Socioeconomic gradient in morbidity and mortality in people with diabetes: cohort study findings from the Whitehall Study and the WHO Multinational Study of Vascular Disease in Diabetes.

OBJECTIVE: To assess whether the inverse socioeconomic mortality gradient observed in the general population persists in diabetic people. DESIGN: The Whitehall cohort study and the London cohort of the WHO multinational study of vascular disease in diabetes. SETTING: London. SUBJECTS: 17,264 male civil servants (17,046 without diabetes, 218 with diabetes) aged 40-64 examined in 1967-9, and 300 people with diabetes aged 35-55 from London clinics examined in 1975-7. Both cohorts were followed up until January 1995. MAIN OUTCOME MEASURES: Mortality from all causes, cardiovascular disease, and ischaemic heart disease. RESULTS: In both cohorts people in the lower social groups were older, had higher blood pressure, and were more likely to smoke. In the Whitehall study, the prevalence of heart disease was higher in the lowest social group compared with the highest group, by 6% among non-diabetic people (P = 0.0001) and by 14% among diabetic subjects (P = 0.02). In the WHO study proteinuria was more common in the lowest social group compared with the highest (27% v 15%, P = 0.01), as was retinopathy (54% v 48%, P = 0.5). There was a clear socioeconomic gradient in all cause mortality in both cohorts, with death rates being about twice as high in the lowest compared with the highest social groups. In the Whitehall study this gradient was similar in both diabetic and non-diabetic subjects, and it persisted for mortality from cardiovascular disease and from ischaemic heart disease. About half of the increased risk of death in the lowest social group was accounted for by blood pressure and smoking. CONCLUSIONS: We confirm the existence of an inverse socioeconomic mortality gradient in diabetic people and suggest that this is largely due to conventional cardiovascular risk factors.     

Unemployment and mortality among Finnish men, 1981-5.

OBJECTIVE--To ascertain whether, after controlling for several relevant background variables simultaneously, unemployment is related to mortality and to assess whether this relation is causal or whether unhealthy people are more likely to become unemployed. DESIGN--Prospective study of mortality in Finland during 1981-5 based on 1980 census data on 30-54 year old wage earner men and with particular attention to unemployment in the year before the census. SETTING--Research project at the University of Helsinki. SUBJECTS--All wage earner men in Finland aged 30-54 at the 1980 census. MAIN OUTCOME MEASURES--Causes of death during 1981-5 and duration of unemployment in the year before the census. Background variables controlled for were age, socioeconomic state, marital state, and health. The data were analysed by log linear regression models. RESULTS--During the study period 1981-5, which covered almost 2.7 million person years, there were 9810 deaths. After controlling for all background variables relative total mortality among unemployed versus employed men was 1.93 (95% confidence interval 1.82 to 2.05). The excess mortality was highest in accidental and violent causes of death (relative mortality 2.51; 95% confidence interval 2.28 to 2.76). For circulatory diseases the relative death rate was 1.54 (95% confidence interval 1.40 to 1.70), but among neoplasms only lung cancer was associated with excess mortality. Selection for unemployment based on age, socioeconomic state, and marital state was evident but no such selection was detected based on health. Effects of unemployment on mortality were more pronounced with increasing duration of unemployment. CONCLUSIONS--The relative excess mortality of unemployed men in Finland cannot fully be explained by demographic, social, and health variables preceding unemployment. Unemployment therefore seems to have an independent causal effect on male mortality. Further studies are needed to elucidate the mechanisms between unemployment and mortality.     

Risk of Cardiovascular Disease and Total Mortality in Adults with Type 1 Diabetes: Scottish Registry Linkage Study

Background

Randomized controlled trials have shown the importance of tight glucose control in type 1 diabetes (T1DM), but few recent studies have evaluated the risk of cardiovascular disease (CVD) and all-cause mortality among adults with T1DM. We evaluated these risks in adults with T1DM compared with the non-diabetic population in a nationwide study from Scotland and examined control of CVD risk factors in those with T1DM.

