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    http://ncp.sagepub.com/Nutrition in Clinical Practice

    http://ncp.sagepub.com/content/27/4/553The online version of this article can be found at:

    DOI: 10.1177/0884533612444535

    2012 27: 553 originally published online 1 June 2012Nutr Clin PractIzabella Candido Carvalho Crochemore, Aline F. P. Souza, Andressa C. F. de Souza and Eliane Lopes Rosad

    Resistance, and Lipemia in Women With Type 2 Diabetes and Obesity

    -3 Polyunsaturated Fatty Acid Supplementation Does Not Influence Body Composition, Insuli

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    The American Society for Parenteral & Enteral Nutrition

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    What is This?

    - Jun 1, 2012OnlineFirst Version of Record

    - Jul 20, 2012Version of Record>>

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    Nutrition in Clinical Practice

    Volume 27 Number 4

    August 2012 553-560

    2012 American Society

    for Parenteral and Enteral Nutrition

    DOI: 10.1177/0884533612444535

    http://ncp.sagepub.com

    hosted at

    http://online.sagepub.com

    Clinical Research

    Diabetes mellitus is a nontransmittable chronic disease (NTCD)

    that affects individuals worldwide.1 The worldwide mortality

    estimate was 987,000 in 2002, which corresponds to 1.7% of

    the total deaths in the world.2 In Brazil, a multicenter popula-

    tion base study carried out in 1988 in 9 capitals of Brazilian

    states demonstrated that the predominance of diabetes mellitus

    and glucose intolerance in the urban population (30 and 69

    years) was 7.6% and 7.8%, respectively, and almost half of this

    total was not aware that they had glucose intolerance (46%). 3

    Type 2 diabetes mellitus (T2DM) is a multiple-etiology dis-

    ease characterized by chronic hyperglycemia, resulting from

    the deficiency of insulin and/or the inability to mediate insulin

    receptor signals, with subsequent insulin resistance (IR).4 Its

    risk reduction and control can be carried out by changes in

    lifestyle. Obesity and sedentarianism are important risk factors

    for T2DM development.5,6

    In addition, obesity is considered a risk factor for insulin

    resistance, mainly the deposition of visceral fat, which can

    result in pathophysiological alterations such as reduced insulin

    extraction by the liver, increased hepatic production of glu-

    cose, and reduced glucose uptake by muscular tissue.7

    T2DM can result in micro- and macrovascular alterations

    over time and is also associated with dyslipidemia, systemic

    hypertension, and endothelial dysfunction.4 Because T2DM is

    one of the main NTCDs that raise the morbidity and mortality

    in the population and is related to IR, dyslipidemia, and obesity,

    it becomes important to propose alternative treatments that

    improve the prognosis of individuals with T2DM. Thus, the

    quantity and quality of the fats in the diet, mainly series 3 poly-

    unsaturated fatty acids (-3 PUFAs), have been considered by

    researchers. -3 PUFAs can be associated with a reduction in

    serum triglyceride (TG) levels, platelet aggregation, and car-

    diac arrhythmias8 and improvement in body composition.9

    Epidemiologic and clinical evidence demonstrates the cardio-

    protective effects of -3 PUFA, despite modest or no changes

    in the concentrations of lipids and lipoproteins in the blood. 10

    . /

    From the Instituto de Nutrio Josu de CastroUniversidade Federal do

    Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.

    Financial disclosure: This work was supported by the Fundao de

    Amparo Pesquisa do Estado do Rio de Janeiro (FAPERJ).

    Dr Crochemore was responsible for creating the concept and design of

    the study; generation, collection, assembly, analysis and interpretation of

    the data; and revision and approval of the final version of the manuscript;

    Dr Rosado was responsible for creating the concept of the study; analysis

    and interpretation of the data; and revision and approval of the final

    version of the manuscript; Drs Aline F. P. Souza and Andressa C. F. de

    Souza were responsible for collaboration in data collection and approval

    of the final version of the manuscript.

    Corresponding Author: Eliane Lopes Rosado, Universidade Federal do

    Rio de Janeiro, Centro de Cincias da SadeInstituto de Nutrio Josu

    de Castro., Avenida Brigadeiro Trompovisky, s/n, Bloco J, 2 andar,

    sala 24CEP: 21949-900, Brazil; e-mail: [email protected],

    [email protected].

