daily vs intermittent restriction of energy: controlled trial to reduce diabetes risk (direct)

Conditions: Individuals at Risk of Developing Diabetes

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.


Eligibility criteria:
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

Keywords: intermittent fasting calorie restriction overweight and obesity