General Practice and Primary Care - Research Publications
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ItemGlobal burden of hypoglycaemia-related mortality in 109 countries, from 2000 to 2014: an analysis of death certificates(SPRINGER, 2018-07)AIMS/HYPOTHESIS: In the context of increasing prevalence of diabetes in elderly people with multimorbidity, intensive glucose control may increase the risk of severe hypoglycaemia, potentially leading to death. While rising trends of severe hypoglycaemia rates have been reported in some European, North American and Asian countries, the global burden of hypoglycaemia-related mortality is unknown. We aimed to investigate global differences and trends of hypoglycaemia-related mortality. METHODS: We used the WHO mortality database to extract information on death certificates reporting hypoglycaemia or diabetes as the underlying cause of death, and the United Nations demographic database to obtain data on mid-year population estimates from 2000 to 2014. We calculated crude and age-standardised proportions (defined as number of hypoglycaemia-related deaths divided by total number of deaths from diabetes [i.e. the sum of hypoglycaemia- and diabetes-related deaths]) and rates (hypoglycaemia-related deaths divided by mid-year population) of hypoglycaemia-related mortality and compared estimates across countries and over time. RESULTS: Data for proportions were extracted from 109 countries (31 had data from all years analysed [2000-2014] available). Combining all countries, the age-standardised proportion of hypoglycaemia-related deaths was 4.49 (95% CI 4.44, 4.55) per 1000 total diabetes deaths. Compared with the overall mean, most Central American, South American and (mainly) Caribbean countries reported higher proportions (five more age-standardised hypoglycaemia-related deaths per 1000 total diabetes deaths in Chile, six in Uruguay, 11 in Belize and 22 in Aruba), as well as Japan (11 more age-standardised hypoglycaemia-related deaths per 1000 total diabetes deaths). In comparison, lower proportions were noted in most European countries, the USA, Canada, New Zealand and Australia. For countries with data available for all years analysed, trend analysis showed a 60% increase in hypoglycaemia-related deaths until 2010 and stable trends onwards. Rising trends were most evident for Argentina, Brazil, Chile, the USA and Japan. Data for rates were available for 105 countries (30 had data for all years analysed [2000-2014] available). Combining all countries, the age-standardised hypoglycaemia-related death rate was 0.79 (95% CI 0.77, 0.80) per 1 million person-years. Most Central American, South American and Caribbean countries similarly reported higher rates of hypoglycaemia-related death, whilst virtually all European countries, the USA, Canada, Japan, New Zealand and Australia reported lower rates compared with the overall mean. Age-standardised rates were very low for most countries (lower than five per 1 million person-years in 89.5% of countries), resulting in small absolute differences among countries. As noted with the proportions analysis, trend analysis showed an overall 60% increase in hypoglycaemia-related deaths until 2010 and stable rate trends onwards; rising rates were particularly evident for Brazil, Chile and the USA. CONCLUSIONS/INTERPRETATION: Most countries in South America, Central America and the Caribbean showed the highest proportions of diabetes-related deaths attributable to hypoglycaemia and the highest rates of hypoglycaemia-related deaths. Between 2000 and 2014, rising trends were observed in Brazil, Chile and the USA for both rates and proportions of hypoglycaemia-related death, and in Argentina and Japan for proportions only. Further studies are required to unravel the contribution of clinical and socioeconomic factors, difference in diabetes prevalence and heterogeneity of death certification in determining lower rates and proportions of hypoglycaemia-related deaths in high-income countries in Europe, North America and Asia. DATA AVAILABILITY: Data used for these analyses are available at https://doi.org/10.17632/ndp52fbz8r.1.