    -3 Polyunsaturated Fatty Acid Supplementation Does Not

    Influence Body Composition, Insulin Resistance, and Lipemia

    in Women With Type 2 Diabetes and Obesity

    Izabella Candido Carvalho Crochemore, MSc; Aline F. P. Souza; Andressa C. F. de Souza;

    and Eliane Lopes Rosado, PhD

    Abstract

    To evaluate the influence of -3 polyunsaturated fatty acid (-3 PUFA) supplementation on body composition, insulin resistance, and

    lipemia of women with type 2 diabetes, the authors evaluated 41 women (60.64 7.82 years) with high blood pressure and diabetes

    mellitus in a randomized and single-blind longitudinal intervention study. The women were divided into 3 groups: GA (2.5 g/d fish

    oil), GB (1.5 g/d fish oil), and GC (control). The capsules with the supplement contained 21.9% of eicosapentaenoic acid and 14.1%

    of docosapentaenoic acid. Biochemical (glucose, glycated hemoglobin, total and fractional cholesterol, triglycerides, and insulin) and

    anthropometric (body mass, stature, waist circumference [WC], and body composition) evaluations were performed before and after the

    30 days of intervention. Homeostasis model assessmentinsulin resistance and the Quantitative Insulin Sensitivity Check Index were usedto evaluate the insulin resistance and insulin sensitivity (IS), respectively. GB presented a greater loss of body mass and WC (P< .05),

    greater frequency of glycemic and total cholesterol reduction, and an increase of high-density lipoprotein cholesterol compared with GA.

    Thus, a high dose of -3 PUFA can reduce IS. A lower dose of -3 PUFA positively influenced body composition and lipid metabolism.

    (Nutr Clin Pract. 2012;27:553-560)

    Keywords

    diabetes mellitus; diabetes mellitus, type 2; fatty acids, -3; hyperlipidemias; body composition; insulin resistance

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    554 Nutrition in Clinical Practice27(4)

    The promising effects of fish oil consumption, a source of

    -3 PUFA, in the health industry are controversial due to

    research that emphasizes the harmful effects in the glycemic

    control of patients with diabetes mellitus.11 However, other

    studies demonstrate that a low intake of PUFAs, mainly -3, is

    associated with an increased risk of T2DM in women.12-14

    The present study suggests that -3 PUFA supplementationcould improve lipemia and glycemia and reduce body weight.

    Therefore, the aim of this study was to evaluate the influence

    of the supplemented diet with different doses of -3 PUFA on

    body composition, insulin resistance, and lipemia in women

    with T2DM.

    Materials and Methods

    Population

    We evaluated women with T2DM who participated in the

    High Blood Pressure and Diabetes Program of the Municipal

    Hospital Carlos Tortely, in Niteri, Rio de Janeiro, Brazil.

    The study was approved by the Research Ethics Committee

    of the Hospital Clementino Fraga Filho (protocol 067/07).

    The eligibility criteria included menopausal women diag-

    nosed with T2DM and grade 1 and 2 hypertension who were

    nonsmokers with noncongenital heart disease and no recent

    infectious diseases.

    Experimental Design

    A randomized, single-blind clinical intervention study was

    conducted.

    After a 12-hour overnight fast, blood samples were col-lected in the antecubital vein for analyses of serum levels of

    glucose, glycated hemoglobin (A1c), total cholesterol, TG, and

    insulin. Afterward, anthropometric evaluation (total body

    mass, stature, waist circumference [WC], and body composi-

    tion) was carried out.

    The women were randomly placed into 3 groups, composed

    of 2 test groups (-3 PUFA supplementation in different doses)

    and 1 control, which received the respective capsules to be

    taken daily for 30 days. The women were instructed to main-

    tain their usual diet and physical activity.

    Follow-up visits occurred every 15 days for intervention

    control and distribution of capsules for the next 15 days. After

    30 days, biochemical and anthropometric evaluations were

    carried out while patients were in a fasting state.

