Summary
In order to determine the possible influence of C-peptide on nerve function, 12 insulin-dependent diabetic (IDDM) patients with symptoms of diabetic polyneuropathy were studied twice under euglycaemic conditions. Tests of autonomic nerve function (respiratory heart rate variability, acceleration and brake index during tilting), quantitative sensory threshold determinations, nerve conduction studies and clinical neurological examination were carried out before and during a 3-h i. v. infusion of either C-peptide (6 pmol · kg−1 · min−1) or physiological saline solution in a double-blind study. Plasma C-peptide concentrations increased from 0.11±0.02 to 1.73±0.04 nmol/l during C-peptide infusion. Clinical neurological examination quantitative sensory threshold evaluations and nerve conduction measurements failed to detect significant changes between C-peptide and saline study periods. Respiratory heart rate variability increased significantly from 13±1 to 20±2% during C-peptide infusion (p<0.001), reaching normal values in five of the subjects; control studies with saline infusion did not alter the heart rate variability (basal, 14±2; saline, 15±2%). A reduced brake index value was found in seven patients and increased significantly during the C-peptide infusion period (4.6±1.0 to 10.3±2.2%, p<0.05) but not during saline infusion (5.9±2 to 4.1±1.1%, NS). It is concluded that short-term (3-h) infusion of C-peptide in physiological amounts may improve autonomic nerve function in patients with IDDM.
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Abbreviations
- IDDM:
-
Insulin-dependent diabetes mellitus
- VT:
-
vibration perception threshold
- CV:
-
conduction velocity
- DL:
-
distal latency
- CMAP:
-
compound action potential
- S:
-
sensory amplitude
- E/I ratio:
-
expiration/inspiration ratio
References
Melton LJ, Dyck PJ (1987) Epidemiology. In: Dyck PJ, Thomas PK, Asbury AK, Winegard AI, Porte Jr (eds) Diabetic neuropathy. W. B. Saunders, Philadelphia, pp 27–35
Ewing DJ, Clarke BF (1986) Diabetic autonomic neuropathy: present insights and future prospects. Diabetes Care 9: 648–665
Thomas PK (1991) Diabetic neuropathy: epidemiology and pathogenesis. In: Pickup JC, Williams G (eds) Textbook of diabetes, Vol 2. Blackwell Scientific Publications, Oxford, pp 613–622
Greene DA, Yagihashi S, Lattimer SA, Sima AAF (1984) Nerve Na+ K+ ATPase, conduction and myo-inositol in the insulin dependent BB rat. Am J Physiol 247: 534–539
Raccah D, Gallice P, Pouget J, Vague P (1992) Hypothesis: low Na/K-ATPase activity in the red cell membrane, a potential marker of the predisposition to diabetic neuropathy. Diabete Metab 18: 236–241
Steiner D (1978) On the role of the proinsulin C-peptide. Diabetes 27: [Suppl 1] 141–148
Johansson B-L, Sjöberg S, Wahren J (1992) The influence of C-peptide on renal function and glucose utilization in type 1 (insulin-dependent) diabetic patients. Diabetologia 35: 121–128
Johansson B-L, Kernell A, Sjöberg S, Wahren J (1993) Influence of combined C-peptide and insulin administration on renal function and metabolic control in diabetes type 1. J Clin Endocrinol Metab 77: 976–981
Johansson B-L, Linde B, Wahren J (1992) Effects of C-peptide on blood flow, capillary diffusion capacity and glucose utilization in the exercising forearm in type 1 (insulin-dependent) diabetic patients. Diabetologia 35: 1151–1158
Ohtomo Y, Aperia A, Sahlgren B, Johansson B-L, Wahren J (1996) C-peptide stimulates rat renal tubular Na+ K+-ATPase activity in synergism with neuropeptide. Diabetologia 39: 199–205
American Diabetes Association, American Academy of Neurology (1988) Consensus statement. Report and recommendations of the San Antonio conference on diabetic neuropathy. Diabetes Care 11: 592–597
Dyck PJ (1988) Detection, characterization and staging of polyneuropathy: assessed in diabetics. Muscle Nerve 11: 21–32
Sundkvist G, Almér L-O, Lilja B (1979) Respiratory influence on heart rate in diabetes mellitus. BMJ 1: 924–925
Sundkvist G, Almér L-O, Lilja B (1980) Abnormal diastolic blood pressure and heart rate reactions to tilting in diabetes mellitus. Diabetologia 19: 433–438
Bergström B, Lilja B, Rosberg K, Sundkvist G (1986) Autonomic nerve function tests. Reference values in healthy subjects. Clin Physiol 6: 523–528
Hansson P, Lindblom U, Lindström P (1991) Graded assessment and classification of impaired temperature sensibility in patients with diabetic polyneuropathy. J Neurol Neurosurg Psychiatr 54: 527–530
