Diabetes Care, Vol 21, Issue 11 1960-1966, Copyright © 1998 by American Diabetes Association

ARTICLES

Effects of autonomic neuropathy on counterregulation and awareness of hypoglycemia in type 1 diabetic patients

C Meyer, R Grossmann, A Mitrakou, R Mahler, T Veneman, J Gerich and RG Bretzel
Third Medical Department, Justus-Liebig-Universitat, Giessen, Germany.

OBJECTIVE: The recent EURODIAB Study has identified autonomic neuropathy as an independent risk factor for severe hypoglycemia in patients with type 1 diabetes. We tested the hypothesis that counterregulatory catecholamine responses and awareness of hypoglycemia are impaired to a greater extent in type 1 diabetic patients with autonomic neuropathy (AN+) than in those without autonomic neuropathy (AN-). RESEARCH DESIGN AND METHODS: We studied 22 type 1 diabetic patients (8 AN+, 14 AN-) matched for age, duration of diabetes, glycemic control, and history of hypoglycemic episodes. We also studied 33 nondiabetic control subjects using the stepped hypoglycemic clamp technique and determined glycemic thresholds and magnitudes of counterregulatory hormone responses and of hypoglycemia symptoms. RESULTS: Both groups of diabetic patients had reduced awareness of hypoglycemia as evidenced by an elevated glycemic threshold for autonomic symptoms > or =2 SD above normal but neither the magnitude nor thresholds for symptoms differed in AN+ patients and AN-patients. Both groups also had impaired glucagon, epinephrine, norepinephrine, growth hormone and cortisol responses to hypoglycemia. However, in AN+ patients compared with AN-patients, magnitudes of epinephrine and norepinephrine responses (194+/-49 vs. 784+/-206 pmol/l, P < 0.007, and 316+/-56 vs. 610+/-87 pmol/l, P < 0.02, respectively) and epinephrine and norepinephrine glycemic thresholds (2.33+/- 0.10 vs. 2.82+/-0.10 mmol/l, P < 0.009 and 2.34+/-0.06 vs. 2.79+/-0.10 mmol/l, P < 0.008, respectively) were impaired to a greater extent. This was associated with a 50% greater requirement of exogenous glucose to prevent more severe hypoglycemia during the 2.3 mmol/l glycemic plateau (P < 0.002). No differences were observed between other counterregulatory hormone responses in AN+ and AN- patients. CONCLUSIONS: We conclude that in patients with type 1 diabetes, autonomic neuropathy further reduces counterregulatory catecholamine responses. Since this should increase the risk for severe hypoglycemia, one might consider safer therapeutic goals in these patients.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. R. Rickels, M. H. Schutta, R. Mueller, S. Kapoor, J. F. Markmann, A. Naji, and K. L. Teff Glycemic Thresholds for Activation of Counterregulatory Hormone and Symptom Responses in Islet Transplant Recipients J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 873 - 879. [Abstract] [Full Text] [PDF]

				C. Meyer, P. Saar, N. Soydan, M. Eckhard, R. G. Bretzel, J. Gerich, and T. Linn A Potential Important Role of Skeletal Muscle in Human Counterregulation of Hypoglycemia J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6244 - 6250. [Abstract] [Full Text] [PDF]

				P. E. Cryer Diverse Causes of Hypoglycemia-Associated Autonomic Failure in Diabetes N. Engl. J. Med., May 27, 2004; 350(22): 2272 - 2279. [Full Text] [PDF]

				P. E. Cryer, S. N. Davis, and H. Shamoon Hypoglycemia in Diabetes Diabetes Care, June 1, 2003; 26(6): 1902 - 1912. [Abstract] [Full Text] [PDF]

				A. I. Vinik, R. E. Maser, B. D. Mitchell, and R. Freeman Diabetic Autonomic Neuropathy Diabetes Care, May 1, 2003; 26(5): 1553 - 1579. [Abstract] [Full Text] [PDF]

				B. W. Paty, E. A. Ryan, A.M. J. Shapiro, J. R.T. Lakey, and R. P. Robertson Intrahepatic Islet Transplantation in Type 1 Diabetic Patients Does Not Restore Hypoglycemic Hormonal Counterregulation or Symptom Recognition After Insulin Independence Diabetes, December 1, 2002; 51(12): 3428 - 3434. [Abstract] [Full Text] [PDF]

				B. Fruehwald-Schultes, W. Kern, K. M. Oltmanns, S. Sopke, B. Toschek, J. Born, H. L. Fehm, and A. Peters Metformin Does Not Adversely Affect Hormonal and Symptomatic Responses to Recurrent Hypoglycemia J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4187 - 4192. [Abstract] [Full Text] [PDF]