    Dietetic Intervention

    Group A (GA) received capsules containing 2.5 g fish oil

    (547.5 mg eicosapentaenoic acid [EPA] and 352.5 mg docosa-

    pentaenoic acid [DHA]) (n = 14), Group B (GB) received 1.5

    g fish oil (328.5 mg EPA and 211.5 mg DHA) (n = 14), and the

    Group C (GC) received the placebo (n = 13). The capsules

    with the supplement contained 21.9% of EPA and 14.1% of

    DHA per gram and were gelatinous, colorless, and oblong.

    The placebo capsules were composed of gelatin. All the cap-

    sules were the same volume (500 mg) and contained vitamin

    E in the same amount. The use of the capsules was controlled

    by counting the remaining capsules during subsequent visits.

    Anthropometric Evaluation and Body

    Composition

    Total body mass and stature were measured according to

    Gibson,15 using a mechanical anthropometric balance (Welmy,

    Santa Brbara dOeste, SP, Brazil), with a maximum capacity of

    150 kg, divided by 100g, and the stadiometer from the anthropo-

    metric balance with a scale of 0.1 cm. The volunteers were

    weighed with minimum clothes possible and while barefoot.

    Based on these variables, body mass index (BMI) was calcu-

    lated.16 To measure the WC, an unextendable and inelastic tape

    was used. The WC was measured at the midpoint between the

    last rib and the iliac crest, with the arms and abdomen relaxed.

    WC values above 80 and 88 cm were associated with an

    increased and very increased risk of metabolic complications

    associated with obesity, respectively.17

    Body composition was evaluated by electric bioimpedance

    (Biodynamics Corp, Seattle WA), which is based on the prin-

    ciple of the bodys resistance to the passage of an electric cur-

    rent in hydrated tissue, making it possible to obtain total body

    water (TBW) and lean mass (LM). The difference of the total

    body mass to LM results in the total body fat (TBF) estimate,

    considering the 2-compartment body model.18

    Biochemical Evaluation

    The serum TG levels were determined by the enzymatic-

    colorimetric method (Triglicrides GPO-ANA Liquiform;

    Diagnostic Labtest S.A., Lagoa Santa, MG, Brazil), as indi-

    cated by McGowan et al.19 The serum concentrations of total

    cholesterol, high-density lipoprotein (HDL)cholesterol and

    glucose were analyzed by the enzymatic-colorimetric method

    (Cholesterol Liquiform, HDL-c LE, and Glucose Pad

    Liquiform, respectively; Diagnostic Labtest S.A., Lagoa

    Santa, MG, Brazil).20-22 The concentrations of low-density

    lipoprotein (LDL)cholesterol were calculated based on the

    Friedwald equation.23 To determine the hemoglobin A1c

    level, the turbidimetric inhibition immunoassay technique

    was carried out (TINIA) on the total hemolysate blood (com-

    mercial kit HBA1C II; Roche Diagnostics, Mannheim,

    Germany). The serum insulin was determined by radioimmu-

    noassay (RIA) (insulin Coat-a-Count; Diagnostic Products

    Corporation, Los Angeles, CA). Homeostasis model assess-

    mentinsulin resistance (HOMA-IR) and Quantitative Insulin

    Sensitivity Check Index (QUICKI) were used to do the insu-

    lin resistance (IR) and insulin sensitivity (IS) calculations,

    respectively.24,25

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    -3 Polyunsaturated Fatty Acid Supplementation in Type 2 Diabetes and Obesity / Crochemore et al 555

    Statistical Analysis

    Data are presented as mean and standard deviation. To assess the

    distribution of continuous variables, the Kolmogorov-Smirnov

    test was used, which showed a nonparametric distribution.

    For comparisons between groups, the nonparametric

    Kruskal-Wallis (3 groups) and Mann-Whitney (2 groups) tests

    were carried out. To verify the effect of the intervention in eachtest group, we carried out the Wilcoxon test.

    Statistical analysis of data was performed using the Statistical

    Package for Social Sciences software Version 16.0 (SPSS, Inc,

    an IBM Company, Chicago, IL), consideringP< .05.

