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Proceeding of the NAVC

North American Veterinary Conference
Jan. 13-27, 2007, Orlando, Florida

www.tnavc.org

Reprinted in the IVIS website with the permission of the NAVC

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Published in IVIS with the permission of the NAVC

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The North American Veterinary Conference 2007

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TRANS FATTY ACIDS ROLE IN PET

DIABETES MELLITUS
Patricia A. Schenck, DVM, PhD
Diagnostic Center for Population and Animal Health
Michigan State University, Lansing, MI
Diabetes mellitus is a chronic endocrine disorder that
affects both dogs and cats. The prevalence of diabetes
mellitus in cats has increased, and the incidence is
estimated to be approximately 1% of cats presented to
small animal veterinarians. Cats having an increased
body weight, or that are greater than 10 years of age are
at increased risk for the development of diabetes
mellitus.1 Clinical signs of diabetes mellitus include
polyuria, polydipsia, and polyphagia, and diagnosis is
based on the presence of clinical signs with persistent
fasting hyperglycemia and glycosuria.
Diabetes mellitus is typically classified as type I or
type II. Type I diabetes mellitus is most common in dogs,
is referred to as insulin-dependent diabetes mellitus
(IDDM), and is due to a lack of endogenous insulin.
IDDM is caused by an autoimmune destruction of the
pancreatic beta cells, and is indicated by the presence of
islet cell antibodies. Type II diabetes mellitus is most
common in cats, and is referred to as non-insulin
dependent diabetes mellitus (NIDDM). As in humans,
Type II diabetes mellitus is characterized by insulin
resistance, with an abnormal pattern of insulin
secretion.2 Insulin resistance occurs when cells become
resistant to the effects of insulin, and an elevated
concentration of insulin is required to maintain normal
blood glucose concentrations. An elevated serum
insulin:glucose ratio is indicative of insulin resistance,
and may precede the development of clinical signs of
diabetes mellitus. Persistent hyperglycemia results in
glucose toxicity which leads to impaired secretion of
insulin and loss of beta cells.3 This loss of beta cells may
lead to a need for exogenous insulin therapy. At a
metabolic level, insulin resistance is characterized by
inefficient insulin function in skeletal muscle, liver, and
adipocytes. The normal role of insulin is impaired, which
results in increased glucose uptake by muscle cells,
increased glycogen synthesis, and a stop in hepatic
glucose production. Especially in abdominal adipocytes,
triglyceride synthesis is negatively affected, and lipolysis
results in high levels of circulating free fatty acids. Any
part of the insulin-signaling pathway may be
compromised, including phosphatidylinositol-3-K (PI-3K), protein kinase B (PKB), protein kinase C (PKC), or
glucose transporter4 (GLUT4).4
LIPID ABNORMALITIES IN DIABETES MELLITUS
Diabetes mellitus is characterized by lipid metabolic
abnormalities in both humans and animals. Serum
triglyceride and cholesterol concentrations are elevated,
and very low density lipoproteins (VLDL) are also
increased due to impaired removal from the
circulation.5,6 Cholesterol synthesis is increased, and
lipoprotein lipase activity decreases with an increase in
free fatty acids. Low density lipoprotein (LDL) receptors

