Individuals at Risk of Developing Diabetes
Conditions
Keywords
intermittent fasting, calorie restriction, overweight and obesity
Brief summary
In this randomized controlled trial, the investigators will compare the long term effectiveness of intermittent fasting (IF) versus an energy matched moderate calorie restriction (CR) over 18 months, and relative to a non-active intervention standard control (SC) in individuals who are at increased risk of developing type 2 diabetes. All participants will be required to attend the blood tests following a 12-hour overnight fast for the A visit at Month 0, 2, 6 (active) and 18 (follow up). Fast424hGlucose: A subset of 100 participants enrolled in either IF or CR group in the parent study will be fitted with a continuous glucose monitor (CGM) to measure 24-hour glycaemic profile at month 0 and month 6. Fast4Switch: Additional bloods will be collected after a B visit at month 6 to compare the fed to fasted switch. The B samples will be collected after a 12-hour overnight fast (CR, SC) or 20-hour fast (IF) to assess the metabolic switch to fasting in metabolites and hormones. Fast4Stress: Additional subcutaneous adipose tissue, urine and saliva samples will be collected in \ 32 men in IF and CR groups at month 0 and 6 at A and B visits to examine changes in stress response and resistance markers. Experience2Fast: In-depth, semi-structured interviews will be carried out at month-8 follow-up visit in a subset of completers from IF or CR groups to explore the experience of intervention diets and understand contributing factors towards change and maintenance of dietary behaviours. Fast4Flux: Additional blood samples will be collected in \ 100 individuals in SC, IF and CR groups at month 0, month 2 and month 6 at A visit to measure autophagic flux in peripheral blood mononuclear cells following treatment of whole blood.
Interventions
Participants will fast 3 days per week. In fasting days, meal replacements at 30% of daily energy requirements will be provided for the first 6 months. Participants will have fortnightly nutrition assessment.
OTHERDaily Restriction (DR)
Participants are instructed to restrict energy intake by 30% of daily energy requirements. Meal replacements will be provided for the first 6 months. Participants will have fortnightly nutrition assessment.
OTHERstandard care (SC)
Participants will receive current practice guidelines in a static information format, will not take part in any counselling or receive meal replacements.
Sponsors
University of Adelaide
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* weight-stable (\< 5 % fluctuation in their body weight for past 6-months at study entry) * score 12 or greater on the AUSDRISK calculator * HbA1c \<48 mmol/mol (measured at screening)
Exclusion criteria
* Personal history/diagnosis (self-reported) of diabetes (type 1 or 2), major psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, eating disorders), gastrointestinal disorders, haematological disorders (i.e. thalassemia, iron-deficiency anaemia) insomnia, or any other medical condition, deemed unstable by the study physician. * Participants currently taking the following medications will be excluded from participating: any medication used to lower blood glucose or antidiabetic medications (metformin, sulfonylureas, Glucagon-like peptide-1 GLP-1 analogues \[i.e. exenatide\], thiazolidinediones or DPP-IV inhibitors \[i.e. 'gliptins'\]), medications affecting weight, appetite or gut motility (i.e. domperidone, cisapride, orlistat, phentermine, topiramate). Participants who are taking stable doses (i.e. \> 12 months) of androgenic medications (i.e. testosterone) or SSRI's will not be excluded. * weight change in past 3 months (\> 5% screening weight) * uncontrolled asthma, current fever, upper respiratory infections * individuals who regularly perform high intensity exercise (\>2 week) * current intake of \> 140g alcohol/week * current smokers of cigarettes/cigars/marijuana/e-cigarettes/vaporisers * current intake of any recreational drugs * regular blood donor * unable to comprehend study protocol due to English language or cognitive difficulties
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postprandial glucose AUC | 6 months | Change in postprandial glucose AUC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c | 2 months, 6 months, 18 months | Change in HbA1c |
| Postprandial glucose | 18 months | Change in postprandial glucose |
| Body weight | 2 months, 6 months, 18 months | Change in body weight in kilograms |
| Body composition | 6 months, 18 months | Change in body fat mass (kg) and fat free mass (kg) |
| Waist and hip circumference | 2 months, 6 months, 18 months | Change in waist and hip circumference |
| Blood lipids | 2 months, 6 months, 18 months | Changes in blood lipid profile (total cholesterol, HDL-, LDL-cholesterol and triglycerides) |
| Dietary intake | 2 months, 6 months, 18 months | Change in food intake measured by self-reported food diaries |
