Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study.

AIMS/HYPOTHESIS: We examined the association of attainment of diabetes remission in the context of a 12 year intensive lifestyle intervention with subsequent incidence of chronic kidney disease (CKD) and CVD. METHODS: The Look AHEAD study was a multi-centre RCT comparing the effect of a 12 year intensive lifestyle intervention with that of diabetes support and education on CVD and other long-term health conditions. We compared the incidence of CVD and CKD among 4402 and 4132 participants, respectively, based on achievement and duration of diabetes remission. Participants were 58% female, and had a mean age of 59 years, a duration of diabetes of 6 year and BMI of 35.8 kg/m2. We applied an epidemiological definition of remission: taking no diabetes medications and having HbA1c <48 mmol/mol (6.5%) at a single point in time. We defined high-risk or very high-risk CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, and CVD incidence as any occurrence of non-fatal acute myocardial infarction, stroke, admission for angina or CVD death. RESULTS: Participants with evidence of any remission during follow-up had a 33% lower rate of CKD (HR 0.67; 95% CI 0.52, 0.87) and a 40% lower rate of the composite CVD measure (HR 0.60; 95% CI 0.47, 0.79) in multivariate analyses adjusting for HbA1c, BP, lipid levels, CVD history, diabetes duration and intervention arm, compared with participants without remission. The magnitude of risk reduction was greatest for participants with evidence of longer-term remission. CONCLUSIONS/INTERPRETATION: Participants with type 2 diabetes with evidence of remission had a substantially lower incidence of CKD and CVD, respectively, compared with participants who did not achieve remission. This association may be affected by post-baseline improvements in weight, fitness, HbA1c and LDL-cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov NCT00017953 DATA AVAILABILITY: https://repository.niddk.nih.gov/studies/look-ahead/.

Improving health outcomes of people with diabetes: target setting for the WHO Global Diabetes Compact.

The Global Diabetes Compact is a WHO-driven initiative uniting stakeholders around goals of reducing diabetes risk and ensuring that people with diabetes have equitable access to comprehensive, affordable care and prevention. In this report we describe the development and scientific basis for key health metrics, coverage, and treatment targets accompanying the Compact. We considered metrics across four domains: factors at a structural, system, or policy level; processes of care; behaviours and biomarkers such as glycated haemoglobin (HbA1c); and health events and outcomes; and three risk tiers (diagnosed diabetes, high risk, or whole population), and reviewed and prioritised them according to their health importance, modifiability, data availability, and global inequality. We reviewed the global distribution of each metric to set targets for future attainment. This process led to five core national metrics and target levels for UN member states: (1) of all people with diabetes, at least 80% have been clinically diagnosed; and, for people with diagnosed diabetes, (2) 80% have HbA1c concentrations below 8·0% (63·9 mmol/mol); (3) 80% have blood pressure lower than 140/90 mm Hg; (4) at least 60% of people 40 years or older are receiving therapy with statins; and (5) each person with type 1 diabetes has continuous access to insulin, blood glucose meters, and test strips. We also propose several complementary metrics that currently have limited global coverage, but warrant scale-up in population-based surveillance systems. These include estimation of cause-specific mortality, and incidence of end-stage kidney disease, lower-extremity amputations, and incidence of diabetes. Primary prevention of diabetes and integrated care to prevent long-term complications remain important areas for the development of new metrics and targets. These metrics and targets are intended to drive multisectoral action applied to individuals, health systems, policies, and national health-care access to achieve the goals of the Global Diabetes Compact. Although ambitious, their achievement can result in broad health benefits for people with diabetes.

Care processes in people in remission from type 2 diabetes: A cohort study using the National Diabetes Audit.

