Mild hyponatremia, hypernatremia and incident cardiovascular disease and mortality in older men: A population-based cohort study.

AIM: To examine the association between serum sodium concentration and incident major cardiovascular disease (CVD) outcomes and total mortality in older men. METHODS AND RESULTS: A prospective study of 3099 men aged 60-79 years without a history of cardiovascular disease followed up for an average 11 years during which there were 528 major CVD events (fatal coronary heart disease [CHD] and non-fatal MI, stroke and CVD death) and 873 total deaths. A U shaped relationship was seen between serum sodium concentration and major CVD events and mortality. Hyponatremia (<136 mEq/L) and low sodium within the normal range (136-138 mEq/L) showed significantly increased risk of major CVD events and total mortality compared to men within the upper normal range (139-143 mEq/L) after adjustment for a wide range of confounders and traditional risk factors [adjusted HRs 1.55 (1.13,2.12) and 1.40 (1.14,1.72) for major CVD events respectively and 1.30 (1.02,1.66) and 1.30 (1.11,1.53) respectively for total mortality]. Hyponatremia was associated with inflammation, NT-proBNP, low muscle mass and alkaline phosphatase; these factors contributed to the increased total mortality associated with hyponatremia but did not explain the increased risk of CVD events associated with hyponatremia or low normal sodium concentration. Hypernatremia (≥145 mEq/L) was associated with significantly increased risk of CVD events and mortality due to CVD causes. CONCLUSION: Mild hyponatremia even within the normal sodium range and hypernatremia are both associated with increased total mortality and major CVD events in older men without CVD which is not explained by known adverse CV risk factors.

Socio-demographic characteristics, lifestyle factors and burden of morbidity associated with self-reported hearing and vision impairments in older British community-dwelling men: a cross-sectional study.

BACKGROUND: Hearing and vision problems are common in older adults. We investigated the association of self-reported sensory impairment with lifestyle factors, chronic conditions, physical functioning, quality of life and social interaction. METHODS: A population-based cross-sectional study of participants of the British Regional Heart Study aged 63-85 years. RESULTS: A total of 3981 men (82% response rate) provided data. Twenty-seven per cent (n = 1074) reported hearing impairment including being able to hear with aid (n = 482), being unable to hear (no aid) (n = 424) and being unable to hear despite aid (n = 168). Three per cent (n = 124) reported vision impairment. Not being able to hear, irrespective of use of hearing aid, was associated with poor quality of life, poor social interaction and poor physical functioning. Men who could not hear despite hearing aid were more likely to report coronary heart disease (CHD) [age-adjusted odds ratios (ORs) 1.89 (95% confidence interval 1.36-2.63)]. Vision impairment was associated with symptoms of CHD including breathlessness [OR 2.06 (1.38-3.06)] and chest pain [OR 1.58 (1.07-2.35)]. Vision impairment was also associated with poor quality of life, poor social interaction and poor physical functioning. CONCLUSIONS: Sensory impairment is associated with poor physical functioning, poor health and poor social interaction in older men. Further research is warranted on pathways underlying these associations.

Neighborhood Deprivation and Changes in Oral Health in Older Age: A Longitudinal Population-Based Study.

