Insulin Resistance, Obesity
Conditions
Keywords
Obesity, Insulin resistance, Omega3 long chain polyunsaturated fatty acids
Brief summary
The purpose of this study is to evaluate if a supplement containing omega-3 long chain polyunsaturated fatty acids for three months reduce obesity and insulin resistance to obese adolescents if administered together with a hypocaloric diet.
Detailed description
Background: In 2006, the prevalence of overweight and obesity combined in scholar and adolescents in Mexico was 26% and 31% respectively, which represents more than double of that reported in year 2000. Together with such increments in the obesity rates, it was observed similar increases in the incidence of other metabolic conditions such as insulin resistance (IR). In a very simplistic manner, it seems that the link between obesity and IR is a chronic inflammatory status because the adipose tissue-derived inflammatory molecules interfere with the uptake of fatty acids and glucose in peripheral tissues. On the other hand, it is accepted that the long-chain polyunsaturated fatty acids (LCPUFA) omega-3 exhibit anti-inflammatory properties. In addition, it has been also demonstrated the beneficial effect exerted by such fatty acids on insulin sensitivity, and in stabilizing the weight lost achieved with hypocaloric diets. At present, the prevalence of overweight and obesity combined are in the range of 41-43% in the adolescent population that attend the four areas of influence of the Mexican Institute of Social Security (IMSS) in Mexico City. Interventions addressed to improve the nutritional status of these groups of age are expected to impact the risk for IR and its associated co-morbidities. Objective: To evaluate the impact of supplementation with LCPUFA omega-3, together with a dietary strategy, on obesity and insulin resistance in a sample of obese adolescents attended in the IMSS. Methods: In a randomized clinical design, 300 obese individuals, 12-18 years old, will be selected. At selection, individuals will be randomly assigned to receive daily a capsule with 1.1 g LCPUFA omega-3 during three mo together with a hypocaloric diet which follows the World Health Organization (WHO) recommendations (D+O3), or to receive daily a capsule with 1.0 g sunflower oil and a similar diet (P+D). After randomization, dietary information (24h-recall and FFQ), anthropometric measurements, and peripheral blood samples, will be obtained. Blood samples will be used to determine fasting plasma glucose and insulin, and erythrocytes fatty acid profile; such determinations will be repeated at three and six mo of follow-up. Anthropometry and 24 h-recalls will be repeated monthly. For follow-up, studied subjects will be evaluated monthly to deliver capsules and to check for dietary adherence. Treatments will be administered during three months and the follow-up will continue throughout six months. At the end of the follow-up it is expect that the D+O3 group will present: a) higher decreases in mean weight and body mass index (BMI), b) greater decreases in the mean fasting insulin concentration, homeostasis model assessment (HOMA) index, and IR frequency, c) longer duration of weight lost. Statistical analyses: Student and paired-t test will be used for inter and intra group comparisons respectively. Logistic regression models and repeated measures analyses will be conducted to evaluate the effect of treatments, adjusting by diet and weight loss, as well as by confounders such as puberty and treatment adherence. Infrastructure: The Unit of Research in Medical Nutrition owes the equipment needed to conduct the laboratory determinations proposed in this research, as well as the personnel qualified to conduct, monitor, analyze and evaluate data from field investigation, specially that related to obesity and IR.
Interventions
Thirty caps with the supplement will be provided every mo during three mo. Supplement will be administered as gel caps containing 1.1 g of DHA and EPA (®MaxEpa, Merck Laboratory) Hypocaloric diet will start at admission and will continue during the six months of follow-up. It will consist in providing a personalized diet including: a) reduction of 700 Kcal from the usual diet considering lipids and carbohydrates, b) increasing fruits and vegetables intake up to six portions daily each, and c) incrementing the intake of fiber to 30 g a day through the inclusion of whole grains.
Thirty caps with the placebo will be provided every mo during three mo. Placebo will be administered as gel caps containing 1g of sunflower oil, which is omega-3 free, and is not expected to produce anti-inflammatory or insulin sensitivity effects. Hypocaloric diet will start at admission and will continue during the six months of follow-up. It will consist in providing a personalized diet including: a) reduction of 700 Kcal from the usual diet considering lipids and carbohydrates, b) increasing fruits and vegetables intake up to six portions daily each, and c) incrementing the intake of fiber to 30 g a day through the inclusion of whole grains.
Sponsors
Study design
Eligibility
Inclusion criteria
* Age between 12 and 18 years, * Male and female * Body mass Index (BMI) above the 95 percentile of the National Center for Health Statistics (NCHS) reference * Informed consent form signed by both parents or legal guardian.