AIMS: People with type 2 diabetes can enter remission but may relapse or develop legacy complications. This analysis assesses whether people with remission from type 2 diabetes continue receiving annual care processes recommended in national guidelines and the potential impacts of formal recognition of remission. METHODS: People with type 2 diabetes with and without formal recognition (diagnostic code) of remission, and with and without evidence of remission (HbA1c < 48 mmol/mol without prescription for glucose-lowering drugs in preceding 26 weeks), included in the 2018/19 National Diabetes Audit (NDA) for England and Wales were followed up to identify care processes received between 1 January 2019 and 31 March 2020. RESULTS: Of the 2,822,145 people with type 2 diabetes in the cohort, 16,460 (0.58%) were coded with remission in the 2018/19 NDA. After adjustment for age, sex, socioeconomic deprivation and ethnicity, people coded with remission were less likely to receive each care process than those without such coding irrespective of HbA1c measurements (relative risk (RR) of receiving all 8 care processes 0.70 (95% CI 0.69-0.72)). For the 339,235 people with evidence of remission, irrespective of diagnostic coding compared to those without such evidence, the RR for receiving all 8 care processes was 0.94 (95% CI 0.93-0.94). CONCLUSIONS: People coded with remission of type 2 diabetes were less likely to receive diabetes care processes than those without such coding. People with evidence of remission had only a slightly reduced likelihood of receiving care processes. Formal recognition of remission may affect the provision or uptake of care processes.

Twenty-year trajectories of cardio-metabolic factors among people with type 2 diabetes by dementia status in England: a retrospective cohort study.

To assess 20-year retrospective trajectories of cardio-metabolic factors preceding dementia diagnosis among people with type 2 diabetes (T2D). We identified 227,145 people with T2D aged > 42 years between 1999 and 2018. Annual mean levels of eight routinely measured cardio-metabolic factors were extracted from the Clinical Practice Research Datalink. Multivariable multilevel piecewise and non-piecewise growth curve models assessed retrospective trajectories of cardio-metabolic factors by dementia status from up to 19 years preceding dementia diagnosis (dementia) or last contact with healthcare (no dementia). 23,546 patients developed dementia; mean (SD) follow-up was 10.0 (5.8) years. In the dementia group, mean systolic blood pressure increased 16-19 years before dementia diagnosis compared with patients without dementia, but declined more steeply from 16 years before diagnosis, while diastolic blood pressure generally declined at similar rates. Mean body mass index followed a steeper non-linear decline from 11 years before diagnosis in the dementia group. Mean blood lipid levels (total cholesterol, LDL, HDL) and glycaemic measures (fasting plasma glucose and HbA1c) were generally higher in the dementia group compared with those without dementia and followed similar patterns of change. However, absolute group differences were small. Differences in levels of cardio-metabolic factors were observed up to two decades prior to dementia diagnosis. Our findings suggest that a long follow-up is crucial to minimise reverse causation arising from changes in cardio-metabolic factors during preclinical dementia. Future investigations which address associations between cardiometabolic factors and dementia should account for potential non-linear relationships and consider the timeframe when measurements are taken.

Interpreting global trends in type 2 diabetes complications and mortality.

International trends in traditional diabetes complications (cardiovascular, renal, peripheral vascular, ophthalmic, hepatic or neurological diseases) and mortality rates are poorly characterised. An earlier review of studies published up to 2015 demonstrated that most data come from a dozen high-income countries (HICs) in North America, Europe or the Asia-Pacific region and that, in these countries at least, rates of acute glycaemic fluctuations needing medical attention and amputations, myocardial infarction and mortality were all declining over the period. Here, we provide an updated review of published literature on trends in type 2 diabetes complications and mortality in adults since 2015. We also discuss issues related to data collection, analysis and reporting that have influenced global trends in type 2 diabetes and its complications. We found that most data on trends in type 2 diabetes, its complications and mortality come from a small number of HICs with comprehensive surveillance systems, though at least some low- and middle-income countries (LMICs) from Africa and Latin America are represented in this review. The published data suggest that HICs have experienced declines in cardiovascular complication rates and all-cause mortality in people with diabetes. In parallel, cardiovascular complications and mortality rates in people with diabetes have increased over time in LMICs. However, caution is warranted in interpreting trends from LMICs due to extremely sparse data or data that are not comparable across countries. We noted that approaches to case ascertainment and definitions of complications and mortality (numerators) and type 2 diabetes (the denominator) vary widely and influence the interpretation of international data. We offer four key recommendations to more rigorously document trends in rates of type 2 diabetes complications and mortality, over time and worldwide: (1) increasing investments in data collection systems; (2) standardising case definitions and approaches to ascertainment; (3) strengthening analytical capacity; and (4) developing and implementing structured guidelines for reporting of data.

Mortality trends in type 1 diabetes: a multicountry analysis of six population-based cohorts.

AIMS/HYPOTHESIS: Mortality has declined in people with type 1 diabetes in recent decades. We examined how the pattern of decline differs by country, age and sex, and how mortality trends in type 1 diabetes relate to trends in general population mortality. METHODS: We assembled aggregate data on all-cause mortality during the period 2000-2016 in people with type 1 diabetes aged 0-79 years from Australia, Denmark, Latvia, Scotland, Spain (Catalonia) and the USA (Kaiser Permanente Northwest). Data were obtained from administrative sources, health insurance records and registries. All-cause mortality rates in people with type 1 diabetes, and standardised mortality ratios (SMRs) comparing type 1 diabetes with the non-diabetic population, were modelled using Poisson regression, with age and calendar time as quantitative variables, describing the effects using restricted cubic splines with six knots for age and calendar time. Mortality rates were standardised to the age distribution of the aggregate population with type 1 diabetes. RESULTS: All six data sources showed a decline in age- and sex-standardised all-cause mortality rates in people with type 1 diabetes from 2000 to 2016 (or a subset thereof), with annual changes in mortality rates ranging from -2.1% (95% CI -2.8%, -1.3%) to -5.8% (95% CI -6.5%, -5.1%). All-cause mortality was higher for male individuals and for older individuals, but the rate of decline in mortality was generally unaffected by sex or age. SMR was higher in female individuals than male individuals, and appeared to peak at ages 40-70 years. SMR declined over time in Denmark, Scotland and Spain, while remaining stable in the other three data sources. CONCLUSIONS/INTERPRETATION: All-cause mortality in people with type 1 diabetes has declined in recent years in most included populations, but improvements in mortality relative to the non-diabetic population are less consistent.

The utility of the Edmonton Obesity Staging System for the prediction of COVID-19 outcomes: a multi-centre study.

BACKGROUND: Patients with obesity have an increased risk for adverse COVID-19 outcomes. Body mass index (BMI) does not acknowledge the health burden associated this disease. The performance of the Edmonton Obesity Staging System (EOSS), a clinical classification tool that assesses obesity-related comorbidity, is compared with BMI, with respect to adverse COVID-19 outcomes. METHODS: 1071 patients were evaluated in 11 COVID-19 hospitals in Mexico. Patients were classified into EOSS stages. Adjusted risk factors for COVID-19 outcomes were calculated and survival analysis for mechanical ventilation and death was carried out according to EOSS stage and BMI category. RESULTS: The risk for intubation was higher in patients with EOSS stages 2 and 4 (HR 1.42, 95% CI 1.02-1.97 and 2.78, 95% CI 1.83-4.24), and in patients with BMI classes II and III (HR 1.71, 95% CI 1.06-2.74, and 2.62, 95% CI 1.65-4.17). Mortality rates were significantly lower in patients with EOSS stages 0 and 1 (HR 0.62, 95% CI 0.42-0.92) and higher in patients with BMI class III (HR 1.58, 95% CI 1.03-2.42). In patients with a BMI ≥ 25 kg/m2, the risk for intubation increased with progressive EOSS stages. Only individuals in BMI class III showed an increased risk for intubation (HR 2.24, 95% CI 1.50-3.34). Mortality risk was increased in EOSS stages 2 and 4 compared to EOSS 0 and 1, and in patients with BMI class II and III, compared to patients with overweight. CONCLUSIONS: EOSS was associated with adverse COVID-19 outcomes, and it distinguished risks beyond BMI. Patients with overweight and obesity in EOSS stages 0 and 1 had a lower risk than patients with normal weight. BMI does not adequately reflect adipose tissue-associated disease, it is not ideal for guiding chronic-disease management.

