Download PDF
Semin Vasc Med 2002; 2(1): 009-020
DOI: 10.1055/s-2002-23093
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

The Microvasculature in Type 1 Diabetes

Angela C. Shore
  • Peninsula Medical School, Exeter, England
Further Information

Publication History

Publication Date:
25 March 2002 (online)

    Permissions and Reprints

ABSTRACT

Alterations in the microvasculature seen early in type 1 diabetes appear to be related to glycemic control. The later abnormalities occur primarily in patients with incipient or overt nephropathy and are likely to represent a more generalized vascular dysfunction as indicated by the increased cardiovascular risk in these groups. The mechanisms involved may be related to genetic susceptibility in combination with impaired hemorheology, dyslipidemia, hypertension, or the toxic effects of hyperglycemia. Many of these effects may relate to a common final pathway such as activation of PKC or increased oxidative stress. Therapeutic interventions to inhibit either PKC effects or decrease oxidative stress have been effective in reducing microangiopathy in diabetic animals. Vitamin C or E supplementation may improve vascular function in type 1 diabetes. The results of ongoing trials of PKC inhibitors are awaited with interest. Whether such interventions will influence the course of microangiopathy remains to be determined.

KEYWORD

Microangiopathy - capillary pressure - endothelial function

REFERENCES

  • 1 Hester R L, Eraslan A, Saito Y. Differences in EDNO contribution to arteriolar diameters at rest and during functional dilation in striated muscle.  Am J Physiol . 1993;  265 H148-H151
    PubMedGoogle Scholar
  • 2 Garland C J, Plane F, Kemp B K, Cocks T M. Endothelium-dependent hyperpolarization: a role in the control of vascular tone.  Trends Pharmacol Sci . 1995;  16 23-30
    CrossrefPubMedGoogle Scholar
  • 3 Shimokawa H, Yasutake H, Fujii K. The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation.  J Cardiovasc Pharmacol . 1996;  28 703-711
    CrossrefPubMedGoogle Scholar
  • 4 Braverman I M. Ultrastructure and organization of the cutaneous microvasculature in normal and pathologic states.  J Invest Dermatol . 1989;  93 2S-9S
    CrossrefPubMedGoogle Scholar
  • 5 Aagenes O, Moe H. Light- and electron-microscopic study of skin capillaries of diabetics.  Diabetes . 1961;  10 253-259
    PubMedGoogle Scholar
  • 6 Williamson J R, Kilo C. Current status of capillary basement-membrane disease in diabetes mellitus.  Diabetes . 1977;  26 65-73
    PubMedGoogle Scholar
  • 7 Malik R A, Tesfaye S, Thompson S D. Endoneurial localisation of microvascular damage in human diabetic neuropathy.  Diabetologia . 1993;  36 454-459
    CrossrefPubMedGoogle Scholar
  • 8 Britland S T, Young R J, Sharma A K, Clarke B F. Relationship of endoneurial capillary abnormalities to type and severity of diabetic polyneuropathy.  Diabetes . 1990;  39 909-913
    PubMedGoogle Scholar
  • 9 Rogers D G, White N H, Santiago J V. Glycemic control and bone age are independently associated with muscle capillary basement membrane width in diabetic children after puberty.  Diabetes Care . 1986;  9 453-459
    PubMedGoogle Scholar
  • 10 Braverman I M, Sibley J, Keh A. Ultrastructural analysis of the endothelial-pericyte relationship in diabetic cutaneous vessels.  J Invest Dermatol . 1990;  95 147-153
    CrossrefPubMedGoogle Scholar
  • 11 Kohner E M, Chibber R. Diabetic retinopathy. In: Tooke JE, ed. Diabetic Angiopathy London: Arnold 1999: 233-247
    Google Scholar
