OBJECTIVE To assess predictors of CVD mortality among men with and without diabetes and to assess the independent effect of diabetes on the risk of CVD death. RESEARCH DESIGN AND METHODS Participants in this cohort study were screened from 1973 to 1975; vital status has been ascertained over an average of 12 yr of follow-up (range 11–13 yr). Participants were 347,978 men aged 35–57 yr, screened in 20 centers for MRFIT. The outcome measure was CVD mortality. RESULTS Among 5163 men who reported taking medication for diabetes, 1092 deaths (603 CVD deaths) occurred in an average of 12 yr of follow-up. Among 342,815 men not taking medication for diabetes, 20,867 deaths were identified, 8965 ascribed to CVD. Absolute risk of CVD death was much higher for diabetic than nondiabetic men of every age stratum, ethnic background, and risk factor level—overall three times higher, with adjustment for age, race, income, serum cholesterol level, sBP, and reported number of cigarettes/day ( P CONCLUSIONS These findings emphasize the importance of rigorous sustained intervention in people with diabetes to control blood pressure, lower serum cholesterol, and abolish cigarette smoking, and the importance of considering nutritional-hygienic approaches on a mass scale to prevent diabetes.

https://www.siditalia.it/pdf/Diabete-ed-Arterosclerosi/MRFIT_Diab_care_1993.pdf

Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.

Context With increasing globalization and East-West exchanges, the increasing epidemic of type 2 diabetes in Asia has far-reaching public health and socioeconomic implications. Objective To review recent data in epidemiologic trends, risk factors, and complications of type 2 diabetes in Asia. Evidence Acquisition Search of MEDLINE using the term diabetes and other relevant keywords to identify meta-analyses, systematic reviews, large surveys, and cohort studies. Separate searches were performed for specific Asian countries. The review was limited to English-language articles published between January 1980 and March 2009; publications on type 1 diabetes were excluded. Evidence Synthesis The prevalence of diabetes in Asian populations has increased rapidly in recent decades. In 2007, more than 110 million individuals in Asia were living with diabetes, with a disproportionate burden among the young and middle aged. Similarly, rates of overweight and obesity are increasing sharply, driven by economic development, nutrition transition, and increasingly sedentary lifestyles. The “metabolically obese” phenotype (ie, normal body weight with increased abdominal adiposity) is common in Asian populations. The increased risk of gestational diabetes, combined with exposure to poor nutrition in utero and overnutrition in later life in some populations, may contribute to the increasing diabetes epidemic through “diabetes begetting diabetes” in Asia. While young age of onset and long disease duration place Asian patients with diabetes at high risk for cardiorenal complications, cancer is emerging as an important cause of morbidity and mortality. Conclusions Type 2 diabetes is an increasing epidemic in Asia, characterized by rapid rates of increase over short periods and onset at a relatively young age and low body mass index. Prevention and control of diabetes should be a top public health priority in Asian populations.

Diabetes in Asia: epidemiology, risk factors, and pathophysiology.

Guidelines and Expert Consensus documents aim to present management and recommendations based on all of the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient, suffering from a specific condition, taking into account not only the impact on outcome, but also the risk benefit ratio of a particular diagnostic or therapeutic procedure. The ESC recommendations for guidelines production can be found on the ESC website†.

In brief, the ESC appoints experts in the field to carry out a comprehensive and critical evaluation of the use of diagnostic and therapeutic procedures and to assess the risk–benefit ratio of the therapies recommended for management and/or prevention of a given condition. The strength of evidence for or against particular procedures or treatments is weighed according to predefined scales for grading recommendations and levels of evidence, as outlined below. Once the document has been finalized and approved by all the experts involved in the Task Force, it is submitted to outside specialists for review. If necessary, the document is revised once more to be finally approved by the Committee for Practice Guidelines and selected members of the Board of the ESC.

The ESC Committee for Practice Guidelines ( CPG ) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups, or consensus panels. The chosen experts in these writing panels are asked to provide disclosure statements of all relationships they may have, which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.

 
| Classes of recommendations |
|:-------------------------- | ------------------------------------------------------------------------------------------------------------------------ |
| Class I | Evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial, useful, and effective |
| Class II | Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment or procedure |
|  Class IIa | Weight of evidence/opinion is in favour of usefulness/efficacy |
|  Class IIb | Usefulness/efficacy is less well established by evidence/opinion |
| Class III | Evidence or general agreement that the treatment or procedure is not useful/effective and, in some cases, may be harmful |

Diabetes and cardiovascular diseases (CVD) often appear …

/pdf/guidelines-on-diabetes-pre-diabetes-and-cardiovascular-4j63bs7fb2.pdf

Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD).

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673608612064.pdf

Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study.

