Nutrition in Clinical Practice

http://ncp.sagepub.com/ -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, Aline F. P. Souza, Andressa C. F. de Souza and Eliane Lopes Rosado Nutr Clin Pract 2012 27: 553 originally published online 1 June 2012 DOI: 10.1177/0884533612444535 The online version of this article can be found at: http://ncp.sagepub.com/content/27/4/553

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444535
Crochemore et alNutrition in Clinical Practice 2012

NCPXXX10.1177/0884533612444535

Clinical Research

-3 Polyunsaturated Fatty Acid Supplementation Does Not

Influence Body Composition, Insulin Resistance, and Lipemia in Women With Type 2 Diabetes and Obesity

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

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 used to 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

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 population 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 disease 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 glucose, 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 polyunsaturated 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 cardiac arrhythmias8 and improvement in body composition.9 Epidemiologic and clinical evidence demonstrates the cardioprotective 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: elianerosado@nutricao.ufrj.br, elianenut@yahoo.com.br.

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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 supplementation could 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.

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 capsules 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 anthropometric 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 calculated.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 principle of the bodys resistance to the passage of an electric current 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

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 diagnosed 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 collected 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 composition) 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 maintain 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.

Biochemical Evaluation
The serum TG levels were determined by the enzymaticcolorimetric method (Triglicrides GPO-ANA Liquiform; Diagnostic Labtest S.A., Lagoa Santa, MG, Brazil), as indicated 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 (commercial kit HBA1C II; Roche Diagnostics, Mannheim, Germany). The serum insulin was determined by radioimmunoassay (RIA) (insulin Coat-a-Count; Diagnostic Products Corporation, Los Angeles, CA). Homeostasis model assessmentinsulin resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) were used to do the insulin resistance (IR) and insulin sensitivity (IS) calculations, respectively.24,25

Dietetic Intervention
Group A (GA) received capsules containing 2.5 g fish oil (547.5 mg eicosapentaenoic acid [EPA] and 352.5 mg docosapentaenoic 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

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

Table 1. Anthropometric and Biochemical Variables (Mean SD) of Groups at Baseline Group A (n = 14) Variables BMI, kg/m WC, cm TBW, L TBF, % LM, % Glucose, mg/dL Glycated hemoglobin, % Insulin, U/mL HOMA-IR QUICKI Cholesterol, mg/dL LDL-cholesterol, mg/dL HDL-cholesterol, mg/dL Triglycerides, mg/dL
2

555

Group B (n = 14) Mean 30.88 96.36 34.86 34.57 65.43 142.93 6.54 8.56 2.89 0.34 199.0 123.79 48.0 149.21 SD 6.76 12.95 4.31 6.85 6.85 50.75 1.45 4.24 1.41 0.03 24.48 25.79 14.71 102.50

Group C (n = 13) Mean 33.82 105.08 35.49 40.33a 59.67a 144.46 6.50 13.77ab 5.30 0.31 203.83 120.92 47.85 161.75 SD 5.17 9.03 6.08 3.21 3.21 49.33 1.39 6.67 4.22 0.03 50.48 36.62 11.13 116.23

P Value .17 .19 .88 .02 .03 .07 .28 .02 .11 .14 .56 .57 .33 .81

Mean 29.86 98.29 35.34 34.90 65.02 197.64 7.94 7.91 3.95 0.33 214.07 137.0 51.43 132.93

SD 5.97 14.02 6.38 6.16 6.16 82.30 2.52 6.15 4.59 0.03 36.52 33.91 10.46 69.35

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 lipoprotein; LM, lean mass; QUICKI, Quantitative Insulin Sensitivity Check Index; TBF, total body fat; TBW, total body water; WC, waist circumference. a P < .05 vs GB. b P < .05 vs GA.

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 each test 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), considering P < .05.

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 intervention, GC differed only from GB. The remaining variables did 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 reduction 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 anthropometric and biochemistry parameters, it was found that 35.7%, 71.4%, and 30.77% of the women in GA, GB, and GC, respectively, 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%,

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). Eighty percent 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 hyperadiposity, fasting hyperglycemia, and IR.

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Table 2. Anthropometric and Biochemical Variables (Mean SD) of Groups After the Intervention Group A (n = 14) Variables BMI, kg/m WC, cm TBW, L TBF, % LM, % Glucose, mg/dL Glycated hemoglobin, % Insulin, U/mL HOMA-IR QUICKI Cholesterol, mg/dL LDL-cholesterol, mg/dL HDL-cholesterol, mg/dL Triglycerides, mg/dL
2

Group B (n = 14) Mean 30.59 94.71 34.54 34.20 65.81 153.07 6.76 10.24 3.99 0.33 196.00 122.86 50.21 120.07 SD 6.55 12.66 4.22 6.17 6.17 62.06 1.88 6.29 2.92 0.04 27.77 22.97 15.90 74.96