    Results

    Characteristics of the Groups at Baseline

    Of 45 women selected, 41 were evaluated (age 60.78 7.82

    years), being GA, GB, and GC (age 60.64 7.37, 60.00

    7.49, and 61.83 9.07 years, respectively; P> .05). Eightypercent of the women used the oral antidiabetic medications

    metformina (metformin) and 61% glibenclamida (glyburide).

    The baseline anthropometric and biochemistry parameters

    of the groups are presented in Table 1. GC presented with

    higher TBF and lower LM levels compared with GB (P< .05);

    however, this did not differ from GA. The serum insulin level

    was greater in GC compared with GA and GB (P< .05). The

    remaining variables did not differ between groups (P> .05).

    All women presented with excess body mass, central hyperadi-

    posity, fasting hyperglycemia, and IR.

    Characteristics of the Groups After the

    Intervention

    The anthropometric and biochemical parameters between

    groups, after the intervention, are presented in Table 2. GC

    presented with higher TBF and lower LM compared with GA

    and GB (P< .05). It is important to note that before the inter-

    vention, GC differed only from GB. The remaining variablesdid not differ between groups (P > .05), except the serum

    insulin level that was greater in GC at baseline.

    After the evaluation of the effect of the intervention in each

    individual group, it could be noted that GB had a reduction in

    BMI and WC. GC experienced an increase in TBW, a reduc-

    tion of TBF, and consequently an increase in LM (P< .05).

    Also, a tendency could be seen in the reduction of BMI (P=

    .08) and an increase of A1C (p=0.09) in GC (Table 3 and

    Figure 1).

    Evaluating the frequency of alterations in the anthropomet-

    ric and biochemistry parameters, it was found that 35.7%,

    71.4%, and 30.77% of the women in GA, GB, and GC, respec-tively, experienced a BMI reduction. The WC decreased in

    64.3%, 64.3%, and 53.8% of the women in GA, GB, and GC,

    respectively. As for TBF, there was a reduction in 64.3%,

    57.14%, and 69.23% of the women in GA, GB, and GC,

    respectively. Hyperglycemia was reduced in 35.7%, 42.9%,

    and 30.8% of the women in GA, GB, and GC, respectively.

    The serum A1C level also decreased in 14.3%, 35.7%, and

    7.69% in the same groups. There was a reduction of serum

    levels of total cholesterol, LDL-cholesterol, and TG in 42.8%,

    54.1%, and 46.1%; 50%, 50%, and 38.5%; and 57.1%, 64.3%,

    Table 1. Anthropometric and Biochemical Variables (Mean SD) of Groups at Baseline

    Group A (n = 14) Group B (n = 14) Group C (n = 13)

    Variables Mean SD Mean SD Mean SD PValue

    BMI, kg/m2

    29.86 5.97 30.88 6.76 33.82 5.17 .17

    WC, cm 98.29 14.02 96.36 12.95 105.08 9.03 .19

    TBW, L 35.34 6.38 34.86 4.31 35.49 6.08 .88

    TBF, % 34.90 6.16 34.57 6.85 40.33a

    3.21 .02

    LM, % 65.02 6.16 65.43 6.85 59.67a

    3.21 .03

    Glucose, mg/dL 197.64 82.30 142.93 50.75 144.46 49.33 .07

    Glycated hemoglobin, % 7.94 2.52 6.54 1.45 6.50 1.39 .28

    Insulin, U/mL 7.91 6.15 8.56 4.24 13.77ab

    6.67 .02

    HOMA-IR 3.95 4.59 2.89 1.41 5.30 4.22 .11

    QUICKI 0.33 0.03 0.34 0.03 0.31 0.03 .14

    Cholesterol, mg/dL 214.07 36.52 199.0 24.48 203.83 50.48 .56

    LDL-cholesterol, mg/dL 137.0 33.91 123.79 25.79 120.92 36.62 .57

    HDL-cholesterol, mg/dL 51.43 10.46 48.0 14.71 47.85 11.13 .33

    Triglycerides, mg/dL 132.93 69.35 149.21 102.50 161.75 116.23 .81

    Differences between groups were tested with the Kruskal-Wallis test at 5% probability, and the Mann-Whitney test was used for analysis posttest. BMI,body mass index; HDL, high-density lipoprotein; HOMA-IR, homeostasis model assessmentinsulin resistance (HOMA-IR); LDL, low-density lipopro-

    tein; LM, lean mass; QUICKI, Quantitative Insulin Sensitivity Check Index; TBF, total body fat; TBW, total body water; WC, waist circumference.aP< .05 vs GB.

    bP< .05 vs GA.