OBJECTIVE —To estimate the global number of excess deaths due to diabetes in the year 2000. RESEARCH DESIGN AND METHODS —We used a computerized generic formal disease model (DisMod II), used by the World Health Organization to assess disease burden through modeling the relationships between incidence, prevalence, and disease-specific mortality. Baseline input data included population structure, age- and sex-specific estimates of diabetes prevalence, and available published estimates of relative risk of death for people with diabetes compared with people without diabetes. The results were validated with population-based observations and independent estimates of relative risk of death. RESULTS —The excess global mortality attributable to diabetes in the year 2000 was estimated to be 2.9 million deaths, equivalent to 5.2% of all deaths. Excess mortality attributable to diabetes accounted for 2–3% of deaths in poorest countries and over 8% in the U.S., Canada, and the Middle East. In people 35–64 years old, 6–27% of deaths were attributable to diabetes. CONCLUSIONS —These are the first global estimates of mortality attributable to diabetes. Globally, diabetes is likely to be the fifth leading cause of death.

https://www.who.int/diabetes/publications/DiabetesMortalityArticle2005.pdf

The Burden of Mortality Attributable to Diabetes: Realistic estimates for the year 2000

We aimed to examine the mortality rates, excess mortality and causes of death in diabetic patients from ten centres throughout the world. A mortality follow-up of 4713 WHO Multinational Study of Vascular Disease in Diabetes (WHO MSVDD) participants from ten centres was carried out, causes of death were ascertained and age-adjusted mortality rates were calculated by centre, sex and type of diabetes. Excess mortality, compared with the background population, was assessed in terms of standardised mortality ratios (SMRs) for each of the 10 cohorts. Cardiovascular disease was the most common underlying cause of death, accounting for 44 % of deaths in Type I (insulin-dependent) diabetes mellitus and 52 % of deaths in Type II (non-insulin-dependent) diabetes mellitus. Renal disease accounted for 21 % of deaths in Type I diabetes and 11 % in Type II diabetes. For Type I diabetes, all-cause mortality rates were highest in Berlin men and Warsaw women, and lowest in London men and Zagreb women. For Type II diabetes, rates were highest in Warsaw men and Oklahoma women and lowest in Tokyo men and women. Age adjusted mortality rates and SMRs were generally higher in patients with Type I diabetes compared with those with Type II diabetes. Men and women in the Tokyo cohort had a very low excess mortality when compared with the background population. This study confirms the importance of cardiovascular disease as the major cause of death in people with both types of diabetes. The low excess mortality in the Japanese cohort could have implications for the possible reduction of the burden of mortality associated with diabetes in other parts of the world. [Diabetologia (2001) 44 [Suppl 2]: S 14–S 21]

/pdf/mortality-and-causes-of-death-in-the-who-multinational-study-1d581mmd9q.pdf

Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes.

Potential risk factors have been examined for association with mortality over a 10–12 year follow-up of the patients of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35–54 year in at entry to the study). Proteinuria has the strongest association with all-cause mortality in univariate analysis being significant in patients of both sexes with Type 2 (non-insulin-dependent) diabetes mellitus and in women with Type 1 (insulin-dependent) diabetes mellitus; both systolic blood pressure (men) and hypertension (both sexes) (as a categorical variable) are significant in Type 1 diabetes. Hypertension is also significantly associated with all-cause mortality in multivariate analysis in both sexes with Type 1 diabetes as proteinuria is in women with Type 2 diabetes. There is an unexpected negative association between plasma creatinine and all-cause mortality in men with Type 2 diabetes. Systolic blood pressure and hypertension are also significantly linked with cardiovascular mortality in Type 1 diabetes, hypertension having an estimated relative risk of 18.6 in multivariate analysis. Serum cholesterol and proteinuria showed the strongest associations with cardiovascular mortality in Type 2 diabetes. Proteinuria is associated with non-cardiovascular mortality in both types of diabetes in univariate but not multivariate analysis. In multivariate analysis hypertension (Type 1 diabetes) and diabetes duration (Type 2 diabetes) are associated with non-cardiovascular mortality. Hypertension and proteinuria have the most consistent associations with mortality in the different analyses with the effect of hypertension appearing stronger in Type 1 diabetes and proteinuria in Type 2 diabetes. Some other proven risk factors in non-diabetic populations had inconstant or absent associations in this group: other, as yet undefined, factors may be important in diabetes.