Group C (n = 13) Mean 33.93 104.92 36.30 39.23a,b 60.77a,b 161.15 7.24 13.69 5.55 0.31 204.62 125.15 47.77 168.15 SD 5.32 9.00 5.80 3.60 3.60 50.08 1.44 5.78 3.52 0.02 45.70 31.93 10.01 105.37

P Value .14 .13 .85 .05 .05 .10 .15 .20 .34 .39 .24 .16 .53 .27

Mean 29.74 97.86 35.81 34.32 65.68 208.71 8.15 10.42 5.23 0.31 218.29 142.43 52.29 123.14

SD 6.02 14.42 6.16 6.67 6.68 85.54 2.26 7.33 4.39 0.03 36.81 29.93 12.52 64.48

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 lipoprotein; LM, lean mass; QUICKI, Quantitative Insulin Sensitivity Check Index; TBF, total body fat; TBW, total body water; WC, waist circumference. a P < .05 vs GB. b P < .05 vs GA.

Table 3. Evolution of Anthropometric and Biochemical Variables (Mean SD) of the Groups After the Intervention Group A (n = 14) Variables BMI, kg/m WC, cm TBW, L TBF, % LM, % Glucose, mg/dL Glycated hemoglobin, % Insulin, mU/mL HOMA-IR QUICKI Cholesterol, mg/dL LDL-cholesterol, mg/dL HDL-cholesterol, mg/dL Triglycerides, mg/dL
2

Group B (n = 14) Basal 30.88 6.76 96.36 12.95 34.86 4.31 34.57 6.85 65.43 6.85 142.9 50.75 6.54 1.45 8.56 4.24 2.89 1.41 0.34 0.03 199.0 24.48 123.8 25.79 48.00 14.71 149.2 102.5 After
a

Group C (n = 13) Basal After 33.93 5.32 104.92 9.00 36.30 5.80a 39.23 3.60a 60.77 3.60a 161.2 50.08 7.24 1.44 13.69 5.78 5.55 3.52 0.31 0.02 204.6 45.70 125.2 31.93 47.77 10.01 168.2 105.4

Basal 29.86 5.97 98.29 14.02 35.34 6.38 34.90 6.16 65.02 6.16 197.6 82.3 7.94 2.52 7.91 6.15 3.95 4.59 0.33 0.03 214.1 36.52 137.0 33.91 51.43 10.46 132.9 69.35

After 29.74 6.02 97.86 14.42 35.81 6.16 34.32 6.67 65.68 6.68 208.7 85.54 8.15 2.26 10.42 7.33 5.23 4.39 0.31 0.03 218.3 36.81 142.4 29.93 52.29 12.52 123.1 64.48

30.59 6.55 33.82 5.17 94.71 12.66a 105.08 9.03 34.54 4.22 35.49 6.08 34.20 6.17 40.33 3.21 65.81 6.17 59.67 3.21 153.1 62.06 144.5 49.33 6.76 1.88 6.50 1.39 10.24 6.29 13.77 6.67 3.99 2.92 5.30 4.22 0.33 0.04 0.31 0.03 196.0 27.77 203.8 50.48 122.9 22.97 120.9 36.62 50.21 15.90 47.85 11.13 120.1 74.96 161.8 116.2

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 Sensitivity Check Index; TBF, total body fat; TBW, total body water; WC, waist circumference. a Significant at 5% probability, by t test.

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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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.

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 important 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 and IS) did not differ between groups at baseline. Despite the maintenance 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 incidence and prevalence of T2DM. The study concluded that either BMI or WC predicted T2DM, regardless of the controversial 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) was reduced in the group supplemented with -3 PUFA (1.8 g) compared with placebo. Derosa et al12 also did not find variation 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 values 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 hyperglycemia 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, elevated 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 followed 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

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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 the consumption 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 consumption of -3 PUFA, which can be explained as a consequence of the alteration in the composition of the serum fatty acid.41 In GB, favorable results were observed in serum lipid levels, as suggested by the greater frequency of reduced serum levels of total cholesterol and TG and increased HDLcholesterol, compared with the other groups. Despite KrisEtherton 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 cholesterol 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-cholesterol levels occurred, the increase in serum HDL-cholesterol concentration might compensate for this result, due to its beneficial effect on CVD. McEwen et al44 observed in their review that diets rich in fish and -3 PUFA may reduce cardiovascular risk in individuals 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 present 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 parameters referring to lipemia and glycemia. This result matches the present 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 frequency in IS reductions. The high dose did not alter body composition 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 supplementation with the intention of controlling body weight, promoting favorable alterations in body composition, and improving lipemia. Still, new studies that aim to confirm the -3 PUFA influence 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 collaboration in laboratory tests.

References
1. Berdanier CD. Diabetes and nutrition: the mitochondrial part. J Nutr. 2001;131:S344-S353. 2. World Health Organization. The World Health Report 2003. Geneva, Switzerland: World Health Organization; 2003.

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