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    556 Nutrition in Clinical Practice27(4)

    Table 2. Anthropometric and Biochemical Variables (Mean SD) of Groups After the Intervention

    Group A (n = 14) Group B (n = 14) Group C (n = 13)

    Variables Mean SD Mean SD Mean SD PValue

    BMI, kg/m2

    29.74 6.02 30.59 6.55 33.93 5.32 .14

    WC, cm 97.86 14.42 94.71 12.66 104.92 9.00 .13

    TBW, L 35.81 6.16 34.54 4.22 36.30 5.80 .85

    TBF, % 34.32 6.67 34.20 6.17 39.23a,b

    3.60 .05

    LM, % 65.68 6.68 65.81 6.17 60.77a,b

    3.60 .05

    Glucose, mg/dL 208.71 85.54 153.07 62.06 161.15 50.08 .10

    Glycated hemoglobin, % 8.15 2.26 6.76 1.88 7.24 1.44 .15

    Insulin, U/mL 10.42 7.33 10.24 6.29 13.69 5.78 .20

    HOMA-IR 5.23 4.39 3.99 2.92 5.55 3.52 .34

    QUICKI 0.31 0.03 0.33 0.04 0.31 0.02 .39

    Cholesterol, mg/dL 218.29 36.81 196.00 27.77 204.62 45.70 .24

    LDL-cholesterol, mg/dL 142.43 29.93 122.86 22.97 125.15 31.93 .16

    HDL-cholesterol, mg/dL 52.29 12.52 50.21 15.90 47.77 10.01 .53

    Triglycerides, mg/dL 123.14 64.48 120.07 74.96 168.15 105.37 .27

    Differences between groups were tested with the Kruskal-Wallis test at 5% probability, and the Mann-Whitney test was used for analysis posttest. BMI,body mass index; HDL, high-density lipoprotein; HOMA-IR, homeostasis model assessmentinsulin resistance (HOMA-IR); LDL, low-density lipopro-

    tein; LM, lean mass; QUICKI, Quantitative Insulin Sensitivity Check Index; TBF, total body fat; TBW, total body water; WC, waist circumference.aP< .05 vs GB.

    bP< .05 vs GA.

    Table 3. Evolution of Anthropometric and Biochemical Variables (Mean SD) of the Groups After the Intervention

    Group A (n = 14) Group B (n = 14) Group C (n = 13)

    Variables Basal After Basal After Basal After

    BMI, kg/m2

    29.86 5.97 29.74 6.02 30.88 6.76 30.59 6.55a

    33.82 5.17 33.93 5.32

    WC, cm 98.29 14.02 97.86 14.42 96.36 12.95 94.71 12.66a

    105.08 9.03 104.92 9.00

    TBW, L 35.34 6.38 35.81 6.16 34.86 4.31 34.54 4.22 35.49 6.08 36.30 5.80

    a

    TBF, % 34.90 6.16 34.32 6.67 34.57 6.85 34.20 6.17 40.33 3.21 39.23 3.60a

    LM, % 65.02 6.16 65.68 6.68 65.43 6.85 65.81 6.17 59.67 3.21 60.77 3.60a

    Glucose, mg/dL 197.6 82.3 208.7 85.54 142.9 50.75 153.1 62.06 144.5 49.33 161.2 50.08

    Glycated hemoglobin, % 7.94 2.52 8.15 2.26 6.54 1.45 6.76 1.88 6.50 1.39 7.24 1.44

    Insulin, mU/mL 7.91 6.15 10.42 7.33 8.56 4.24 10.24 6.29 13.77 6.67 13.69 5.78

    HOMA-IR 3.95 4.59 5.23 4.39 2.89 1.41 3.99 2.92 5.30 4.22 5.55 3.52

    QUICKI 0.33 0.03 0.31 0.03 0.34 0.03 0.33 0.04 0.31 0.03 0.31 0.02

    Cholesterol, mg/dL 214.1 36.52 218.3 36.81 199.0 24.48 196.0 27.77 203.8 50.48 204.6 45.70

