Interaction of sulfonylureas and exercise on glucose homeostasis in type 2 diabetic patients.
OBJECTIVE
To determine whether the plasma glucose-lowering effects of sulfonylureas and acute submaximal exercise are additive and, accordingly, to determine whether they may increase the risk of hypoglycemia when combined in fasting patients.


METHODS
Eight postabsorptive type 2 diabetic patients were examined at three occasions: after oral sulfonylurea (7 mg glibenclamide), during 60 min of ergometer cycle exercise at 57 +/- 3% of VO2max, and during exercise after glibenclamide.


RESULTS
Heart rate, VO2, and lactate responses to exercise were comparable (P > 0.05) on days with and without glibenclamide. Plasma insulin concentrations were always increased by glibenclamide, and they were lowered identically by exercise with and without glibenclamide. However, throughout exercise, absolute concentrations of insulin were lower on days without glibenclamide compared with days with glibenclamide (34.5 +/- 4.7 vs. 47.4 +/- 5.5 pmol/l; P < 0.05). At the start of exercise, glucose concentrations were similar between experiments (P > 0.05). The rate of decrease in glucose during exercise was higher (P < 0.05) on days with both glibenclamide and exercise, compared with days with glibenclamide alone and days with exercise alone (-0.035 +/- 0.009 vs. -0.016 +/- 0.002 and -0.022 +/- 0.005 mmol.l-1.min-1, respectively). Consequently, the glucose nadir was lower on days with glibenclamide and exercise than on days with glibenclamide or exercise alone (6.7 +/- 1.1 vs. 8.1 +/- 0.9 and 7.6 +/- 1.0 mmol/l, respectively; P < 0.05). During exercise, the rate of appearance of plasma glucose determined by 3-[3H]glucose infusion was lower on days with glibenclamide than on days without glibenclamide (2.3 +/- 0.1 vs. 2.9 +/- 0.1 mg.min-1.kg-1; P < 0.05). In contrast, glucose clearance was identical (P > 0.05).


CONCLUSIONS
In postabsorptive type 2 diabetic patients, the hypoglycemic action of glibenclamide and exercise is enhanced when the treatments are combined. The interaction reflects an increased inhibition by glibenclamide-enhanced insulin levels of hepatic glucose production when hepatic glucose production is accelerated by exercise.
Larsen
J J
JJ
Department of Medical Physiology, Panum Institute, Copenhagen, Denmark. j.j.larsen@mfi.ku.dk
Dela
F
F
Madsbad
S
S
Vibe-Petersen
J
J
Galbo
H
H
D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000628:therapy*; D004837:Epinephrine / Q000097:blood; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005934:Glucagon / Q000097:blood; D005905:Glyburide / Q000627:therapeutic use; D006706:Homeostasis; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D005082:Physical Exertion / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D019382:Human Growth Hormone; D005934:Glucagon; D005905:Glyburide; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine