The frequent occurrence of hypoglycemia in people with type 1 diabetes is a
ttributed to abnormalities in the blood glucose counterregulatory response.
In view of recent findings indicating that the kidney contributes to preve
nt and correct hypoglycemia in healthy subjects, we decided to investigate
the role of renal glucose handling in hypoglycemia in type 1 diabetes. Twel
ve type 1 diabetic patients and 14 age-matched normal individuals were rand
omized to hyperinsulinemic-euglycemic (n = 6 diabetic subjects and n = 8 co
ntrol subjects) or hypoglycemic (n = 6 each) clamps wit blood glucose maint
ained either stable near 100 mg/dl (5.6 mmol/l) or reduced to 54 mg/dl (3.0
mmol/l). All study subjects had their renal vein catheterized under fluoro
scopy, and net renal glucose balance and renal glucose production and utili
zation rates were measured using a combination of arteriovenous concentrati
on difference with stable isotope dilution technique. Blood glucose and ins
ulin were comparable in both groups in all studies. In patients with diabet
es, elevations in plasma glucagon, epinephrine, and norepinephrine were blu
nted, and both the compensatory rise in endogenous glucose production and i
n the net glucose output by the kidney seen in normal subjects with equival
ent hypoglycemia were absent. Renal glucose balance switched from a mean +/
- SE baseline net uptake of 0.6 +/- 0.4 to a net output of 4.5 +/- 1.3 mu m
ol.kg(-1).min(-1) in normal subjects, but in patients with diabetes there w
as no net renal contribution to blood glucose during similar hypoglycemia (
mean +/- SE net glucose uptake [baseline 0.7 +/- 0.41 remained at 0.4 +/- 0
.3 mu mol(-1).kg(-1).min(-1) in the final 40 min of hypoglycemia; P < 0.01
between groups). We conclude that adrenergic stimulation of glucose output
by the kidney, which represents an additional defense mechanism against hyp
oglycemia in normal subjects, is impaired in patients with type 1 diabetes
and contributes to defective glucose counterregulation.