  • 12 Bollinger A, Frey J, Jager K, Furrer J, Seglias J, Siegenthaler W. Patterns of diffusion through skin capillaries in patients with long-term diabetes.  N Engl J Med . 1982;  307 1305-1310
    CrossrefPubMedGoogle Scholar
  • 13 Kastrup J, Norgaard T, Parving H-H, Henriksen O, Lassen N A. Impaired autoregulation of blood flow in subcutaneous tissue of long-term type 1(insulin-dependent) diabetic patients with microangiopathy: an index of arteriolar dysfunction.  Diabetologia . 1985;  28 711-717
    PubMedGoogle Scholar
  • 14 Braverman I M, Keh-Yen A. Ultrastructural abnormalities of the microvasculature and elastic fibers in the skin of juvenile diabetics.  J Invest Dermatol . 1984;  82 270-274
    CrossrefPubMedGoogle Scholar
  • 15 Nitenberg A, Valensi P, Sachs R, Dali M, Aptecar E, Attali J-R. Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function.  Diabetes Care . 1993;  42 1017-1025
    PubMedGoogle Scholar
  • 16 Strauer B E, Motz W, Vogt M, Schwartzkopff B. Evidence for reduced coronary flow reserve in patients with insulin-dependent diabetes. A possible cause for diabetic heart disease in man.  Exp Clin Endocrinol Diabetes . 1997;  105 15-20
    PubMedGoogle Scholar
  • 17 Mathiesen E R, Hilsted J, Feldt-Rasmussen B, Bonde Petersen F, Christensen N J, Parving H-H. The effect of metabolic control on hemodynamics in short-term insulin-dependent diabetic patients.  Diabetes . 1985;  34 1301-1305
    PubMedGoogle Scholar
  • 18 Grunwald J E, Riva C E, Sinclair S H, Brucker A J, Petrig B L. Laser doppler velocimetry study of retinal circulation in diabetes mellitus.  Arch Ophthalmol . 1986;  104 991-996
    PubMedGoogle Scholar
  • 19 Grunwald J E, Riva C E, Martin D B, Quint A R, Epstein P A. Effect of an insulin-induced decrease in blood glucose on the human diabetic retinal circulation.  Ophthalmology . 1987;  94 1614-1620
    PubMedGoogle Scholar
  • 20 Kohner E M. The problems of retinal blood flow in diabetes.  Diabetes . 1976;  25 (suppl 2) 839-844
    PubMedGoogle Scholar
  • 21 Skyrme-Jones R A, Berry K L, O'Brien R C, Meredith I T. Basal and exercise-induced skeletal muscle blood flow is augmented in type I diabetes mellitus.  Clin Sci . 2000;  98 111-120
    PubMedGoogle Scholar
  • 22 Christiansen J S, Gammelgaard J, Frandsen M, Parving H-H. Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics.  Diabetologia . 1991;  20 451-456
    PubMedGoogle Scholar
  • 23 Houben A H M J, Schaper N C, Slaaf D W, Tangelder G J, Kruseman A CN. Skin blood cell flux in insulin-dependent diabetic subjects in relation to retinopathy or incipient nephropathy.  Eur J Clin Invest . 1992;  22 67-72
    PubMedGoogle Scholar
  • 24 Viberti G. Etiology and prognostic significance of albuminuria in diabetes.  Diabetes Care . 1988;  11 845
    PubMedGoogle Scholar
  • 25 Feng D, Bursell S E, Clermont A C. von Willebrand factor and retinal circulation in early-stage retinopathy of type 1 diabetes.  Diabetes Care . 2000;  23 1694-1698
    PubMedGoogle Scholar
  • 26 Cuypers M H, Kasanardjo J S, Polak B C. Retinal blood flow changes in diabetic retinopathy measured with the Heidelberg scanning laser Doppler flowmeter.  Grefes Arch Clin Exp Ophthalmol . 2000;  238 935-941
    PubMedGoogle Scholar
  • 27 Tymms D J, Tooke J E. The effect of continuous subcutaneous insulin infusion (CSII) on microvascular blood flow in diabetes mellitus.  Int J Microcirc Clin Exp . 1988;  7 347-356
    PubMedGoogle Scholar
  • 28 Tooke J E, Lins P-E, Östergren J, Fagrell B. Skin microvascular autoregulatory responses in type I diabetes: the influence of duration and control.  Int J Microcirc Clin Exp . 1985;  4 249-256
    PubMedGoogle Scholar
