INVESTIGATIONS INTO HYPERLIPIDEMIA AND ITS POSSIBLE ...

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67 The presence of hypertriglyceridemia in dogs with pancreatitis might be due to a pre-existing disorder in lipid metabolism, which may or may not be related to the etiology of pancreatitis, or it might be the result of pancreatitis. 252 Although it is widely believed that hypertriglyceridemia can develop as a result of pancreatitis, this has not been convincingly shown in dogs with naturally occurring pancreatitis. Furthermore, with the exception of the results of an older study, 261 hypertriglyceridemia does not seem to be a consequence of experimental pancreatitis in dogs. 18-20 In order for hypertriglyceridemia to be considered as a possible etiologic factor for pancreatitis it should precede the development of pancreatitis. Hypertriglyceridemia that precedes the development of pancreatitis might be primary such as hypertriglyceridemia of certain breeds such as Miniature Schnauzers or secondary to other diseases including diabetes mellitus, hyperadrenocorticism, hypothyroidism or drug administration (such as glucocorticoids). 252 A possible role of hypertriglyceridemia as a cause of pancreatitis in Miniature Schnauzers or other dog breeds has been suspected based on knowledge extrapolated from human medicine, where severe hypertriglyceridemia is a well recognized cause of pancreatitis, 255,257,258,267 in vitro or in experimental studies, 144,260 and anecdotal clinical impressions. 165 The possibility of hypertriglyceridemia potentially developing as a result of pancreatitis complicates the determination of the role of hypertriglyceridemia as an etiologic factor of pancreatitis in both humans and dogs. 252,255 One approach that is often used in human studies in order to overcome this obstacle is the measurement of serum triglyceride concentrations after pancreatitis has resolved. 256,267-270 This is based on the
68 logical assumption that a defect in lipid metabolism causing hypertriglyceridemia must be a pre-existing condition in order for a patient to develop pancreatitis as a result of hypertriglyceridemia. If this is the case, hypertriglyceridemia should also persist after resolution of pancreatitis. 256,267-270 In contrast, hypertriglyceridemia secondary to pancreatitis should resolve when pancreatitis is no longer present. Therefore, the presence of hypertriglyceridemia soon after resolution of pancreatitis provides retrospective evidence of a pre-existing condition, which if severe enough, could be considered as an etiologic factor for pancreatitis. 256,267-270 Studies investigating disorders of lipid metabolism in patients with a history of naturally occurring pancreatitis have been reported in humans but not in veterinary species. The aim of this study was to compare serum triglyceride concentrations between Miniature Schnauzers with a recent history of pancreatitis and those without such a recent history of pancreatitis. Materials and methods Study design This study is a prospective case-control study. Dogs with pancreatitis (Group 1) Over a 2-year period (November 2006 – November 2008), a total of 35 Miniature Schnauzers with a diagnosis of pancreatitis were initially considered for prospective enrollment into this study. The diagnosis of pancreatitis was based on the presence of at
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INVESTIGATIONS INTO HYPERLIPIDEMIA
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INVESTIGATIONS INTO HYPERLIPIDEMIA
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iv was found to be useful for the s
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vi ACKNOWLEDGEMENTS I would like to
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viii TABLE OF CONTENTS Page ABSTRAC
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x LIST OF FIGURES FIGURE Page 1 Cor
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xii FIGURE Page 20 1-dimensional sl
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2 the results of these initial stud
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4 and HDL 1 concentrations and a de
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6 and, in smaller concentrations, L
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8 HDL molecules can be further subd
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10 reach the vasculature, they acqu
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12 Endocrine disease Most commonly,
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14 with varying frequencies in dogs
Page 29 and 30: 16 hypercholesterolemia was found o
Page 31 and 32: 18 Primary hyperlipidemia with hype
Page 33 and 34: 20 Atherosclerosis Although dogs ap
Page 35 and 36: 22 Dietary management Typically, th
Page 37 and 38: 24 therapy when the latter fails to
Page 39 and 40: 26 followed from the 1970s until to
Page 41 and 42: 28 this theory, zymogen granules th
Page 43 and 44: 30 be quite different, especially i
Page 45 and 46: 32 Drugs As in humans, drug-induced
Page 47 and 48: 34 Signalment Dogs of any age, bree
Page 49 and 50: 36 erroneously direct the clinician
Page 51 and 52: 38 of changes over time in serum Sp
Page 53 and 54: 40 they have been shown to have a l
Page 55 and 56: 42 revealed either a normal pancrea
Page 57 and 58: 44 At present, a definitive diagnos
Page 59 and 60: 46 factors should always be investi
Page 61 and 62: 48 associated pancreatitis is much
Page 63 and 64: 50 clear whether hyperlipidemia was
Page 65 and 66: 52 hepatobiliary disease in both Mi
