Mortality after cancer among patients with diabetes mellitus: effect of diabetes duration and treatment

Aims/hypothesis

The prognostic role of different diabetes treatment types has not been studied in detail. We compared mortality rates among cancer patients with and without diabetes, accounting for diabetes treatment and diabetes duration.

Methods

This register-based study included all cancer patients diagnosed in Denmark during 1995–2009. The patients were classified into four groups according to diabetes status at the time of cancer diagnosis: no diabetes, diabetes without medication, diabetes with only oral hypoglycaemic agent (OHA) or diabetes with insulin treatment. Poisson models were used to examine the association between pre-existing diabetes in cancer patients and mortality relative to the non-diabetic cancer population.

Results

Among 426,129 patients with incident cancer, we identified 42,205 patients with diabetes prior to cancer diagnosis. Overall, cancer patients with diabetes had higher mortality rates than non-diabetic cancer patients, highest among OHA- or insulin-treated patients. For all cancers combined and diabetes duration of 2 years at cancer diagnosis, insulin-treated patients experienced the highest mortality rate ratios starting from 3.7 (95% CI 2.7, 5.1) for men and 4.4 (3.1, 6.5) for women 1 year after cancer diagnosis, increasing to 5 (3.5, 7.0) for men and 6.5 (4.2, 9.3) for women 9 years after cancer diagnosis.

Conclusions/interpretation

Our study provides strong evidence that cancer patients with pre-existing diabetes experience higher mortality than cancer patients without diabetes. The higher mortality seen among cancer patients treated with OHAs or insulin is in accordance with the existing evidence that more intensive diabetes treatment reflects a larger degree of comorbidity at the time of cancer diagnosis, and hence poorer survival.     

Do men develop type 2 diabetes at lower body mass indices than women?

Aims/hypothesis

To describe the associations between age, sex and BMI at diagnosis of type?2 diabetes, and test the hypothesis that men are diagnosed with diabetes at lower average BMI than women of similar age.

Methods

Linear regression was used to estimate and compare the relationship between age and BMI at diagnosis among 51,920 men and 43,137 women included in a population-based diabetes register in Scotland for whom an index BMI measurement was taken within 1?year of diabetes diagnosis. We also examined HbA_1c values by sex within the same timescale.

Results

Mean BMI closest to date of diagnosis of type?2 diabetes mellitus was 31.83?kg/m² (SD 5.13) in men and 33.69?kg/m² (SD 6.43) in women. The inverse relationship between age and BMI at diagnosis of type?2 diabetes mellitus was significantly steeper in women than in men (slope estimate in men ?0.12?kg/m² per year [95% CI ?0.13, ?0.12] women ?0.18?kg/m² per year [95% CI ?0.18, ?0.17], p?1c levels within 1?year of diagnoses were broadly similar in men and women.

Conclusions/interpretation

Men are diagnosed with type?2 diabetes at lower BMI than women across the age range. This observation may help explain why type?2 diabetes is more common among middle-aged men in populations of European extraction. Whether the same pattern is also observed in other ethnic groups requires confirmation.     

Oral disease and subsequent cardiovascular disease in people with type 2 diabetes: a prospective cohort study based on the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial

Aims/hypothesis

While there are plausible biological mechanisms linking oral health with cardiovascular disease (CVD) and mortality rates, no study, to our knowledge, has examined this association in a representative population of people with type 2 diabetes.

Methods

We used the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study, a large, detailed, randomised controlled trial among a general population of individuals with type 2 diabetes. For the purposes of the present analyses, data from the trial are used within a prospective cohort study design. A total of 10,958 men and women, aged 55 to 88 years and with type 2 diabetes, participated in a baseline medical examination, during which they counted their number of natural teeth and reported the number of days that their gums had bled over the preceding year. Study members were followed up for mortality and morbidity over 5 years.

Results

After controlling for a range of potential confounding factors, the group with no teeth had a markedly increased risk of death due to all causes (HR 1.48, 95% CI 1.24–1.78), CVD (1.35, 1.05–1.74) and non-CVD (1.64, 1.26–2.13), relative to the group with the most teeth (≥22 teeth). Frequency of bleeding gums was not associated with any of the outcomes of interest. There was no suggestion that treatment group or sex modified these relationships.