Methods and Findings

The Scottish Care Information-Diabetes Collaboration database was used to identify all people registered with T1DM and aged ≥20 years in 2005–2007 and to provide risk factor data. Major CVD events and deaths were obtained from the national hospital admissions database and death register. The age-adjusted incidence rate ratio (IRR) for CVD and mortality in T1DM (n = 21,789) versus the non-diabetic population (3.96 million) was estimated using Poisson regression. The age-adjusted IRR for first CVD event associated with T1DM versus the non-diabetic population was higher in women (3.0: 95% CI 2.4–3.8, p<0.001) than men (2.3: 2.0–2.7, p<0.001) while the IRR for all-cause mortality associated with T1DM was comparable at 2.6 (2.2–3.0, p<0.001) in men and 2.7 (2.2–3.4, p<0.001) in women. Between 2005–2007, among individuals with T1DM, 34 of 123 deaths among 10,173 who were <40 years and 37 of 907 deaths among 12,739 who were ≥40 years had an underlying cause of death of coma or diabetic ketoacidosis. Among individuals 60–69 years, approximately three extra deaths per 100 per year occurred among men with T1DM (28.51/1,000 person years at risk), and two per 100 per year for women (17.99/1,000 person years at risk). 28% of those with T1DM were current smokers, 13% achieved target HbA_1c of <7% and 37% had very poor (≥9%) glycaemic control. Among those aged ≥40, 37% had blood pressures above even conservative targets (≥140/90 mmHg) and 39% of those ≥40 years were not on a statin. Although many of these risk factors were comparable to those previously reported in other developed countries, CVD and mortality rates may not be generalizable to other countries. Limitations included lack of information on the specific insulin therapy used.

Conclusions

Although the relative risks for CVD and total mortality associated with T1DM in this population have declined relative to earlier studies, T1DM continues to be associated with higher CVD and death rates than the non-diabetic population. Risk factor management should be improved to further reduce risk but better treatment approaches for achieving good glycaemic control are badly needed. Please see later in the article for the Editors'' Summary     

Sex-specific outcomes of diabetic patients with acute myocardial infarction who have undergone percutaneous coronary intervention: a register linkage study

ABSTRACT: BACKGROUND: The presence of diabetes mellitus poses a challenge in the treatment of patients with acute myocardial infarction (AMI). We aimed to evaluate the sex-specific outcomes of diabetic and non-diabetic patients with AMI who have undergone percutaneous coronary intervention (PCI). METHODS: Data of the Estonian Myocardial Infarction Registry for years 2006[EN DASH]2009 were linked with the Health Insurance Fund database and the Population Registry. Hazard ratios (HRs) with the 95 % confidence intervals (CIs) for the primary composite outcome (non-fatal AMI, revascularization, or death whichever occurred first) and for the secondary outcome (all cause mortality) were calculated comparing diabetic with non-diabetic patients by sex. RESULTS: In the final study population (n = 1652), 14.6 % of the men and 24.0 % of the women had diabetes. Overall, the diabetics had higher rates of cardiovascular risk factors, co-morbidities, and 3[EN DASH]4 vessel disease among both men and women (p < 0.01). Among women, the diabetic patients were younger, they presented later and less often with typical symptoms of chest pain than the non-diabetics (p < 0.01). Women with diabetes received aspirin and reperfusion for ST-segment elevation AMI less often than those without diabetes (p < 0.01). During a follow-up of over two years, in multivariate analysis, diabetes was associated with worse outcomes only in women: the adjusted HR for the primary outcome 1.44 (95 % CI 1.05 [MINUS SIGN] 1.96) and for the secondary outcome 1.83 (95 % CI 1.17 [MINUS SIGN] 2.89). These results were largely driven by a high (12.0 %) mortality during hospitalization of diabetic women. CONCLUSIONS: Diabetic women with AMI who have undergone PCI are a high-risk group warranting special attention in treatment strategies, especially during hospitalization. There is a need to improve the expertise to detect AMI earlier, decrease disparities in management, and find targeted PCI strategies with adjunctive antithrombotic regimes in women with diabetes.     

Lifetime socioeconomic position and mortality: prospective observational study.

