Different effects of acarbose and glibenclamide on proinsulin and insulin profiles in people with Type 2 diabetes.
OBJECTIVE
In a double-blind, placebo-controlled study, we compared the effect of acarbose (A) and glibenclamide (G) on post-prandial (pp) and 24-h profiles of proinsulin and insulin.


METHODS
Twenty-seven patients with Type 2 diabetes mellitus insufficiently controlled with diet alone were randomised to receive acarbose, 100 mg thrice daily, glibenclamide, 1 mg thrice daily, or placebo. Before and after 16 weeks of treatment, 24-h profiles of proinsulin, insulin and glucose (fasting, 1 h after breakfast and every 3-h for a 24-h period) were measured under metabolic ward conditions with standardised meals.


RESULTS
With acarbose, a reduced 24-h level of proinsulin was observed compared with glibenclamide (AUC 1096 +/- 118 vs. 1604 +/- 174 pmol/l per h, P<0.05) at 16 weeks. The breakfast increment of proinsulin was lower with acarbose than glibenclamide (6.8 vs. 19.3 pmol/l, P<0.05) as was the level at that time (37.3 +/- 5.3 vs. 56.4 +/- 7.5 pmol/l, P<0.05). A lower AUC of insulin after treatment was also observed with acarbose than glibenclamide (7.9 +/- 0.9 vs. 14.8 +/- 4.5 nmol/l per h, P<0.05), as also for 1-h increment (81 +/- 26, vs. 380 +/- 120 pmol/l, P<0.01) and 1-h level (325 +/- 30 vs. 621 +/- 132 pmol/l, P<0.01). Acarbose reduced 1-h breakfast glucose increment (baseline 6.3 +/- 0.6, 16-week 3.5 +/- 0.6 mmol/l, P<0.01) and 1-h glucose level (18.1 +/- 1.1 and 14.5 +/- 1.3 mmol/l, P<0.01), whereas glibenclamide did not (6.6 +/- 0.7 vs. 5.4 +/- 0.6 mmol/l and 18.9 +/- 1.5 vs. 15.3 +/- 1.3 mmol/l).


CONCLUSIONS
Measurement of circadian excursions of proinsulin and insulin reveals distinct differences in meal-time proinsulin and insulin increment and level between acarbose and glibenclamide whereas fasting levels of these insulin fractions remained unaffected.
Hanefeld
M
M
Centre for Clinical Studies GWT TU Dresden, Technical University, Dresden, Germany. hanefeld@gwt-tud.de
Haffner
S M
SM
Menschikowski
M
M
Koehler
C
C
Temelkova-Kurktschiev
T
T
Wildbrett
J
J
Fischer
S
S
D020909:Acarbose / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D019518:Postprandial Period; D011384:Proinsulin / Q000097:blood*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D011384:Proinsulin; D005905:Glyburide; D020909:Acarbose