    LDL-cholesterol, mg/dL 137.0 33.91 142.4 29.93 123.8 25.79 122.9 22.97 120.9 36.62 125.2 31.93

    HDL-cholesterol, mg/dL 51.43 10.46 52.29 12.52 48.00 14.71 50.21 15.90 47.85 11.13 47.77 10.01

    Triglycerides, mg/dL 132.9 69.35 123.1 64.48 149.2 102.5 120.1 74.96 161.8 116.2 168.2 105.4

    Differences between groups were tested with the Wilcoxon test at 5% probability. BMI, body mass index; HDL, high-density lipoprotein; HOMA-IR,

    homeostasis model assessmentinsulin resistance (HOMA-IR); LDL, low-density lipoprotein; LM, lean mass; QUICKI, Quantitative Insulin SensitivityCheck Index; TBF, total body fat; TBW, total body water; WC, waist circumference.aSignificant at 5% probability, by ttest.

    and 53.8% in GA, GB, and GC, respectively. There was an

    increase of serum HDL-cholesterol concentration in 42.9%,

    50%, and 38.9% of the women in GA, GB, and GC,

    respectively.

    The HOMA-IR decreased in 21.4%, 35.7%, and 38.5% of

    the women in GA, GB, and GC, respectively. Regarding the

    QUICKI, which represents the IS, there was a reduction of

    85.7%, 57.1%, and 61.5% in these groups.

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    -3 Polyunsaturated Fatty Acid Supplementation in Type 2 Diabetes and Obesity / Crochemore et al 557

    Discussion

    The incidence of T2DM has increased markedly worldwide,

    particularly in association with cardiovascular disease (CVD),

    especially among women. Studies indicate that IR is an impor-

    tant factor for the pathogenesis of T2DM.25, 26 Genetic factors

    and high body weight, particularly visceral adiposity, are

    directly associated with the pathogenesis of IR and T2DM

    development.27

    In the present study, the groups were homogeneous in terms

    of gender, age, and the remaining anthropometric and dietetic

    parameters, except TBF, LM, and serum insulin levels, which

    were higher in GC. However, the parameters of interest (IR andIS) did not differ between groups at baseline. Despite the main-

    tenance of the diet habitually ingested by the volunteers, an

    influence from supplementation with -3 PUFA was observed

    in body weight, with a greater loss of total body mass in GB. The

    largest dose of -3 PUFA did not influence weight and body

    composition. GB experienced a reduction of WC, an important

    marker of visceral adiposity, which can represent a reduction of

    metabolic complication risks associated with obesity.17

    The measurement of WC accurately predicts the quantity of

    adipose visceral tissue, although Desprs28 reported that the

    way in which body fat is distributed is more important than the

    quantity to determine individual risk of NTCDs. The excess of

    total body mass and/or obesity is present in a majority of

    patients with T2DM, which can result in an increased risk of

    CVD.29 Qiao and Nyamdori30 conducted a systematic review

    using 17 prospective and 35 cross-sectional studies in adults

    aged 1874 years, with the aim of comparing the BMI, WC,

    and waist-to-hip ratio (WHR) and their relation to the inci-

    dence and prevalence of T2DM. The study concluded that

    either BMI or WC predicted T2DM, regardless of the contro-

    versial results about what is a best obesity indicator.

    Other researchers have evaluated the effect of -3 fatty

    acids on body fat. Kabir et al31 analyzed the effect of -3 PUFA

    supplementation for 2 months on the reduction of adiposity

    and of some atherogenic effects in 26 women with T2DM in a

    randomized and double-blind controlled study. They did not

    observe changes in total body mass; however, the fat mass

    (mainly in the region between the shoulders and hip) wasreduced in the group supplemented with -3 PUFA (1.8 g)

    compared with placebo. Derosa et al12 also did not find varia-

    tion of body weight or BMI between groups that consumed 1 g

    -3 PUFA vs placebo. Peyron-Caso et al32 observed the same

    result in their study. In the present study, GC had reductions of

    TBF, which was not observed in the supplemented groups.