Frusthorfer H, Lindblom U, Schmidt WG (1976) Method for quantitative estimation of thermal threshold in patients. J Neurol Neurosurg Psychiatr 39: 1071–1075
Lindblom U (1981) Quantitative testing of sensibility including pain. In: Stålberg SE, Young RR (eds) Clinical neurophysiology, neurology 1. Butterworth, London, pp 168–190
Goldberg JM, Lindblom U (1979) Standardized method of determining vibratory perception thresholds for diagnosis and screening in neurological investigation. J Neurol Neurosurg Psychiatr 42: 793–803
Ziegler D, Mayer P, Gries FA (1988) Evaluation of thermal, pain and vibration sensation in newly diagnosed type 1 diabetic patients. J Neurol Neurosurg Psychiatr 51: 1420–1424
Arnqvist H, Olson PO, Von Schenk H (1987) Free and total insulin determined after precipitation with polyethylene glycol: analytic characteristics and effects of sample handling and storage. Clin Chem 33: 93–96
The Diabetic Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329: 977–986
Reichard P, Nilsson B-Y, Rosenqvist U (1993) The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 329: 304–309
Fedele D, Negrin P, Cardone C et al. (1984) Influence of continuous subcutaneous insulin infusion (CSII) treatment on diabetic somatic and autonomic neuropathy. J Endocrinol Invest 7(6): 623–628
Sundkvist G, Lilja B, Rosén I, Agardh C-D (1987) Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function. Acta Med Scand 221: 445–453
Jaspan JB, Herold K, Bartkus C (1985) Effects of sorbinil therapy in diabetic patients with painful peripheral neuropathy and autonomic neuropathy. Am J Med 79: [Suppl 5 A] 24–37
Kennedy WR, Navarro X, Goetz FC, Sutherland DER, Najarian JS (1990) Effects of pancreatic transplantation on diabetic neuropathy. New Engl J Med 322: 1031–1037
Solders G, Tyden G, Persson A, Groth C-G (1992) Improvement of nerve conduction in diabetic neuropathy — a follow-up study 4 yr after combined pancreatic and renal transplantation. Diabetes 41: 948–951
Nusser J, Scheuer R, Abendroth D, Illner W-D, Land W, Landgraf R (1991) Effect of pancreatic and/or renal transplantation on diabetic autonomic neuropathy. Diabetologia 34: [Suppl 1] 118–120
Guy RJC, Clark CA, Malcom PN, Watkins PI (1985) Evaluation of thermal and vibration sensation in diabetic neuropathy. Diabetologia 28: 131–137
Navarro X, Kennedy WR (1991) Evaluation of thermal and pain sensitivity in type 1 diabetic patients. J Neurol Neurosurg Psychiatr 54: 60–64
Fagius J, Wahren LK (1981) Variability of sensory threshold determination in clinical use. J Neurol Sci 51: 11–27
Watkins PJ (1992) Clinical observations and experiments in diabetic neuropathy. Diabetologia 35: 2–11
Williams E, Timperley WR, Ward JD, Duckworth T (1980) Electron microscopical studies of vessels in diabetic neuropthy. J Clin Pathol 33: 462–470
Dyck PJ, Lais A, Karnes JL, O'Brien P, Rizza R (1986) Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy. Ann Neurol 19: 425–439
Tesfaye S, Harris ND, Wilson RM, Ward JD (1992) Exercise-induced conduction velocity increment: a marker of impaired peripheral nerve blood flow in diabetic neuropathy. Diabetologia 35: 155–159
Young RJ, Macintyre CCA, Martyn CN et al. (1986) Progression of subclinical polyneuropathy in young patients with type 1 (insulin-dependent) diabetes: associations with glycemic control and microangiopathy (microvascular complications). Diabetologia 29: 156–161
Lindström K, Johansson C, Johansson E, Haraldsson B (1996) Acute effects of C-peptide on the microvasculature of isolated perfused skeletal muscles and kidneys in rat. Acta Physiol Scand 156: in press
Daube J, Service FJ, Dyck PJ (1980) Acute effects on nerve conduction of strict control of blood sugar with an artificial pancreas. Muscle Nerve 9: 347
The St. Thomas Diabetic Study Group (1986) Failure of improved glycaemic control to reverse diabetic autonomic neuropathy. Diabet Med 3: 330–334
Johansson B-L, Fernqvist-Forbes E, Wahren J (1995) Effects of C-peptide on nephropathy and neuropathy in IDDM patients — a clinical study. Diabetes 44: [Suppl 1] 33 A (Abstract)
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Johansson, B.L., Borg, K., Fernqvist-Forbes, E. et al. C-peptide improves autonomic nerve function in IDDM patients. Diabetologia 39, 687–695 (1996). https://doi.org/10.1007/BF00418540
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DOI: https://doi.org/10.1007/BF00418540