Hyperinsulinemia, Insulin Resistance, PCOS
Conditions
Keywords
PCOS, Intermittent Fasting, Fasting, Hyperinsulinemia, Insulin Resistance
Brief summary
Polycystic ovarian syndrome (PCOS) is associated with metabolic symptoms such as hyperinsulinemia. Time-restricted eating may reduce serum insulin and improve insulin resistance in patients with PCOS. Currently, there are few studies investigating time-restricted eating in patients with PCOS. The investigators plan to test the feasibility of time-restricted eating in the management of PCOS by means of a real-world clinical intervention. The investigators will determine if an 18:6 eating protocol reduces insulin levels by means of a randomised controlled crossover trial.
Detailed description
Background: Polycystic ovarian syndrome (PCOS) is the most common reproductive endocrinopathy in women of reproductive age with many associated metabolic symptoms, in particular hyperinsulinemia, insulin resistance and a high lifetime risk of type 2 diabetes mellitus. The effects of time-restricted eating on metabolic profiles have been investigated in many endocrinopathies, but there are minimal data in PCOS. Methods: This study will investigate the feasibility of time-restricted eating in the management of PCOS, and its effects on insulin levels and other metabolic parameters. To achieve this, the investigators will recruit 20 patients with PCOS (normal weight, overweight, obese). In a randomised cross-over design, participants will be observed for two consecutive 12 week periods (with a 4 weeks washout period in between) following either 'time-restricted eating' or 'usual eating', detailed below. 1. 18:6 protocol: 18 hours of fasting and a 6-hours eating window, with no other specific dietary advice. Participants choose their own 6-hour period according to their lifestyle and preference. 2. Usual eating: follow usual eating patterns, no time restriction, no other dietary advice When fasting, participants are permitted to consume plain water, unflavoured/unsweetened sparkling water, black breakfast tea and black coffee. Dietary intake will be determined at baseline, at midpoint of each study arm, and at the end of the study using Nutritics software. Participants will self-record dietary intake using the Nutritics 'app'. The primary endpoints will be serum insulin and feasibility of the intervention as well as safety, acceptability, and compliance with time-restricted eating. Secondary endpoints will be insulin resistance (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)), androgens (testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, 17-Hydroxyprogesterone (17-OHP) and sex hormone binding globulin (SHBG)), appetite (10-point visual analogue scale), hunger/satiety (glucagon-like peptide 1 (GLP-1), grehlin, PYY and oxyntomodulin, fasting glucose, HbA1c, lipid profile, lipoprotein lipid A, apolipoprotein A1, apolipoprotein B, anthropometrics (weight, body mass index, hip and waist circumference), dietary intake (calorie and macronutrient intake; micronutrient intake including iron, calcium; dietary pattern including timing). Results: Safety and acceptability will be measured by adverse event reporting and measurement of adherence. Paired t-test will be used to assess between baseline and post intervention measurements. Results considered statistically significant if p\<0.05. Discussion: Time-restricted eating has potential to aid in improvement of insulin resistance in patients with PCOS based on studies in other populations. There is no substantial literature on this subject to date in the PCOS patient cohort, with this being the first randomised study to date. The investigators will discuss the effects of time-restricted eating on insulin levels in the specific population of women with PCOS based on the results.
Interventions
OTHERTime restricted eating
Following a 3 day baseline dietary assessment using the Nutritics 'app', patients will immediately commence time-restricted eating on a 18:6 basis (18 hours fasting, 6 hours eating window) for 12 weeks. Participants will consume all their meals within a daily 6-hour period of their choosing, and this may change according to patient's lifestyle and preference to reflect a real-world situation. Participants may eat ad libitum / according to appetite during the eating period. Participants will fast for 18 hours per day, consuming only plain water, unflavoured/unsweetened sparkling water, black breakfast tea or black coffee. Alcohol must not be consumed during fasting periods Dietary intake will again be measured using the Nutritics 'app' midpoint through the 12-week period (week 6 +/- 1 week) and in the last week of the intervention (week 11/12).