  • 29 Jorneskog G, Brismar K, Fagrell B. Pronounced skin capillary ischemia in the feet of diabetic patients with bad metabolic control.  Diabetologia . 1998;  41(4) 410-415
    CrossrefPubMedGoogle Scholar
  • 30 Forst T, Pfutzner A, Kunt T. Skin microcirculation in patients with type I diabetes with and without neuropathy after neurovascular stimulation.  Clin Sci . 1998;  94 255-261
    PubMedGoogle Scholar
  • 31 Fulesdi B, Limburg M, Bereczki D. Impairment of cerebrovascular reactivity in long-term type 1 diabetes.  Diabetes . 1997;  46 1840-1845
    PubMedGoogle Scholar
  • 32 Sandhagen B, Ewald U, Tuvemo T. Hemorheology in insulin-dependent diabetes is still normal five years after onset of the disease.  Acta Pediatr Suppl . 1997;  418 21-23
    PubMedGoogle Scholar
  • 33 Koscielny J, Latza R, Wolf S, Kiesewetter H, Jung F. Early rheological and microcirculatory changes in children with type I diabetes mellitus.  Clin Hemorheol Microcirc . 1998;  19 139-150
    PubMedGoogle Scholar
  • 34 Parving H-H, Viberti G C, Keen H, Christiansen J S, Lassen N A. Hemodynamic factors in the genesis of diabetic microangiopathy.  Metabolism . 1983;  32 943-949
    CrossrefPubMedGoogle Scholar
  • 35 Rayman G, Malik R A, Sharma A K, Day J L. Microvascular response to tissue injury and capillary ultrastructure in the foot skin of type 1 diabetic patients.  Clin Sci . 1995;  89 467-474
    PubMedGoogle Scholar
  • 36 Kastrup J, Norgaard T, Parving H-H, Lassen N A. Decreased distensibility of resistance vessels of the skin in type 1 (insulin-dependent) diabetic patients with microangiopathy.  Clin Sci . 1987;  72 123-130
    PubMedGoogle Scholar
  • 37 Ajjam Z S, Barton S, Corbett M, Owens D, Marks R. Quantitative evaluation of the dermal vasculature of diabetics.  Q J Med . 1985;  54 229-239
    PubMedGoogle Scholar
  • 38 Hostetter T H, Troy J L, Brenner B M. Glomerular hemodynamics in experimental diabetes mellitus.  Kidney Int . 1981;  19 410-415
    CrossrefPubMedGoogle Scholar
  • 39 Lafayette R A, Mayer G, Park S K, Meyer T W. Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass.  J Clin Invest . 1992;  90 766-771
    PubMedGoogle Scholar
  • 40 Zatz R, Dunn B R, Meyer T W, Anderson S, Rennke H G, Brenner B M. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension.  J Clin Invest . 1986;  77 1925-1930
    PubMedGoogle Scholar
  • 41 Cooper M E, Allen T J, Macmillan P A, Clarke B E, Jerums G, Doyle E. Enalapril retards glomerular basement membrane thickening and albuminuria in the diabetic rat.  Diabetologia . 1989;  32 326-328
    CrossrefPubMedGoogle Scholar
  • 42 Sandeman D D, Shore A C, Tooke J E. Relation of skin capillary pressure in patients with insulin-dependent diabetes mellitus to complications and metabolic control.  N Engl J Med . 1992;  327 760-764
    PubMedGoogle Scholar
  • 43 Chien S, Li S, Shyy Y S. Effects of mechanical forces on signal transduction and gene expression in endothelial cells.  Hypertension . 1998;  31 162-169
    PubMedGoogle Scholar
  • 44 Michel C C, Curry F E. Microvascular permeability.  Physiol Rev . 1999;  79 703-761
    PubMedGoogle Scholar
  • 45 Rutledge J C, Curry F E, Blanche P, Krauss R M. Solvent drag of LDL across mammalian endothelial barriers with increased permeability.  Am J Physiol . 1995;  268 H1982-1991
    PubMedGoogle Scholar
  • 46 Neal C R, Michel C C. Openings in frog microvascular endothelium induced by high intravascular pressures.  J Physiol . 1996;  492 39-52
    PubMedGoogle Scholar
  • 47 Robinson G B, Walton H A. Glomerular basement membrane as a compressible ultrafilter.  Microvasc Res . 1989;  38 36-48