Conclusions/interpretation

In people with type 2 diabetes, oral disease, as indexed by fewer teeth, was related to an increased risk of death from all causes and of death due to CVD and non-CVD.     

Data-driven metabolic subtypes predict future adverse events in individuals with type 1 diabetes

Aims/hypothesis

Previously, we proposed that data-driven metabolic subtypes predict mortality in type 1 diabetes. Here, we analysed new clinical endpoints and revisited the subtypes after 7 years of additional follow-up.

Methods

Finnish individuals with type 1 diabetes (2059 men and 1924 women, insulin treatment before 35 years of age) were recruited by the national multicentre FinnDiane Study Group. The participants were assigned one of six metabolic subtypes according to a previously published self-organising map from 2008. Subtype-specific all-cause and cardiovascular mortality rates in the FinnDiane cohort were compared with registry data from the entire Finnish population. The rates of incident diabetic kidney disease and cardiovascular endpoints were estimated based on hospital records.

Results

The advanced kidney disease subtype was associated with the highest incidence of kidney disease progression (67.5% per decade, p < 0.001), ischaemic heart disease (26.4% per decade, p < 0.001) and all-cause mortality (41.5% per decade, p < 0.001). Across all subtypes, mortality rates were lower in women compared with men, but standardised mortality ratios (SMRs) were higher in women. SMRs were indistinguishable between the original study period (1994–2007) and the new period (2008–2014). The metabolic syndrome subtype predicted cardiovascular deaths (SMR 11.0 for men, SMR 23.4 for women, p < 0.001), and women with the high HDL-cholesterol subtype were also at high cardiovascular risk (SMR 16.3, p < 0.001). Men with the low-cholesterol or good glycaemic control subtype showed no excess mortality.

Conclusions/interpretation

Data-driven multivariable metabolic subtypes predicted the divergence of complication burden across multiple clinical endpoints simultaneously. In particular, men with the metabolic syndrome and women with high HDL-cholesterol should be recognised as important subgroups in interventional studies and public health guidelines on type 1 diabetes.

     

Prevalence of type 1 diabetes mellitus in Karnal district, Haryana state, India

Background

Little work has been done on the prevalence of type 1 diabetes in north India. This paper reports the prevalence of type 1 diabetes in Karnal district of Haryana state, India.

Materials and methods

Prevalence of type 1 diabetes was assessed by a hospital-based registry and by analysis of data contributed by chemists and other physicians.

Results

The overall prevalence of type 1 diabetes in Karnal district is 10.20/100,000 population, with a higher prevalence in urban (26.6/100,000) as compared to rural areas (4.27/100,000). Karnal city, with a population of 222017, has a relatively high prevalence of type 1 diabetes (31.9/100,000). The prevalence in men is higher (11.56/100,000) than in women (8.6/100,000). In the 5 to 16 years age group, the prevalence is 22.22/100,000, while in the 0-5 years age group, prevalence is 3.82/100,000.

Conclusions

This report highlights the urban-rural and male-female gradient in the prevalence of type 1 diabetes in Karnal, north India.     

Type 2 diabetes, smoking, insulin use, and mortality from hepatocellular carcinoma: a 12-year follow-up of a national cohort in Taiwan

Background

The effect of smoking and insulin use in the association between diabetes and hepatocellular carcinoma (HCC) is not known.

Materials and methods

Age-standardized HCC mortality trends during 1995–2006 in the general population were calculated. A total of 88,694 type 2 diabetic patients aged ≥25 years recruited in 1995–1998 were followed till 2006. Age- and sex-specific mortality rates and the mortality rate ratios (vs. the average mortality rates in the general population) were calculated. Risk factors were evaluated by Cox regression.