| Postprandial triglyceride | 6 months, 18 months | Change in postprandial triglyceride levels |
| Changes in physical Activity assessed by accelerometer | 2 months, 6 months, 18 months | Change in average step counts measured with waist-worn actigraphy monitors |
| Fasting glucose | 2 months, 6 months, 18 months | Change in fasting glucose |
| Fasting insulin | 2 months, 6 months, 18 months | Change in fasting insulin |
| Fasting non-esterified fatty acids (NEFA) | 2 months, 6 months, 18 months | Change in fasting NEFA levels |
| Fasting triglyceride | 2 months, 6 months, 18 months | Change in fasting triglyceride levels |
| Postprandial insulin | 6 months, 18 months | Change in postprandial insulin |
| Postprandial non-esterified fatty acids (NEFA) | 6 months, 18 months | Change in postprandial NEFA levels |
| Blood pressure | 2 months, 6 months, 18 months | Change in systolic blood pressure and diastolic blood pressure (mmHg) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in insulin (DIRECT- Fast4Switch) | 6 months | Change in insulin levels |
| Change in triglycerides (DIRECT- Fast4Switch) | 6 months | Change in triglycerides levels |
| 24 hours glycaemia (DIRECT-Fast424hGlucose) | 6 months | Changes in 24 hours glycaemia assessed by continuous glucose monitor |
| Salivary cortisol (DIRECT-Fast4Stress) | 6 months | Change in salivary cortisol |
| Change in perceived hunger and fullness assessed by visual analogue scales (VAS) | 6 months, 18 months | Change in subjective hunger and fullness ratings measured by 0-100 mm VAS scales |
| Change in urinary adrenaline (DIRECT- Fast4Stress) | 6 months | Change in urinary adrenaline |
| Change in urinary noradrenaline (DIRECT- Fast4Stress) | 6 months | Change in urinary noradrenaline |
| Qualitative analysis (DIRECT-Experience2Fast) | 8 months | Patterns of participant's behaviour, characteristics and motivation that assist in or hinder from weight loss achievement by semi-structured interviews |
| Change in autophagic flux (DIRECT-Fast4flux) | 2 months, 6 months | Change in autophagic machinery protein LC3B-II in peripheral blood mononuclear cells following treatment of whole blood. |
| Gene expression (DIRECT- Fast4Stress) | 6 months | Change in gene expression |
| Change in perceived sleep quality | 2 months, 6 months, 18 months | Change in perceived sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI), with a range from 0-21 scores, higher score reflect poorer sleep quality |
| Change in perceived eating behaviour | 2 months, 6 months, 18 months | Change in perceived eating behaviour assessed by Three Factor Eating Questionnaire (TFEQ), which consists of 51 items to assess dietary restraint (21 items), disinhibition (16 items) and hunger (14 items), higher scores reflect higher levels on each subscale |
| Change in perceived quality of life | 2 months, 6 months, 18 months | Change in perceived quality of life assessed by 36-item Short Form (SF-36) health survey, with a range from 0-100 scores, higher scores reflect better quality of life |
| Change in perceived well-being | 2 months, 6 months, 18 months | Change in perceived well-being assessed by Personal Well-being Index, with a range from 0-10 scores, higher scores reflect greater satisfication |
| Change in food addition score | 6 months, 18 months | Change in self-reported food addiction assessed by Yale Food Addiction Score (YFAS), with a range from 0-7 scores, higher scores reflect greater food addiction symptoms |
| Change in psychological distress | 6 months, 18 months | Change in self-reported psychological distress assessed by Kessler Psychological Distress Scale (K10) , with a range from 10-50 scores, higher scores reflect higher psychological distress |
| Change in self-reported depression, anxiety and stress level | 2 months, 6 months, 18 months | Change in self-reported depression, anxiety and stress level assessed by Depression, Anxiety and Stress Scale (DASS), with a range from 0-42 scores on each subscale, higher scores reflect higher levels on each subscale |
| Change in self-reported mood | 2 months, 6 months, 18 months | Change in self-reported mood assessed by Positive and Negative Affect Schedule (PANAS), with a range from 0-100 scores, higher scores reflect more positive mood and negative mood. |
| Change in glucagon-like peptide 1 (GLP-1) | 6 months | Change in glucagon-like peptide 1 (GLP-1) |
| Change in peptide YY | 6 months | Change in peptide YY |
| Change in ghrelin | 6 months | Change in ghrelin |
| Change in gastric inhibitory polypeptide (GIP) | 6 months | Change in gastric inhibitory polypeptide (GIP) |
| Change in estradiol | 6 months | Change in estradiol |
| Change in testosterone | 6 months | Change in testosterone |
| Change in glucose (DIRECT- Fast4Switch) | 6 months | Change in glucose levels |
| Change in non-esterified fatty acids (DIRECT- Fast4Switch) | 6 months | Change in non-esterified fatty acids levels (NEFA) |
Countries
Australia
Outcome results
None listed