OBJECTIVES: To assess the influence of socioeconomic position over a lifetime on risk factors for cardiovascular disease, on morbidity, and on mortality from various causes. DESIGN: Prospective observational study with 21 years of follow up. Social class was determined as manual or non-manual at three stages of participants'' lives: from the social class of their father''s job, the social class of their first job, and the social class of their job at the time of screening. A cumulative social class indicator was constructed, ranging from non-manual social class at all three stages of life to manual social class at all three stages. SETTING: 27 workplaces in the west of Scotland. PARTICIPANTS: 5766 men aged 35-64 at the time of examination. MAIN OUTCOME MEASURES: Prevalence and level of risk factors for cardiovascular disease; morbidity; and mortality from broad causes of death. RESULTS: From non-manual social class locations at all three life stages to manual at all stages there were strong positive trends for blood pressure, body mass index, current cigarette smoking, angina, and bronchitis. Inverse trends were seen for height, cholesterol concentration, lung function, and being an ex-smoker. 1580 men died during follow up. Age adjusted relative death rates in comparison with the men of non-manual social class locations at all three stages of life were 1.29 (95% confidence interval 1.08 to 1.56) in men of two non-manual and one manual social class; 1.45 (1.21 to 1.73) in men of two manual and one non-manual social class; and 1.71 (1.46 to 2.01) in men of manual social class at all three stages. Mortality from cardiovascular disease showed a similar graded association with cumulative social class. Mortality from cancer was mainly raised among men of manual social class at all three stages. Adjustment for a wide range of risk factors caused little attenuation in the association of cumulative social class with mortality from all causes and from cardiovascular disease; greater attenuation was seen in the association with mortality from non-cardiovascular, non-cancer disease. Fathers having a manual [corrected] occupation was strongly associated with mortality from cardiovascular disease: relative rate 1.41 (1.15 to 1.72). Participants'' social class at the time of screening was more strongly associated than the other social class indicators with mortality from cancer and from non-cardiovascular, non-cancer causes. CONCLUSIONS: Socioeconomic factors acting over the lifetime affect health and risk of premature death. The relative importance of influences at different stages varies for the cause of death. Studies with data on socioeconomic circumstances at only one stage of life are inadequate for fully elucidating the contribution of socioeconomic factors to health and mortality risk.     

Impact of cardiovascular risk factors on coronary heart disease and mortality among middle aged diabetic men: a general population study.

OBJECTIVE--To investigate the effect of cardiovascular risk factors on coronary heart disease and all cause mortality in middle aged diabetic men. DESIGN--Prospective population study based on data collected from second screening (from 1974 to 1977) in the multifactor primary prevention trial and follow up until March 1983. SETTING--Gothenburg, Sweden. SUBJECTS--6897 Men aged 51 to 59, of whom 232 were self reported diabetics and 6665 were non-diabetic; none had a history of myocardial infarction. MAIN OUTCOME MEASURES--Incidences of coronary heart disease and mortality from all causes. RESULTS--Diabetic men with a serum cholesterol concentration greater than 7.3 mmol/l had a significantly higher incidence of coronary heart disease during follow up than those with a concentration less than or equal to 5.5 mmol/l (28.3% v 5.4%; p = 0.020); corresponding figures for non-diabetic men were 9.4% and 2.4% respectively. In multivariate logistic regression analyses serum cholesterol concentration and smoking habit were independent predictors of coronary heart disease (odds ratio serum cholesterol concentration 6.1 (95% confidence interval 2.1 to 17.6) current smoking 2.9 (1.1 to 7.5)) and of all cause mortality (3.2 (1.3 to 7.9), 3.0 (1.4 to 6.7) respectively) in diabetic men whereas systolic blood pressure, body mass index, family history, marital state, and alcohol abuse were not. Low occupational class was an independent predictor of mortality (2.4 (1.01 to 5.5)), but not of coronary heart disease, in diabetic men. CONCLUSIONS--Middle aged diabetic men with hypercholesterolaemia are at very high risk of developing coronary heart disease and of dying prematurely. Lowering serum cholesterol concentration in such subjects seems to be warranted.     

Contribution of deaths related to alcohol use of socioeconomic variation in mortality: register based follow up study.

OBJECTIVE: To estimate the contribution of excessive alcohol use to socioeconomic variation in mortality among men and women in Finland. DESIGN: Register based follow up study. SUBJECTS: The population covered by the 1985 and 1990 censuses, aged > or = 20 in the follow up period 1987-93. MAIN OUTCOME MEASURES: Total mortality and alcohol related mortality from all causes, from diseases, and from accidents and violence according to socioeconomic position. The excess mortality among other classes compared with upper non-manual employees and differences in life expectancy between the classes were used to measure mortality differentials. RESULTS: Alcohol related mortality constituted 11% of all mortality among men aged > or = 20 and 2% among women and was higher among manual workers than among other classes. It accounted for 14% of the excess all cause mortality among manual workers over upper non-manual employees among men and 4% among women and for 24% and 9% of the differences in life expectancy, respectively. Half of the excess mortality from accidents and violence among male manual workers and 38% among female manual workers was accounted for by alcohol related deaths, whereas in diseases the role of alcohol was modest. The contribution of alcohol related deaths to relative mortality differentials weakened with age. CONCLUSIONS: Class differentials in alcohol related mortality are an important factor in the socioeconomic mortality differentials in Finland, especially among men, among younger age groups, and in mortality from accidents and violence.     