Results

The age-standardized mortality trend slightly increased significantly in women but was steady in men. For diabetic patients aged ≥25 years, 830 men and 515 women died of HCC during 1995–2006. Mortality rate ratios (95 % confidence interval) were larger with the decreasing age: 7.36 (6.52, 8.31), 2.48 (2.22, 2.78), 1.79 (1.59, 2.02), and 1.87 (1.51, 2.32) for age 25–54, 55–64, 65–74, and ≥75 years for men, respectively, 10.12 (7.73, 13.25), 4.08 (3.57, 4.67), 2.45 (2.15, 2.78), and 1.71 (1.34, 2.19) for women. Age, male sex, lower BMI, smoking, and insulin use were associated with HCC mortality, but diabetes duration was not. Smoking and insulin use carried a significantly higher risk of 22–29 % and 37–58 %, respectively, without interaction. A dose-responsive pattern between the duration of insulin use and HCC mortality was noted, with a relative risk of 1.5–1.7 in those who used insulin for ≥10 years.

Conclusions

Diabetic patients have a higher risk of HCC mortality, which is more remarkable in the younger age. Smoking and insulin are potentially modifiable risk factors.     

Validation of metabolic syndrome score by confirmatory factor analysis in children and adults and prediction of cardiometabolic outcomes in adults

Aims/hypothesis

We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men.

Methods

We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17–18 years in middle-aged men.

Results

We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r?=?0.84–0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score.

Conclusions

The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice.     

Fertility in people with childhood-onset type 1 diabetes

Aims/hypothesis

To assess the number of live births in a population-based, retrospective cohort of women and men with childhood-onset type 1 diabetes, and matched controls.

Methods

The reproductive histories of people in a Finnish cohort of 2,307 women and 2,819 men with type 1 diabetes and two matched controls (for each case) were obtained from National Population Register data. All persons with diabetes were diagnosed with the disease in 1965–1979 at the age of 17 or under. A proportional hazards model was used to model the association between the rate of live births as a function of the age of an individual and the observed covariates (sex and age at onset of diabetes).

Results

Both women and men with diabetes had a smaller number of live births than the controls; the HR of having a first child for diabetic women compared with controls was 0.66 (95% CI 0.62, 0.71) and for men was 0.77 (95% CI 0.72, 0.83). In women, a birth cohort effect was detected; in more recent birth cohorts, the difference between diabetic women and controls as regards having children was significantly smaller than in earlier cohorts. Later age at onset of diabetes was associated with a higher rate of having a first child among men (p?=?0.04) and having a second live birth among women (p?=?0.002).

Conclusions/interpretation

Type 1 diabetes affects the number of live births in both women and men. The age at onset of diabetes is associated with the pattern of reproduction in both diabetic women and men.     

Association of physical activity with all-cause mortality and incident and prevalent cardiovascular disease among patients with type 1 diabetes: the EURODIAB Prospective Complications Study

Aims/hypothesis

The aim of this study was to examine the association of physical activity (PA) with all-cause mortality and incident and prevalent cardiovascular disease (CVD) among patients with type 1 diabetes.

Methods

The EURODIAB Prospective Complications Study is a cohort including 3,250 male and female patients with type 1 diabetes (mean age 32.7?±?10.2 years) from 16 European countries, of whom 1,880 participated in follow-up examinations. In analysis 1 (longitudinal), the association of baseline PA (based on the reported number of hours per week spent in mild, moderate and vigorous PA) with all-cause mortality and incident CVD was examined by performing survival analysis. In analysis 2 (cross-sectional), we focused on the association between PA at follow-up (data on sports, walking distance and regular bicycling) and prevalent CVD by performing logistic regression analysis. Adjustments were made for age, sex, BMI, smoking, consumption of alcohol, consumption of certain nutrients and diabetic complications.

Results

Analysis 1 (longitudinal): participation in moderate or vigorous PA once a week or more was borderline inversely associated with all-cause mortality (men and women combined) (HR 0.66, 95% CI 0.42, 1.03) and incident CVD (women only) (HR 0.66, 95% CI 0.40, 1.08). No association was found in men. Analysis 2 (cross-sectional): total PA (indexed by sports, walking, bicycling) and distance walked were inversely associated with prevalent CVD (OR_totalPA 0.66, 95% CI 0.45, 0.97; and OR_walking 0.61, 95% CI 0.42, 0.89).