Associations of progression to diabetes and regression to normal glucose tolerance with development of cardiovascular and microvascular disease among people with impaired glucose tolerance: a secondary analysis of the 30 year Da Qing Diabetes Prevention Outcome Study.

AIMS/HYPOTHESIS: We aimed to determine associations of regression to normal glucose tolerance (NGT), maintaining impaired glucose tolerance (IGT) or progression to diabetes with subsequent risks of CVD and microvascular disease among Chinese adults with IGT. METHODS: We conducted an observational study among 540 participants in the Da Qing Diabetes Prevention Study, a 6 year lifestyle intervention trial in people with IGT, defined by 1985 WHO criteria as fasting plasma glucose <7.8 mmol/l and 2 h post-load plasma glucose ≥7.8 and <11.1 mmol/l. At the end of the trial, the groups that had regressed to NGT, remained with IGT or progressed to diabetes were identified. Participants were then followed for 24 years after completion of the trial, during which we compared the incidence and hazard ratios for CVD and microvascular disease in each group and estimated the differences in their median time to onset from parametric Weibull distribution models. RESULTS: At the end of the 6 year trial, 252 (46.7%) participants had developed diabetes, 114 (21.1%) had remained with IGT and 174 (32.2%) had regressed to NGT. Compared with those who developed diabetes during the trial, the median time to onset of diabetes was delayed by 14.86 years (95% CI 12.49, 17.25) in the NGT and 9.87 years (95% CI 8.12, 11.68) in the IGT groups. After completion of the trial, among those with diabetes, IGT and NGT, the 24 year cumulative incidence of CVD was 64.5%, 48.5% and 45.1%, respectively, and 36.8%, 21.7% and 16.5% for microvascular diseases. Compared with participants who had progressed to diabetes during the trial, those who regressed to NGT had a 37% (HR 0.63; 95% CI 0.47, 0.85) reduction in CVD incidence and a median delay of 7.45 years (95% CI 1.91, 12.99) in onset, and those who remained with IGT had a 34% (HR 0.66; 95% CI 0.47, 0.91) lower CVD incidence with a median delay in onset of 5.69 years (95% CI 1.0, 10.38). Participants with NGT had a 66% (HR 0.34; 95% CI 0.20, 0.56) lower incidence of microvascular diseases and a median delay in the onset of 18.66 years (95% CI 6.08, 31.24), and those remaining with IGT had a 52% (HR 0.48; 95% CI 0.29, 0.81) lower incidence with a median delay of 12.56 years (95% CI 2.49, 22.63). CONCLUSIONS/INTERPRETATION: People with IGT who reverted to NGT or remained with IGT at the end of the 6 year trial subsequently had significantly lower incidences of CVD and microvascular disease than those who had developed diabetes.

Cohort profile: National Diabetes Audit for England and Wales.

The National Diabetes Audit (NDA) collates and analyses data on the quality and variation in clinical care and outcomes for people with diabetes. It also provides opportunities to assess trends, determinants, and outcomes of diabetes to help guide clinical and public health priorities. COHORT: Between 1 January 2003 and 31 March 2020, a total of 5,280,885 people diagnosed with diabetes were included in at least one NDA data collection. To this date, median follow-up was 12 and 8 years for people with type 1 diabetes and type 2 diabetes respectively. Comparisons with the 2019/20 Quality and Outcomes Framework show it included 98% of adults in England and Wales with diagnosed type 1 and type 2 diabetes. Data include demographic characteristics (age, sex, ethnicity, age at diagnosis, deprivation), risk factors (HbA1c , blood pressure, cholesterol, body mass index, smoking status) diabetic and cardiovascular complications and deaths. SECONDARY ANALYSIS: Secondary analyses have included comparisons of HbA1c and blood pressure measurements in cohorts with similar characteristics to the Epidemiology of Diabetes Interventions and Complications study and the UK Prospective Diabetes Study; COVID-19 related mortality in people with type 1 and type 2 diabetes and incidence of type 2 diabetes following admission to intensive care units. FUTURE PLANS: Commissioned NDA reports will continue to inform service development in England and Wales. The same data, with or without linkages to other external datasets, are also a rich resource for clinically orientated research.

