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Abnormal glucose handling by the kidney in response to hypoglycemia in type 1 diabetes
E Cersosimo1, P Garlick, J Ferretti
1Department of Medicine, State University of New York-Stony Brook, Stony Brook, New York, USA.
Abstract:
The frequent occurrence of hypoglycemia in people with type 1 diabetes is attributed to abnormalities in the blood glucose counterregulatory response. In view of recent findings indicating that the kidney contributes to prevent and correct hypoglycemia in healthy subjects, we decided to investigate the role of renal glucose handling in hypoglycemia in type 1 diabetes. Twelve type 1 diabetic patients and 14 age-matched normal individuals were randomized to hyperinsulinemic-euglycemic (n = 6 diabetic subjects and n = 8 control subjects) or hypoglycemic (n = 6 each) clamps with blood glucose maintained 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 fluoroscopy, and net renal glucose balance and renal glucose production and utilization rates were measured using a combination of arteriovenous concentration difference with stable isotope dilution technique. Blood glucose and insulin were comparable in both groups in all studies. In patients with diabetes, elevations in plasma glucagon, epinephrine, and norepinephrine were blunted, and both the compensatory rise in endogenous glucose production and in the net glucose output by the kidney seen in normal subjects with equivalent 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 micromol x kg(-1) x min(-1) in normal subjects, but in patients with diabetes there was no net renal contribution to blood glucose during similar hypoglycemia (mean +/- SE net glucose uptake [baseline 0.7 +/- 0.4] remained at 0.4 +/- 0.3 micromol x kg(-1) x 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 hypoglycemia in normal subjects, is impaired in patients with type 1 diabetes and contributes to defective glucose counterregulation.
Insights
Hypoglycemia in type 1 diabetes is worsened by impaired kidney glucose production. The kidney normally helps correct low blood sugar, but this defense mechanism is defective in diabetic patients.
Area of Science:
- Endocrinology
- Nephrology
- Metabolic Diseases
Background:
- Hypoglycemia is a common complication in type 1 diabetes, often linked to impaired counterregulatory responses.
- Recent research suggests the kidney plays a role in preventing and correcting hypoglycemia in healthy individuals.
Purpose of the Study:
- To investigate the role of renal glucose handling in the context of hypoglycemia in patients with type 1 diabetes.
- To compare renal glucose production and utilization during hypoglycemia between type 1 diabetic patients and healthy individuals.
Main Methods:
- Employed hyperinsulinemic-euglycemic and hypoglycemic clamp techniques in 12 type 1 diabetic patients and 14 healthy controls.
- Utilized renal vein catheterization and stable isotope dilution techniques to measure net renal glucose balance, production, and utilization.
Main Results:
- In healthy subjects, hypoglycemia stimulated a significant net glucose output from the kidneys.
- Type 1 diabetic patients exhibited blunted counterregulatory hormone responses (glucagon, epinephrine, norepinephrine) during hypoglycemia.
- The kidney did not contribute to glucose production during hypoglycemia in type 1 diabetic patients, unlike in healthy controls (P < 0.01).
Conclusions:
- Adrenergic stimulation of renal glucose output is an important defense mechanism against hypoglycemia in normal subjects.
- This renal glucose counterregulatory mechanism is impaired in patients with type 1 diabetes, contributing to defective glucose control.