Conclusions/interpretation

PA showed a borderline inverse association with both all-cause mortality (both sexes) and incident CVD (women only) in patients with type 1 diabetes. Since this is an under-researched clinical population, future longitudinal studies with objective PA measurements are needed to expand on these results.     

Body-Mass Index and All-Cause Mortality in US Adults With and Without Diabetes

BACKGROUND

Previous studies found normal weight compared to overweight/obese adults with type 2 diabetes had a higher mortality risk, and body-mass index (BMI)–mortality studies do not typically account for baseline diabetes status.

OBJECTIVE

To determine if diabetes influences the BMI–mortality relationship.

DESIGN

Using a prospective study design, we analyzed data from a nationally representative sample of US adults participating in the National Health Interview Survey from 1997 to 2002, and followed for mortality through 2006.

PARTICIPANTS

Excluding those with heart disease or cancer, our final analytic sample included 74,710 (34,805 never smoker) adults.

MAIN MEASURES

BMI was calculated from self-reported height and weight. Diabetes status was based on self-reported diagnosis from a health professional. We used direct age standardization to calculate all-cause mortality rates and adjusted Cox models for all-cause mortality hazard ratios by BMI quintile; this was done separately for adults with diabetes and without diabetes.

KEY RESULTS

Among never smokers, mean age was 50.1 years and 43 % were men. Mean BMI was 27.4 kg/m², 26 % were obese, and 2,035 (5 %) reported diagnosed diabetes. After 9 years, there were 4,355 deaths (754 of 4,740 with diabetes; 3,601 of 69,970 without) among 74,710 participants, and 1,238 (247 of 2,035 with diabetes; 991 of 32,770 without) among 34,805 never smokers. We observed a qualitative interaction with diabetes on the BMI–mortality relationship (p?=?0.002). Death rates were substantially higher among participants with diabetes compared to those without diabetes across all BMI quintiles. However, death rates in participants with diabetes fell with increasing BMI quintile, while rates followed a J-shaped curve among those without diabetes. In adjusted Cox models, BMI was positively associated with mortality in adults without diabetes, but inversely associated with mortality among participants with diabetes.

CONCLUSIONS

Mortality increased with increasing BMI in adults without diabetes, but decreased with increasing BMI among their counterparts with diabetes. Future studies need to be better designed to answer the question of whether normal weight adults with diabetes have a higher risk of mortality, by minimizing the possibility of reverse causation. Future studies should also account for prevalent diabetes in all investigations of the BMI–mortality relationship.     

Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Aims/hypothesis

Oxidative stress plays a key role in the development of type 2 diabetes mellitus. We previously showed that the circulating antioxidant peroxiredoxin 4 (Prx4) is associated with cardiometabolic risk factors. We aimed to evaluate the association of Prx4 with type 2 diabetes risk in the general population.

Methods

We analysed data on 7,972 individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (49% men, aged 28–75 years) with no diabetes at baseline. Logistic regression models adjusted for age, sex, smoking, waist circumference, hypertension and family history of diabetes were used to estimate the ORs for type 2 diabetes.

Results

During a median follow up of 7.7 years, 496 individuals (288 men; 58%) developed type 2 diabetes. The median (Q1–Q3) Prx4 level was 0.84 (0.53–1.40) U/l in individuals who developed type 2 diabetes and 0.68 (0.43–1.08) U/l in individuals who did not develop type 2 diabetes. For every doubling of Prx4 levels, the adjusted OR (95% CI) for type 2 diabetes was 1.16 (1.05–1.29) in the whole population; by sex, it was 1.31 (1.14–1.50) for men and 1.03 (0.87–1.21) for women. Further adjustment for other clinical measures did not materially change the results. The addition of Prx4 to a validated diabetes risk score significantly improved the prediction of type 2 diabetes in men (p?=?0.002 for reclassification improvement).