Efficacy of lifestyle intervention in adults with impaired glucose tolerance with and without impaired fasting plasma glucose: A post hoc analysis of Da Qing Diabetes Prevention Outcome Study.

AIMS: The extent that pre-diabetic fasting plasma glucose (FPG) levels influence the effectiveness of lifestyle interventions in preventing type 2 diabetes (T2DM) is uncertain. We aimed to determine if the outcome of lifestyle intervention in people with impaired glucose tolerance (IGT) differs in those with normal or impaired FPG levels. MATERIALS AND METHODS: Data were used from the Da Qing Diabetes Prevention Outcome Study, which was a 30-year follow-up of a 6-year randomized trial of lifestyle intervention in 576 people with IGT. We then conducted a post-hoc analysis to compare the efficacy of intervention to reduce the incidence of T2DM and its complications in those with baseline FPG <100 mg/dL and FPG ≥100 mg/dL. RESULTS: Lifestyle intervention reduced the cumulative incidence of T2DM by 37%-46% in those with baseline FPG <100 mg/dL and by 47%-51% in those with FPG ≥100 mg/dL. The FPG <100 mg/dL group had a lower cumulative incidence of diabetes and 6.41 years median delay in its onset compared with 2.21 years delay in the FPG ≥100 mg/dL group. In those with FPG <100 mg/dL intervention was associated with at least as great a reduction in cardiovascular disease and all-cause mortality as in the FPG ≥100 mg/dL group. CONCLUSIONS: Lifestyle intervention reduced the incidence of T2DM in people with IGT regardless of baseline FPG levels, and in those with FPG <100 mg/dL led to a substantial delay in its onset. All persons with IGT, with normal or impaired FPG levels, may benefit from lifestyle intervention to delay its onset and mitigate the incidence of T2DM.

Completion of annual diabetes care processes and mortality: A cohort study using the National Diabetes Audit for England and Wales.

AIM: To conduct an analysis to assess whether the completion of recommended diabetes care processes (glycated haemoglobin [HbA1c], creatinine, cholesterol, blood pressure, body mass index [BMI], smoking habit, urinary albumin, retinal and foot examinations) at least annually is associated with mortality. MATERIALS AND METHODS: A cohort from the National Diabetes Audit of England and Wales comprising 179 105 people with type 1 and 1 397 790 people with type 2 diabetes, aged 17 to 99 years on January 1, 2009, diagnosed before January 1, 2009 and alive on April 1, 2013 was followed to December 31, 2019. Cox proportional hazards models adjusting for demographic characteristics, smoking, HbA1c, blood pressure, serum cholesterol, BMI, duration of diagnosis, estimated glomerular filtration rate, prior myocardial infarction, stroke, heart failure, respiratory disease and cancer, were used to investigate whether care processes recorded January 1, 2009 to March 31, 2010 were associated with subsequent mortality. RESULTS: Over a mean follow-up of 7.5 and 7.0 years there were 26 915 and 388 093 deaths in people with type 1 and type 2 diabetes, respectively. Completion of five or fewer, compared to eight, care processes (retinal screening not included as data were not reliable) had a mortality hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.28-1.46) in people with type 1 and 1.32 (95% CI 1.30-1.35) in people with type 2 diabetes. The HR was higher for respiratory disease deaths and lower in South Asian ethnic groups. CONCLUSIONS: People with diabetes who have fewer routine care processes have higher mortality. Further research is required into whether different approaches to care might improve outcomes for this high-risk group.

Cost-Effectiveness of the New 2018 American College of Physicians Glycemic Control Guidance Statements Among US Adults With Type 2 Diabetes.