/pdf/a-prospective-study-of-mortality-among-middle-aged-diabetic-o1h994ebpq.pdf

A prospective study of mortality among middle-aged diabetic patients (the London cohort of the WHO multinational study of vascular disease in diabetics). I, Causes and death rates

We have examined the relationship between baseline variables and the incidence of new macrovascular complications amongst the 497 members of the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics over a mean 8.33-year follow-up. In univariate logistic regression analysis the incidence of new ischaemic electrocardiographic abnormality was significantly associated with systolic and diastolic blood pressure, diabetes duration and hypertension in patients with insulin-dependent diabetes, and with smoking in patients with non-insulin-dependent diabetes. New myocardial infarction was associated with systolic blood pressure, plasma cholesterol, proteinuria and smoking in patients with non-insulin-dependent diabetes; there were no significant associations among patients with insulin-dependent diabetes. All new ischaemic heart disease was associated with hypertension in patients with insulin-dependent diabetes, and plasma cholesterol and smoking in patients with non-insulin-dependent diabetes. New cerebrovascular disease was associated with systolic and diastolic blood pressure, ECG abnormality and hypertension. New peripheral vascular disease was associated with smoking. Multivariate analysis showed the following significant associations 1) in patients with insulin-dependent diabetes: ECG abnormality; hypertension, myocardial infarction; smoking, ischaemic heart disease; hypertension, diabetes duration and smoking, 2) in patients with non-insulin-dependent diabetes: ECG abnormality; smoking, myocardial infarction; serum cholesterol, proteinuria and smoking, ischaemic heart disease; smoking. For new cerebrovascular disease, proteinuria and ECG abnormality were significant predictors in multivariate analysis. Patients with diabetes share many of the established risk factors for non-diabetic subjects, in addition proteinuria may be of significance in the prediction of macrovascular disease in diabetes.

/pdf/risk-factors-for-macrovascular-disease-in-diabetes-mellitus-58teng6lnr.pdf

Risk factors for macrovascular disease in diabetes mellitus: the London follow-up to the WHO Multinational Study of Vascular Disease in Diabetics.

We report on the incidence of new macrovascular disease among the 497 members of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35–54 years at recruitment) over a mean 8.33 year follow-up period. Overall at the end of the follow-up period the prevalence of macrovascular disease in the cohort was 45%; 43% of the subjects showed evidence of ischaemic heart disease, 4.5% of cerebrovascular disease and 4.2% of peripheral vascular disease. The incidence rates for new disease in those subjects who were free at baseline expressed per 1000 patient years of follow-up were: ischaemic ECG abnormality 23.6 (patients with insulin-dependent diabetes 19.8, patients with non-insulin-dependent diabetes 28.1), myocardial infarction 17.6 (patients with insulin-dependent diabetes 16.5, patients with non-insulin-dependent diabetes 18.8), all ichaemic heart disease 31.7 (patients with insulin-dependent diabetes 30.3, patients with non-insulin-dependent diabetes 33.4), cerebrovascular disease 5.9 and peripheral vascular disease 5.2. Incidence rates were generally similar among men and women except for myocardial infarction in patients with non-insulin-dependent diabetes where men had a significantly higher incidence rate. Macrovascular disease is a major problem in patients with diabetes and in this age group is mainly manifested as ischaemic heart disease.

/pdf/incidence-of-macrovascular-disease-in-diabetes-mellitus-the-2lsrzqtffr.pdf

Incidence of macrovascular disease in diabetes mellitus: the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics.

SummaryPotential risk factors have been examined for association with mortality over a 10–12 year follow-up of the patients of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35–54 year in at entry to the study). Proteinuria has the strongest association with all-cause mortality in univariate analysis being significant in patients of both sexes with Type 2 (non-insulin-dependent) diabetes mellitus and in women with Type 1 (insulin-dependent) diabetes mellitus; both systolic blood pressure (men) and hypertension (both sexes) (as a categorical variable) are significant in Type 1 diabetes. Hypertension is also significantly associated with all-cause mortality in multivariate analysis in both sexes with Type 1 diabetes as proteinuria is in women with Type 2 diabetes. There is an unexpected negative association between plasma creatinine and all-cause mortality in men with Type 2 diabetes. Systolic blood pressure and hypertension are also significantly linked with cardiovascular mortality in Type 1 diabetes, hypertension having an estimated relative risk of 18.6 in multivariate analysis. Serum cholesterol and proteinuria showed the strongest associations with cardiovascular mortality in Type 2 diabetes. Proteinuria is associated with non-cardiovascular mortality in both types of diabetes in univariate but not multivariate analysis. In multivariate analysis hypertension (Type 1 diabetes) and diabetes duration (Type 2 diabetes) are associated with non-cardiovascular mortality. Hypertension and proteinuria have the most consistent associations with mortality in the different analyses with the effect of hypertension appearing stronger in Type 1 diabetes and proteinuria in Type 2 diabetes. Some other proven risk factors in non-diabetic populations had inconstant or absent associations in this group: other, as yet undefined, factors may be important in diabetes.

A prospective study of mortality among middle-aged diabetic patients (the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics) II: associated risk factors.

N. J. Morrish

Papers

Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes.

A prospective study of mortality among middle-aged diabetic patients (the London cohort of the WHO multinational study of vascular disease in diabetics). I, Causes and death rates

Risk factors for macrovascular disease in diabetes mellitus: the London follow-up to the WHO Multinational Study of Vascular Disease in Diabetics.

Incidence of macrovascular disease in diabetes mellitus: the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics.

A prospective study of mortality among middle-aged diabetic patients (the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics) II: associated risk factors.