Conclusions/interpretation

Our findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes. For men, taking Prx4 into consideration can improve type 2 diabetes prediction over a validated diabetes risk score; in contrast, there is no improvement in risk prediction for women.     

Diabetes and pregnancy: national trends over a 15 year period

Aims/hypothesis

We aimed to examine time trends in national perinatal outcomes in pregnancies complicated by pre-existing type 1 or type 2 diabetes.

Methods

We analysed episode-level data on all obstetric inpatient delivery events (live or stillbirth) between 1 April 1998 and 31 March 2013 (n?=?813,921) using the Scottish Morbidity Record (SMR02). Pregnancies to mothers with type 1 (n?=?3229) and type 2 (n?=?1452) diabetes were identified from the national diabetes database (Scottish Care Information-Diabetes), and perinatal outcomes were compared among women with type 1 diabetes, type 2 diabetes and those without diabetes.

Results

The number of pregnancies complicated by diabetes increased significantly, by 44% in type 1 diabetes and 90% in type 2 diabetes, across the 15 years examined, to rates of 1 in 210 and 1 in 504 deliveries, respectively. Compared with women without diabetes, delivery occurred 2.6 weeks earlier (type 1 diabetes 36.7?±?2.3 weeks) and 2 weeks earlier (type 2 diabetes 37.3?±?2.4 weeks), respectively, showing significant reductions for both type 1 (from 36.7 weeks to 36.4 weeks, p?=?0.03) and type 2 (from 38.0 weeks to 37.2 weeks, p?<?0.001) diabetes across the time period. The proportions of preterm delivery were markedly increased in women with diabetes (35.3% type 1 diabetes, 21.8% type 2 diabetes, 6.1% without diabetes; p?<?0.0001), and these proportions increased with time for both groups (p?<?0.005). Proportions of elective Caesarean sections (29.4% type 1 diabetes, 30.5% type 2 diabetes, 9.6% without diabetes) and emergency Caesarean sections (38.3% type 1 diabetes, 29.1% type 2 diabetes, 14.6% without diabetes) were greatly increased in women with diabetes and increased over time except for stable rates of emergency Caesarean section in type 1 diabetes. Gestational age-, sex- and parity-adjusted z score for birthweight (1.33?±?1.34; p?<?0.001) were higher in type 1 diabetes and increased over time from 1.22 to 1.47 (p?<?0.001). Birthweight was also increased in type 2 diabetes (0.94?±?1.34; p?<?0.001) but did not alter with time. There were 65 perinatal deaths in offspring of mothers with type 1 diabetes and 39 to mothers with type 2 diabetes, representing perinatal mortality rates of 20.1 (95% CI 14.7, 24.3) and 26.9 (16.7, 32.9) per 1000 births, respectively, and rates 3.1 and 4.2 times, respectively, those observed in the non-diabetic population (p?<?0.001). Stillbirth rates in type 1 and type 2 diabetes were 4.0-fold and 5.1-fold that in the non-diabetic population (p?<?0.001). Perinatal mortality and stillbirth rates showed no significant fall over time despite small falls in the rates for the non-diabetic population.

Conclusions/interpretation

Women with diabetes are receiving increased intervention in pregnancy (earlier delivery, increased Caesarean section rates), but despite this, higher birthweights are being recorded. Improvements in rates of stillbirth seen in the general population are not being reflected in changes in stillbirth or perinatal mortality in our population with diabetes.

     

Changes in coffee intake and subsequent risk of type 2 diabetes: three large cohorts of US men and women

Aims/hypothesis

Coffee and tea consumption has been associated with a lower type 2 diabetes risk but little is known about how changes in coffee and tea consumption influence subsequent type 2 diabetes risk. We examined the associations between 4 year changes in coffee and tea consumption and risk of type 2 diabetes in the subsequent 4 years.

Methods

We prospectively followed 48,464 women in the Nurses’ Health Study (NHS; 1986–2006), 47,510 women in NHS II (1991–2007) and 27,759 men in the Health Professionals Follow-up Study (HPFS; 1986–2006). Diet was assessed every 4 years using a validated food-frequency questionnaire. Self-reported cases of incident type 2 diabetes were validated by supplementary questionnaires.