OBJECTIVES: This study aims to estimate the national impact and cost-effectiveness of the 2018 American College of Physicians (ACP) guidance statements compared to the status quo. METHODS: Survey data from the 2011-2016 National Health and Nutrition Examination were used to generate a national representative sample of individuals with diagnosed type 2 diabetes in the United States. Individuals with A1c <6.5% on antidiabetic medications are recommended to deintensify their A1c level to 7.0% to 8.0% (group 1); individuals with A1c 6.5% to 8.0% and a life expectancy of <10 years are recommended to deintensify their A1c level >8.0% (group 2); and individuals with A1c >8.0% and a life expectancy of >10 years are recommended to intensify their A1c level to 7.0% to 8.0% (group 3). We used a Markov-based simulation model to evaluate the lifetime cost-effectiveness of following the ACP recommended A1c level. RESULTS: 14.41 million (58.1%) persons with diagnosed type 2 diabetes would be affected by the new guidance statements. Treatment deintensification would lead to a saving of $363 600 per quality-adjusted life-year (QALY) lost for group 1 and a saving of $118 300 per QALY lost for group 2. Intensifying treatment for group 3 would lead to an additional cost of $44 600 per QALY gain. Nationally, the implementation of the guidance would add 3.2 million life-years and 1.1 million QALYs and reduce healthcare costs by $47.7 billion compared to the status quo. CONCLUSIONS: Implementing the new ACP guidance statements would affect a large number of persons with type 2 diabetes nationally. The new guidance is cost-effective.

Adults with early-onset type 2 diabetes (aged 18-39 years) are severely underrepresented in diabetes clinical research trials.

AIMS/HYPOTHESIS: Early-onset adult type 2 diabetes (diagnosed between ages 18 and 39 years) is increasingly prevalent and associated with poor long-term outcomes. We hypothesised that individuals with early-onset adult type 2 diabetes were underrepresented in the prominent research trials that underpin type 2 diabetes management guidelines. METHODS: We reviewed the mean age of the study populations recruited to 90 prominent trials in type 2 diabetes, including 37 cardio-renal outcomes trials across a range of pharmacological, non-pharmacological and multifactorial interventions, 28 trials from the phase III programmes of three representative glucose-lowering therapies used routinely in clinical practice (empagliflozin, liraglutide and sitagliptin) and 25 prominent trials of diabetes self-management education and support or intensive lifestyle interventions (diet or supervised exercise training). We then estimated the number of individuals within these trials who were aged between 18 and 39 years. RESULTS: Across all 90 trials, the mean age of 268,978 participants was 63 years (range 51-69 years in individual trials). In 73 trials (81%), <5% of participants were estimated to be aged 18-39 years, despite this age group representing ~15-20% of the adult type 2 diabetes population. Twenty-nine of these trials (32%; total 164,953 participants) excluded individuals below 40 years of age altogether. CONCLUSIONS/INTERPRETATION: Guidelines for early-onset adult type 2 diabetes are extrapolated predominantly from evidence in older individuals. Strategies to support the participation of individuals with early-onset adult type 2 diabetes in future research are imperative to ensure guidelines for these high-risk individuals are evidence-based.

Trends in cancer mortality among people with vs without diabetes in the USA, 1988-2015.

AIMS/HYPOTHESIS: Cancer-related death is higher among people with vs without diabetes. However, it is not known if this excess risk has changed over time or what types of cancer may be driving these changes. METHODS: To estimate rates of site-specific cancer mortality in adults with vs without self-reported diagnosed diabetes, we used data from adults aged ≥18 years at the time of the interview who participated in the 1985-2012 National Health Interview Survey. Participants' data were linked to the National Death Index by the National Center for Health Statistics to determine vital status and cause of death through to the end of 2015. Cancer deaths were classified according to underlying cause of death. Death rates for five time periods (1988-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2015) were estimated using discrete Poisson regression models adjusted for age, sex and race/ethnicity with p for linear trend reported (ptrend). Site-specific cancer mortality rates were stratified by diabetes status and period, and total cancer mortality rates were additionally stratified by sex, race/ethnicity, education and BMI status. RESULTS: Among adults with diabetes, age-adjusted cancer mortality rates (per 10,000 person-years) declined 25.5% from 39.1 (95% CI 30.1, 50.8) in 1988-1994 to 29.7 (26.6, 33.1) in 2010-2015, ptrend < 0.001. Among adults without diabetes, rates declined 25.2% from 30.9 (28.6, 33.4) in 1988-1994 to 23.2 (22.1, 24.2) in 2010-2015, ptrend < 0.01. Adults with diabetes remained approximately 30% more likely to die from cancer than people without diabetes, and this excess risk did not improve over time. In adults with diabetes, cancer mortality rates did not decline in some population subgroups (including black people, people with lower levels of education and obese people), and the excess risk increased for obese adults with vs without diabetes. Declines in total cancer mortality rates in adults with diabetes appear to be driven by large relative declines in cancers of the pancreas (55%) and breast (65%), while for lung cancer, declines are modest (7%). CONCLUSIONS/INTERPRETATION: Declines in cancer mortality rates were observed in adults with and without diabetes. However, adults with diabetes continue to be more likely to die from cancer than people without diabetes. This study highlights the continued need for greater cancer risk-factor mitigation, especially in adults with diabetes.

