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Daily vs Intermittent Restriction of Energy: Controlled Trial to Reduce Diabetes Risk (DIRECT)

Not Applicable
Completed
Conditions
Individuals at Risk of Developing Diabetes
Interventions
Other: Intermittent Fasting (IF)
Other: standard care (SC)
Other: Daily Restriction (DR)
Registration Number
NCT03689608
Lead Sponsor
University of Adelaide
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
209
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intermittent Fasting (IF)Intermittent Fasting (IF)3 days fasting per week
standard care (SC)standard care (SC)usual care
Daily Restriction (DR)Daily Restriction (DR)daily energy restriction
Primary Outcome Measures
NameTimeMethod
Postprandial glucose AUC6 months

Change in postprandial glucose AUC

Secondary Outcome Measures
NameTimeMethod
Postprandial triglyceride6 months, 18 months

Change in postprandial triglyceride levels

Waist and hip circumference2 months, 6 months, 18 months

Change in waist and hip circumference

Dietary intake2 months, 6 months, 18 months

Change in food intake measured by self-reported food diaries

Body composition6 months, 18 months

Change in body fat mass (kg) and fat free mass (kg)

Postprandial glucose18 months

Change in postprandial glucose

Fasting glucose2 months, 6 months, 18 months

Change in fasting glucose

Fasting triglyceride2 months, 6 months, 18 months

Change in fasting triglyceride levels

HbA1c2 months, 6 months, 18 months

Change in HbA1c

Blood lipids2 months, 6 months, 18 months

Changes in blood lipid profile (total cholesterol, HDL-, LDL-cholesterol and triglycerides)

Blood pressure2 months, 6 months, 18 months

Change in systolic blood pressure and diastolic blood pressure (mmHg)

Postprandial insulin6 months, 18 months

Change in postprandial insulin

Postprandial non-esterified fatty acids (NEFA)6 months, 18 months

Change in postprandial NEFA levels

Body weight2 months, 6 months, 18 months

Change in body weight in kilograms

Changes in physical Activity assessed by accelerometer2 months, 6 months, 18 months

Change in average step counts measured with waist-worn actigraphy monitors

Fasting insulin2 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

Trial Locations

Locations (1)

University of Adelaide

🇦🇺

Adelaide, South Australia, Australia

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