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ItemEfficacy of low- and very-low-energy diets in people with type 2 diabetes mellitus: A systematic review and meta-analysis of interventional studies(WILEY, 2019-07)AIMS: To review systematically and quantify the weight loss achieved through low- (LEDs) and very-low-energy diets (VLEDs) in people with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Studies reporting the effects of diet-only interventions of up to 1600 kcal/d in people with T2DM were searched in MEDLINE, EMBASE and CINAHL up to July 2018. Changes in the primary (body weight and body mass index [BMI]) and secondary outcomes (glycated haemoglobin, blood lipids) according to energy restriction and duration of diet were modelled using restricted cubic splines. RESULTS: Forty-four studies (3817 participants) were included. The overall quality of the evidence was moderate and limited to short-term interventions up to 4 months. Baseline mean weight and BMI were 92.1 kg and 36.6 kg/m2 . VLEDs of 400 kcal/d led to 5.4% weight loss at 2 weeks, increasing to 17.9% at 3 months. More modest reductions of 7.3% were observed on LEDs of 1200 kcal/d and 2.0% on 1600 kcal/d after 3 months. No clear patterns emerged for secondary outcomes. Publication bias was significant for primary outcomes. CONCLUSIONS: Through modelling, we were able to describe effective dietary deficit strategies to achieve weight reduction up to 4 months in people with T2DM. High-quality studies are required to further support clinical practice with evidence-based dietary interventions.
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ItemIntensive versus standard multifactorial cardiovascular risk factor control in screen-detected type 2 diabetes: 5-year and longer-term modelled outcomes of the ADDITION-Leicester study(WILEY, 2019-03)AIMS: Diabetes treatment algorithms recommend intensive intervention in those with a shorter duration of disease. Screening provides opportunities for earlier multifactorial cardiovascular risk factor control. Using data from the ADDITION-Leicester study (NCT00318032), we estimated the effects of this approach on modelled risk of diabetes-related complications in screen-detected patients. METHODS: A total of 345 (41% South Asian) people with screen-detected type 2 diabetes were cluster randomised to receive 5 years of (1) intensive multifactorial risk factor intervention or (2) standard treatment according to national guidance. Estimated 10 to 20-year risk of ischaemic heart disease, stroke, congestive cardiac failure, and death was calculated using UK-PDS risk equations. RESULTS: Compared with standard care, mean treatment differences for intensive management at 5 years were -11.7(95%CI: -15.0, -8.4) and -6.6(-8.8, -4.4) mmHg for systolic and diastolic blood pressure, respectively; -0.27 (-0.66, -0.26) % for HbA1c; and -0.46(-0.66; -0.26), -0.34 (-0.51; -0.18), and -0.19 (-0.28; -0.10) mmol/L for total cholesterol, LDL-cholesterol, and triglycerides, respectively. There was no significant weight gain in the intensive group despite additional medication use. Modelled risks were consistently lower for intensively managed patients. Absolute risk reduction associated with intensive treatment at 10 and 20 years were 3.5% and 6.2% for ischaemic heart disease and 6.3% and 8.8% for stroke. Risk reduction for congestive heart failure plateaued after 15 years at 5.3%. No differences were observed for blindness and all-cause death. CONCLUSION: Intensive multifactorial intervention in a multi-ethnic population with screen-detected type 2 diabetes results in sustained improvements in modelled ischaemic heart disease, stroke, and congestive cardiac failure.
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ItemCardiovascular, cancer and mortality events after bariatric surgery in people with and without pre-existing diabetes: A nationwide study(WILEY, 2019-04)BACKGROUND: Bariatric surgery reduces cardiovascular events and mortality risk in obese individuals. However, it is unclear whether diabetes modifies this effect. This study examined mortality, cardiovascular, and cancer risk following bariatric surgery in adults with and without pre-existing diabetes. METHODS: Using mortality-linked Hospital Episodes Statistics (2006-14) from England, the risk of death, myocardial infarction, stroke, unstable angina, heart failure, and cancer following bariatric surgery was examined; the risk of death in people undergoing surgery was also compared with mortality rates of the general population. RESULTS: Of the 35 887 people undergoing bariatric surgery, 9175 (25.6%) had pre-existing diabetes. During a mean follow-up of 5.3 years, 801 people died, of whom 293 (36.6%) had pre-existing diabetes. The risk of all-cause mortality was 26% higher in people with than without diabetes (adjusted hazard ratio [aHR] 1.26, 95% confidence interval [CI] 1.08-1.46), whereas the risk of cancer was 21% higher (aHR 1.21; 95% CI 1.14-1.77). The risk of cardiovascular events was higher for patients with than without diabetes (aHRs [95% CIs] 2.08 [1.42-3.05], 1.80 [1.29-2.52], 1.61 [1.18-2.19], and 1.42 [1.14-1.77] for myocardial infarction, unstable angina, stroke, and heart failure, respectively). Compared with the general population, the age-standardized mortality rate ratio was 1.70 (1.52-1.91) and 1.35 (1.23-1.48) in people with and without pre-existing diabetes, respectively. CONCLUSIONS: For patients with pre-existing diabetes, the risk of death, cardiovascular events, and cancer after bariatric surgery was higher than for those without diabetes, whose mortality risk after surgery remains 35% higher than that of the general population.
