INVESTIGATIONS INTO HYPERLIPIDEMIA AND ITS POSSIBLE ...

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51 CHAPTER II ASSOCIATION BETWEEN SERUM TRIGLYCERIDE <strong>AND</strong> CANINE PANCREATIC LIPASE IMMUNOREACTIVITY CONCENTRATIONS IN MINIATURE SCHNAUZERS* Introduction Primary (idiopathic) hypertriglyceridemia is a common condition in Miniature Schnauzers in the United States. 84 In a recent study, hypertriglyceridemia was present in 32.8% of 192 Miniature Schnauzers investigated. Also, hypertriglyceridemia was shown to be age-related, with a much higher prevalence in older Miniature Schnauzers. 84 Hypertriglyceridemia in Miniature Schnauzers has previously been shown to be associated with an abnormal accumulation of VLDL (very low density lipoproteins) or a combination of VLDL and chylomicrons, with or without hypercholesterolemia. 17,83 The fact that hypertriglyceridemia is especially prevalent within a certain breed suggests a hereditary mechanism, but the metabolic and genetic bases of this disorder have not been identified. 49,83 Investigations into the disease conditions potentially associated with hypertriglyceridemia have only recently been reported in dogs. For example, as is the case in humans, hypertriglyceridemia has been recently reported to be associated with ___________ *Xenoulis PG, et al. Association between serum triglyceride and canine pancreatic lipase immunoreactivity concentrations in miniature schnauzers. J Am Anim Hosp Assoc 2010;46(4):229-34. Reprinted with permission from the Journal of the American Animal Hospital Association.
52 hepatobiliary disease in both Miniature Schnauzers and dogs of other breeds. 121,123 In humans, severe hypertriglyceridemia is also a known risk factor for pancreatitis. 254,255,262 Miniature Schnauzers are generally considered to have a high incidence of pancreatitis. 63,163,165,216 In a recent study, bivariable screening showed that Miniature Schnauzers were 4.1 times (95% CI, 1.9 to 9.2; P < 0.001) more likely to have pancreatitis than dogs of other breeds. 163 The basis for this predisposition is unknown, but hypertriglyceridemia has long been considered as a possible cause of pancreatitis in the Miniature Schnauzer. 17,83,165 However, studies investigating any association between these 2 disorders in dogs are lacking, and this consideration is mainly based on clinical impressions. In vitro studies support the concept that hypertriglyceridemia can initiate pancreatic inflammation, and there is evidence that high fat diets or even a single fatty meal can induce pancreatitis in dogs. 144,165,260 In contrast to hypertriglyceridemia, hypercholesterolemia does not appear to be a risk factor for pancreatitis in humans or dogs. 33,254,255 Recognition of an association between hypertriglyceridemia and pancreatitis in Miniature Schnauzers is clinically important because management of hypertriglyceridemia with low-fat diets and/or lipid-lowering drugs may prevent or resolve pancreatitis in these dogs. Until recently, a clinical diagnosis of pancreatitis was problematic in dogs because no specific and sensitive tests were available. However, the recent development and analytical validation of an ELISA specific for canine pancreatic lipase, canine pancreatic lipase immunoreactivity (cPLI), has facilitated the diagnosis of pancreatitis in dogs as it has been reported to be sensitive (reported sensitivity ranging from 64% for
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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
Page 13 and 14: xii FIGURE Page 20 1-dimensional sl
Page 15 and 16: 2 the results of these initial stud
Page 17 and 18: 4 and HDL 1 concentrations and a de
Page 19 and 20: 6 and, in smaller concentrations, L
Page 21 and 22: 8 HDL molecules can be further subd
Page 23 and 24: 10 reach the vasculature, they acqu
Page 25 and 26: 12 Endocrine disease Most commonly,
Page 27 and 28: 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: 50 clear whether hyperlipidemia was
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 and 80: 66 CHAPTER III SERUM TRIGLYCERIDE C
Page 81 and 82: 68 logical assumption that a defect
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
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101 (Eigenvalues=0.5455; P=0.00017;
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103 Figure 12: Representative lipop
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105 Figures 14A and 14B: Representa
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107 Specifically, 97% of non-hypert
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109 The fraction of TRLs was a sign
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111 Schnauzers without hyperlipidem
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113 Footnotes a Roche/Hitachi MODUL
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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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