Effect of onset of type 2 diabetes on risks of cardiovascular disease and heart failure among new Zealanders with impaired glucose tolerance over 25 years: tapered-matched landmark analysis

BackgroundThis study aimed to examine the association between the incident onset of T2DM and 5- and 10-year risks of CVD and HF in people with IGT identified in primary care in South and West Auckland, New Zealand (NZ) between 1994 and 2019.MethodsWe compared CVD and HF risks in patients with IGT and with/without T2D newly diagnosed within the exposure window (1–5 years). Tapered matching and landmark analysis (to account for immortal bias) were used to control for potential effects of known confounders.ResultsAmong 26,794 patients enrolled with IGT, 845 had T2D newly diagnosed within 5 years from enrolment (landmark date) and 15,452 did not have T2D diagnosed. Patients progressing to T2D (vs. those not progressing) had a similar 5-year risk for CVD (hazard ratio 1.19; 95% CI 0.61–2.32) but significantly higher 10-year risk of CVD (2.45(1.40–4.29)), 5-year risk of HF (1.94(1.20–3.12)) and 10-year risk of HF (2.84(1.83–4.39). The association between the onset of T2D and risk of 10-year risk of CVD, 5-year and 10-year risk of HF was more likely among men, the socioeconomically deprived, those currently smoking, patients with higher metabolic measures and/or those with lower renal function. Patients of NZ European ethnicity had a lower 10-year risk of CVD.ConclusionsThe study suggests that the diagnosis of T2D mediates the risk of CVD and HF in people with IGT. The development of risk scores to identify and better manage individuals with IGT at high risk of T2D is warranted

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Association Between Onset of Type 2 Diabetes and Risk of Atrial Fibrillation in New Zealanders With Impaired Glucose Tolerance Over 25 Years

Background The association between the onset of type 2 diabetes (T2D) and atrial fibrillation (AF) risk in individuals with impaired glucose tolerance (IGT) remains unclear. This study aimed to investigate the relationship between the incident onset of T2D and 5‐ and 10‐year (after the landmark period) risks of AF in people with IGT identified in South and West Auckland primary care settings between 1994 and 2019. Methods and Results We compared AF risk in patients with IGT with and without newly diagnosed T2D within a 1‐ to 5‐year exposure window. Tapered matching and landmark analysis (to address immortal bias) were used to control for confounding variables. The cohorts incorporated 785 patients who had T2D newly diagnosed within 5 years from enrollment (landmark date) and 15 079 patients without a T2D diagnosis. Patients progressing to T2D exhibited significantly higher 5‐year (after the landmark period) AF risk (hazard ratio [HR], 1.34 [95% CI, 1.10–1.63]) and 10‐year (after the landmark period) AF risk (HR, 1.28 [95% CI, 1.02–1.62]) compared with those without incident T2D. The association was more pronounced among men, older patients, socioeconomically deprived individuals, current smokers, those with higher metabolic measures, and lower renal function. New Zealand European ethnicity was associated with a lower 5‐ and 10‐year risk of AF. Conclusions This study found a mediating effect of T2D on the risk of AF in a population with IGT in New Zealand. The development of risk scores and future replication studies can help identify and guide management of individuals with IGT at the highest risk of AF following incident T2D

All-cause, premature, and cardiovascular death attributable to socioeconomic and ethnic disparities among New Zealanders with type 1 diabetes 1994–2019: a multi-linked population-based cohort study