Prediction of mortality using a multi-bed vascular calcification score in the Diabetes Heart Study

Background

Diabetes is associated with a high risk of death due to coronary artery disease (CAD). People with diabetes suffering from CAD are frequently treated with revascularization procedures. We aim to compare trends in the use and outcomes of coronary revascularization procedures in diabetic and non-diabetic patients in Spain between 2001 and 2011.

Methods

We identified all patients who had undergone coronary revascularization procedures, percutaneous coronary interventions (PCI) and coronary artery bypass graft (CABG) surgeries, using national hospital discharge data. Discharges were grouped by diabetes status: type 2 diabetes and no diabetes. The incidence of discharges attributed to coronary revascularization procedures were calculated stratified by diabetes status. We calculated length of stay and in-hospital mortality (IHM). We apply joinpoint log-linear regression to identify the years in which changes in tendency occurred in the use of PCI and CABG in diabetic and non-diabetic patients. Multivariate analysis was adjusted by age, sex, year and comorbidity (Charlson comorbidity index).

Results

From 2001 to 2011, 434,108 PCIs and 79,986 CABGs were performed. According to the results of the joinpoint analysis, we found that sex and age-adjusted use of PCI increased by 31.4% per year from 2001 to 2003, by 15.9% per year from 2003 to 2006 and by 3.8% per year from 2006 to 2011 in patients with diabetes. IHM among patients with diabetes who underwent a PCI did not change significantly over the entire study period (OR 0.99; 95% CI 0.97-1.00). Among patients with diabetes who underwent a CABG, the sex and age-adjusted CABG incidence rate increased by 10.4% per year from 2001 to 2003, and then decreased by 1.1% through 2011. Diabetic patients who underwent a CABG had a 0.67 (95% CI 0.63-0.71) times lower probability of dying during hospitalization than those without diabetes.

Conclusions

The annual percent change in PCI procedures increased in diabetic and non-diabetic patients. Higher comorbidity and the female gender are associated with a higher IHM in PCI procedures. In diabetic and non-diabetic patients, we found a decrease in the use of CABG procedures. IHM was higher in patients without diabetes than in those with diabetes.     

Mortality associated with HIV-1 infection over five years in a rural Ugandan population: cohort study.

OBJECTIVE: To assess the impact of HIV-1 infection on mortality over five years in a rural Ugandan population. DESIGN: Longitudinal cohort study followed up annually by a house to house census and medical survey. SETTING: Rural population in south west Uganda. SUBJECTS: About 10,000 people from 15 villages who were enrolled in 1989-90 or later. MAIN OUTCOME MEASURES: Number of deaths from all causes, death rates, mortality fraction attributable to HIV-1 infection. RESULTS: Of 9777 people resident in the study area in 1989-90, 8833 (90%) had an unambiguous result on testing for HIV-1 antibody; throughout the period of follow up adult seroprevalence was about 8%. During 35,083 person years of follow up, 459 deaths occurred, 273 in seronegative subjects and 186 in seropositive subjects, corresponding to standardised death rates of 8.1 and 129.3 per 1000 person years. Standardised death rates for adults were 10.4 (95% confidence interval 9.0 to 11.8) and 114.0 (93.2 to 134.8) per 1000 person years respectively. The mortality fraction attributable to HIV-1 infection was 41% for adults and was in excess of 70% for men aged 25-44 and women aged 20-44 years. Median survival from time of enrollment was less than three years in subjects aged 55 years or more who were infected with HIV-1. Life expectancy from birth in the total population resident at any time was estimated to be 42.5 years (41.4 years in men; 43.5 years in women), which compares with 58.3 years (56.5 years in men; 60.5 years in women) in people known to be seronegative. CONCLUSIONS: These data confirm that in a rural African population HIV-1 infection is associated with high death rates and a substantial reduction in life expectancy.     

