severe insulin deficiency
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Treatment of Patients with Severe Insulin
Deficiency: What We Have Learned Over
the Past 2 Years
Am J Med. 2004;116(3A):17S–22S.
Timely Initiation of Basal Insulin
Am J Med 2004;116(3A):3S–9S.
Present era of insulin therapy
1996 Lispro
2001 Aspart, Glargine
Early intervention was necessary
in severe insulin deficiency (UKPDS)
As treatment of DM CV
complications improved,
population with severe insulin
deficiency ↑
type Onset(hr
)
peak duration time
Rapid
Lispro 0.25-0.5 0.5-1.5 3-5 1996
Regular 0.5-1 2-4 6-8 1970s
Intermediate
NPH 1-2 6-12 18-24 1946
Lente 1-3 6-12 18-26 1950s
Long acting
Ultralente 4-6 10-16 24-48
PZI 3-8 14-24 24-40 1936
Glargine 4-6 6-24 >24 2001
Glucose infusion rate is an index of glucose metabolism
Basal 6
Physiology
Hepatic glucose production is the leading
determining FPG.
Sulfonaurea and Metformin providing
enough basal insulin effect in the liver
When oral therapy no use, begin with basal
insulin therapy
Basal insulin
Basal hyperglycemia contributes more to
total hyperglycemia than dose
postprandial hyperglycemia
When fasting plasma glucose (FPG) is
higher, the relative contribution from basal
hyperglycemia is greater
Basal 1
Basal 2
Basal 3
Basal 4
Role of rapid-acting insulin analogues
Lispro and Aspart v.s RI :
1. superior prandial insulin replacement
2. Less hypoglycemia
3. Combine with conventional insulin: not
sufficient to meticulous glycemic control
Aspart v.s RI + bedtime NPH
Randomized, 90 type DM, 4 weeks then Ⅰ
crossed to the other 4 weeks (1998) Diabetes
Care.1998;21:1904–1909.
Aspart
1. Superior 24hr glycemic control
2. 22% fewer glucose excurtion
3. Superior daytime glycemic control
4. Inferior nighttime control
fig2
Rossetti
Diabetes Care. 2003;26:1490–1496.
When basal insulin was better replaced in
a multiple daily injection regimen,
improvement of HbA1c was seen.
(1 Glargine v.s. 4 NPH )+ mealtime Lispro
once daily Glargine with both less
hypoglycemia and lower HbA1c
Zinman: Insulin pump
Diabetes. 1997;46:440–443.
Insulin pump: in type DM using the pumpⅠ
Mealtime insulin Lispro resulted in less blunting
of post-prandial glycemic peaks than RI
Crossover study after 3 months HbA1c
Lispro vs RI = ( 7.66% vs 8%) p=0.004
Rapid RI analogue have become standard insulin
for use with pump
Fig 3
Mealtime NPH
Italy, type DM Ⅰ Diabetes Care. 1999;22:468–477.
NPH to cover prandial requirement
A day 7 injection
Mealtime (Lispro + NPH) + bedtime NPH
1 year, excellent glycemic control
Lispro v.s RI: 6.34% v.s 6.71% p < 0.002
Lispro: 1/3 fewer episodes of hypoglycemia
Glargine
Action are highly reproducible from day to day
NPH and Ultralente have prominent peaks of
action
Glargine’s effect is much better
suited to basal insulin
supplementation.
Basal 6
Glargine
Day-to day consistency, lack of peak, long
duration: ↓hypoglycemia major barrier to
initiation insulin treatment
Glargine
Oral diabetic agent + NPH vs Glargine 426 pts
HbA1c 8.2% vs 8.3%
Symptomatic hypoglycemia 33% vs 43% p<0.04
At night 10% vs 24% p<0.001
Late afternoon glycemia was better controlled
by Glargine p<0.035
Better basal insulin supplement
Dose of insulin glargine
Dose glargine similar to dose with an insulin
pump
Total dose of insulin: 50% as basal insulin
Then subtract 20% from the basal insulin.
Result: Glargine dose 1/3 too high, 1/3
correctly, 1/3 too low
It is easier to add basal insulin than to teach Pts
to adjust prandial dose
Glargine
Eliminate to role of snack in managing blood
glucose
With older insulin, snacks was essential for
prevention of hypoglycemia, at least for those
with excellent glycemia control
Glargine + rapid-acting insulin: easier time to
lose weight, no longer have to snack to avoid
hypoglycemia.
Less exercise-induced hypoglycemia
24 hr glucose sensor: NPH causing more
nocturnal hypoglycemia than anticipated
