Sleep behaviours and associated habits and the progression of pre-diabetes to type 2 diabetes mellitus in adults: A systematic review and meta-analysis.

INTRODUCTION: Certain sleep behaviours increase risk of type 2 diabetes mellitus (T2DM) in the general population, but whether they contribute to the progression from pre-diabetes to T2DM is uncertain. We conducted a systematic review to assess this. METHODS: Structured searches were performed on bibliographic databases (MEDLINE, EMBASE and CINAHL) from inception to 26/04/2021 for longitudinal studies/trials consisting of adults⩾18 years with pre-diabetes and sleep behaviours (short or long sleep duration (SD), late chronotype, insomnia, obstructive sleep apnoea, daytime napping and/or night-shift employment) that reported on incident T2DM or glycaemic changes. The Newcastle-Ottawa Scale was used for quality assessment. RESULTS: Six studies were included. Meta-analysis of three studies (n = 20,139) demonstrated that short SD was associated with greater risk of progression to T2DM, hazard ratio (HR) 1.59 (95% CI 1.29-1.97), I2 heterogeneity score 0%, p < 0.0001, but not for long SD, HR 1.50 (0.86-2.62), I2 heterogeneity 77%, p = 0.15. The systematic review showed insomnia and night-shift duty were associated with higher progression to T2DM. Studies were rated as moderate-to-high quality. CONCLUSIONS: Progression from pre-diabetes to T2DM increases with short SD, but only limited data exists for insomnia and night-shift duty. Whether manipulating sleep could reduce progression from pre-diabetes to T2DM needs to be examined.

The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.

INTRODUCTION: To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes. METHODS: Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality. RESULTS: Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p = 0.093) and 1.18 (95% CI 0.90-1.54, p = 0.226) in DM+C and DM-C, respectively. CONCLUSIONS: Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.

Simulating the impact of targeting lower systolic blood pressure and LDL-cholesterol levels on type 2 diabetes complication rates.

AIMS: There are few data available on the incremental benefits of risk factor modification in type 2 diabetes mellitus (T2DM). We simulated the potential benefits of achieving lower systolic blood pressure (SBP) and LDL-cholesterol targets. METHODS: We used the UKPDS Outcomes Model v2.0 to estimate 10-year event rates for complications using baseline data from 5717 participants with T2DM in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin Study. All risk factor values were held constant over 10 years. In separate analyses, different levels of SBP between 160 and 120 mm Hg and LDL-cholesterol between 5.0 and 1.0 mmol/l were imposed on the cohort. Cumulative relative risk reductions (CRRR) at each 10 mm Hg and 1.0 mmol/l decrements respectively were compared using Kruskal-Wallis tests. RESULTS: CRRRs for each 10 mm Hg SBP decrement from 160 mm Hg were 2.2%, 4.5%, 7.0% and 10.0% for myocardial infarction (MI); 12.5%, 24.8%, 35.6% and 44.9% for stroke; 5.4%, 10.9%, 16.2% and 20.9% for blindness; 7.4%, 14.7%, 21.6% and 27.4% for amputation, respectively. CRRRs for each 1.0 mmol/l LDL-cholesterol decrement from 5.0 mmol/l were 16.9%, 30.8%, 41.2% & 51.0% for MI; 9.2%, 19.7%, 29.6% & 38.8% for stroke (p < 0.001 in all cases). CONCLUSIONS: These simulated outcomes illustrate the potential benefits of targeting progressively lower SBP and LDL-cholesterol values.

The association of the triglyceride-to-HDL cholesterol ratio with insulin resistance in White European and South Asian men and women.

INTRODUCTION: There is recent interest surrounding the use of the triglyceride-to-HDL cholesterol ratio as a surrogate marker of insulin resistance in clinical practice, as it may identify people at high risk of developing diabetes or its complications. However, it has been suggested using this lipid ratio may not be appropriate for measuring insulin resistance in African-Americans, particularly women. We investigated if this inconsistency extended to South Asian women in a UK multi-ethnic cohort of White Europeans and South Asians. METHODS: Cross-sectional analysis was done of 729 participants from the ADDITION-Leicester study from 2005 to 2009. The association between tertiles of triglyceride-to-HDL cholesterol ratio to fasting insulin, homeostatic model of assessment for insulin resistance (HOMA1-IR), quantitative insulin sensitivity check index (QUICKI) and glucose: insulin ratio was examined with adjustment for confounding variables. RESULTS: Incremental tertiles of the triglyceride-to-HDL cholesterol ratio demonstrated a significant positive association with levels of fasting insulin, HOMA1-IR, glucose: insulin ratio and a negative association with QUICKI in White European men (n = 255) and women (n = 250) and South Asian men (n = 124) (all p<0.05), but not South Asian women (n = 100). A significant interaction was demonstrated between sex and triglyceride-to-HDL cholesterol ratio tertiles in South Asians only (p<0.05). The area under the receiver operating characteristic curve for triglyceride-to-HDL cholesterol ratio to detect insulin resistance, defined as the cohort HOMA1-IR ≥ 75(th) percentile (3.08), was 0.74 (0.67 to 0.81), 0.72 (0.65 to 0.79), 0.75 (0.66 to 0.85) and 0.67 (0.56 to 0.78) in White European men and women, South Asian men and women respectively. The optimal cut-points for detecting insulin resistance were 0.9-1.7 in mmol/l (2.0-3.8 in mg/dl) for the triglyceride-to-HDL ratio. CONCLUSION: In South Asian women the triglyceride-to-HDL cholesterol ratio was not associated with insulin resistance; therefore there may be limitations in its use as a surrogate marker in this group.

Independent effect of ethnicity on glycemia in South Asians and white Europeans.

OBJECTIVE: HbA(1c) levels are higher in most ethnic groups compared with white Europeans (WEs) independent of glycemic control. This comparison has not been performed between South Asians (SAs) and WEs. We analyzed the independent effect of ethnicity on HbA(1c) and fasting and 2-h plasma glucose (FPG and 2 hrPG, respectively) between these groups. RESEARCH DESIGN AND METHODS: Analysis of the ADDITION-Leicester study, in which 4,688 WEs and 1,352 SAs underwent oral glucose tolerance testing, HbA(1c), and other risk factor measurements. RESULTS: Significant associations with HbA(1c) included ethnicity, FPG, 2 hrPG, and homeostasis model assessment of ß-cell function (P < 0.001); age and sex (P < 0.01); and fasting insulin and potassium (P < 0.05). After adjusting for these and other risk factors, SAs demonstrated higher HbA(1c) (6.22 and 6.02%, mean difference 0.20%, 0.10-0.30, P < 0.001), FPG (5.15 and 5.30 mmol/L, mean difference 0.15 mmol/L, 0.09-0.21, P < 0.001), and 2 hrPG (5.82 and 6.57 mmol/L, mean difference 0.75 mmol/L, 0.59-0.92, P < 0.001) compared with WEs, respectively. CONCLUSIONS: HbA(1c), FPG, and 2 hrPG levels were higher in SAs independent of factors affecting glycemic control.

A comparison of cost per case detected of screening strategies for Type 2 diabetes and impaired glucose regulation: modelling study.

BACKGROUND: To determine a cost per case detected for different screening strategies for both Type 2 diabetes alone and in combination with impaired glucose regulation. METHODS: Bayesian framework modelling study using data from the ADDITION-Leicester screening study in UK multi-ethnic primary care setting. There were 5794 people aged 40-75 years (77.4% white European; 22.6% south Asian) without previously known diabetes. We compared 212 screening strategies including blood tests, a computer practice data score and a risk score, as part of a multi-stage process that all used an oral glucose tolerance test as the diagnostic test. Simulation models were created using sensitivity estimates for the expected cost per case. RESULTS: The estimated costs per case identified for the 18 most sensitive strategies varied from £457 to £1639 (€526-1886, for £1=€1.15) for diabetes and £148-913 (€170-1050) for both diabetes and impaired glucose regulation. The lowest costing diabetes strategies ranged from £457 to £523 (€526-601) involving a two-stage screening strategy, a non-invasive risk stratifying tool followed by a blood test, producing sensitivities ranging from 67.1 to 82.4%. CONCLUSION: Screening a population using a non-invasive risk stratification tool followed by a screening blood test is the most cost-effective method of screening for diabetes and abnormal glucose tolerance.

Should glycated haemoglobin (HbA1c) be used to detect people with type 2 diabetes mellitus and impaired glucose regulation?

There is a need to simplify screening tests for type 2 diabetes mellitus (T2DM) so patients can be identified earlier and more efficiently. Glycated haemoglobin (HbA1c) has been recommended by some international organisations as a diagnostic tool for detecting T2DM and impaired glucose regulation (IGR, also termed prediabetes and includes impaired fasting glucose and/or impaired glucose tolerance). The HbA1c cut-point of ≥6.5% (48 mmol/mol) has been selected as diagnostic for T2DM, while the cut-points for IGR are debated by the different international organisations: an International Expert Committee has suggested using HbA1c 6.0-6.4% (42-46 mmol/mol); however, the American Diabetes Association has recommended using HbA1c 5.7-6.4% (39-46 mmol/mol). Some countries will adopt a new method of reporting HbA1c values in millimoles per mole (mmol/mol). Use of HbA1c has some logistical advantages over using an oral glucose tolerance test (OGTT). As patients do not need to fast, appointments do not need to be limited to the morning. The HbA1c result reflects longer term glycaemia and is less affected by recent physical/emotional stress. However, there is some debate as to whether HbA1c should replace fasting plasma glucose or the OGTT. As the two tests detect different people, some individuals with diabetes detected on OGTT will no longer be classified as having T2DM using HbA1c ≥6.5% criteria. Furthermore, some medical conditions can result in HbA1c assay measurements not reflecting glycaemic control over the last 2-3 months; these include haematological disorders, renal failure, and chronic excess alcohol consumption.

The potential impact and optimal cut-points of using glycated haemoglobin, HbA1c, to detect people with impaired glucose regulation in a UK multi-ethnic cohort.

INTRODUCTION: Recommended diagnostic cut-points to detect impaired glucose regulation (IGR, also termed prediabetes: impaired fasting glucose and/or impaired glucose tolerance based on WHO 1999 criteria) are HbA1c 6.0-6.4% and 5.7-6.4% from an International Expert Committee and American Diabetes Association, respectively. We investigated the impact on prevalence/phenotype from using these criteria compared to IGR detected on oral glucose tolerance testing (OGTT) and determined optimal HbA1c cut-points for IGR in a multi-ethnic cohort. METHODS: Analysis of 8696 participants in the LEADER study of primary care individuals aged 40-75 years without diabetes, in Leicestershire (UK) who underwent OGTT and had HbA1c measured. RESULTS: Use of OGTT detected less people with IGR (n=1407, 16.2%) compared to HbA1c 6.0-6.4% (n=1610, 18.5%) and HbA1c 5.7-6.4%(n=3904, 44.9%), a 1.1- and 2.8-fold increase in prevalence, respectively. There were 930 (10.7%) and 534 (6.1%) people with IGR on OGTT not detected using HbA1c 6.0-6.4% and 5.7-6.4%, respectively. From ROC curve analysis, the optimal cut-point for detecting IGR in white Europeans was HbA1c>or=5.8%, sensitivity/specificity 61.5%/67.9%, but in south Asians HbA1c>or=6.0%, sensitivity/specificity 63.8%/69.4%. CONCLUSION: Recommended HbA1c cut-points to detect IGR significantly increase numbers detected, however introduce a change in people identified. Using HbA1c 6.0-6.4% lacks sensitivity in white Europeans, but is a reasonable option in south Asians.