decrease, and there is increased delivery of cholesterol

to extrahepatic tissues.
Atherosclerosis is a specific type of arteriosclerosis
with deposition of lipid and cholesterol in arterial tunica
intima and tunica media. Dogs and cats are typically
resistant to the development of atherosclerosis since
they are HDL (high density lipoprotein) mammals where
HDL is the predominant cholesterol-carrying lipoprotein
(unlike humans).7 However, naturally occurring
atherosclerosis has been reported in association with
diabetes mellitus in dogs.8 Atherosclerosis in the
abdominal aorta, coronary, renal, arcuate, and carotid
arteries was noted at necropsy in a dog with poorly
controlled diabetes mellitus. In a more recent study of 30
dogs with atherosclerosis confirmed at necropsy, dogs
with atherosclerosis were 53 times more likely to have
diabetes mellitus.9
TYPES OF FATTY ACIDS IN FOODS
There are four major types of fatty acids in foods:
saturated, monounsaturated, polyunsaturated, and
trans-fatty acids. All fatty acids are chains of carbon
atoms with hydrogen atoms attached. Saturated fatty
acids contain no double bonds between carbon atoms,
and thus the carbons are saturated with the maximum
number of hydrogen atoms. Saturated fats are usually
solid at room temperature, and are quite stable so they
do not become rancid very quickly. Saturated fats are
found in meats and whole-milk dairy products.
Monounsaturated fatty acids contain one double bond in
the carbon chain. They are liquid at room temperature
but start to become solid when refrigerated.
Monounsaturated fats are found in canola, olive, and
peanut oils, and most nuts. Polyunsaturated fats have
multiple double bonds in the carbon chain.
Polyunsaturated fats are liquid at both room temperature
and in refrigeration. They are less stable, and will easily
combine with oxygen to become rancid. Polyunsaturated
fats are found in fatty fish (salmon, mackerel), corn,
soybean, safflower, sesame, and sunflower oils, and
walnuts.
Trans-fatty acids (TFA) are a specific type of
monounsaturated or polyunsaturated fats. Most naturally
occurring unsaturated fatty acids are in the cisconfiguration, meaning that the hydrogen atoms are on
the same side of the double bond. In a trans-fatty acid,
the hydrogen atoms are on opposite sides of the double
bond. TFA are found naturally in meat (beef, pork, and
lamb) and dairy products due to the microbial
hydrogenation of cis-unsaturated fatty acids in the rumen
or intestines. The predominant trans-fat in ruminants is
vaccenic acid, from which conjugated linoleic acid (CLA)
can be formed. High levels of TFA are created in
partially hydrogenated vegetable or fish oils, and TFA
may also be found in refined edible oils or ruminant fats
due to the high temperatures used in the deodorization
process. Vegetable and fish oils have a high content of
unsaturated fatty acids, and are prone to oxidation.
Industrial hydrogenation increases the stability, and
extends the shelf-life of the oil. The TFA content of
partially hydrogenated oils can range from 10 to 60 g

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Small Animal Nutrition

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per 100 g of oil, with an average of about 45 g TFA/
100 g oil. The concentration of TFA in ruminant fats is
approximately 5 to 8 g/100 g fat.10
HEALTH RISKS OF TRANS-FATTY ACIDS
In recent years, a great deal of research has focused
on the health effects of dietary TFA in humans. In almost
85,000 women followed for 16 years, trans-fat intake
was positively associated with the incidence of diabetes,
with an increased risk of 39% in the highest TFA intake
group.11 Dietary TFA appear to potentiate insulin
secretion which reflects chronic alterations in insulin
sensitivity.12 In cultured pancreatic beta cells, both cisand trans-fatty acids caused a dose-dependent increase
in glucose-stimulated insulin secretion; however, the
trans-isomers elicited a higher insulin release than did
cis-isomers.13 In humans with type II diabetes mellitus
fed 5% energy (5 E%) from TFA, the serum postprandial
insulin concentrations were higher as compared to when
saturated fatty acids were fed (no TFA present in the
diet).14 When 1 E% from cis-linoleic acid was replaced
with TFA in the diet, insulin sensitivity of adipocytes
decreased significantly in rats, indicating an increase in
insulin resistance.15 In a 14-year prospective study with
humans, an increase of 2 E% from TFA substantially
increased the risk of type II diabetes mellitus, and it was
estimated that replacing 2 E% from TFA with
polyunsaturated fat would lead to a 40% lower risk for
the development of type II diabetes mellitus.16 In recent
years, conjugated linoleic acid (CLA) has received
national attention due to its reported effects resulting in
weight loss. However, both the trans-10, cis-12 and
cis-9, trans-11 isomers of CLA have been shown to
increase proinsulin, and decrease cellular insulin
sensitivity, which is worrisome since these TFA are
included in many over-the-counter weight loss
preparations.17
Dietary TFA may influence the expression of insulin
resistance in those that are genetically predisposed. A
polymorphism at codon 54 in fatty acid-binding protein 2
(FABP2) has been suggested to modify interactions
between dietary fat and insulin sensitivity. In humans
with this polymorphism, a single meal containing TFA
significantly increased insulin resistance and contributed
to partitioning of glucose to triglycerides.18 Other
mechanisms of the effects of TFA on insulin resistance
are being explored. Trans-10, cis-12 CLA resulted in
suppression of insulin-stimulated glucose uptake by
human adipocytes, with decreased plasma membrane
glucose transporter 4 proteins.19 In rats, the feeding of
1.5% TFA upregulated the mRNA levels of resistin, and
downregulated the peroxisome proliferator-activated
receptor gamma (PPARgamma).20 TFA also decreased
lipoprotein lipase (LPL) activity, which is an important
enzyme for chylomicron and VLDL clearance. Results
have suggested that TFA alter the expression of different
genes associated with insulin sensitivity in adipocytes.
Dietary TFA also affect lipid metabolism and increase
the risk of cardiac disease. TFA intake is positively
associated with markers of systemic inflammation, and is
associated with systemic inflammation in those with pre-