    PubMedGoogle Scholar
  • 48 Riser B L, Cortes P, Zhao X. Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.  J Clin Invest . 1992;  90 1932-1943
    PubMedGoogle Scholar
  • 49 Acevedo A D, Bowser S S, Gerritsen M E, Bizios R. Morphological and proliferative responses of endothelial cells to hydrostatic pressure: role of fibroblast growth factor.  J Cell Physiol . 1993;  157 603-614
    CrossrefPubMedGoogle Scholar
  • 50 Stamer W D, Roberts B C, Epstein D L. Hydraulic pressure stimulates adenosine 3′,5′-cyclic monophosphate accumulation in endothelial cells from Schlemm's canal.  Invest Ophthalmol Vis Sci . 1999;  40 1983-1988
    PubMedGoogle Scholar
  • 51 Salwen S A, Szarowski D H, Turner J N, Bizios R. Three-dimensional changes of the cytoskeleton of vascular endothelial cells exposed to sustained hydrostatic pressure.  Med Biol Eng Comput . 1998;  36 520-527
    PubMedGoogle Scholar
  • 52 Parving H-H, Rasmussen S M. Transcapillary escape rate of albumin and plasma volume in short- and long-term juvenile diabetics.  Scand J Clin Lab Invest . 1973;  32 81-87
    PubMedGoogle Scholar
  • 53 Parving H-H. Increased microvascular permeability to plasma proteins in short- and long-term juvenile diabetics.  Diabetes . 1976;  25 (suppl 2) 884-889
    PubMedGoogle Scholar
  • 54 Parving H-H, Noer I, Deckert T. The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics.  Diabetologia . 1976;  12 161-166
    CrossrefPubMedGoogle Scholar
  • 55 Alpert J S, Coffman J D, Balodimos M C, Koncz L, Soeldner J S. Capillary permeability and blood flow in skeletal muscle of patients with diabetes mellitus and genetic prediabetes.  N Engl J Med . 1972;  286 454-460
    PubMedGoogle Scholar
  • 56 Jaap A J, Shore A C, Gartside I B, Gamble J, Tooke J E. Increased microvascular fluid permeability in young type 1 (insulin-dependent) diabetic patients.  Diabetologia . 1993;  36 648-652
    CrossrefPubMedGoogle Scholar
  • 57 Poulsen H L. Subcutaneous interstitial fluid concentrations of albumin and immunoglobin G in relation to the serum values in normal hypertensive and diabetic men.  Bibl Anat . 1975;  13 74-75
    PubMedGoogle Scholar
  • 58 Trap-Jensen J. Increased capillary permeability to iodide and EDTA in the exercising forearm of long-term diabetics.  Clin Sci . 1970;  39 39-49
    PubMedGoogle Scholar
  • 59 Leinonen H, Matikainen E, Juntunen J. Permeability and morphology of skeletal muscle capillaries in type 1 (insulin-dependent) diabetes mellitus.  Diabetologia . 1982;  22 158-162
    PubMedGoogle Scholar
  • 60 Oomen P H, Jager J, Hoogenberg K, Dullaart R P, Reitsma W D, Smit A J. Capillary permeability is increased in normo- and microalbuminuric type 1 diabetic patients: amelioration by ACE-inhibition.  Eur J Clin Invest . 1999;  29 1035-1040
    CrossrefPubMedGoogle Scholar
  • 61 Fauchald P, Norseth J, Jervell J. Transcapillary colloid osmotic gradient, plasma volume and interstitial fluid volume in long-term type I (insulin-dependent) diabetes.  Diabetologia . 1985;  28 269-273
    CrossrefPubMedGoogle Scholar
  • 62 Hommel E, Mathiesen E R, Aukland K, Parving H-H. Pathophysiological aspects of edema formation in diabetic nephropathy.  Kidney Int . 1990;  38 1187-1192
    PubMedGoogle Scholar
  • 63 Baumgartner-Parzer S M, Wagner L, Pettermann M, Gessl A, Waldhausl W. Modulation by high glucose of adhesion molecule expression in cultured endothelial cells.  Diabetologia . 1995;  38 1367-1370
    PubMedGoogle Scholar
  • 64 Tarsio J F, Reger L A, Furcht L T. Molecular mechanisms in basement membrane complications of diabetes: alterations in heparin, laminin and type IV collagen association.  Diabetes . 1988;  37 532-539