Secular decline in mortality from coronary heart disease in adults with diabetes mellitus: cohort study

Objective To examine trends in fatal coronary heart disease in adults with and without diabetes.Design Cohort study.Setting Two surveys of the Nord-Trøndelag health study (HUNT), a population based study in Norway.Participants 74 914 men and women from the first survey (1984-6) and 64 829 from the second survey (1995-7).Main outcome measure Age specific mortality from coronary heart disease among adults with and without diabetes during two consecutive nine year follow-up periods.Results A total of 2623 men and 1583 women died from coronary heart disease. Mortality rates were substantially lower during the most recent follow-up period: among men aged 70-79 without diabetes, deaths per 1000 person years declined from 16.38 to 8.79 (reduction 48%, 95% confidence interval 39% to 55%) and among women aged 70-79 from 6.84 to 2.68 (62%, 52% to 70%). Among the same age group with diabetes, deaths per 1000 person years in men declined from 38.97 to 17.89 (54%, 32% to 69%) and in women from 28.15 to 11.83 (59%, 37% to 73%). The reduction was more noticeable in age groups younger than 70 at baseline, and less pronounced among people aged 80 or more. Mortality from coronary heart disease was more than twofold higher in people with than without diabetes, with a slightly stronger association in women. The difference in mortality by diabetes status remained almost unchanged from the first to the second survey.Conclusion The strong general reduction in mortality rates from coronary heart disease from the first to the second follow-up period also benefited people with diabetes, but the more than twofold higher mortality from coronary heart disease associated with diabetes persisted over time.     

How can we best prolong life? Benefits of coronary risk factor reduction in non-diabetic and diabetic subjects.

OBJECTIVE--To compare the theoretical benefits of different approaches to reduce risk factors for coronary heart disease in subjects at risk. DESIGN--The results of findings from meta-analyses of intervention studies on cause specific mortality and of observational studies on smokers and ex-smokers were applied to observational data on 10 year cause specific mortality derived from the multiple risk factor intervention trial. Lifetable analyses were used to estimate gains in life expectancy. SUBJECTS--Diabetic and non-diabetic men initially 35-57 years of age. MAIN OUTCOME MEASURES--10 year mortality from coronary heart disease, 10 year total mortality, man years of intervention to prevent one death and one death from coronary heart disease, gain in life expectancy, and drug costs per year of additional life in diabetic and non-diabetic men of 45. RESULTS--In non-diabetic men a 10 year mortality from coronary heart disease of 14.4 per 1000 would be reduced by a mean of 0.58, 0.82, 2.64, and 2.74 per 1000 by antihypertensive treatment, lowering cholesterol concentration, taking aspirin, and stopping smoking respectively; a 10 year total mortality of 44.1 per 1000 would fall by a mean of 1.06, 5.16, and 8.65 per 1000 with antihypertensive and aspirin treatment and stopping smoking respectively and increased by a mean of 0.07 per 1000 with the lowering of cholesterol concentration. In diabetic men the reductions in mortality from coronary heart disease would be between three and five times greater, and total mortality would show mean reductions of 5.81, 0.56, 16.17, and 20.84 per 1000 respectively, with all interventions of significant benefit except the lowering of cholesterol concentration. Between 2400 and 3800 man years of pharmacological intervention were calculated as being necessary to prevent one death from coronary heart disease in a non-diabetic man, and between 800 and 1200 man years in a diabetic man. The loss of life expectancy associated with smoking and hypertension is greater than that accruing from hypercholesterolaemia, but stopping smoking would prolong life by a mean of around four years in a 45 year old non-diabetic man and three years in a diabetic man, whereas aspirin and antihypertensive treatment would provide approximately one year of additional life expectancy in both categories. CONCLUSIONS--Studies to date have shown little impact of drugs that lower cholesterol concentration and blood pressure on either coronary heart disease or total mortality. Although new treatments for hypercholesterolaemia and hypertension might help prevent coronary heart disease, other approaches to reduce the burden of premature death are required.     

Vulnerability to winter mortality in elderly people in Britain: population based study

Objective To examine the determinants of vulnerability to winter mortality in elderly British people.Design Population based cohort study (119 389 person years of follow up).Setting 106 general practices from the Medical Research Council trial of assessment and management of older people in Britain.Participants People aged ≥ 75 years.Main outcome measures Mortality (10 123 deaths) determined by follow up through the Office for National Statistics.Results Month to month variation accounted for 17% of annual all cause mortality, but only 7.8% after adjustment for temperature. The overall winter:non-winter rate ratio was 1.31 (95% confidence interval 1.26 to 1.36). There was little evidence that this ratio varied by geographical region, age, or any of the personal, socioeconomic, or clinical factors examined, with two exceptions: after adjustment for all major covariates the winter:non-winter ratio in women compared with men was 1.11 (1.00 to 1.23), and those with a self reported history of respiratory illness had a winter:non-winter ratio of 1.20 (1.08 to 1.34) times that of people without a history of respiratory illness. There was no evidence that socioeconomic deprivation or self reported financial worries were predictive of winter death.Conclusion Except for female sex and pre-existing respiratory illness, there was little evidence for vulnerability to winter death associated with factors thought to lead to vulnerability. The lack of socioeconomic gradient suggests that policies aimed at relief of fuel poverty may need to be supplemented by additional measures to tackle the burden of excess winter deaths in elderly people.     

