Abstract
Purpose
We assessed the impact of an acute bout of hyperglycaemia on nitric oxide (NO)-mediated microvascular function in the skin of adolescents with type 1 diabetes (T1DM).
Methods
Twelve subjects (12–18 years) with T1DM were randomised into a control (n = 6) or hyperglycaemia (n = 6) group. Hyperinsulinaemic clamps were used to manipulate blood glucose level (BGL). Following a baseline period, where all subjects were euglycaemic (20 min), the experimental phase began. During the experimental phase, BGL was elevated to 16.7 ± 0.9 mmol L−1 in the hyperglyceamic group, while it was maintained at euglycaemia (5.5 ± 0.1 mmol L−1) in the control group. Simultaneously, cutaneous microvascular function (% max cutaneous vascular conductance, CVC%) was assessed using laser Doppler fluxometry following stimulation of skin blood flow using localised heating (42 °C). To determine the NO contribution to skin blood flow, two microdialysis sites were assessed, one perfused with Ringers and the other with the NO blocker, NG-monomethyl-l-arginine (l-NMMA).
Results
In the hyperglycaemic group, acute increase in BGL was not associated with changes in skin blood flow (CVC% 82.4 ± 8.7 % at 5.5 ± 0.1 mmol L−1 vs 79.5 ± 9.1 % at 16.7 ± 0.9 mmol L−1, unpaired t tests, P = 0.588) or the contribution of NO to vasodilation.
Conclusions
These results suggest that, in our group of adolescents with type 1 diabetes, acute hyperglycaemia did not affect skin microvascular NO-mediated function.
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Abbreviations
- BGL:
-
Blood glucose level
- CVC:
-
Cutaneous vascular conductance
- CVC%:
-
Percentage of max cutaneous vascular conductance
- LDF:
-
Laser Doppler flux
- l-NMMA:
-
NG-monomethyl-l-arginine
- MAP:
-
Mean arterial pressure
- NO:
-
Nitric oxide
- PU:
-
Perfusion units
- SNP:
-
Sodium nitroprusside
- T1DM:
-
Type 1 diabetes (T1DM)
References
Akbari C, Saouaf R, Barnhill D, Newman P, LoGerfo F, Veves A (1998) Endothelium-dependent vasodilatation is impaired in both microcirculation and macrocirculation during acute hyperglycemia. J Vasc Surg 28:687–694
Black M, Green D, Cable N (2008) Exercise prevents age-related decline in nitric-oxide-mediated vasodilator function in cutaneous microvessels. J Physiol 586(14):3511–3524. doi:10.1113/jphysiol.2008.153742
Boric M, Figueroa X, Donoso M, Paredes A, Poblete I, Huidobro-Toro J (1999) Rise in endothelium-derived NO after stimulation of rat perivascular sympathetic mesenteric nerves. Am J Physiol Heart Circ Physiol 277:H1027–H1035
Bruck H, Gössl M, Spitthöver R, Schäfers R, Kohnle M, Philipp T, Wenzel R (2001) The nitric oxide synthase inhibitor l-NMMA potentiates noradrenaline-induced vasoconstriction: effects of the alpha2-receptor antagonist yohimbine. J Hypertens 19(5):907–911
Celermajer D, Sorensen K, Gooch V, Spiegelhalter D, Miller O, Sullivan I, Lloyd J, Deanfield J (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115
Charkoudian N, Vella A, Reed A, Minson C, Shah P, Rizza R, Joyner M (2002) Cutaneous vascular function during acute hyperglycemia in healthy young adults. J Appl Physiol 93(4):1243–1250. doi:10.1152/japplphysiol.0.0345.2002
Cracowski JL, Minson CT, Salvat-Melis M, Halliwill JR (2006) Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci 27:503–508
De Fronzo R, Tobin J, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223
Elliott T, Cockcroft J, Groop P, Viberti G, Ritter J (1993) Inhibition of nitric oxide synthesis in forearm vasculature of insulin-dependent diabetic patients: blunted vasoconstriction in patients with microalbuminuria. Clin Sci 85(6):687–693
Forst T, Kunt T, Pohlmann T, Goitom K, Lobig M, Engelbach M, Beyer J, Pfutzer A (1998) Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals. Exp Clin Endocrinol Diabetes 106:454–459
Halkin A, Benjamin N, Doktor H, Todd S, Viberti G, Ritter J (1991) Vascular responsiveness and cation exchange in insulin-dependent diabetes. Clin Sci 81(2):223–232
Johnstone M, Creager S, Scales K, Cusco J, Lee B, Creager M (1993) Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 88:2510–2516
Katz A, Ekberg K, Johansson B, Wahren J (2001) Diminished skin blood flow in Type I diabetes: evidence for non-endothelium-dependent dysfunction. Clin Sci 101:59–64
Khan F, Greene S, Elhadd T, Belch J (2000) Impaired skin microvascular function in children, adolescents, and young adults with type 1 diabetes. Diabetes Care 23(2):215–220
Lestradet H, Papoz L, Hellouin de Menibus C, Levavasseur F, Besse J, Billaud L, Battistelli F, Tric P, Lestradet F (1981) Long-term study of mortality and vascular complications in juvenile-onset (type 1) diabetes. Diabetes 30:175–179
McNally P, Watt P, Rimmer T, Burden A, Hearnshaw J, Thurston H (1994) Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus. Clin Sci 87(1):31–36
Oomen P, Kant G, Dullaart R, Reitsma W, Smit A (2002) Acute hyperglycemia and hyperinsulinemia enhance vasodilatation in type 1 diabetes mellitus without increasing capillary permeability and inducing endothelial dysfunction. Microvasc Res 63(1):1–9. doi:10.1006/mvre.2001.2347
Smits P, Kapma J, Jacobs M, Lutterman J, Thien T (1993) Endothelium-dependent vascular relaxation in patients with type I diabetes. Diabetes 42(1):148–153
Steinberg H, Brechtel G, Johnson A, Fineberg N, Baron A (1994) Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 94:1172–1179
Tooke J (1995) Microvascular function in human diabetes. A physiological perspective. Diabetes 44:721–726
Veves A, Saoaf R, Donaghue V, Mullooly C, Kistler J, Giurini J, Horton E, Fielding R (1997) Aerobic exercise capacity remains normal despite impaired endothelial function in the micro- and macrocirculation of physically active IDDM patients. Diabetes 46(11):1846–1852
Acknowledgments
We would like to thank all the subjects and their families for their participation in this study. This study was supported by the National Heart Foundation of Australia (Grant Number G08P3666), and the Australian Paediatric Endocrinology Group Research Grant. LHN is supported by the BrightSpark Foundation. DJG is supported by funding from the Australian Research Council, National Hearth and the Medical Research Council and National Heart Foundation of Australia.
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The authors declare that they have no conflict of interest.
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Communicated by David C. Poole.
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Naylor, L.H., Yusof, N.M., Paramalingam, N. et al. Acute hyperglycaemia does not alter nitric oxide-mediated microvascular function in the skin of adolescents with type 1 diabetes. Eur J Appl Physiol 114, 435–441 (2014). https://doi.org/10.1007/s00421-013-2785-6
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DOI: https://doi.org/10.1007/s00421-013-2785-6