A systematic review of trends in all-cause mortality among people with diabetes.

AIMS/HYPOTHESIS: We examined all-cause mortality trends in people with diabetes and compared them with trends among people without diabetes. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for observational studies published from 1980 to 2019 reporting all-cause mortality rates across ≥2 time periods in people with diabetes. Mortality trends were examined by ethnicity, age and sex within comparable calendar periods. RESULTS: Of 30,295 abstracts screened, 35 studies were included, providing data on 69 separate ethnic-specific or sex-specific populations with diabetes since 1970. Overall, 43% (3/7), 53% (10/19) and 74% (32/43) of the populations studied had decreasing trends in all-cause mortality rates in people with diabetes in 1970-1989, 1990-1999 and 2000-2016, respectively. In 1990-1999 and 2000-2016, mortality rates declined in 75% (9/12) and 78% (28/36) of predominantly Europid populations, and in 14% (1/7) and 57% (4/7) of non-Europid populations, respectively. In 2000-2016, mortality rates declined in 33% (4/12), 65% (11/17), 88% (7/8) and 76% (16/21) of populations aged <40, 40-54, 55-69 and ≥70 years, respectively. Among the 33 populations with separate mortality data for those with and without diabetes, 60% (6/10) of the populations with diabetes in 1990-1999 and 58% (11/19) in 2000-2016 had an annual reduction in mortality rates that was similar to or greater than in those without diabetes. CONCLUSIONS/INTERPRETATION: All-cause mortality has declined in the majority of predominantly Europid populations with diabetes since 2000, and the magnitude of annual mortality reduction matched or exceeded that observed in people without diabetes in nearly 60% of populations. Patterns of diabetes mortality remain uncertain in younger age groups and non-Europid populations. REGISTRATION: PROSPERO registration ID CRD42019095974. Graphical abstract.

Association of technologically assisted integrated care with clinical outcomes in type 2 diabetes in Hong Kong using the prospective JADE Program: A retrospective cohort analysis.

BACKGROUND: Diabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings. METHODS AND FINDINGS: The web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1-4, low-high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007-2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007-2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35-140.18]), the non-JADE group had higher (145.32 [95% CI 138.68-152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12-74.91]; P < 0.001). The adjusted hazard ratios (aHRs) for the primary composite outcome were 1.22 (95% CI 1.15-1.30) and 0.70 (95% CI 0.66-0.75), respectively, independent of risk profiles, education levels, drug usage, self-care, and comorbidities at baseline. We reported consistent results in propensity-score-matched analyses and after accounting for loss to follow-up. Potential limitations include its nonrandomized design that precludes causal inference, residual confounding, and participation bias. CONCLUSIONS: ICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings.

Global trends in diabetes complications: a review of current evidence.