Background: New Zealand (NZ) research into type 1 diabetes mellitus (T1DM) mortality can inform policy and future research. In this study we aimed to quantify the magnitude to which ethnicity and socioeconomic disparities influenced mortality at the population level among people with Type 1 diabetes (T1DM) in Auckland, New Zealand (NZ). Methods: The cohort data were derived from the primary care diabetes audit program the Diabetes Care Support Service (DCSS), and linked with national primary care, pharmaceutical claims, hospitalisation, and death registration databases. People with T1DM enrolled in DCSS between 1994–2018 were included. All-cause, premature, and cardiovascular mortalities were estimated by Poisson regression models with adjustment for population-level confounders. The mortality rates ratio (MRR) was standardized against the DCSS type 2 diabetes population. Mortality rates were compared by ethnic group (NZ European (NZE) and non-NZE) and socioeconomic deprivation quintile. The population attributable fraction (PAF) was estimated for ethnic and socioeconomic disparities by Cox regression adjusting for demographic, lifestyle, and clinical covariates. The adjusted slope index inequality (SII) and relative index of inequality (RII) were used to measure the socioeconomic disparity in mortalities. Results: Overall, 2395 people with T1DM (median age 34.6 years; 45% female; 69% NZE) were enrolled, among whom the all-cause, premature and CVD mortalities were 6.69 (95% confidence interval: 5.93–7.53), 3.30 (2.77–3.90) and 1.77 (1.39–2.23) per 1,000 person-years over 25 years. The overall MRR was 0.39 (0.34–0.45), 0.65 (0.52–0.80), and 0.31 (0.24–0.41) for all-cause, premature and CVD mortality, respectively. PAF attributable to ethnicity disparity was not significantly different for mortality. The adjusted PAF indicated that 25.74 (0.84–44.39)% of all-cause mortality, 25.88 (0.69–44.69)% of premature mortality, 55.89 (1.20–80.31)% of CVD mortality could be attributed to socioeconomic inequality. The SII was 8.04 (6.30–9.78), 4.81 (3.60–6.02), 2.70 (1.82–3.59) per 1,000 person-years and RII was 2.20 (1.94–2.46), 2.46 (2.09–2.82), and 2.53 (2.03–3.03) for all-cause, premature and CVD mortality, respectively. Conclusions: Our results suggest that socioeconomic disparities were responsible for a substantial proportion of all-cause, premature and CVD mortality in people with T1DM in Auckland, NZ. Reducing socioeconomic barriers to management and self-management would likely improve clinical outcomes

Long-term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered-matched landmark analysis over 25 years

INTRODUCTIONWe aimed to investigate the association between the onset of type 2 diabetes (T2D) and dementia incidence rates (IR) in the population with impaired glucose tolerance (IGT) identified in primary care in New Zealand (NZ) over 25 years.METHODSTapered matching and landmark analysis (accounting for immortal bias) were used to control for potential effects of known confounders. The association between T2D onset and 5- and 10-year IR of dementia was estimated by weighted Cox models.RESULTSThe onset of T2D was significantly associated with the 10-year IR of dementia, especially in the socioeconomically deprived, those of non-NZ European ethnicity, those currently smoking, and patients with higher metabolic measures.DISCUSSIONOur findings suggest that the onset of T2D is a significant risk factor for dementia in individuals with IGT. Dementia screening and structured diabetes prevention are vital in the population with IGT, particularly those from deprived or ethnic minority backgrounds

Cancer risk following onset of type 2 diabetes in New Zealanders with impaired glucose tolerance over 25 years: a matched prospective cohort study

Abstract Background In people with prediabetes, the link between developing type 2 diabetes (T2D) and cancer risk among those with impaired glucose tolerance (IGT) remains uncertain. We examined this association in IGT individuals from primary care in South and West Auckland, New Zealand, spanning 1994–2019, assessing 5- and 10-year cancer risks. Methods Study cohorts were extracted from the Diabetes Care Support Service in Auckland, New Zealand, linking it with national registries for death, cancer, hospital admissions, pharmaceutical claims, and socioeconomic status. We compared cancer risks in individuals with IGT newly diagnosed with or without T2D within a 1–5-year exposure window. Employing tapered matching and landmark analysis to address potential confounding effects, we formed comparative IGT cohorts. Weighted Cox regression models were then employed to assess the association between T2D onset and 5- and 10-year cancer risks. Results The study included 26,794 patients with IGT, with 629 newly diagnosed with T2D within 5 years and 13,007 without such a diagnosis. Those progressing to T2D had similar 5-year cancer risk but significantly higher 10-year risk (HR 1.35; 95% CI 1.09–1.68). This association was stronger in older individuals, the socioeconomically deprived, current smokers, those with worse metabolic measures, and lower renal function. Patients with IGT of NZ European ethnicity had lower 10-year cancer risk. Conclusions T2D diagnosis influences cancer risk in individuals with IGT. Developing risk scores for high-risk IGT individuals and implementing cancer screening and structured diabetes prevention, especially in deprived or minority ethnic populations, is essential

Association between within-target risk factors and life expectancy free from cardiovascular disease, cancer, and dementia in individuals with type 2 diabetes in New Zealand between 1994 and 2018: a multi-ethnic cohort study

