Treatment of Patients with Severe Insulin

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• Treatment of Patients with Severe Insulin
• Deficiency What We Have Learned Over the Past 2
  Years
• Am J Med. 2004116(3A)17S22S.
• Timely Initiation of Basal Insulin
• Am J Med 2004116(3A)3S9S.

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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 ?

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Glucose infusion rate is an index of glucose
metabolism
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Basal 6
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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

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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

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Basal 1
10
Basal 2
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Basal 3
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Basal 4
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Role of rapid-acting insulin analogues

• Lispro and Aspart v.s RI
• superior prandial insulin replacement
• Less hypoglycemia
• Combine with conventional insulin not sufficient
  to meticulous glycemic control

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Aspart v.s RI bedtime NPH

• Randomized, 90 type?DM, 4 weeks then crossed to
  the other 4 weeks (1998) Diabetes
  Care.19982119041909.
• Aspart
• Superior 24hr glycemic control
• 22 fewer glucose excurtion
• Superior daytime glycemic control
• Inferior nighttime control

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fig2
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RossettiDiabetes Care. 20032614901496.

• 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

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Zinman Insulin pump Diabetes. 199746440443.

• Insulin pump in type?DM using the pump
• 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) p0.004
• Rapid RI analogue have become standard insulin
  for use with pump

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Fig 3
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Mealtime NPH

• Italy, type?DM Diabetes Care. 199922468477.
• 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 lt 0.002
• Lispro 1/3 fewer episodes of hypoglycemia

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Glargine

• Action are highly reproducible from day to day
• NPH and Ultralente have prominent peaks of action
• Glargines effect is much better suited to basal
  insulin supplementation.

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Basal 6
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Glargine

• Day-to day consistency, lack of peak, long
  duration ?hypoglycemia ----major barrier to
  initiation insulin treatment

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Glargine

• Oral diabetic agent NPH vs Glargine 426 pts
• HbA1c 8.2 vs 8.3
• Symptomatic hypoglycemia 33 vs 43 plt0.04
• At night 10 vs 24 plt0.001
• Late afternoon glycemia was better controlled by
  Glargine plt0.035
• Better basal insulin supplement

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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

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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

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Starting insulin therapy

• Begin with a simple regimen, even in HbA1c gt 10
  ( who need basal and prandial insulin)
• Twice-daily premixed NPH RI may be acceptable.
• Shift to bedtime Glargine rapid-acting insulin

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Thank you by
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