Results

During 1,663,319 person-years of follow-up, we documented 7,269 cases of incident type 2 diabetes. Participants who increased their coffee consumption by more than 1 cup/day (median change?=?1.69 cups/day) over a 4 year period had an 11% (95% CI 3%, 18%) lower risk of type 2 diabetes in the subsequent 4 years compared with those who made no changes in consumption. Participants who decreased their coffee intake by more than 1 cup/day (median change?=??2 cups/day) had a 17% (95% CI 8%, 26%) higher risk for type 2 diabetes. Changes in tea consumption were not associated with type 2 diabetes risk.

Conclusions/interpretation

Our data provide novel evidence that increasing coffee consumption over a 4 year period is associated with a lower risk of type 2 diabetes, while decreasing coffee consumption is associated with a higher risk of type 2 diabetes in subsequent years.     

Mortality among veterans with type 2 diabetes initiating metformin, sulfonylurea or rosiglitazone monotherapy

Aims/hypotheses

Despite oral hypoglycaemic medications being the most commonly used pharmacological treatments for type 2 diabetes, research is limited on their comparative safety, particularly their effects on overall mortality. We compared mortality risk with monotherapy initiation of four oral hypoglycaemic medications in a nationwide cohort of US veterans with type 2 diabetes.

Methods

We identified new users of oral hypoglycaemic medication monotherapy between 2004 and 2009 who received care for at least 1 year from the Veterans Health Administration. Patients were followed until initial monotherapy discontinuation, addition of another diabetes pharmacotherapy, death or end of follow-up. Mortality HRs were estimated using Cox regression adjusted for potential confounding factors.

Results

Among new users of metformin, sulfonylureas and rosiglitazone (185,360 men, 7,812 women), 4,256 (2.2%) died during follow-up. Average duration of medication use ranged from 1.4 to 1.7 years. Significantly higher mortality risk was seen for glibenclamide (known as glyburide in the USA and Canada) (HR 1.38, 95% CI 1.27, 1.50) or glipizide (HR 1.55, 95% CI 1.43, 1.67) compared with metformin monotherapy, and for glipizide compared with rosiglitazone (HR 1.27, 95% CI 1.01, 1.59) or glibenclamide monotherapy (HR 1.12, 95% CI 1.02, 1.23). A significant sex–rosiglitazone interaction was seen (p?=?0.034) compared with metformin monotherapy, with women having a higher HR (HR 4.36, 95% CI 1.34, 14.20) than men (HR 1.19, 95% CI 0.95, 1.49).

Conclusions/interpretations

Significantly higher mortality was associated with glibenclamide, glipizide and rosiglitazone use compared with metformin, and with glipizide use compared with rosiglitazone or glibenclamide. The potential for residual confounding by indication should be considered in interpreting these results.     

Cause-specific mortality in Scottish patients with colorectal cancer with and without type 2 diabetes (2000–2007)

Aims/hypothesis

The objective of this study was to use Scottish national data to assess the influence of type 2 diabetes on (1) survival (overall and cause-specific) in multiple time intervals after diagnosis of colorectal cancer and (2) cause of death.

Methods

Data from the Scottish Cancer Registry were linked to data from a population-based national diabetes register. All people in Scotland diagnosed with non-metastatic cancer of the colon or rectum in 2000–2007 were included. The effect of pre-existing type 2 diabetes on survival over four discrete time intervals (<1, 1–2, 3–5 and >5 years) after cancer diagnosis was assessed by Cox regression. Cumulative incidence functions were calculated representing the respective probabilities of death from the competing causes of colorectal cancer, cardiovascular disease, other cancers and any other cause.

Results

Data were available for 19,505 people with colon or rectal cancer (1,957 with pre-existing diabetes). Cause-specific mortality analyses identified a stronger association between diabetes and cardiovascular disease mortality than that between diabetes and cancer mortality. Beyond 5 years after colon cancer diagnosis, diabetes was associated with a detrimental effect on all-cause mortality after adjustment for age, socioeconomic status and cancer stage (HR [95% CI]: 1.57 [1.19, 2.06] in men; 1.84 [1.36, 2.50] in women). For patients with rectal cancer, diabetes was not associated with differential survival in any time interval.

