Research design and methods
This study used data from the UK Biobank (https://www.ukbiobank.ac.uk/). The UK Biobank is a large general population cohort of 502 624 middle-aged or older-aged participants (40–69 years old at recruitment) who were recruited at 22 centers across the UK between March 2006 and December 2010.8 During recruitment, participants provided detailed demographic, lifestyle and medical history information and biological samples, and anthropometric measurements were taken. Inclusion in this study was restricted to participants who identified themselves as white, Indian, Pakistani, Bangladeshi, black African, black Caribbean, or Chinese. To provide sufficient statistical power, Indian, Pakistani, and Bangladeshi participants were amalgamated into South Asian, and black African and black Caribbean participants were amalgamated into black.
All participants gave written informed consent before enrollment in the study.
Deprivation status was based on the Townsend Deprivation Index derived from the postcode of residence at recruitment. Body mass index (BMI) was calculated from weight/height2 and categorized into underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2), according to the WHO classification. A lifestyle score, previously shown to be associated with all-cause mortality, was used to characterize overall lifestyle as described previously.9 10 Lifestyle factors, self-reported at baseline, included smoking status (current, former, or never), physical activity (time spent doing moderate and vigorous physical activity per week, converted to metabolic equivalents (METs)-min/week and dichotomized into inactive (<600 METs-min/week) and active (≥600 METs-min/week) according to the physical activity guidelines11), sedentary time (watching television, using a computer, and non-work-related driving), adequate sleep, and optimal dietary intake of fruit and vegetables (≥5/day), red meat (<70 g/day) and processed meat (never or less than once a week), oily fish (≥1/week), and alcohol (<14 units/week). The overall lifestyle score ranged from 0 (most unhealthy; highest risk of all-cause mortality) to 9 (most healthy; lowest risk of all-cause mortality). Sampling procedures for UK Biobank biomarkers have been described and validated previously.12 13 Briefly, biochemistry analyses were performed at a dedicated central laboratory on 480 000 samples between 2014 and 2017 and included plasma glycated hemoglobin (HbA1c) (VARIANT II TURBO Hemoglobin Testing System; Bio-Rad). Data were adjusted for preanalytical variables by the UK Biobank centrally before release.
Known diabetes was defined as at least one of the following: type 1 or type 2 diabetes self-reported by the participant at baseline and/or taking insulin or other diabetes-related medications (metformin, sulfonylurea, meglitinides/glinides/prandial glucose regulators, alpha-glucosidase inhibitors, thiazolidinedione/glitazones, dipeptidyl peptidase-4 (DPP-4) inhibitors/gliptins, incretin mimetics/glucagon-like peptide-1 (GLP-1) analogs, and amylin analogs). Participants with known diabetes were excluded from the study. Among the remaining participants, pre-diabetes and undiagnosed diabetes were ascertained from HbA1c concentrations and defined as HbA1c 42–47.9 mmol/mol and ≥48 mmol/mol, respectively.14
Sensitivity analyses were conducted excluding participants with self-reported cardiovascular disease at baseline (heart attack, angina, stroke, or transient ischemic attack), since such individuals are likely to be already in receipt of preventive pharmaceutical or lifestyle interventions.
Participants were stratified by ethnicity and sex and their baseline characteristics summarized using percentages for categorical variables and mean and SD, or median and IQR, for continuous variables. Crude prevalence was calculated by dividing the total number of cases by the total number of the population in each category. Crude prevalence was derived overall and by age, gender, and ethnic subgroup. The 2011 Census data15 were used to standardize the prevalence rates to the age, gender, and ethnic breakdown of the UK general population, within the age group recruited to the UK Biobank. Briefly, sex-specifc and ethnic-specific prevalence rates obtained from the UK Biobank were used to estimate the total cases in the UK general population, according to the total of men and women in each of the ethnic group in the 40–70 age group only, and the corresponding UK population prevalence rates for all 40–70 years old were recalculated. The yield (average number needed to test to detect a case) was derived from inversion of the prevalence.