Page 67 and 68: 54 the reference range, while Group
Page 69 and 70: 56 ROC analysis and calculation of
Page 71 and 72: 58 Figure 3. Serum cPLI concentrati
Page 73 and 74: 60 There was no significant differe
Page 75 and 76: 62 severe (typically ≥1,000 mg/dl
Page 77 and 78: 64 gastrointestinal signs or suspec
Page 79: 66 CHAPTER III SERUM TRIGLYCERIDE C
Page 83 and 84: 70 pancreatitis. For the same reaso
Page 85 and 86: 72 Spec cPL concentrations were mea
Page 87 and 88: 74 were significantly more likely t
Page 89 and 90: 76 Figure 5. Comparison of serum tr
Page 91 and 92: 78 Figure 7. Comparison of serum tr
Page 93: 80 pancreatitis as it cannot be pre
Page 96 and 97: 83 Although serum cholesterol conce
Page 98 and 99: 85 Footnotes a Spec cPL ® , IDEXX
Page 100 and 101: 87 several subfractions, with diffe
Page 102 and 103: 89 Miniature Schnauzers (Group 2) T
Page 104 and 105: 91 Assays Serum triglyceride (refer
Page 106 and 107: 93 Figure 8. Custom-built fluoresce
Page 108 and 109: 95 range HDL 1 has not been accurat
Page 110 and 111: 97 mg/dL) were significantly higher
Page 112 and 113: 99 Figure 10: Serum cholesterol con
Page 114 and 115: 101 (Eigenvalues=0.5455; P=0.00017;
Page 116 and 117: 103 Figure 12: Representative lipop
Page 118 and 119: 105 Figures 14A and 14B: Representa
Page 120 and 121: 107 Specifically, 97% of non-hypert
Page 122 and 123: 109 The fraction of TRLs was a sign
Page 124 and 125: 111 Schnauzers without hyperlipidem
Page 126 and 127: 113 Footnotes a Roche/Hitachi MODUL
Page 128 and 129: 115 The biochemical, metabolic, and
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117 Study design Each one of the do
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119 Questionnaires and consent form
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121 a target intensity of 30%, and
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123 might affect lipid metabolism (
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125 Figure 16. Serum triglyceride c
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127 Figure 18. Serum Spec cPL conce
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129 Figure 19. 1-dimensional sliced
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131 Dogs that did not respond to th
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133 Hypertriglyceridemia has been l
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135 degrees. One possible explanati
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137 Footnotes a Royal Canin Gastroi
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139 concentrations and lipoprotein
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141 inclusion criteria for the stud
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143 light source j , located in a d
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146 Serum triglyceride and choleste
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148 Figure 22. Serum triglyceride c
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150 Figure 24. 1-dimensional sliced
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152 Discussion The purpose of the p
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154 fraction of these dogs (about 3
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156 of lipoproteins might also have
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158 Footnotes a Roche/Hitachi MODUL
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160 the etiology of pancreatitis, b
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162 times (P=0.0343) for a serum cP
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164 peaks than dogs of other breeds
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166 19.3; 95% CI, 2.0-184.0; P=0.00
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168 4) Specific lipoprotein classes
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170 REFERENCES 1949;8:96-97. 1. Lew
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172 17. Whitney MS, Boon GD, Rebar
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174 33. Ford RB. Clinical managemen
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176 50. Nelson RW, Turnwald GH, Wil
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178 66. Williams DA, Steiner JM. Ca
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180 82. Yilmaz Z, Senturk S. Charac
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182 97. Fojo SS, Stalenhoef AF, Mar
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184 111. Lam CW, Yuen YP, Cheng WF,
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186 127. Crispin SM. Ocular manifes
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188 144. Lindsay S, Entenmann C, Ch
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190 161. Steiner JM. Canine pancrea
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192 176. Steiner JM, Teague SR, Wil
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194 191. Steiner JM. Diagnosis of p
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196 208. Talukdar R, Vege S. Recent
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198 224. Koch K, Drewelow B, Liebe
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200 241. Petrov MS, van Santvoort H
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202 258. Ewald N, Hardt PD, Kloer H
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204 274. Otvos JD, Jeyarajah EJ, Be
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206 289. Carpentier YA, Scruel O. C
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