The aim of this study was to examine the extent to which neighborhood-level socioeconomic factors (objective and perceived) are associated with poor oral health in older adults over time, independent of individual socioeconomic position. Data for this cross-sectional and longitudinal observation study came from a socially and geographically representative cohort of men aged 71 to 92 y in 2010-12 (n = 1,622), drawn from British general practices, which was followed up in 2018-19 (aged 78-98 y; N = 667). Dental measures at both times included number of teeth, periodontal pocket depth, self-rated oral health, and dry mouth. Neighborhood deprivation was based on Index of Multiple Deprivation (IMD) and a cumulative index measuring perceptions about local environment. Individual-level socioeconomic position was based on longest-held occupation. Multilevel and multivariate logistic regressions, adjusted for relevant sociodemographic, behavioral, and health-related factors, were performed to examine the relationships of dental measures with IMD and perceived neighborhood quality index, respectively. Cross-sectionally, risks of tooth loss, periodontal pockets, and dry mouth increased from IMD quintiles 1 to 5 (least to most deprived); odds ratios (ORs) for quintile 5 were 2.22 (95% confidence interval [CI], 1.41-3.51), 2.82 (95% CI, 1.72-4.64), and 1.51 (95% CI, 1.08-2.09), respectively, after adjusting for sociodemographic, behavioral, and health-related factors. Risks of increased pocket depth and dry mouth were significantly greater in quintile 5 (highest problems) of perceived neighborhood quality index compared to quintile 1. Over the 8-y follow-up, deterioration of dentition (tooth loss) was significantly higher in the most deprived IMD quintiles after full adjustment (OR for quintile 5 = 2.32; 95% CI, 1.09-4.89). Deterioration of dentition and dry mouth were significantly greater in quintile 5 of perceived neighborhood quality index. Neighborhood-level factors were associated with poor oral health in older age, both cross-sectionally and longitudinally, particularly with tooth loss, and dry mouth, independent of individual-level socioeconomic position.

The Relationships of Dentition, Use of Dental Prothesis and Oral Health Problems with Frailty, Disability and Diet Quality: Results from Population-Based Studies of Older Adults from the UK and USA.

OBJECTIVES: This study examined the relationships of dental status, use and types of dental prothesis and oral health problems, individually and combined, with diet quality, frailty and disability in two population-based studies of older adults. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Men form the British Regional Heart Study (BRHS) (aged 85±4 years in 2018; n=1013) and Men and Women from the Health, Aging, and Body Composition (HABC) Study (aged 75±3 years in 1998-99; n=1975). MEASUREMENTS: Physical and dental examinations and questionnaires were collected with data available for dental status, oral problems related to eating, diet quality, Fried frailty phenotype, disability based on mobility limitations, and activities of daily living (ADL). The associations of dental status and oral health problems, individually and combined, with risk of frailty and disability were quantified. The relationship with diet quality was also assessed. RESULTS: In the BRHS, but not HABC Study, impaired natural dentition without the use of dentures was associated with frailty independently. This relationship was only established in the same group in those with oral problems (OR=3.24; 95% CI: 1.30-8.03). In the HABC Study, functional dentition with oral health problems was associated with greater risk of frailty (OR=2.21; 95% CI: 1.18-4.15). In both studies those who wore a full or partial denture in one or more jaw who reported oral problems were more likely to have disability. There was no association with diet quality in these groups. CONCLUSION: Older adults with impaired dentition even who use dentures who experience self-report oral problems related to eating may be at increased risk of frailty and disability. Further research is needed to establish whether improving oral problems could potentially reduce the occurrence of frailty and disability.

Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women's Heart Health Study.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with greater relative risk of CHD in women than in men, which is not fully explained by conventional cardiovascular risk factors. We assessed whether cardiovascular risk factors including more novel factors such as markers of insulin resistance, inflammation, activated coagulation and endothelial dysfunction differ more between diabetic and non-diabetic women than between diabetic and non-diabetic men, and the role of insulin resistance. METHODS: A cross-sectional study of non-diabetic and diabetic men and women (n = 7,529) aged 60-79 years with no previous myocardial infarction who underwent an examination was conducted. Measurements of anthropometry, blood pressure and fasting measurements of lipids, insulin, glucose and haemostatic and inflammatory markers were taken. RESULTS: Non-diabetic women tended to have more favourable risk factors and were less insulin resistant than non-diabetic men, but this was diminished in the diabetic state. Levels of waist circumference, BMI, von Willebrand factor (VWF), WBC count, insulin resistance (HOMA-IR), diastolic blood pressure, HDL-cholesterol, tissue plasminogen activator (t-PA) and factor VIII differed more between diabetic and non-diabetic women than between diabetic and non-diabetic men (test for diabetes × sex interaction p < 0.05). The more adverse effect of diabetes on these risk markers in women was associated with, and thereby largely attenuated by, insulin resistance. CONCLUSIONS/INTERPRETATION: The greater adverse influence of diabetes per se on adiposity and HOMA-IR and downstream blood pressure, lipids, endothelial dysfunction and systemic inflammation in women compared with men may contribute to their greater relative risk of coronary heart disease.