existing heart disease.21 Concentrations of C-reactive

protein, tumor necrosis factor receptors, E-selectin,
interleukin-6, and vascular cell adhesion molecules are
all unfavorably affected by TFA intake. TFA induce
higher fatty acid oxidation than do cis-isomers,22 and
adversely affect endothelial function,23 both of which can
contribute to the development of atherosclerosis. Dietary
TFA are associated with an increase in LDL cholesterol
with a decrease in HDL.24 Replacement of dietary
saturated fats by TFA impaired flow-mediated
vasodilation of arteries which increases the risk for
cardiac disease. In addition, TFA may increase the risk
of endothelial cell calcification.25 All of these effects
could potentiate the development of atherosclerosis,
especially in those patients with type II diabetes mellitus
and other concurrent lipid abnormalities.
Not all TFA appear to be metabolized the same with
equal actions. Pro-inflammatory effects appear to be
stronger from trans-isomers of linoleic acid (trans-C18:2)
and oleic acid (trans-C18:1) than from trans-palmitoleic
acid (trans-C16:1).26 Humans fed trans-10, cis-12 CLA
had higher triglyceride, cholesterol, and LDL-cholesterol
concentrations than did those fed cis-9, trans-11 CLA.27
In humans in the United States, the average
consumption of TFA is 5.8 g/day,10 but this consumption
may be much higher in those consuming an excess of
products containing highly processed oils (margarine,
chocolate, fried-foods).28 Because of the health risks
associated with an increased consumption of TFA, the
Danish government mandated that fats and oils
containing more than 2% TFA would not be sold after
2003,28 and the Health Council of the Netherlands
recommended limiting TFA to 1% of energy
consumption.29 In Denmark, consumption of TFA has
decreased from 8.5 g/day in 1976 to 2.6 g/day. A
simultaneous 50% decrease in deaths from heart
disease has been observed in the Danish population
over this period.28 In 1999, the FDA proposed to require
TFA content on food labels. After deliberation, in 2003
the FDA issued the ruling requiring that TFA and
saturated fatty acids be itemized separately in the
Nutrition Facts label of food products, with an effective
date of January 1, 2006.10
Currently, little is known regarding the presence and
effects of TFA in animal diets. Commercial pet diets may
contain fats from various sources (chicken, beef, pork,
vegetable), and these fats are often processed, refined
and deodorized. In addition, TFA especially in the form
of CLA are likely to be present in pet foods, as they are
derived from animal meats. In initial analysis of a
number of commercial over-the-counter and prescription
dog and cat diets, a wide variation in TFA concentration
has been observed. Some diets provide TFA at
concentrations greater than 1 E%, which in other
species, has been shown to increase insulin resistance.
Since trans-fatty acids may interfere with cell membrane
functions, there is reason to believe that TFA intake
could affect insulin sensitivity and diabetes risk in pets.
In addition, it is possible that low amounts of TFA
consumed over long time periods may be clinically
relevant.30 Certainly, insulin resistance and cardiac

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Proceedings of the NAVC Congress, Orlando Florida 2007

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The North American Veterinary Conference 2007

______________________________________________________________________________________________
abnormalities related to TFA intake have been shown in
many human studies, and it would most likely be wise to
minimize the TFA content of foods designed for those
patients with diabetes mellitus, or at risk for development
of diabetes.
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