INVESTIGATIONS INTO HYPERLIPIDEMIA AND ITS POSSIBLE ...

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159 CHAPTER VII SUMMARY <strong>AND</strong> CONCLUSIONS An association between hyperlipidemia and pancreatitis was first noted in humans by Speck in 1865. 253 Several clinical and experimental studies in humans and animals, respectively, have been conducted since then, and today, severe hypertriglyceridemia is a well recognized risk factor for pancreatitis in humans. 254-257 The mechanism by which hypertriglyceridemia induces pancreatitis is not clear, but it has been suggested that serum triglycerides are hydrolyzed by the action of pancreatic lipase, leading to excessive production of free fatty acids, which are toxic to the pancreatic acinar cell. 259,260 Another possible hypothesis is that hyperviscosity develops as a result of increased chylomicrons and/or VLDLs within the capillaries, which in turn leads to ischemia of pancreatic tissue. 258 Finally, genetic factors, such as mutations of the cystic fibrosis transmembrane conductance regulator gene or the SPINK1 gene may play a role by sensitizing the pancreas to the effects of hypertriglyceridemia. 258 A similar relationship between hypertriglyceridemia and pancreatitis has been suggested for dogs, and co-existence of the 2 conditions has been frequently described. 15,33,34,37,49,52,66,83,165 However, this association remains obscure in dogs because the etiology of hypertriglyceridemia cannot always be determined in these studies. It has been speculated that the presence of hypertriglyceridemia in dogs with pancreatitis might be due to a pre-existing disorder of lipid metabolism, which may or may not be related to
160 the etiology of pancreatitis, but might also be the result of pancreatitis, or it might just be an incidental finding in some cases. 252 Miniature Schnauzers are a unique breed in regards to both hyperlipidemia and pancreatitis. Miniature Schnauzers have been reported to develop pancreatitis more commonly than dogs of other breeds, and this high prevalence of pancreatitis in Miniature Schnauzers has been attributed to the fact that dogs of this breed commonly develop hypertriglyceridemia. 33,49,66,165 Available clinical and experimental data to support these hypotheses are limited, however. Clinical studies have shown an association between hyperlipidemia and pancreatitis in dogs, although it is not clear whether hyperlipidemia was the cause or the result of pancreatitis, or even just an incidental finding in some cases. 15,19,21,63-66 Secondary hyperlipidemia seen in dogs with some endocrinopathies (e.g., hyperadrenocorticism) or obesity may be responsible for the increased risk for pancreatitis associated with these diseases. 11,65,65,172 The hypotheses of the present study were that: 1) hypertriglyceridemia, especially when severe, is a risk factor for pancreatitis in Miniature Schnauzers, 2) primary hypertriglyceridemia and possibly subclinical pancreatic inflammation in Miniature Schnauzers will respond, at least partially, to feeding an ultra low-fat diet, and 3) dogs with pancreatitis will exhibit changes in their serum triglyceride and cholesterol concentrations, as well as in their lipoprotein profiles when compared to healthy dogs. The objectives of the present study were: 1) to investigate a possible associations between serum triglyceride and canine pancreatic lipase immunoreactivity (cPLI) concentrations in Miniature Schnauzers, 2) to compare serum triglyceride concentrations
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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
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16 hypercholesterolemia was found o
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18 Primary hyperlipidemia with hype
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20 Atherosclerosis Although dogs ap
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22 Dietary management Typically, th
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24 therapy when the latter fails to
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26 followed from the 1970s until to
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28 this theory, zymogen granules th
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30 be quite different, especially i
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32 Drugs As in humans, drug-induced
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34 Signalment Dogs of any age, bree
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36 erroneously direct the clinician
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38 of changes over time in serum Sp
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40 they have been shown to have a l
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42 revealed either a normal pancrea
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44 At present, a definitive diagnos