Longitudinal associations of socioeconomic position in childhood and adulthood with decline in lung function over 20 years: results from a population-based cohort of British men.

BACKGROUND: Associations of socioeconomic position with lung function are reported mostly from cross-sectional studies. The aim of this study was to investigate the associations between socioeconomic position both in adulthood and childhood with changes in lung function over a 20-year period. METHODS: A socioeconomically representative cohort of 7735 British men aged 40-59 years was followed-up from 1978-1980 to 1998-2000. Lung function (height-standardised forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)) was assessed at both time points in 4252 survivors. Adult socioeconomic position was derived from longest-held occupation in middle age and childhood socioeconomic position from father's longest-held occupation. RESULTS: Both FEV(1) and FVC declined over time; the decline increased progressively from social class I (highest) to V (lowest); p for trend ≤ 0.0001. The mean difference in decline comparing manual versus non-manual groups was -0.13 litres (95% CI -0.16 to -0.10) for FEV(1) and -0.09 litres (95% CI -0.13 to -0.05) for FVC. These differences remained after adjustment for age, cigarette smoking, body mass index, physical activity and history of bronchitis. Similar differences in lung function decline were observed comparing manual with non-manual childhood social classes, although the differences were reduced by adjustment for adult social class and risk factors. Men in manual social classes in both childhood and adulthood had the greatest decline in lung function compared to those in non-manual groups in childhood and adulthood. CONCLUSIONS: Socioeconomic position across the life course could have a significant impact on decline in lung function in later life. The role of environmental factors associated with socioeconomic position merits further exploration.

The potential for a two-stage diabetes risk algorithm combining non-laboratory-based scores with subsequent routine non-fasting blood tests: results from prospective studies in older men and women.

AIM: To develop strategies based on simple clinical assessment and blood markers to identify older individuals at high risk for Type 2 diabetes. METHODS: A prospective study of non-diabetic men (n = 3523) and women (n = 3404) aged 60-79 years followed for 7 years, during which there were 297 incident cases of Type 2 diabetes. Logistic regression was used to develop scores to predict incident cases, starting with clinical predictors and adding blood markers that predicted the incidence of diabetes. Receiving operating characteristic analyses were used to assess improvement in prediction. RESULTS: The area under the curve for a simple clinical assessment score, which included age, sex, family history of diabetes, smoking status, BMI, waist circumference, hypertension and recall of doctor diagnosis of coronary heart disease was 0.765 (0.740, 0.791); sensitivity and specificity in the top quintile of the score were 50.3 and 81.4%, respectively. Addition of simple fasting blood markers HDL cholesterol, triglyceride and glucose improved prediction [area under the curve = 0.817 (0.793, 0.840), P < 0.0001; sensitivity 63.8%; specificity 82.0%]. An alternative model adding blood markers not dependent on fasting yielded similar results. Further addition of C-reactive protein made no improvement. Blood measurements made small differences to reclassification of risk in those in the lowest three quintiles of the non-laboratory score. CONCLUSION: In large population settings, simple clinical assessments could be used in the first instance to identify older adults who would benefit from further testing with routine (non-fasting) blood markers to identify those at most likely to be at elevated diabetes risk.

Assessing prediction of diabetes in older adults using different adiposity measures: a 7 year prospective study in 6,923 older men and women.

