LETTER
Intensive Therapy Preserves Insulin Secretion
Zeno L. Charles-Marcel, MD
1 December 1998 | Volume 129 Issue 11 Part 1 | Page 914
TO THE EDITOR:
The most recent article by the DCCT Research Group [1] was intriguing and thought-provoking. I wish to hypothesize another potential benefit of sustaining islet-cell function apart from maintenance of C-peptide secretion. The hypothesis may also partially explain the better metabolic control and lower risk for hypoglycemia seen in the C-peptide responders.
Amylin (islet amyloid polypeptide) is normally co-secreted with insulin by pancreatic ß cells [2]. It is reasonable to assume that preservation of ß-cell function in patients with type 1 diabetes should not only permit a residual insulin (C-peptide) response but also maintain detectable plasma amylin levels, albeit low levels. Preserved amylin secretion would be expected to contribute to improved glycemic control by reducing postprandial hyperglycemic excursions through retarding gastric emptying and inhibiting amino acid-stimulated glucagon secretion [3].
Suppressed glucagon secretion may result in reduced postprandial hepatic glucose production but would not inhibit the counterregulatory glucagon response to hypoglycemia [4], thus reducing the risk for severe hypoglycemic events. The reduced incidence of hypoglycemia may also be due to residual amylin's effect of increasing plasma concentrations of growth hormone and cortisol and by the release of gluconeogenic substrates, such as lactate, from skeletal muscles [5]. In the fasting state, lactate may also help to replenish depleted glycogen stores.
I believe that these mechanisms warrant attention and would merit a reanalysis of any stored plasma samples from DCCT participants for the presence of physiologic levels of amylin.
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Author and Article Information
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Loma Linda University School of Medicine; Loma Linda, CA 92354
1. Effect of intensive therapy and residual ß-cell function in patients with type 1 diabetes in the Diabetes Control and Complications Trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann Intern Med. 1998; 128:517-23.
2. Hartter E, Svoboda T, Ludvik B, Schuller M, Lell B, Kuenberg E, et al. Basal and stimulated plasma levels of pancreatic amylin indicate its co-secretion with insulin in humans. Diabetologia. 1991; 34:52-4.
3. Young A. Role of amylin in nutrient update-animal studies. Diabet Med. 1997; 14(Suppl 2):S14.
4. Nyholm B, Moller N, Gravholt CH, Orskov L, Mengel A, Bryan G, et al. Acute effects of the human amylin analog AC137 on basal and insulin-stimulated euglycemic and hypoglycemic fuel metabolism in patients with insulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1996; 81:1083-9.
5. Schmitz O, Nyholm B, Orskov L, Gravholt C, Moller N. Effects of amylin agonist pramlintide on glucose metabolism. Diabet Med. 1997; 14(Suppl 2):S19-23.
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