Background: The extent to which type 2 diabetes (T2D) reduces life expectancy depends on the risk of complications. We aimed to characterise the relationship between risk factors for diabetes complications and life expectancy, in individuals with T2D, free from major chronic disease, in a regional database linked with national New Zealand health databases. Methods: A prospective cohort study design was employed, analysing data from individuals with T2D drawn from the comprehensive Diabetes Care Support Service database (1994–2018). Participants with known values for all five within-target risk factors (WTRF +) including blood pressure, glycaemia, and LDL cholesterol, alongside being non-smoking with normal renal function at baseline, were included. Life expectancy free from cardiovascular disease (CVD), cancer, and dementia at age 50 years was estimated using multistate life tables, adjusting for demographics and clinical metrics. Results: Women and men with no WTRF + at enrolment had a life expectancy free from CVD, cancer, or dementia of 13.1 (95% confidence interval: 9.1–19.0) and 11.2 (6.7–18.6) years, respectively. For the most socioeconomically deprived groups or Māori with no WTRF + at baseline, life expectancies were markedly lower. Life expectancies were 23.7 (18.9–29.7) years for women and 23.2 years (17.2–31.4) years for men with four or five WTRF + at baseline, respectively. While an increasing number of WTRF + at baseline was significantly associated with improved outcomes in men and certain subgroups (e.g. Other ethnicity group), this trend was not statistically significant for women overall or in most subgroups. Conclusions: Having multiple WTRF + at baseline is associated with a considerable increase in life expectancy free from major chronic disease among individuals with T2D. This highlights the importance of lifestyle and clinical interventions in the management of T2D and in the prevention and management of associated chronic conditions

Cancer risk following onset of type 2 diabetes in New Zealanders with impaired glucose tolerance over 25 years: a matched prospective cohort study

Background: In people with prediabetes, the link between developing type 2 diabetes (T2D) and cancer risk among those with impaired glucose tolerance (IGT) remains uncertain. We examined this association in IGT individuals from primary care in South and West Auckland, New Zealand, spanning 1994–2019, assessing 5- and 10-year cancer risks. Methods: Study cohorts were extracted from the Diabetes Care Support Service in Auckland, New Zealand, linking it with national registries for death, cancer, hospital admissions, pharmaceutical claims, and socioeconomic status. We compared cancer risks in individuals with IGT newly diagnosed with or without T2D within a 1–5-year exposure window. Employing tapered matching and landmark analysis to address potential confounding effects, we formed comparative IGT cohorts. Weighted Cox regression models were then employed to assess the association between T2D onset and 5- and 10-year cancer risks. Results: The study included 26,794 patients with IGT, with 629 newly diagnosed with T2D within 5 years and 13,007 without such a diagnosis. Those progressing to T2D had similar 5-year cancer risk but significantly higher 10-year risk (HR 1.35; 95% CI 1.09–1.68). This association was stronger in older individuals, the socioeconomically deprived, current smokers, those with worse metabolic measures, and lower renal function. Patients with IGT of NZ European ethnicity had lower 10-year cancer risk. Conclusions: T2D diagnosis influences cancer risk in individuals with IGT. Developing risk scores for high-risk IGT individuals and implementing cancer screening and structured diabetes prevention, especially in deprived or minority ethnic populations, is essential

Additional file 1 of All-cause, premature, and cardiovascular death attributable to socioeconomic and ethnic disparities among New Zealanders with type 1 diabetes 1994–2019: a multi-linked population-based cohort study

Additional file 1: Supplemental Table 1. Technical notes for slope index of inequality and relative index of inequality. Supplemental Table 2. Comparison of Demographic Characteristics Between DCSS Type 1 Diabetes Population and the National Registry of Type 1 Diabetes. Supplemental table 3. Excess mortality for ethnicity and socioeconomic inequality by overall, sex, enrol age, and clinical measurements. Supplemental table 4. Adjusted Mortality rates ratio and excess mortality for ethnicity and socioeconomic inequality. Supplemental Table 5. Population attributable fractions of mortality restriction by socioeconomic deprivation and ethnicity. Supplemental Table 6. Mortality rates ratio (MRR) of clinical events among people with type 1 diabetes in DCSS between 1994-201