AIMS/HYPOTHESIS: The aim of this study was to examine whether waist circumference (WC) or WHR improve diabetes prediction beyond body mass index in older men and women, and to define optimal cut-off points. METHODS: In this prospective study, non-diabetic men (n = 3,519) and women (n = 3,404) aged 60-79 years were followed up for 7 years. There were 169 and 128 incident cases of type 2 diabetes in men and women, respectively. RESULTS: BMI, WC and WHR all showed strong associations with incident type 2 diabetes independent of potential confounders. In men, the adjusted relative risks (top vs lowest quartile) were 4.71 (95% CI 2.45-9.03) for BMI, 3.53 (95% CI 1.92-6.48) for WC and 2.76 (95% CI 1.58-4.82) for WHR. For women, the corresponding relative risks were 4.10 (95% CI 2.16-7.79), 12.18 (95% CI 4.83-30.74) and 5.61 (95% CI 2.84-11.09) for BMI, WC and WHR, respectively. Receiver-operating characteristic curve analysis revealed similar associations for BMI and WC in predicting diabetes in men (AUC = 0.726 and 0.713, respectively); WHR was the weakest predictor (AUC = 0.656). In women, WC was a significantly stronger predictor (AUC = 0.780) than either BMI (AUC = 0.733) or WHR (AUC = 0.728; p < 0.01 for both). Inclusion of both WC and BMI did not improve prediction beyond BMI alone in men or WC alone in women. Optimal sensitivity and specificity for the prediction of type 2 diabetes was observed at a WC of 100 cm in men and 92 cm in women. CONCLUSIONS/INTERPRETATION: In older men, BMI and WC yielded similar prediction of risk of type 2 diabetes, whereas WC was clearly a superior predictor in older women.

Evidence of an accelerating increase in prevalence of diagnosed Type 2 diabetes in British men, 1978-2005.

BACKGROUND: The prevalence of Type 2 diabetes is increasing worldwide; predictions suggest that the disease will reach epidemic proportions this century. This study aims to estimate the extent of the increase in prevalence of diagnosed Type 2 diabetes in British men between 1978 and 2005. METHODS: A representative cohort of 7722 British men aged 40-59 years at entry in 1978-1980 were selected from general practices in 24 British towns. Seven sequential questionnaire surveys were carried out between 1978 and 2005, recording recall of a doctor diagnosis of diabetes at each time point. Logistic regression models with generalized estimating equations were fitted to provide age-adjusted estimates of the calendar year increases in odds of Type 2 diabetes, both overall and for consecutive periods, each of approximately 5 years. RESULTS: The crude prevalence of Type 2 diabetes increased from 1.2% in 1978-1980 to 12.1% in 2005. The age-adjusted average annual increase in Type 2 diabetes prevalence for the 27-year study period was 7.0% [95% confidence interval (CI) 5.4%, 8.6%]. However, the age-adjusted annual rate of increase increased over time, from 4.3% (95% CI 0.4%, 8.2%) between 1979 and 1984 to 11.8% (95% CI 8.4%, 15.4%) between 2003 and 2005; P (trend) = 0.01. The highest annual increases occurred in subjects with higher mean body mass index levels and in towns in Scotland. CONCLUSIONS: The prevalence of Type 2 diabetes has risen substantially in Britain during the last three decades; the recent rate of increase has been almost three times greater than that in the early 1980s.

The metabolic syndrome and cardiovascular risk in the British Regional Heart Study.

OBJECTIVE: To evaluate the metabolic syndrome as an overall risk assessment tool for cardiovascular disease (CVD) and diabetes in middle-aged British men. DESIGN: Prospective study. SUBJECTS: A total of 5128 men aged 40-59 years with no history of CVD or diabetes drawn from general practices in 24 British towns and followed up for 20 years. RESULTS: The metabolic syndrome (National Cholesterol Expert Panel definition) is associated with a significant increase in risk of total CHD (myocardial infarction, angina or CHD death) (relative risk (RR), 95% CI: 1.57, 1.39-1.97), stroke (1.61, 95% CI: 1.26-2.06) and type 2 diabetes (3.57, 95% CI: 2.83-4.50) and is a far stronger predictor of diabetes than of total CHD and stroke in middle-aged men. The metabolic syndrome was inferior to the Framingham Risk Score in predicting total CHD or major CVD over 20 years (area under the curve (AUC) 0.58 vs 0.66 for both CHD and CVD; P<0.0001 for difference) but was superior in predicting diabetes (AUC 0.70 vs 0.60; P<0.001). However, absolute risk of developing CVD or diabetes over 20 years in those with three or more abnormalities was very high, ranging from 41.8% in those with three abnormalities to over a 50% chance in those with four of five abnormalities, comparable to the absolute incidence rates in the top 2 fifths of the Framingham distribution. CONCLUSION: While the initial aim to use the metabolic syndrome to improve risk prediction of CHD has been disappointing, the syndrome identifies patients at high risk of both diabetes and CVD who may derive benefit from lifestyle intervention.