Exclusion criteria
* Those diagnosed as with Diabetes Mellitus Type 2 (DMT2), Cardiovascular disease (CVD) or kidney disease * Those who are allergic to fish.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insulin Resistance | At baseline (at diagnosis), three months, throughout six months. | Change from baseline in insulin resistance at three and six months. Changes in insulin resistance evaluated through Homeostasis Model Assessment Index (HOMA), calculated by formula: (glucose, mg \* insulin,µU)/405. Where HOMA\>3.16 indicated insulin resistance index. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nutritional Status | At baseline (at diagnosis), three months, throughout six months. | Nutritional status was determined by registering body mass index (BMI) calculated by formula: kg/m\^2. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Insulin Resistance Through Fasting Insulin | At baseline (at diagnosis), three months, throughout six months. | Change from baseline in insulin resistance at three and six months. Changes in insulin resistance evaluated through fasting insulin (µU/mL) |
| Nutritional Status Through Waist Circumference | At baseline (at diagnosis), three months, throughout six months. | Nutritional status was determined by registering waist circumference in cm. |
Countries
Mexico
Participant flow
Recruitment details
Adolescents were recruited between July 2012 and December 2015, from three Family Medicine clinics of the Mexican Institute of Social Security (IMSS) in Mexico City.
Participants by arm
| Arm | Count |
|---|---|
| Omega 3 and an Hypocaloric Diet Participants will receive a supplement containing omega 3: DHA and EPA fatty acids together with an hypocaloric diet.
Omega3 and an hypocaloric diet.: Thirty caps with the supplement will be provided every mo during three mo. Supplement will be administered as gel caps containing 1.1 g of DHA and EPA (®MaxEpa, Merck Laboratory) Hypocaloric diet will start at admission and will continue during the six months of follow-up. It will consist in providing a personalized diet including: a) reduction of 700 Kcal from the usual diet considering lipids and carbohydrates, b) increasing fruits and vegetables intake up to six portions daily each, and c) incrementing the intake of fiber to 30 g a day through the inclusion of whole grains. | 119 |
| Placebo Participants will receive a supplement containing sunflower oil with an hypocaloric diet.
Sunflower oil with an hypocaloric diet.: Thirty caps with the placebo will be provided every mo during three mo. Placebo will be administered as gel caps containing 1g of sunflower oil, which is omega-3 free, and is not expected to produce anti-inflammatory or insulin sensitivity effects. Hypocaloric diet will start at admission and will continue during the six months of follow-up. It will consist in providing a personalized diet including: a) reduction of 700 Kcal from the usual diet considering lipids and carbohydrates, b) increasing fruits and vegetables intake up to six portions daily each, and c) incrementing the intake of fiber to 30 g a day through the inclusion of whole grains. | 126 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Incomplete data | 4 | 2 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Received medication | 3 | 2 |
| Overall Study | Withdrawal by Subject | 56 | 49 |
Baseline characteristics
| Characteristic | Placebo | Total | Omega 3 and an Hypocaloric Diet |
|---|---|---|---|
| Age, Categorical <=18 years | 126 Participants | 245 Participants | 119 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 13.58 years STANDARD_DEVIATION 1.79 | 13.66 years STANDARD_DEVIATION 1.87 | 13.73 years STANDARD_DEVIATION 1.97 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Mexico | 126 Participants | 245 Participants | 119 Participants |
| Sex: Female, Male Female | 69 Participants | 129 Participants | 60 Participants |
| Sex: Female, Male Male | 57 Participants | 116 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 119 | 0 / 126 |
| other Total, other adverse events | 0 / 119 | 0 / 126 |
| serious Total, serious adverse events | 0 / 119 | 0 / 126 |
Outcome results
Change in Insulin Resistance
Change from baseline in insulin resistance at three and six months. Changes in insulin resistance evaluated through Homeostasis Model Assessment Index (HOMA), calculated by formula: (glucose, mg \* insulin,µU)/405. Where HOMA\>3.16 indicated insulin resistance index.
Time frame: At baseline (at diagnosis), three months, throughout six months.
Population: Of the participants analyzed at baseline and at month 3 (119 in omega 3 and an hypocaloric diet group and 126 Placebo group) only 80 and 82 participants respectively finished the study at month 6. The participants who did not finish the study, were because they did not want to take another blood sample at month 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omega 3 and an Hypocaloric Diet | Change in Insulin Resistance | Homeostasis Model Assessment (HOMA) at baseline | 7.38 HOMA-IR Index | Standard Deviation 4.21 |
| Omega 3 and an Hypocaloric Diet | Change in Insulin Resistance | Homeostasis Model Assessment (HOMA) at 3 mo | 6.73 HOMA-IR Index | Standard Deviation 3.71 |
| Omega 3 and an Hypocaloric Diet | Change in Insulin Resistance | Homeostasis Model Assessment (HOMA) at 6 mo | 6.02 HOMA-IR Index | Standard Deviation 3.21 |
| Placebo | Change in Insulin Resistance | Homeostasis Model Assessment (HOMA) at 3 mo | 6.28 HOMA-IR Index | Standard Deviation 3.53 |
| Placebo | Change in Insulin Resistance | Homeostasis Model Assessment (HOMA) at baseline | 6.89 HOMA-IR Index | Standard Deviation 3.55 |
| Placebo | Change in Insulin Resistance | Homeostasis Model Assessment (HOMA) at 6 mo | 5.41 HOMA-IR Index | Standard Deviation 3.21 |
Nutritional Status
Nutritional status was determined by registering body mass index (BMI) calculated by formula: kg/m\^2.