    PubMedGoogle Scholar
  • 65 Serne E H, Gans R O, ter Maaten C J, ter Wee M P, Donker A J, Stehouwer C D. Capillary recruitment is impaired in essential hypertension and relates to insulin's metabolic and vascular actions.  Cardiovasc Res . 2001;  49 161-168
    CrossrefPubMedGoogle Scholar
  • 66 McLaren M, Elhadd T A, Greene S A, Belch J J. Elevated plasma vascular endothelial cell growth factor and thrombomodulin in juvenile diabetic patients.  Clin Appl Thromb Hemost . 1999;  5 21-24
    PubMedGoogle Scholar
  • 67 Elhadd T A, Kennedy G, Hill A. Abnormal markers of endothelial cell activation and oxidative stress in children, adolescents and young adults with type 1 diabetes with no clinical vascular disease.  Diabetes Metab Res Rev . 1999;  15 405-411
    CrossrefPubMedGoogle Scholar
  • 68 Elhadd T A, Khan F, Kirk G. Influence of puberty on endothelial dysfunction and oxidative stress in young patients with type 1 diabetes.  Diabetes Care . 1998;  21 1990-1996
    PubMedGoogle Scholar
  • 69 Stehouwer C DA, Fischer H RA, van Kuijk W R A, Polak B CP, Donker A JM. Endothelial dysfunction precedes development of microalbuminuria in IDDM.  Diabetes . 1995;  44 561-564
    PubMedGoogle Scholar
  • 70 Jensen T, Bjerre Knudsen J, Feldt-Rasmussen B, Decker T. Features of endothelial dysfunction in early diabetic nephropathy.  Lancet . 1989;  461-463
    PubMedGoogle Scholar
  • 71 Gruden G, Cavallo-Perin P, Bazzan M, Stella S, Vuolo A, Pagano G. PAI-1 and factor VII activity are higher in IDDM patients with microalbuminuria.  Diabetes . 1994;  43 426-429
    PubMedGoogle Scholar
  • 72 Zimmermann J, Schramm L, Wanner C. Hemorheology, plasma protein composition and von Willebrand factor in type 1 diabetic nephropathy.  Clin Nephrol . 1996;  46(4) 230-236
    PubMedGoogle Scholar
  • 73 Barouch F C, Miyamoto K, Allport J R. Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes.  Invest Ophthalmol Vis Sci . 2000;  41 1153-1158
    PubMedGoogle Scholar
  • 74 Rattan V, Shen Y, Sultana C, Kumar D, Kalra V K. Diabetic RBC-induced oxidant stress leads to transendothelial migration of monocyte-like HL-60 cells.  Am J Physiol . 1997;  273 E369-375
    PubMedGoogle Scholar
  • 75 Enderle M-D, Benda N, Schmuelling R-M, Hering H U, Pfohl M. Preserved endothelial function in IDDM patients, but not in NIDDM patients, compared with healthy subjects.  Diabetes Care . 1998;  21 271-277
    CrossrefPubMedGoogle Scholar
  • 76 Lambert J, Aarsen M, Donker A JM, Stehouwer C DA. Endothelium-dependent and -independent vasodilation of large arteries in normoalbuminuric insulin-dependent diabetes mellitus.  Arterioscler Thromb Vasc Biol . 1996;  16 705-711
    PubMedGoogle Scholar
  • 77 Schalkwijk C G, Smulders R A, Lambert J, Donker A J, Stehouwer C D. ACE-inhibition modulates some endothelial functions in healthy subjects and in normotensive type 1 diabetic patients.  Eur J Clin Invest . 2000;  30 853-860
    CrossrefPubMedGoogle Scholar
  • 78 Donaghue K C, Robinson J, McCredie R, Fung A, Silink M, Celermajer D S. Large vessel dysfunction in diabetic adolescents and its relationship to small vessel complications.  J Pediatr Endocrinol Metab . 1997;  10 593-598
    PubMedGoogle Scholar
  • 79 Zenere B M, Arcaro G, Saggiani F, Rossi L, Muggeo M, Lechi A. Noninvasive detection of functional alterations of the arterial wall in IDDM patients with and without microalbuminuria.  Diabetes Care . 1995;  18 975-982
    PubMedGoogle Scholar
  • 80 Clarkson P, Celemajer D S, Donald E. Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels.  JACC . 1996;  28(3) 573-579