Are social inequalities in mortality in Britain narrowing? Time trends from 1978 to 2005 in a population-based study of older men.

OBJECTIVE: To examine whether social inequalities in all-cause and coronary heart disease (CHD) mortality in Britain have reduced between 1978 and 2005. DESIGN: A prospective study of a socioeconomically representative population. SETTING: 24 British towns. PARTICIPANTS: 7735 Men, aged 40-59 years at recruitment in 1978-1980 and followed up until 2005 through the National Health Service Central Register (164 120 person-years). MAIN OUTCOME MEASURES: Relative hazards and absolute risk differences for all-cause and CHD death comparing manual with non-manual social classes, calculated for different calendar periods. RESULTS: 3009 Deaths from all causes (1003 from CHD) occurred during follow-up. The overall hazard ratio (manual versus non-manual) was 1.56 (95% CI 1.45 to 1.69, p<0.001) for all-cause mortality and 1.54 (95% CI 1.35 to 1.76, p<0.001) for CHD mortality. The relative difference between these social groups tended to increase over time. The overall relative increase in hazard ratio comparing manual with non-manual groups over a 20-year calendar period was 1.22 (95% CI 0.83 to 1.80, p = 0.31) for all-cause mortality and 1.75 (95% CI 0.89 to 3.45, p = 0.11) for CHD mortality. The absolute difference in probability of survival to age 65 years between non-manual and manual groups fell from 29% in 1981 to 19% in 2001 for all-cause mortality and from 17% to 7% for CHD mortality. CONCLUSION: Relative differences in all-cause and CHD mortality between manual and non-manual social class groups persisted and may have increased during this period. Absolute differences in mortality between these social groups decreased as a result of falling overall mortality rates. Greater effort is needed to reduce social inequalities in all-cause and CHD mortality in the new millennium.

Inter-relationships of interleukin-6, cardiovascular risk factors and the metabolic syndrome among older men.

OBJECTIVES: Interleukin-6 (IL-6) has been implicated in the development of cardiovascular disease. We have examined the relationship between plasma IL-6 and insulin resistance, and metabolic, inflammatory and hemostatic markers. METHODS: We examined 3490 men aged 60-79 years who were drawn from general practices in 24 British towns. The men were not diabetic and were not taking warfarin. RESULTS: IL-6 was significantly associated with age, body mass index (BMI), waist circumference (WC), cigarette smoking, low physical activity, social class and alcohol intake (U-shaped). IL-6 showed no association with insulin resistance or its other components (blood glucose, triglycerides, blood pressure) except high-density lipoprotein-cholesterol (inversely), and no association with hematocrit, factor (F) VII or adiponectin after adjustment for age and WC. IL-6 was strongly associated with markers of inflammation (C-reactive protein, fibrinogen, white cell count); plasma viscosity; elevated markers of coagulation (fibrin D-dimer, FVIII, FIX); markers of endothelial dysfunction (von Willebrand factor, tissue plasminogen activator); and to a smaller extent with platelet count, APC ratio and gamma glutamyltransferase. Risk of the metabolic syndrome increased significantly with increasing IL-6 but was attenuated after adjustment for BMI. CONCLUSION: IL-6 may have a potential role as a mediator between cardiovascular risk factors and several biological mechanisms for cardiovascular disease.

Are childhood socio-economic circumstances related to coronary heart disease risk? Findings from a population-based study of older men.