Type 1 and Type 2 Diabetes and Cancer Mortality in the 2002-2009 Cohort of 39 811 French Dialyzed Patients

End-stage renal disease is a chronic and progressive pathology associated with several comorbidities, particularly diabetes. Indeed, diabetes is the first cause of end-stage renal disease and, in France, 42% of incident patients had diabetes in 2012. In the general population, diabetes is associated with increased cancer risk. The aim of this study was to examine the association between risk of cancer death and diabetes in a large French cohort of patients with end-stage renal disease. Data on all patients with end-stage renal disease who initiated dialysis in France between 2002 and 2009 were extracted from the Renal Epidemiology Information Network registry. The risk of dying by cancer was studied using the Fine and Gray model to take into account the competing risk of death by other causes. We analyzed 39 811 patients with end-stage renal disease. Their mean age was 67.7±15 years, 39.4% had diabetes and 55.3% at least one cardiovascular disease. Compared with the non-diabetic group, patients with diabetes were older and had more cardiovascular and respiratory comorbidities when they started dialysis. Conversely, fewer diabetic patients had also a tumor at the beginning of the renal replacement therapy. Cancer was indicated as the cause of death for 6.7% of diabetic and 13.4% of non-diabetic patients. The Fine and Gray multivariate analyses indicated that diabetes (HR=0.72 95% CI: [0.68-0.95], p<0.001) and also female gender, peritoneal dialysis, cardio-vascular disease and kidney transplantation were associated with decreased risk of death by cancer. In this French cohort of patients with end-stage renal disease, diabetes was not associated with a significant increased risk of dying from cancer. Studies on the incidence of cancer in patients with ESRD are now needed to evaluate the potential association between diabetes and specific malignancies in this population.     

Social influences and cardiovascular risk factors as determinants of plasma fibrinogen concentration in a general population sample of middle aged men.

OBJECTIVE--To analyse the relation between fibrinogen concentration and social class and other social factors found to be related to mortality. The results regarding cardiovascular disease are unpublished, as yet. DESIGN--Cross sectional population study. SETTING--City of Gothenburg, Sweden. SUBJECTS--639 Men from a population sample of 1016 men aged 50 in 1983. They were all employed and had no history of myocardial infarction or stroke. Fibrinogen values were available for all of them. MAIN OUTCOME MEASURE--Fibrinogen concentration in relation to socioeconomic state according to occupation, and other social influences determined as number of people in the household and scores of social activities and activities in and outside the house. RESULTS--Men with low scores for activities at home had a mean plasma fibrinogen concentration of 3.34 g/l (95% confidence interval 3.21 to 3.47), whereas those with an intermediate score had a mean concentration of 3.16 (3.00 to 3.32) g/l and those with a high score 3.02 (2.95 to 3.10) g/l. Similar inverse relations were noted for the two other activity scores and for occupational class (class 1 being unskilled and semiskilled workers and class 5 professionals and executives) and the number of people in the household. Smoking exerted a strong influence on fibrinogen concentration, the relations between fibrinogen concentration and social factors being evident only in non-smokers. The mean difference in fibrinogen value between the non-smokers with the lowest activity scores at home and those with the highest scores was 0.36 (0.19 to 0.54) g/l, and similar differences were seen for the two other activity scores. Multiple regression analyses showed smoking, body mass index, the sum of all activities (inverse relation), and diabetes to be independently associated with fibrinogen value, whereas occupational class (p = 0.81) and the number of people in the household (p = 0.09) were not. CONCLUSIONS--Psychosocial influences seem to influence the coagulation system in the body in a way that is associated with cardiovascular disease and premature death.     

Risk factors for early death in non-insulin dependent diabetes and men with known glucose tolerance status.