    PubMedGoogle Scholar
  • 81 Meeking D R, Cummings M H, Thorne S. Endothelial dysfunction in Type 1 diabetes subjects with and without microalbuminuria.  Diabet Med . 1999;  16 841-847
    CrossrefPubMedGoogle Scholar
  • 82 Mullen M J, Wright D, Donald E, Thorne S, Thomson H, Deanfield J E. Atorvastatin but not L-arginine improves endothelial function in type I diabetes mellitus: a double-blind study.  J Am Coll Cardiol . 2000;  36 410-416
    CrossrefPubMedGoogle Scholar
  • 83 Mullen M J, Clarkson P, Donald E. Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study.  J Am Coll Cardiol . 1998;  31 1330-1335
    CrossrefPubMedGoogle Scholar
  • 84 Hu J, Norman M, Wallensteen M, Gennser G. Dynamic properties of the aorta and of the foot microcirculation in adolescents with diabetes mellitus.  Acta Pediatr . 1997;  86 620-625
    PubMedGoogle Scholar
  • 85 Calver A, Collier J, Vallance P. Inhibition and stimulation of nitric oxide synthesis in the human forearm arterial bed of patients with insulin-dependent diabetes.  J Clin Invest . 1993;  90 2548-2554
    PubMedGoogle Scholar
  • 86 Halkin A, Benjamin N, Doktor H S, Dodd S D, Viberti G, Ritter J M. Vascular responsiveness and cation exchange in insulin-dependent diabetes.  Clin Sci . 1991;  81 223-232
    PubMedGoogle Scholar
  • 87 Smits P, Kapma J-A, Jacobs M-C, Lutterman J, Thien T. Endothelium-dependent vascular relaxation in patients with type 1 diabetes.  Diabetes . 1993;  42 148-153
    PubMedGoogle Scholar
  • 88 Elliott T G, Cockcroft J R, Groop P-H, Viberti G C, Ritter J M. Inhibition of nitric oxide synthesis in forearm vasculature of insulin-dependent diabetic patients: blunted vasoconstriction in patients with microalbuminuria.  Clin Sci . 1993;  85 687-693
    PubMedGoogle Scholar
  • 89 Huvers F C, De Leeuw W P, Houben A H M J. Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions.  Diabetes . 1999;  48 1300-1307
    PubMedGoogle Scholar
  • 90 Johnstone M T, Creager S J, Scales K M, Cusco J A, Lee B K, Creager M A. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.  Circulation . 1993;  88 2510-2516
    PubMedGoogle Scholar
  • 91 Makimattila S, Virkamaki A, Groop P-H. Chronic hyperglycemia impairs endothelial function and insulin sensitivity via different mechanisms in insulin-dependent diabetes mellitus.  Circulation . 1996;  94 1276-1282
    PubMedGoogle Scholar
  • 92 Wiggam M I, Hunter S J, Ennis C N, Sheridan B, Atkinson A B, Bell P M. Insulin action and skeletal muscle blood flow in patients with Type 1 diabetes and microalbuminuria.  Diabetes Res Clin Pract . 2001;  53 73-83
    CrossrefPubMedGoogle Scholar
  • 93 McIntyre C A, Hadoke P W, Williams B C, Lindsay R M, Elliott A I, McKnight J A. Selective enhancement of sensitivity to endothelin-1 despite normal endothelium-dependent relaxation in subcutaneous resistance arteries isolated from patients with Type I diabetes.  Clin Sci . 2001;  100 311-318
    PubMedGoogle Scholar
  • 94 McNally P G, Watt P AC, Rimmer T, Burden A C, Hearnshaw J R, Thurston H. Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus.  Clin Sci . 1994;  87 31-36
    PubMedGoogle Scholar
  • 95 Gooding K M, Hannemann M M, Clough G F, Tooke J E, Shore A C. The role of nitric oxide in the induction of maximum hyperemia by local heating [abstract]. Seventh World Congress of Microcirculation. Sydney August 2001
    Google Scholar
  • 96 Shore A C, Price K J, Sandeman D D, Green E M, Tripp J H, Tooke J E. Impaired microvascular hyperemic response in children with diabetes mellitus.  Diabet Med . 1991;  8 619-623
    PubMedGoogle Scholar