    However, the reduction of TBF could be the result of the larger

    TBF presented by these women at baseline.32

    Favorable results in GB were observed in terms of glucose

    metabolism, found by the greater frequency of hyperglycemia

    and A1C reduction, compared with the other groups. However,

    the fasting insulin difference that existed at baseline (higher

    insulin levels in GC compared with the other groups) was not

    maintained after the intervention, suggesting that women who

    did not receive the supplementation reached insulinemia val-

    ues similar to those of the supplemented groups. Furthermore,

    despite the absence of statistical differences, there was an

    absolute increase in the serum insulin concentrations in the

    supplemented groups, which did not occur with placebo.

    In the 1980s, it was observed that supplementation with -3

    PUFA resulted in an increase of insulin requirements, serum

    A1C concentrations, and fasting and postprandial hyperglyce-

    mia in patients with type 1 and type 2 diabetes mellitus.11,33

    However, some of these earlier studies did not have a control

    group, and the dosage of -3 PUFA was, in some cases, ele-vated for diabetic and nondiabetic patients (1016 g/d instead

    of 3 g/d). In another study, -3 PUFA supplements did not

    cause adverse effects in glycemic control.34

    Sirtori et al35 carried out a randomized multicenter study

    evaluating 89 patients with T2DM supplemented with EPA +

    DHA for 6 months, initially with 2.6 g/d (2 months) and fol-

    lowed by 1.7 g/d (4 months) using olive oil as a placebo.

    Differences were not observed between the groups in terms of

    fasting glucose and insulin. Supplementation was offered with

    1.7 g/d to all patients for 6 additional months, and worsening

    in glycemic control was not found after 1 year of treatment.

    Despite some reports of worsening metabolic during treatment

    with -3 PUFA, the authors suggest that it could be a result of

    the natural course of the disease.

    The results in the present study suggest a tendency for there

    to be a negative influence from supplementation and its dosage

    on glycemic control, considering that the group that received

    the largest dose of the -3 PUFA showed a tendency toward

    reduction of IS and a high frequency of reduced serum glucose

    levels. IR increased in all the groups, similar to the study by

    Geloneze et al36 carried out with Brazilian individuals with

    Figure 1. Evolution of anthropometric variables (mean

    standard deviation) that differed after intervention by group.

    BMI 1, body mass index baseline; BMI 2, body mass index final;

    WC 1, waist circumference baseline; WC 2, waist circumference

    final; TBW 1, total body water baseline; TBW 2, total body water

    final; TBF 1, total body fat baseline; TBF 2, total body fat final;

    LM 1, lean mass baseline; LM 2, lean mass final. * represents

    statistically different variables.

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    558 Nutrition in Clinical Practice27(4)

    metabolic syndrome. It is worth pointing out that the women in

    the current study had a high WC and were hypertensive and

    obese, thus having metabolic syndrome characteristics.

    On the other hand, studies have also demonstrated that

    high-PUFA diets, particularly -3, present antiobesity effects

    and improve insulin action through several metabolic

    effects.37,38

    The IS can improve as a result of the effects of theconsumption of fatty acids in the fluid membrane.39,40 The

    increase in glucose uptake occurs after the membrane is

    enriched with PUFA, apparently related to GLUT4 (glucose

    transporter 4) in the plasmatic membrane, which drives the

    intracellular expansion of glucose-6-phosphate and the

    increase in glycogen synthesis in the skeletal muscle.40 These

    effects on IS and glycemic metabolism are a result of the con-

    sumption of -3 PUFA, which can be explained as a conse-

    quence of the alteration in the composition of the serum fatty

    acid.41

    In GB, favorable results were observed in serum lipid lev-

    els, as suggested by the greater frequency of reduced serum

    levels of total cholesterol and TG and increased HDL-

    cholesterol, compared with the other groups. Despite Kris-

    Etherton et al42 affirming that supplementation with -3 PUFA

    at the maximum dose of 4 g/d is recommended for individuals

    with hypertriglyceridemia, the present study demonstrated that

    the lower dose (GB) was more efficient in reducing total cho-

    lesterol and TG compared with the high dose.

