Abnormal glucose handling by the kidney in response to hypoglycemia in type 1 diabetes

Citation
E. Cersosimo et al., Abnormal glucose handling by the kidney in response to hypoglycemia in type 1 diabetes, DIABETES, 50(9), 2001, pp. 2087-2093
Citations number
35
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
DIABETES
ISSN journal
00121797 → ACNP
Volume
50
Issue
9
Year of publication
2001
Pages
2087 - 2093
Database
ISI
SICI code
0012-1797(200109)50:9<2087:AGHBTK>2.0.ZU;2-K
Abstract
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.