BACKGROUND: The independent influence of childhood social circumstances on health in later life remains uncertain. We examined the extent to which childhood socio-economic circumstances are related to the risk of coronary heart disease (CHD) in older British men, taking account of adult social class and behavioural risk factors. METHODS: A socio-economically representative sample of 5552 British men (52-74 years) with retrospective assessment of childhood socio-economic circumstances (father's occupation and childhood household amenities) who were followed up for CHD (fatal and non-fatal) for 12 years. RESULTS: Men whose childhood social class was manual had an increased hazard ratio (HR) 1.34 (95% CI 1.11-1.63)-this effect was diminished when adjusted for adult social class and adult behavioural risk factors (cigarette smoking, alcohol, physical activity and body weight) (HR 1.19; 95% CI 0.97-1.46). Men whose family did not own a car in their childhood were at increased CHD risk even after adjustments for adult social class and behaviours (HR 1.35, 95% CI 1.04-1.75). Men with combined exposure to both childhood and adult manual social class had the highest risk of CHD (HR 1.51; 95% CI 1.19-1.91); this was substantially reduced by adjustment for adult behavioural risk factors (adjusted HR 1.28; 95% CI 0.99-1.65). CONCLUSIONS: Less affluent socio-economic conditions in childhood may have a modest persisting influence on risk of CHD in later life.

Effects of older age on fibrin D-dimer, C-reactive protein, and other hemostatic and inflammatory variables in men aged 60-79 years.

BACKGROUND: Previous studies have suggested that several hemostatic and inflammatory variables, which are risk predictors for arterial or venous thrombosis, increase with age. However, there is a lack of data from large population studies for reliable estimates of reference ranges. OBJECTIVES: To establish reliable reference ranges of hemostatic and inflammatory variables for 5-year age groups in older men and their implications for pathogenesis and diagnosis. PATIENTS AND METHODS: A total of 3861 men aged 60-79 years at the 20 years follow-up of the British Regional Heart Study. RESULTS: Several variables increased with age. The greatest median increases between 60-64 and 75-79 years age groups were observed for fibrin D-dimer (91%) and C-reactive protein (CRP) (57%). Significant median increases were also observed for von Willebrand factor antigen (23%), tissue plasminogen activator antigen (11%), factor VIII (10%), and fibrinogen (8%). In contrast, levels of classical cardiovascular risk factors neither decreased nor increased substantially with age, with the exception of systolic blood pressure (median increase 10%). CONCLUSIONS: The exponential increases in risk of arterial and venous thrombotic events in men between age 60 and 79 years (when most such events occur) may be related in part to increasing activation of blood coagulation, fibrinolysis, and inflammation; possibly related to the increasing inflammatory burden of both atherosclerotic and non-vascular disease. These increases also have implications for diagnosis of suspected acute venous thromboembolism (D-dimer), and recently proposed screening for prediction of coronary heart disease risk and detection of occult disease (CRP).

Physical activity and mortality in older men with diagnosed coronary heart disease.

BACKGROUND: We have studied the relations between physical activity, types of physical activity, and changes in physical activity and all-cause mortality in men with established coronary heart disease (CHD). METHODS AND RESULTS: In 1992, 12 to 14 years after the initial screening (Q1) of 7735 men 40 to 59 years of age from general practices in 24 British towns, 5934 (91% of available survivors, mean age 63 years) provided further information on physical activity (Q92) and were followed up for 5 years; 963 had a physician's diagnosis of CHD (myocardial infarction or angina). After exclusions, there were 772 men with established CHD, 131 of whom died of all causes. The lowest risks for all-cause and cardiovascular mortality were seen in light and moderate activity groups (adjusted relative risk compared with inactive/occasionally active: light, 0.42 (0.25, 0.71); moderate, 0.47 (0.24, 0.92); and moderately vigorous/vigorous, 0.63 (0.39, 1.03). Recreational activity of >/=4 hours per weekend, moderate or heavy gardening, and regular walking (>40 min/d) were all associated with a significant reduction in all-cause mortality. Nonsporting activity was more beneficial than sporting activities. Men sedentary at Q1 who began at least light activity by Q92 showed lower mortality rates on follow-up than those who remained sedentary (relative risk 0.58, 95% CI 0.33 to 1.03; P:=0.06). CONCLUSIONS: Light or moderate activity in men with established CHD is associated with a significantly lower risk of all-cause mortality. Regular walking and moderate or heavy gardening were sufficient to achieve this benefit.