  • 97 Ewald U, Tuvemo T. Reduced vascular reactivity in diabetic children and its relation to diabetic control.  Acta Pediatr Scand . 1985;  74 77-84
    PubMedGoogle Scholar
  • 98 Khan F, Elhadd T A, Greene S A, Belch J J. Impaired skin microvascular function in children, adolescents, and young adults with type 1 diabetes.  Diabetes Care . 2000;  23 215-220
    PubMedGoogle Scholar
  • 99 Shore A C, Morris M J, Tooke J E. Impaired skin microvascular endothelial responses in IDDM patients with microalbuminuria. British Diabetic Association, Harrogate.  Diabet Med . 1997;  14 (suppl 1) A54
    PubMedGoogle Scholar
  • 100 Calver A, Collier J, Moncada S, Vallance P. Effect of local intra-arterial Ng-monomethyl-L-arginine in patients with hypertension: the nitric oxide dilator mechanism appears abnormal.  J Hypertens . 1992;  10 1025-1031
    PubMedGoogle Scholar
  • 101 Christlieb A R, Janka H-U, Kraus B. Vascular reactivity to angiotensin II and to norepinephrine in diabetic subjects.  Diabetes . 1976;  25 268-274
    PubMedGoogle Scholar
  • 102 Wiegmann T B, Herron K G, Chonko A M, Macdougall M L, Moore W V. Effect of angiotensin-converting enzyme inhibition on renal function and albuminuria in normotensive Type 1 diabetic patients.  Diabetes . 1992;  41 62-67
    PubMedGoogle Scholar
  • 103 Mathiesen E R, Hommel E, Giese J, Parving H-H. Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.  BMJ . 1991;  303 81-87
    PubMedGoogle Scholar
  • 104 Smulders R A, Stehouwer C DA, Olthof C G. Plasma endothelin levels and vascular effects of intravenous L-arginine infusion in subjects with uncomplicated insulin-dependent diabetes mellitus.  Clin Sci . 1994;  87 37-43
    PubMedGoogle Scholar
  • 105 Sarman B, Farkas K, Toth M, Somogyi A, Tulassay Z. Circulating plasma endothelin-1, plasma lipids and complications in Type 1 diabetes mellitus.  Diabetes Nutr Metab . 2000;  13 142-148
    PubMedGoogle Scholar
  • 106 Peppa-Patrikiou M, Dracopoulou M, Dacou-Voutetakis C. Urinary endothelin in adolescents and young adults with insulin-dependent diabetes mellitus: relation to urinary albumin, blood pressure, and other factors.  Metabolism . 1998;  47 1408-1412
    CrossrefPubMedGoogle Scholar
  • 107 Miller V M, Komori K, Burnett Jr C J, Vanhoutte P M. Differential sensitivity to endothelin in canine arteries and veins.  Am J Physiol . 1989;  257 H1127-H1131
    PubMedGoogle Scholar
  • 108 Dhein S, Hochreuther S, Aus Dem Spring C, Bollig K, Hufnagel C, Raschack M. Long-term effects of the endothelin(A) receptor antagonist LU 135252 and the angiotensin-converting enzyme inhibitor trandolapril on diabetic angiopathy and nephropathy in a chronic type I diabetes mellitus rat model.  J Pharmacol Exp Ther . 2000;  293 351-359
    PubMedGoogle Scholar
  • 109 Hocher B, Schwarz A, Reinbacher D. Effects of endothelin receptor antagonists on the progression of diabetic nephropathy.  Nephron . 2001;  87 161-169
    CrossrefPubMedGoogle Scholar
  • 110 Bell D, Collier A, Nicoll J J. Reduced venous compliance and increased transcapillary escape of protein in insulin-dependent diabetic patients.  Diabet Med . 1988;  5 454-458
    PubMedGoogle Scholar
  • 111 Schaper N C, Houben A H M J, Schoon Y, Kooman J P, Huvers F C, Nieuwenhuijzen Kruseman C A. Venous compliance and the venodilatory effect of nitroglycerin in insulin-dependent diabetic patients with and without (incipient) nephropathy.  Eur J Clin Invest . 1994;  24 382-387
    PubMedGoogle Scholar
  • 112 Bodmer C W, Patrick A W, How T V, Williams G. Exaggerated sensitivity to NE-induced vasoconstriction in IDDM patients with microalbuminuria: possible etiology and diagnostic implications.  Diabetes . 1992;  41 209-214
