1. Insulins in Type 2 Diabetes
Mellitus
Dr. Sharat S. Kolke MD, DNB

2. When
Why
How?

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……

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®)

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?

18. Are Analogues better?

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

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.