    West et al43 found similar results with the supplementation

    of -3 PUFA (replacing 7.8% of EPA and DHA of 50 g fat

    from high oleic safflower and canola oils) in adults with

    T2DM, in which a reduction in serum TG concentrations in

    individuals who presented with hypertriglyceridemia was

    observed. Although a small increase in serum LDL-cholesterollevels occurred, the increase in serum HDL-cholesterol con-

    centration might compensate for this result, due to its benefi-

    cial effect on CVD.

    McEwen et al44 observed in their review that diets rich in

    fish and -3 PUFA may reduce cardiovascular risk in individu-

    als with DM by inhibiting platelet aggregation, improving

    lipid profiles, and reducing mortality from CVD.

    It should be emphasized that the results presented in the

    studies are contradictory because of variations in the number

    of evaluated patients, as well as the dose of -3 PUFA used

    and the intervention period. In a review published by De

    Caterina et al,45 85.4% of the total evaluated studies included

    studies with fewer than 40 subjects, 14.6% of interventions

    were carried out for a month, 19.5% of studies supplemented

    individuals with -3 PUFA for less than a month, and 73.2% of

    studies had less than a month of intervention.

    Despite our suggestion that the increase in monitoring time

    could account for results distinct from those found in the pres-

    ent study, the results still remain inconclusive. A study carried

    out by Popp-Snijders et al46 with 6 T2DM patients who

    received a dose of 3 g/d of -3 PUFA for 8 weeks showed a

    reduction in serum TG levels. Annuzzi et al47 evaluated 8

    patients with T2DM who received 3 g/d -3 PUFA for 2 weeks

    and also showed a reduction in TG. However, they also had an

    increase in LDL-cholesterol. On the other hand, Pelikanova et

    al48 evaluated 20 patients with T2DM for 3 weeks with a dose

    of 3.1 g/d -3 PUFA and did not find alterations in the param-

    eters referring to lipemia and glycemia. This result matches thepresent study, although Pelikanova et al studied fewer numbers

    of patients for less time, despite the higher dose.

    Kris-Etherton et al42 recommend as the ingestion of up to

    4 g EPA + DHA for patients with hypertriglyceridemia, but they

    do not determine the time of intervention, which might lead to

    poor glycemic control, as was observed in the present study,

    because GA presented a tendency of IS reduction. However, the

    lipemia might be favored by the supplementation, because

    Axelrod et al49 evaluated 20 individuals with T2DM for 6

    weeks receiving 2.5 g/d -3 PUFA, showing a reduction of

    serum concentrations of total cholesterol and LDL-cholesterol,

    although an increase in HDL-cholesterol and TG was seen.

    Our results demonstrated that a lower dose of -3 PUFA

    was more effective than control or higher dose of -3 PUFA in

    reducing total body mass and WC, and there was also less fre-

    quency in IS reductions. The high dose did not alter body com-

    position and resulted in a tendency to reduce the IS. As such, it

    does not justify the increase of the -3 PUFA dose in the form

    of supplements because the results with a smaller dose, likely

    reached with a weekly consumption of 2 portions of fish with

    high fat, presented themselves to be more effective on body

    composition and lipemia in T2DM and obesity, without

    hypertriglyceridemia.

    It was concluded that a sample of women with T2DM using

    oral hypoglycemics would not need -3 PUFA supplementa-tion with the intention of controlling body weight, promoting

    favorable alterations in body composition, and improving lipe-

    mia. Still, new studies that aim to confirm the -3 PUFA influ-

    ence on the evaluated parameters in this study are necessary,

    such as the establishment of the best dose indicated for patients

    with an increased risk of NTCDs, besides the supplementation

    time, which reflects satisfactory results and the reduction of

    harmful effects. Also, other studies of interventions similar to

    ours, in other population groups with diabetes mellitus, such as

    children and adolescents, should be encouraged.

    Acknowledgments

    We thank Fundao Oswaldo Cruz (FIOCRUZ) and Associao

    dos Pais e Amigos dos Excepcionais (APAE) for their collabora-

    tion in laboratory tests.

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