    PubMedGoogle Scholar
  • 113 Bodmer C W, Schaper N C, Janssen M, De Leeuw W P, Williams G. Selective enhancement of alpha 2-adrenoceptor-mediated vasoconstriction in insulin-dependent diabetic patients with microalbuminuria.  Clin Sci (Colch) . 1995;  88 421-426
    PubMedGoogle Scholar
  • 114 Skyrme-Jones R A, O'Brien R C, Luo M, Meredith I T. Endothelial vasodilator function is related to low-density lipoprotein particle size and low-density lipoprotein vitamin E content in type 1 diabetes.  J Am Coll Cardiol . 2000;  35 292-299
    CrossrefPubMedGoogle Scholar
  • 115 Pinkney J H, Downs L, Hopton M, Mackness M I, Bolton C H. Endothelial dysfunction in Type 1 diabetes mellitus: relationship with LDL oxidation and the effects of vitamin E.  Diabet Med . 1999;  16 993-999
    CrossrefPubMedGoogle Scholar
  • 116 Seaquist E R, Goetz F C, Rich S, Barbosa J. Familial clustering of diabetic kidney disease.  N Engl J Med . 1989;  320 1161-1165
    CrossrefPubMedGoogle Scholar
  • 117 Viberti G C, Keen H, Wiseman M J. Raised arterial pressure in parents of proteinuric insulin dependent diabetics.  Br Med J (Clin Res Ed) . 1987;  295 515-517
    PubMedGoogle Scholar
  • 118 Roglic G, Colhoun H M, Stevens L K, Lemkes H H, Manes C, Fuller J H. Parental history of hypertension and parental history of diabetes and microvascular complications in insulin-dependent diabetes mellitus: the EURODIAB IDDM Complications Study.  Diabet Med . 1998;  15 418-426
    CrossrefPubMedGoogle Scholar
  • 119 McAllister A S, Atkinson A B, Johnston G D, McCance D R. Endothelial function in offspring of Type 1 diabetic patients with and without diabetic nephropathy.  Diabet Med . 1999;  16 298-303
    CrossrefPubMedGoogle Scholar
  • 120 Nannipieri M, Penno G, Pucci L. Pronatriodilatin gene polymorphisms, microvascular permeability, and diabetic nephropathy in type 1 diabetes mellitus.  J Am Soc Nephrol . 1999;  10 1530-1541
    PubMedGoogle Scholar
  • 121 Poirier O, Nicaud V, Vionnet N. Polymorphism screening of four genes encoding advanced glycation end-product putative receptors. Association study with nephropathy in type 1 diabetic patients.  Diabetes . 2001;  50 1214-1218
    PubMedGoogle Scholar
  • 122 Hadjadj S, Belloum R, Bouhanick B. Prognostic value of angiotensin-I converting enzyme I/D polymorphism for nephropathy in type 1 diabetes mellitus: a prospective study.  J Am Soc Nephrol . 2001;  12 541-549
    PubMedGoogle Scholar
  • 123 The Diabetes Control and Complications Research Group. 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 . 1993;  329 978-986
    PubMedGoogle Scholar
  • 124 Idris I, Gray S, Donnelly R. Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes.  Diabetologia . 2001;  44 659-673
    CrossrefPubMedGoogle Scholar
  • 125 di Mario U, Pugliese G. 15th Golgi Lecture: From hyperglycemia to the dysregulation of vascular remodelling in diabetes.  Diabetologia . 2001;  44 674-692
    CrossrefPubMedGoogle Scholar
  • 126 Timimi F K, Ting H H, Haley E A, Roddy M A, Ganz P, Creager M A. Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.  J Am Coll Cardiol . 1998;  31 552-557
    CrossrefPubMedGoogle Scholar
  • 127 Skyrme-Jones R A, O'Brien R C, Berry K L, Meredith I T. Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study.  J Am Coll Cardiol . 2000;  36 94-102
    CrossrefPubMedGoogle Scholar
  • 128 Bursell S E, Clermont A C, Aiello L P. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes.  Diabetes Care . 1999;  22 1245-1251
    PubMedGoogle Scholar
      >