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ItemModerate increases in daily step count are associated with reduced IL6 and CRP in women with PCOS(BIOSCIENTIFICA LTD, 2018-12)Aims Physical activity has been proposed to be an effective non-pharmacological method of reducing systemic inflammation and therefore may prove particularly efficacious for women with polycystic ovary syndrome (PCOS) who have been shown to have high levels of inflammation and an increased risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD). Therefore, the aim of the present study was to assess whether modest changes in daily step count could significantly reduce levels of inflammatory markers in women with PCOS. Subjects and Methods Sixty-five women with PCOS were assessed at baseline and again at 6 months. All had been provided with an accelerometer and encouraged to increase activity levels. Multivariate linear regression analyses (adjusted for age, ethnicity, baseline step count, change in BMI and change in accelerometer wear-time) were used to assess changes in daily step count against clinical and research biomarkers of inflammation, CVD and T2DM. Results Mean step count/day at baseline was 6337 (±270). An increase in step count (by 1000 steps) was associated with a 13% reduction in IL6 (β: -0.81 ng/L; 95% CI, -1.37, -0.25, P = 0.005) and a 13% reduction in CRP (β: -0.68 mg/L; 95% CI, -1.30, -0.06, P = 0.033). Additionally, there was a modest decrease in BMI (β: 0.20 kg/m2; 95% CI, -0.38, -0.01, P = 0.038). Clinical markers of T2DM and CVD were not affected by increased step count. Conclusions Modest increases in step count/day can reduce levels of inflammatory markers in women with PCOS, which may reduce the future risk of T2DM and CVD.
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ItemCardiovascular and mortality events in type 2 diabetes cardiovascular outcomes trials: a systematic review with trend analysis(SPRINGER-VERLAG ITALIA SRL, 2019-03)AIMS: To investigate cardiovascular disease and mortality trends in control arm participants of diabetes cardiovascular outcome trials (CVOTs). METHODS: We electronically searched CVOTs published before October 2017. Data on all-cause mortality, cardiovascular mortality and events, and baseline characteristics were collected, along with study calendar years. Trends were estimated using negative binomial regressions and reported as rate ratio (RR) per 5-year intervals. RESULTS: 26 CVOTs, conducted from 1961 to 2015, included 86788 participants with 6543 all-cause deaths, 3265 cardiovascular deaths, and 7657 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke). In unadjusted analysis, there was an increasing trend for 3-P MACE rates over time (5-year RR 1.57; 95% CI 1.34, 1.84); a small increasing trend for cardiovascular disease mortality rates (1.13; 1.01, 1.26); and stable rates for all-cause death. Adjusting for age, sex, previous myocardial infarction, and diabetes duration, there was no evidence of trends for 3-P MACE or cardiovascular disease mortality rates, while reducing rates were observed for nonfatal myocardial infarction (5-year RR: 0.72; 0.54, 0.96), total stroke (0.76; 0.66, 0.88), and nonfatal stroke (0.60; 0.43, 0.82). CONCLUSIONS: In contrast to real-world data, there was no evidence of an improvement in all-cause and cardiovascular mortality in type 2 diabetes participants included in control arms of randomised clinical trials across 5 decades. Further studies should investigate whether and how dissimilarities in populations, procedures, and assessments of exposures and outcomes explain the differences between real-world setting and clinical trials.