Time frame: At baseline (at diagnosis), three months, throughout six months.
Population: Of the participants analyzed at baseline and at month 3 (119 in omega 3 and an hypocaloric diet group and 126 Placebo group) only 80 and 82 participants respectively finished the study at month 6. The participants who did not finish the study, were because they did not want to take another blood sample at month 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omega 3 and an Hypocaloric Diet | Nutritional Status | Body Mass Index at baseline | 31.53 kg/m^2 | Standard Deviation 4.92 |
| Omega 3 and an Hypocaloric Diet | Nutritional Status | Body Mass Index at 3 months | 30.89 kg/m^2 | Standard Deviation 4.97 |
| Omega 3 and an Hypocaloric Diet | Nutritional Status | Body Mass Index at 6 months | 31.1 kg/m^2 | Standard Deviation 8.35 |
| Placebo | Nutritional Status | Body Mass Index at baseline | 31.16 kg/m^2 | Standard Deviation 3.79 |
| Placebo | Nutritional Status | Body Mass Index at 3 months | 30.40 kg/m^2 | Standard Deviation 3.79 |
| Placebo | Nutritional Status | Body Mass Index at 6 months | 30.25 kg/m^2 | Standard Deviation 3.95 |
Change in Insulin Resistance Through Fasting Insulin
Change from baseline in insulin resistance at three and six months. Changes in insulin resistance evaluated through fasting insulin (µU/mL)
Time frame: At baseline (at diagnosis), three months, throughout six months.
Population: Of the participants analyzed at baseline and at month 3 (119 in omega 3 and an hypocaloric diet group and 126 Placebo group) only 80 and 82 participants respectively finished the study at month 6. The participants who did not finish the study, were because they did not want to take another blood sample at month 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omega 3 and an Hypocaloric Diet | Change in Insulin Resistance Through Fasting Insulin | Fasting insulin at baseline | 33.05 µU/mL | Standard Deviation 16.5 |
| Omega 3 and an Hypocaloric Diet | Change in Insulin Resistance Through Fasting Insulin | Fasting insulin at 3 mo | 30.55 µU/mL | Standard Deviation 15.52 |
| Omega 3 and an Hypocaloric Diet | Change in Insulin Resistance Through Fasting Insulin | Fasting insulin at 6 mo | 29.40 µU/mL | Standard Deviation 12.57 |
| Placebo | Change in Insulin Resistance Through Fasting Insulin | Fasting insulin at baseline | 31.30 µU/mL | Standard Deviation 15.05 |
| Placebo | Change in Insulin Resistance Through Fasting Insulin | Fasting insulin at 3 mo | 29.09 µU/mL | Standard Deviation 15.1 |
| Placebo | Change in Insulin Resistance Through Fasting Insulin | Fasting insulin at 6 mo | 27.23 µU/mL | Standard Deviation 12.63 |
Nutritional Status Through Waist Circumference
Nutritional status was determined by registering waist circumference in cm.
Time frame: At baseline (at diagnosis), three months, throughout six months.
Population: Of the participants analyzed at baseline and at month 3 (119 in omega 3 and an hypocaloric diet group and 126 Placebo group) only 80 and 82 participants respectively finished the study at month 6. The participants who did not finish the study, were because they did not want to take another blood sample at month 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omega 3 and an Hypocaloric Diet | Nutritional Status Through Waist Circumference | Waist circumference at baseline | 100.44 cm | Standard Deviation 12.37 |
| Omega 3 and an Hypocaloric Diet | Nutritional Status Through Waist Circumference | Waist circumference at 3 months | 98.83 cm | Standard Deviation 12.33 |
| Omega 3 and an Hypocaloric Diet | Nutritional Status Through Waist Circumference | Waist circumference at 6 months | 96.99 cm | Standard Deviation 11.68 |
| Placebo | Nutritional Status Through Waist Circumference | Waist circumference at baseline | 99.40 cm | Standard Deviation 9.81 |
| Placebo | Nutritional Status Through Waist Circumference | Waist circumference at 3 months | 97.66 cm | Standard Deviation 9.61 |
| Placebo | Nutritional Status Through Waist Circumference | Waist circumference at 6 months | 97.11 cm | Standard Deviation 10.1 |