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46 factors should always be investi
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48 associated pancreatitis is much
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50 clear whether hyperlipidemia was
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52 hepatobiliary disease in both Mi
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54 the reference range, while Group
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56 ROC analysis and calculation of
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58 Figure 3. Serum cPLI concentrati
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60 There was no significant differe
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62 severe (typically ≥1,000 mg/dl
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64 gastrointestinal signs or suspec
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66 CHAPTER III SERUM TRIGLYCERIDE C
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68 logical assumption that a defect
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70 pancreatitis. For the same reaso
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72 Spec cPL concentrations were mea
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74 were significantly more likely t
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76 Figure 5. Comparison of serum tr
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78 Figure 7. Comparison of serum tr
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80 pancreatitis as it cannot be pre
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83 Although serum cholesterol conce
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85 Footnotes a Spec cPL ® , IDEXX
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87 several subfractions, with diffe
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89 Miniature Schnauzers (Group 2) T
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91 Assays Serum triglyceride (refer
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93 Figure 8. Custom-built fluoresce
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95 range HDL 1 has not been accurat
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97 mg/dL) were significantly higher
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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
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
Page 130 and 131: 117 Study design Each one of the do
Page 132 and 133: 119 Questionnaires and consent form
Page 134 and 135: 121 a target intensity of 30%, and
Page 136 and 137: 123 might affect lipid metabolism (
Page 138 and 139: 125 Figure 16. Serum triglyceride c
Page 140 and 141: 127 Figure 18. Serum Spec cPL conce
Page 142 and 143: 129 Figure 19. 1-dimensional sliced
Page 144 and 145: 131 Dogs that did not respond to th
Page 146 and 147: 133 Hypertriglyceridemia has been l
Page 148 and 149: 135 degrees. One possible explanati
Page 150 and 151: 137 Footnotes a Royal Canin Gastroi
Page 152 and 153: 139 concentrations and lipoprotein
Page 154 and 155: 141 inclusion criteria for the stud
Page 156 and 157: 143 light source j , located in a d
Page 159 and 160: 146 Serum triglyceride and choleste
Page 161 and 162: 148 Figure 22. Serum triglyceride c
Page 163 and 164: 150 Figure 24. 1-dimensional sliced
Page 165 and 166: 152 Discussion The purpose of the p
Page 167 and 168: 154 fraction of these dogs (about 3
Page 169 and 170: 156 of lipoproteins might also have
Page 171: 158 Footnotes a Roche/Hitachi MODUL
Page 175 and 176: 162 times (P=0.0343) for a serum cP
Page 177 and 178: 164 peaks than dogs of other breeds
Page 179 and 180: 166 19.3; 95% CI, 2.0-184.0; P=0.00
Page 181 and 182: 168 4) Specific lipoprotein classes
Page 183 and 184: 170 REFERENCES 1949;8:96-97. 1. Lew
Page 185 and 186: 172 17. Whitney MS, Boon GD, Rebar
Page 187 and 188: 174 33. Ford RB. Clinical managemen
Page 189 and 190: 176 50. Nelson RW, Turnwald GH, Wil
Page 191 and 192: 178 66. Williams DA, Steiner JM. Ca
Page 193 and 194: 180 82. Yilmaz Z, Senturk S. Charac
Page 195 and 196: 182 97. Fojo SS, Stalenhoef AF, Mar
Page 197 and 198: 184 111. Lam CW, Yuen YP, Cheng WF,
Page 199 and 200: 186 127. Crispin SM. Ocular manifes
Page 201 and 202: 188 144. Lindsay S, Entenmann C, Ch
Page 203 and 204: 190 161. Steiner JM. Canine pancrea
Page 205 and 206: 192 176. Steiner JM, Teague SR, Wil
Page 207 and 208: 194 191. Steiner JM. Diagnosis of p
Page 209 and 210: 196 208. Talukdar R, Vege S. Recent
Page 211 and 212: 198 224. Koch K, Drewelow B, Liebe
Page 213 and 214: 200 241. Petrov MS, van Santvoort H
Page 215 and 216: 202 258. Ewald N, Hardt PD, Kloer H
Page 217 and 218: 204 274. Otvos JD, Jeyarajah EJ, Be
Page 219 and 220: 206 289. Carpentier YA, Scruel O. C
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