In recent decades, large increases in diabetes prevalence have been demonstrated in virtually all regions of the world. The increase in the number of people with diabetes or with a longer duration of diabetes is likely to alter the disease profile in many populations around the globe, particularly due to a higher incidence of diabetes-specific complications, such as kidney failure and peripheral arterial disease. The epidemiology of other conditions frequently associated with diabetes, including infections and cardiovascular disease, may also change, with direct effects on quality of life, demands on health services and economic costs. The current understanding of the international burden of and variation in diabetes-related complications is poor. The available data suggest that rates of myocardial infarction, stroke and amputation are decreasing among people with diabetes, in parallel with declining mortality. However, these data predominantly come from studies in only a few high-income countries. Trends in other complications of diabetes, such as end-stage renal disease, retinopathy and cancer, are less well explored. In this review, we synthesise data from population-based studies on trends in diabetes complications, with the objectives of: (1) characterising recent and long-term trends in diabetes-related complications; (2) describing regional variation in the excess risk of complications, where possible; and (3) identifying and prioritising gaps for future surveillance and study.

Trends in cause-specific mortality among adults with and without diagnosed diabetes in the USA: an epidemiological analysis of linked national survey and vital statistics data.

BACKGROUND: Large reductions in diabetes complications have altered diabetes-related morbidity in the USA. It is unclear whether similar trends have occurred in causes of death. METHODS: Using data from the National Health Interview Survey Linked Mortality files from 1985 to 2015, we estimated age-specific death rates and proportional mortality from all causes, vascular causes, cancers, and non-vascular, non-cancer causes among US adults by diabetes status. FINDINGS: From 1988-94, to 2010-15, all-cause death rates declined by 20% every 10 years among US adults with diabetes (from 23·1 [95% CI 20·1-26·0] to 15·2 [14·6-15·8] per 1000 person-years), while death from vascular causes decreased 32% every 10 years (from 11·0 [9·2-12·2] to 5·2 [4·8-5·6] per 1000 person-years), deaths from cancers decreased 16% every 10 years (from 4·4 [3·2-5·5] to 3·0 [2·8-3·3] per 1000 person-years), and the rate of non-vascular, non-cancer deaths declined by 8% every 10 years (from 7·7 [6·3-9·2] to 7·1 [6·6-7·5]). Death rates also declined significantly among people without diagnosed diabetes for all four major mortality categories. However, the declines in death rates were significantly greater among people with diabetes for all-causes (pinteraction<0·0001), vascular causes (pinteraction=0·0214), and non-vascular, non-cancer causes (pinteration<0·0001), as differences in all-cause and vascular disease death between people with and without diabetes were reduced by about a half. Among people with diabetes, all-cause mortality rates declined most in men and adults aged 65-74 years of age, and there was no decline in death rates among adults aged 20-44 years. The different magnitude of changes in cause-specific mortality led to large changes in the proportional mortality. The proportion of total deaths among adults with diabetes from vascular causes declined from 47·8% (95% CI 38·9-58·8) in 1988-94 to 34·1% (31·4-37·1) in 2010-15; this decline was offset by large increases in the proportion of deaths from non-vascular, non-cancer causes, from 33·5% (26·7-42·1) to 46·5% (43·3-50·0). The proportion of deaths caused by cancer was relatively stable over time, ranging from 16% to 20%. INTERPRETATION: Declining rates of vascular disease mortality are leading to a diversification of forms of diabetes-related mortality with implications for clinical management, prevention, and disease monitoring. FUNDING: None.

Analysing detection of chronic diseases with prolonged sub-clinical periods: modelling and application to hypertension in the U.S.

BACKGROUND: We recently introduced a system of partial differential equations (PDEs) to model the prevalence of chronic diseases with a possibly prolonged state of asymptomatic, undiagnosed disease preceding a diagnosis. Common examples for such diseases include coronary heart disease, type 2 diabetes or cancer. Widespread application of the new method depends upon mathematical treatment of the system of PDEs. METHODS: In this article, we study the existence and the uniqueness of the solution of the system of PDEs. To demonstrate the usefulness and importance of the system, we model the age-specific prevalence of hypertension in the US 1999-2010. RESULTS: The examinations of mathematical properties provide a way to solve the systems of PDEs by the method of characteristics. In the application to hypertension, we obtain a good agreement between modeled and surveyed age-specific prevalences. CONCLUSIONS: The described system of PDEs provides a practical way to examine the epidemiology of chronic diseases with a state of undiagnosed disease preceding a diagnosis.