OBJECTIVE--To identify risk factors for all cause mortality according to glucose tolerance status. DESIGN--Cohort study with an average 15.6 years'' follow up. SETTING--Paris, France. SUBJECTS--7166 working men aged 44-55 in 1968-72 in the Paris prospective study cohort, with non-insulin dependent diabetes or known result of two hour 75 g oral glucose tolerance test. MAIN OUTCOME MEASURES--Risk factors for death from all causes. RESULTS--128 men were known to be diabetic, 180 had diabetes diagnosed, and 697 had impaired glucose tolerance diagnosed. Compared with normoglycaemic men the relative risks of death in these groups were 2.0 (95% confidence interval 1.4 to 3.0), 2.7 (2.0 to 3.6), and 1.6 (1.3 to 2.0) respectively. Obesity, smoking, high blood pressure, and high non-esterified fatty acid concentration were risk factors for death in all subjects and were unaffected by glucose tolerance. The risks for fasting and two hour insulin concentrations and mean corpuscular volume were two times higher in known diabetic men than in men not known to be diabetic. Central obesity was significant only in men not known to be diabetic (1.6 (1.4 to 1.9)). In known diabetic men a two hour glucose concentration higher than 11.1 mmol/l carried a relative risk of death of 3.8 (1.4 to 9.4). CONCLUSIONS--Diabetic men have similar risk factors for early mortality to other men but are at higher risk from hyperinsulinaemia, hyperglycaemia, and high mean corpuscular volume.     

The Incidence of End-Stage Renal Disease in the Diabetic (Compared to the Non-Diabetic) Population: A Systematic Review

End-stage renal disease (ESRD) in diabetes is a life threatening complication resulting in a poor prognosis for patients as well as high medical costs. The aims of this systematic review were (1) to evaluate the incidence of ESRD due to all causes and due to diabetic nephropathy in the diabetic population and differences between incidences of ESRD with respect to sex, ethnicity, age and regions, (2) to compare incidence rates in the diabetic and non-diabetic population, and (3) to investigate time trends. The systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in the biomedical databases until January 3^rd 2015; thirty-two studies were included. Among patients with incident type 1 diabetes the 30-year cumulative incidence ranged from 3.3% to 7.8%. Among patients with prevalent diabetes, incidence rates of ESRD due to all causes ranged from 132.0 to 167.0 per 100,000 person-years, whereas incidence rates of ESRD due to diabetic nephropathy varied from 38.4 to 804.0 per 100,000 person-years. The incidence of ESRD in the diabetic population was higher compared to the non-diabetic population, and relative risks varied from 6.2 in the white population to 62.0 among Native Americans. The results regarding time trends were inconsistent. The review conducted demonstrates the considerable variation of incidences of ESRD among the diabetic population. Consistent findings included an excess risk when comparing the diabetic to the non-diabetic population and ethnic differences. We recommend that newly designed studies should use standardized methods for the determination of ESRD and population at risk.     

Body weight: implications for the prevention of coronary heart disease,stroke, and diabetes mellitus in a cohort study of middle aged men.

OBJECTIVE: To determine the body mass index associated with the lowest morbidity and mortality. DESIGN: Prospective study of a male cohort. SETTING: One general practice in each of 24 British towns. SUBJECTS: 7735 men aged 40-59 years at screening. MAIN OUTCOME MEASURES: All cause death rate, heart attacks, and stroke (fatal and non-fatal) and development of diabetes, or any of these outcomes (combined end point) over an average follow up of 14.8 years. RESULTS: There were 1271 deaths from all causes, 974 heart attacks, 290 strokes, and 245 new cases of diabetes mellitus. All cause mortality was increased only in men with a body mass index (kg/m2) < 20 and in men with an index > or = 30. However, risk of cardiovascular death, heart attack, and diabetes increased progressively from an index of < 20 even after age, smoking, social class, alcohol consumption, and physical activity were adjusted for. For the combined end point the lowest risks were seen for an index of 20.0-23.9. In never smokers and former smokers, deaths from any cause rose progressively from an index of 20.0-21.9 and for the combined end point, from 20.0-23.9. Age adjusted levels of a wide range of cardiovascular risk factors rose or fell progressively from an index < 20. CONCLUSION: A healthy body mass index in these middle aged British men seems to be about 22.     