Conclusions/interpretation

Poorer survival observed for colon cancer associated with type 2 diabetes in Scotland may be explained by higher mortality from causes other than cancer.     

Nonlinear association of BMI with all-cause and cardiovascular mortality in type 2 diabetes mellitus: a systematic review and meta-analysis of 414,587 participants in prospective studies

Aims/hypothesis

The relationship between BMI and mortality has been extensively investigated in the general population; however, it is less clear in people with type 2 diabetes. We aimed to assess the association of BMI with all-cause and cardiovascular mortality in individuals with type 2 diabetes mellitus.

Methods

We searched electronic databases up to 1 March 2016 for prospective studies reporting associations for three or more BMI groups with all-cause and cardiovascular mortality in individuals with type 2 diabetes mellitus. Study-specific associations between BMI and the most-adjusted RR were estimated using restricted cubic splines and a generalised least squares method before pooling study estimates with a multivariate random-effects meta-analysis.

Results

We included 21 studies including 24 cohorts, 414,587 participants, 61,889 all-cause and 4470 cardiovascular incident deaths; follow-up ranged from 2.7 to 15.9 years. There was a strong nonlinear relationship between BMI and all-cause mortality in both men and women, with the lowest estimated risk from 31–35 kg/m² and 28–31 kg/m² (p value for nonlinearity <0.001) respectively. The risk of mortality at higher BMI values increased significantly only in women, whilst lower values were associated with higher mortality in both sexes. Limited data for cardiovascular mortality were available, with a possible inverse linear association with BMI (higher risk for BMI <27 kg/m²).

Conclusions/interpretation

In type 2 diabetes, BMI is nonlinearly associated with all-cause mortality with lowest risk in the overweight group in both men and women. Further research is needed to clarify the relationship with cardiovascular mortality and assess causality and sex differences.

     

Impact of age at diagnosis and duration of type 2 diabetes on mortality in Australia 1997–2011

Aims/hypothesis

Current evidence suggests that type 2 diabetes may have a greater impact on those with earlier diagnosis (longer duration of disease), but data are limited. We examined the effect of age at diagnosis of type 2 diabetes on the risk of all-cause and cause-specific mortality over 15 years.

Methods

The data of 743,709 Australians with type 2 diabetes who were registered on the National Diabetes Services Scheme (NDSS) between 1997 and 2011 were examined. Mortality data were derived by linking the NDSS to the National Death Index. All-cause mortality and mortality due to cardiovascular disease (CVD), cancer and all other causes were identified. Poisson regression was used to model mortality rates by sex, current age, age at diagnosis, diabetes duration and calendar time.

Results

The median age at registration on the NDSS was 60.2 years (interquartile range [IQR] 50.9–69.5) and the median follow-up was 7.2 years (IQR 3.4–11.3). The median age at diagnosis was 58.6 years (IQR 49.4–67.9). A total of 115,363 deaths occurred during 7.20 million person-years of follow-up. During the first 1.8 years after diabetes diagnosis, rates of all-cause and cancer mortality declined and CVD mortality was constant. All mortality rates increased exponentially with age. An earlier diagnosis of type 2 diabetes (longer duration of disease) was associated with a higher risk of all-cause mortality, primarily driven by CVD mortality. A 10 year earlier diagnosis (equivalent to 10 years’ longer duration of diabetes) was associated with a 1.2–1.3 times increased risk of all-cause mortality and about 1.6 times increased risk of CVD mortality. The effects were similar in men and women. For mortality due to cancer (all cancers and colorectal and lung cancers), we found that earlier diagnosis of type 2 diabetes was associated with lower mortality compared with diagnosis at an older age.

Conclusions/interpretation

Our findings suggest that younger-onset type 2 diabetes increases mortality risk, and that this is mainly through earlier CVD mortality. Efforts to delay the onset of type 2 diabetes might, therefore, reduce mortality.