin discovered by Banting and Best 1923 – Insulin commercially available 1930s to 1940s – PZI, NPH and lente insulin 1960s to 1970s – Purified animal insulin 1980s – Human insulin by r DNA technology 2000 – Insulin analogues
  • 7. Onset of Peak (h) Duration of Action (h) Action (h) Human insulin 0.5-1 2-4 6-10 Regular NPH 1-3 5-7 10-20 Lente® 1-3 4-8 10-20 Ultralente® 2-4 Unpredictable 16-20 Analogs Lispro 5 min-15 min 1 4-5 (Humalog®) Aspart 5 min-15 min 1 4-5 (Novolog®) Glargine 1-2 Flat ~24 (Lantus®)
  • 8.
  • 9. Serum Insulin level Endogenous insulin Time (hrs) Dynamic nature of normal endogenous insulin secretion. Main components are basal insulin and postprandial insulin.
  • 10. Split self mixed Insulin treatment Regimens Split pre mixed Basal bolus
  • 11. Split self mixed Effective for helping patients achieve glycemic control Problems with mixing technique Inaccurate dosing ratios Reducing the effectiveness of the short-acting insulin.
  • 12. Self pre-mixed The benefits of premixed insulin formulations (such as a human insulin 30/70 mixed suspension) 1. reduced errors 2. and improved dosing accuracy 3. the convenience of using a single vial.
  • 13. Applying the Basal/Bolus Insulin Concept Basal insulin • Nearly constant day-long insulin level • Suppress hepatic glucose production between meals and overnight • Cover 50% of daily needs Bolus insulin (mealtime) • Immediate rise and sharp peak at 1 hour • Limit postmeal hyperglycemia • Cover 10% to 20% of total daily insulin requirement at each meal Ideally, each component should come from a different insulin, with a specific profile
  • 14. Barriers Reassurances with Insulin Therapy Insulin resistance Improves insulin sensitivity by reducing glucotoxicity Cardiovascular No evidence of atherosclerotic effects (CV) risk May reduce CV risk Weight gain Modest Hypoglycemia Rarely causes severe events
  • 15. Practical guidelines – Combination regimens Average patient Early combination of insulin secretagogue and insulin sensitizer Most simple and cost-effective –Start low-dose, once-daily sulfonylurea with increasing doses of Metformin –Full-dose sulfonylurea in combination with maximally tolerated Metformin For marked insulin resistance Combination of Metformin + Glitazone If target HbA1c <7% not achieved Try triple oral therapy or Add evening basal insulin while continuing oral therapy
  • 16. Practical guidelines – Starting Basal Insulin … Continue oral agent(s) at same dosage (eventually reduce) Add single, evening insulin dose (around 10 units) Glargine (bedtime or anytime?) NPH (bedtime) Adjust dose according to fasting blood glucose (FBG) monitoring Increase insulin dose weekly as needed Increase by 2 units if FBG >120 mg/dL Increase by 4 units if FBG >140 mg/dL Increase by 6 units if FBG >180 mg/dL
  • 17. Practical guidelines – Advancing to Basal Bolus insulin Indicated when FBG acceptable but HbA1c >7% and/or SBGM before dinner >160-180 mg/dL Insulin options To glargine, add mealtime lispro or aspart To bedtime NPH, add morning NPH and mealtime lispro or aspart Oral agent options Continue sulfonylurea for endogenous secretion? Continue metformin for weight control? Continue glitazone for glycemic stability?
  • 19. What are the different analogues available? Insulin Lispro (Humalog) Insulin Aspart (Novorapid R) Insulin Glargine (Lantus) Insulin Detemir (Levemir) How do they differ from conventional insulin? The main difference is usually in the ‘time action profile’. This means the new insulin either works faster and for shorter periods or have a more prolonged course of action for twenty four hours.
  • 20. What are the potential benefits?  • Timing of injections – can be injected immediately before meals • Risk of hypoglycaemia may be less particularly nocturnal hypoglycaemia • Compliance may be improved with use of once daily long acting analogues • The need for snacks between meals may be reduced with short acting analogues • Some advantages in terms of weight gain
  • 21. Are analogues more effective than conventional insulin? The advantage in terms of improved glycaemic control is not that great. It is possible to achieve equally good control using conventional insulin. Are they safe to use during Pregnancy? These drugs have not as yet been licensed for use in pregnancy
  • 22.
  • 23.
  • 24.
  • 25.
  • 26.
  • 27.
  • 28. In conclusion…..  Strict glycemic control is the only to prevent chronic complications.  Strict glycemic control without hypoglycemia.  Insulin regimens that closely mimic physiologic insulin secretory patterns must be used.  The older conventional insulin products do not have time-action profiles that closely mimic normal secretory patterns.  Analogues offer the physician the ability to closely approximate endogenous insulin secretory patterns.