Metformin increases cancer specific survival in colorectal cancer patients—National cohort study

PurposeWe aimed to assess oncological outcomes in colorectal cancer patients with type 2 diabetes mellitus (T2DM) using metformin.MethodsPatients with colorectal cancer and T2DM during 2000–2012 period were identified form Lithuanian Cancer Registry and the National Health Insurance Fund database. Colorectal cancer-specific survival (CS) was the primary outcome. It was measured from date of colorectal cancer diagnosis to date of death due to colorectal cancer, or last known date alive.Results15,052 people who met eligibility criteria for this analysis, including 1094 (7.27%) with pre-existing type 2 diabetes (271 metformin never users and 823 metformin users) and 13 958 people without diabetes assessed. During follow-up (mean follow-up time was 4.4 years, with range from 1 day to 17 years) there were 10,927 deaths including 8559 from colorectal cancer. Significantly lower risk in CS between diabetic and non-diabetic people with lower risk of cancer-specific mortality (HR 0.87, 95% CI 0.80–0.94) in diabetic patient population was seen. After adjustment for age, stage at diagnosis and metformin usage, significant difference in colorectal CS between metformin users in diabetic patient population compared to non-diabetics and metformin non-users in diabetic patient population was found (0.80 (0.72–0.89) vs 1.00 and vs 1.05 (0.91–1.23)). Overall survival (OS) was better for diabetic patients with significant difference in diabetic metformin users (HR 0.91, 95% CI 0.79–0.94).ConclusionsColorectal cancer patients with T2DM treated with metformin as part of their diabetic therapy appear to have a superior OS and CS. However, prospective controlled studies are still needed to evaluate the efficacy of metformin as an anti-tumor agent.     

Cognitive impairment and mortality in a cohort of elderly people.

OBJECTIVES--To investigate the relation between cognitive function and cause specific mortality in people aged 65 and over. DESIGN-A 20 year follow up study of a cohort of randomly selected elderly people living in the community who in 1973-4 had taken part in a nutritional survey funded by the Department of Health and Social Security. SETTING--Eight areas in Britain (five in England, two in Scotland, and one in Wales). SUBJECTS--921 men and women whose cognitive function was assessed by a geriatrician in 1973-4 and for whom data on health, socioeconomic circumstances, and diet had been recorded. RESULTS--Cognitive impairment was associated with increased mortality, in particular death from ischaemic stroke. Those who scored 7 or less on the Hodkinson mental test had a relative risk of dying from stroke of 2.8 (95% confidence interval 1.4 to 5.5), compared with those who gained the maximum score (10), after adjustment for age, sex, blood pressure, serum cholesterol concentration, and vitamin C intake. These associations were independent of illness or social class. At the time of the nutritional survey, cognitive function was poorest in those with the lowest vitamin C status, whether measured by dietary intake or plasma ascorbic acid concentration. The relation between vitamin C status and cognitive function was independent of age, illness, social class, or other dietary variables. CONCLUSION--The relation between cognitive function and risk of death from stroke suggests that cerebrovascular disease is an important cause of declining cognitive function. Vitamin C status may be a determinant of cognitive function in elderly people through its effect on atherogenesis. A high vitamin C intake may protect against both cognitive impairment and cerebrovascular disease.     

Patterns of mortality in second generation Irish living in England and Wales: longitudinal study.

OBJECTIVE--To examine the mortality of second generation Irish living in England and Wales. DESIGN--Longitudinal study of 1% of the population of England and Wales (longitudinal study by the Office of Population Censuses and Surveys (now the Office for National Statistics)) followed up from 1971 to 1989. SUBJECTS--3075 men and 3233 women aged 15 and over in 1971. MAIN OUTCOME MEASURES--Age and sex specific standardised mortality ratios for all causes, cancers, coronary heart disease, cerebrovascular diseases, respiratory diseases, and injuries and poisonings. Deaths were also analysed by socioeconomic indicators. RESULTS--786 deaths were traced to men and 762 to women. At working ages (men, aged 15-64; women, 15-59) the mortality of men (standardised mortality ratio 126) and women (129) was significantly higher than that of all men and all women. At ages 15-44, relative disadvantages were even greater both for men (145) and for women (164). Mortality was raised for most major causes of death. Significant excess mortality from cancers was seen for men of working age (132) and for women aged 60 and over (122). At working ages mortality of the second generation Irish in every social class and in the categories of car access and housing tenure was higher than that of all men and all women in the corresponding categories. Adjusting for these socioeconomic indicators did not explain the excess mortality. CONCLUSION--Mortality of second generation Irish men and women was higher than that of all men and all women and for most major causes of death. While socioeconomic factors remain important, cultural and lifestyle factors are likely to contribute to this adverse mortality.