Improved postprandial metabolic control after subcutaneous injection of a short-acting insulin analog in IDDM of short duration with residual pancreatic beta-cell function.
OBJECTIVE
To compare postprandial metabolic control after subcutaneous injection of a short-acting insulin analog [Lys(B289),Pro(B29)] (Lispro) or human regular insulin (Humulin R U-100 [Hum-R]) in insulin-dependent diabetes mellitus (IDDM) of short duration with residual beta-cell function.


METHODS
Six IDDM patients (age 25 +/- 2 years, diabetes duration 14 +/- 2 months, HbA1c 6.4 +/- 0.5%) with residual pancreatic beta-cell function (fasting plasma C-peptide 0.19 +/- 0.02 nmol/l) were studied on three different occasions. Postbreakfast plasma glucose was maintained at approximately 7.1 mmol/l by means of intravenous insulin until either 1200 when 0.1 U/kg Hum-R was injected or until 1225 when 0.1 U/kg of either Hum-R or Lispro was injected subcutaneously. Lunch (mixed meal, 692 Kcal) was served at 1230 (0 min). Six nondiabetic control subjects were also studied.


RESULTS
After Lispro administration, the 120-min plasma glucose decreased more (6.1 +/- 0.3 mmol/l) than after injection of Hum-R at -30 min (7.7 +/- 0.3 mmol/l) or -5 min (9.9 +/- 0.2 mmol/l). By the end of the study, plasma glucose was still lower after Lispro was injected (6.7 +/- 0.3 mmol/l) than after Hum-R was injected at -30 min (7.6 +/- 0.3 mmol/l) or -5 min (7.3 +/- 0.2 mmol/l) (P < 0.05). Two IDDM patients required glucose to prevent hypoglycemia after being injected with Lispro, but four required glucose after being injected with Hum-R at -5 min (Lispro approximately 27 mmol glucose infused between 90 and 240 min; Hum-R approximately 80 mmol between 240 and 390 min). After Lispro, plasma insulin peaked earlier (at 30 min, 342 +/- 29 pmol/l) than after Hum-R injection at -30 min (at 90 min, 198 +/- 28 pmol/l) and was superimposable on that of nondiabetic subjects. In Hum-R injected at -5 min, plasma insulin peaked later (at 120 min) and subsequently remained greater than in the two other studies.


CONCLUSIONS
Despite the lack of a time interval between injection and meal, Lispro controls postprandial plasma glucose concentration better than Hum-R given 30 min before meals and, to an even greater extent, better than Hum-R given 5 min before meals. In addition, Lispro minimizes the risk of postprandial hypoglycemia, thus closely mimicking the postprandial glucose homeostasis of nondiabetic subjects. IDDM patients with residual pancreatic beta-cell function are the ideal candidates for prandial use of Lispro because they can maintain near-normoglycemia longer after subcutaneous analog injection because of residual endogenous insulin secretion.
Pampanelli
S
S
Dipartimento di Medicina Interna, Università di Perugia, Italy.
Torlone
E
E
Ialli
C
C
Del Sindaco
P
P
Ciofetta
M
M
Lepore
M
M
Bartocci
L
L
Brunetti
P
P
Bolli
G B
GB
D020155:3-Hydroxybutyric Acid; D000328:Adult; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004435:Eating; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D005990:Glycerol / Q000097:blood; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007003:Hypoglycemia / Q000139:chemically induced; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D061268:Insulin Lispro; D007515:Islets of Langerhans / Q000378:metabolism*; D007773:Lactates / Q000097:blood; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D012016:Reference Values; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D061268:Insulin Lispro; D007773:Lactates; D011994:Recombinant Proteins; D005934:Glucagon; D000409:Alanine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid