Emer M. Brady

Self-Reported Sitting Time and Markers of Inflammation, Insulin Resistance, and Adiposity

BACKGROUND Sedentary behavior is emerging as an independent risk factor for chronic disease; however, potential mechanisms underpinning these observations are not well understood. PURPOSE This study aimed to investigate the association of self-reported weekday sitting time with biomarkers linked to chronic low-grade inflammation, insulin resistance, and adiposity. METHODS This study reports data from individuals attending a diabetes screening program, United Kingdom, 2004-2007; analysis was conducted in 2010. Sitting time and physical activity were measured using the International Physical Activity Questionnaire; biochemical outcomes included fasting and 2-hour postchallenge glucose, fasting insulin, C-reactive protein (CRP), leptin, adiponectin, and interleukin-6 (IL-6). RESULTS This study included 505 (female=46%; South-Asian ethnicity=19%, aged 59±10 years, BMI=29.5±4.7) individuals with valid sitting data. Increased sitting time was positively associated with fasting insulin, leptin, leptin/adiponectin ratio, CRP, and IL-6 in women, but not men, after adjustment for age, ethnicity, social deprivation, and smoking and medication status; interaction analysis revealed that the gender-specific differences were significant. The associations for women remained significant after additional adjustment for total moderate- to vigorous-intensity physical activity; however all associations were attenuated when further adjusted for BMI. There was no association between sitting time and glycemic status. CONCLUSIONS Total self-reported weekday sitting time was associated with biomarkers linked to chronic low-grade inflammation and poor metabolic health in women, but not men, independent of physical activity.

Defining Obesity Cut-Off Points for Migrant South Asians

Background Body mass index (BMI) and waist circumference (WC) are used to define cardiovascular and type 2 diabetes risk. We aimed to derive appropriate BMI and WC obesity cut-off points in a migrant South Asian population. Methods 4688 White Europeans and 1333 South Asians resident in the UK aged 40–75 years inclusive were screened for type 2 diabetes. Principal components analysis was used to derive a glycaemia, lipid, and a blood pressure factor. Regression models for each factor, adjusted for age and stratified by sex, were used to identify BMI and WC cut-off points in South Asians that correspond to those defined for White Europeans. Findings For South Asian males, derived BMI obesity cut-off points equivalent to 30.0 kg/m2 in White Europeans were 22.6 kg/m2 (95% Confidence Interval (95% CI) 20.7 kg/m2 to 24.5 kg/m2) for the glycaemia factor, 26.0 kg/m2 (95% CI 24.7 kg/m2 to 27.3 kg/m2) for the lipid factor, and 28.4 kg/m2 (95% CI 26.5 kg/m2 to 30.4 kg/m2) for the blood pressure factor. For WC, derived cut-off points for South Asian males equivalent to 102 cm in White Europeans were 83.8 cm (95% CI 79.3 cm to 88.2 cm) for the glycaemia factor, 91.4 cm (95% CI 86.9 cm to 95.8 cm) for the lipid factor, and 99.3 cm (95% CI 93.3 cm to 105.2 cm) for the blood pressure factor. Lower ethnicity cut-off points were seen for females for both BMI and WC. Conclusions Substantially lower obesity cut-off points are needed in South Asians to detect an equivalent level of dysglycemia and dyslipidemia as observed in White Europeans. South Asian ethnicity could be considered as a similar level of risk as obesity (in White Europeans) for the development of type 2 diabetes.

The effect of glucagon-like peptide 1 receptor agonists on weight loss in type 2 diabetes: A systematic review and mixed treatment comparison meta-analysis

Aims To determine the effects of glucagon-like peptide-1 receptor agonists compared with placebo and other anti-diabetic agents on weight loss in overweight or obese patients with type 2 diabetes mellitus. Methods Electronic searches were conducted for randomised controlled trials that compared a glucagon-like peptide-1 receptor agonist therapy at a clinically relevant dose with a comparator treatment (other type 2 diabetes treatment or placebo) in adults with type 2 diabetes and a mean body mass index ≥ 25kg/m2. Pair-wise meta-analyses and mixed treatment comparisons were conducted to examine the difference in weight change at six months between the glucagon-like peptide-1 receptor agonists and each comparator. Results In the mixed treatment comparison (27 trials), the glucagon-like peptide-1 receptor agonists were the most successful in terms of weight loss; exenatide 2mg/week: -1.62kg (95% CrI: -2.95kg, -0.30kg), exenatide 20μg: -1.37kg (95% CI: -222kg, -0.52kg), liraglutide 1.2mg: -1.01kg (95%CrI: -2.41kg, 0.38kg) and liraglutide 1.8mg: -1.51 kg (95% CI: -2.67kg, -0.37kg) compared with placebo. There were no differences between the GLP-1 receptor agonists in terms of weight loss. Conclusions This review provides evidence that glucagon-like peptide-1 receptor agonist therapies are associated with weight loss in overweight or obese patients with type 2 diabetes with no difference in weight loss seen between the different types of GLP-1 receptor agonists assessed.

A randomized controlled trial comparing the GLP-1 receptor agonist liraglutide to a sulphonylurea as add on to metformin in patients with established type 2 diabetes during Ramadan: the Treat 4 Ramadan Trial.

To compare a sulphonylurea with the glucagon like peptide‐1 (GLP‐1) receptor agonist liraglutide in combination with metformin in patients on mono/dual oral therapy with established type 2 diabetes fasting during Ramadan.

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≥75th 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.

Walking and inflammatory markers in individuals screened for type 2 diabetes

OBJECTIVE To investigate the association of walking activity with inflammatory markers and fasting insulin in a bi-ethnic population screened for type 2 diabetes in Leicester, United Kingdom, between 2005 and 2006. METHOD Physical activity, adipocytokine, high-sensitivity C-reactive protein and fasting insulin measurements were available for 400 individuals screened for type 2 diabetes. Of the 400 participants, 56% were diagnosed with normal glucose control, 36% with prediabetes and 8% with diabetes. RESULTS Multivariate statistical analysis showed that those who reported walking for at least 30 min on at least 5 days/week had lower levels of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha compared to those who reported lower walking activity levels, after adjustment for other modes of moderate-to-vigorous intensity physical activity, age, ethnicity, sex, social deprivation and smoking status. Further adjustment for waist circumference attenuated the association of walking with tumor necrosis factor-alpha. CONCLUSION Walking activity, independent of other forms of physical activity, is associated with lower levels of circulating pro-inflammatory markers.

Guidelines for managing diabetes in Ramadan.

Globally there are approximately 90 million Muslims with diabetes of which approximately 400 000 reside within the UK. The holy month of Ramadan is a fundamental practice of this religion of which fasting from sun‐rise to sun‐set is an integral part. This poses many potential risks for those with diabetes who wish to observe Ramadan.

Effect of physical activity measurement type on the association between walking activity and glucose regulation in a high-risk population recruited from primary care

BACKGROUND We investigate associations of self-reported and objectively assessed walking activity with measures of glucose regulation in a multi-ethnic population at high risk of type 2 diabetes. METHODS This study reports data from a 2009-2011 screening programme for impaired glucose regulation (IGR) within a high-risk primary care population in Leicestershire, UK; 2532 participants (38% women, 8% South Asian) with a mean age of 64 ± 8 years and an average BMI of 32.1 ± 5.6 kg/m(2) were included. Walking activity was measured by self-report (International Physical Activity Questionnaire) and objectively (pedometer). Glucose regulation assessments included 2h post-challenge glucose, fasting glucose and HbA1c. RESULTS Higher levels of self-reported walking activity and pedometer steps were associated with lower 2h post-challenge glucose after controlling for several known confounding variables, including BMI. Similarly, when categorized in tertiles, both measures were associated with a lower odds of having any form of IGR; odds ratio for lowest vs highest tertile was 0.64 (0.51-0.80) for self-report and 0.69 (0.55-0.87) for pedometer steps. There was no significant difference between self-reported and objective measures in the strength of associations with glucose regulation; associations with self-report were maintained when further adjusted for pedometer steps. Stronger associations between self-reported walking activity and glucose regulation were observed in South Asians compared with White Europeans. CONCLUSIONS Self-reported and objectively measured walking activity were equally associated with indices of glucose regulation. Associations with self-reported walking activity were maintained when further adjusted for pedometer steps, suggesting that self-reported walking activity may measure facets of physical activity that are beyond total volume.

Safety and effectiveness of non‐insulin glucose‐lowering agents in the treatment of people with type 2 diabetes who observe Ramadan: a systematic review and meta‐analysis

To determine which non‐insulin glucose‐lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan.

An Investigation into the Relationship Between Sleep-Disordered Breathing, the Metabolic Syndrome, Cardiovascular Risk Profiles, and Inflammation Between South Asians and Caucasians Residing in the United Kingdom

BACKGROUND The aim of this study was to determine the prevalence of sleep-disordered breathing (SDB) in a South Asian and a Caucasian population and to compare the cardiovascular risk factors in those with SDB within these ethnic groups and determine if SDB is independently associated with the metabolic syndrome and markers of inflammation. METHODS A total of 1,598 participants within a U.K. multiethnic population underwent an oral glucose tolerance test, completed the Berlin Sleep Questionnaire, and provided anthropometric data and fasting bloods. Metabolic syndrome was classified according to National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS The prevalence of SDB was 28.3% and did not differ between the two ethnic groups. South Asians with SDB had a higher body fat percentage (38.4±10% vs. 35.6±9%, P=0.016), glycosylated hemoglobin (5.6±0.5% vs. 5.6±0.5%, P=0.001) and lower high-density lipoprotein cholesterol (1.21±0.23 mmol/L vs. 1.29±0.34 mmol/L, P=0.002) compared to Caucasians with SDB, who were older (59.6±8.6 years vs. 50.4±10.3 years, P<0.001) and had higher systolic blood pressure (139.8±18.5 mmHg vs. 131.7±18.6 mmHg, P<0.001). SDB was associated with metabolic syndrome after adjustment for age, gender, ethnicity, and waist circumference (odds ratio=1.54, 95% confidence interval 1.12-2.09, P=0.01). There was no independent association between SDB and markers of inflammation. CONCLUSION The relationship between SDB and metabolic syndrome is not driven via the inflammatory pathway. The prevalence of SDB is significantly higher in those with metabolic syndrome although these South Asians had a greater cardiovascular disease (CVD) risk profile the relationship is independent of ethnicity. Routine screening for SDB within primary/secondary care may have a role in the prevention of CVD and type 2 diabetes mellitus.