OTHERNormal ad libitum diet
Following a 3-day baseline dietary assessment using the Nutritics 'app', participants with be directed to continue with their usual dietary intake without any time-related restrictions for 12 weeks. There will be no defined eating window and fasting or restrictions regarding types of food or drink consumed. Dietary intake will again be measured using the Nutritics 'app' midpoint through the 12-week period (week 6 +/- 1 week) and in the last week of the intervention (week 11/12).
Sponsors
Tallaght University Hospital
Ruairí Floyd
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
Yes
Inclusion criteria
* Adult women of reproductive age with confirmed diagnosis of PCOS (Rotterdam Criteria, including at least 2 of 3 characteristics: oligomenorrhea, clinical and/or biochemical hyperandrogenism and ultrasound criteria) * No BMI restriction * Able and willing to provide explicit, informed consent
Exclusion criteria
* Type 1 diabetes, medication-controlled type 2 diabetes * Pregnancy * Currently participating in weight loss programme, or reported weight change in last 3 months (\>5% of current body weight) * Documented history of eating disorder * Ovulation medication, such as clomiphene citrate * Weight loss medication affecting weight or appetite in last 6 months, including weight loss medications, antipsychotic drugs or other medications as determine by the physician (eg. Semaglutide, liraglutide, orlistat, amphetamines, Qsymia (phentermine-topiramate), bupropion-naltrexone (Contrave)) * Known liver, renal or thyroid dysfunction (not including non-alcoholic fatty liver disease with hypothyroidism on treatment or subclinical hypothyroidism seen in a large proportion of patients with PCOS) * Unable to participate in follow-up for at least 24 weeks * Unable or unwilling to provide explicit, informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drop-out rate | 6 weeks | Assessing intervention feasibility |
| Adverse outcomes as assessed by CTCAE v4.0 | 6 weeks | Assessing intervention feasibility |
| Change in serum insulin | 6 weeks | Measured with serum insulin levels to assess effects |
| Change in food diaries | 6 weeks | Assessment of change of eating behaviours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in androstenedione levels | 6 weeks | Assessed by plasma androstenedione |
| Change in sex hormone binding globulin (SHBG) levels | 6 weeks | Assessed by plasma sex hormone binding globulin (SHBG) |
| Change in 17-Hydroxyprogesterone (17-OHP) levels | 6 weeks | Assessed by 17-Hydroxyprogesterone (17-OHP) |
| Change in appetite | 6 weeks | Measured by a validated 10-point visual analogue scale on a scale of 1-10, 1 being not hungry at all and 10 being very hungry |
| Change in markers of satiety | 6 weeks | Assess by plasma GLP-1 |
| Change in markers of hunger | 6 weeks | Assess by plasma ghrelin |
| Change in fasting glucose | 6 weeks | Assessed in serum glucose measurements |
| Change in insulin resistance | 6 weeks | Assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and other ratio calculations measuring insulin resistance |
| Change in lipids | 6 weeks | Assessed by Lipid profile |
| Change in body weight | 6 weeks | Body weight (kg) |
| Change in body mass index | 6 weeks | BMI (kg/m2) |
| Change in anthropometric measurements (waist circumference) | 6 weeks | Waist circumference (cm) |
| Change in anthropometric measurements (waist-hip ratio) | 6 weeks | Waist-hip ratio |
| Change in dietary intake | 6 weeks | Assessed using interval dietary assessments with Nutritics 'app' |
| Change in HbA1c | 6 weeks | Assessed in serum HbA1c measurements |
| Change in testosterone levels | 6 weeks | Assessed by plasma testosterone |
| Change in free testosterone levels | 6 weeks | Assessed by plasma free testosterone |
| Change in dehydroepiandrosterone sulfate (DHEA-S) levels | 6 weeks | Assessed by plasma dehydroepiandrosterone sulfate (DHEA-S) |
Countries
Ireland
Contacts
Primary ContactRuairí Floyd, BSc BMBS
Outcome results
None listed