Hematocrit and risk of NIDDM.

There is limited evidence that raised hematocrit levels may be associated with insulin resistance, which links cardiovascular disease with NIDDM. The association between hematocrit level at screening and the subsequent development of physician-diagnosed NIDDM during 12.8 years of follow-up was examined in a prospective study of 7,735 middle-aged men drawn at random from general practice in 24 British towns. With the exclusion of men with missing hematocrit data and men with diabetes at screening, data were available for 7,193 men, in whom there were 187 new cases of NIDDM during follow-up. The risk of NIDDM increased significantly with increasing hematocrit levels. There was more than a fourfold increase in relative risk (RR) of diabetes among men with a hematocrit of > or = 48% relative to those with a hematocrit <42%, adjusted for age and BMI (RR 4.5; 95% CI 2.5-6.3). On further adjustment for predictors of NIDDM with which hematocrit is correlated, there remained a strong linear association with the risk of diabetes. There was a nearly fourfold increased risk of NIDDM in the highest relative to the lowest hematocrit group in the fully adjusted proportional hazard model (RR 3.6; 95% CI 1.7-7.6). The strong positive association between hematocrit level and risk of diabetes was seen even after exclusion of men with preexisting ischemic heart disease. The findings suggest that a raised hematocrit level, which is a major determinant of whole blood viscosity, should be added to the cluster of risk factors that link NIDDM with atheromatous, vascular disease.

Physical activity, metabolic factors, and the incidence of coronary heart disease and type 2 diabetes.

OBJECTIVE: To examine the role of nonfasting serum insulin level and components of the insulin resistance syndrome in the relationship between physical activity and the incidence of coronary heart disease and type 2 diabetes. METHODS: Prospective study of 5159 men aged 40 to 59 years with no history of coronary heart disease, type 2 diabetes, or stroke drawn from general practices in 18 British towns. During an average follow-up period of 16.8 years, there were 616 cases of major coronary heart disease events (fatal and nonfatal) and 196 incident cases of type 2 diabetes. RESULTS: After adjustment for potential confounders (lifestyle characteristics and preexisting disease), physical activity was inversely related to coronary heart disease rates, with the lowest rates in the men undertaking moderate physical activity and with no further benefit thereafter. For type 2 diabetes, risk decreased progressively with increasing levels of physical activity. Physical activity was associated with serum insulin level and with factors associated with insulin, ie, heart rate, hyperuricemia, diastolic blood pressure, and high-density lipoprotein cholesterol level, and with gamma-glutamyltransferase level, a possible marker of hepatic insulin resistance. Adjustment for insulin and associated factors made little difference to the relationship between physical activity and risk of coronary heart disease. By contrast, these factors together with gamma-glutamyltransferase level appear to explain a large proportion of the reduction in risk of type 2 diabetes associated with physical activity. CONCLUSIONS: The relationship between physical activity and type 2 diabetes appears to be mediated by serum true insulin level and components of the insulin resistance syndrome. However, these factors do not appear to explain the inverse relationship between physical activity and coronary heart disease.

Lifestyle and 15-year survival free of heart attack, stroke, and diabetes in middle-aged British men.

BACKGROUND: To examine the relationship between modifiable lifestyle factors (smoking, physical activity, alcohol intake, and body mass index [BMI]) and the likelihood of 15-year survival free of major cardiovascular end points and diabetes in middle-aged men. METHODS: A prospective study of 7142 men aged 40 to 59 years at screening with no history of coronary heart disease, diabetes, and stroke drawn from 1 general practice in each of 24 British towns and followed up for 15 years. MAIN OUTCOME MEASURES: Death from any cause and a combined end point, including survival free of heart attacks or stroke or the development of diabetes over a follow-up of 15 years for each man. RESULTS: During the 15-year follow-up, there were 1064 deaths from all causes, 770 major heart attacks (fatal and nonfatal), 247 stroke events (fatal and nonfatal), and 252 cases of diabetes among the 7142 men. After adjustment for age and each of the other modifiable lifestyle factors, the risk of the combined end point (death or having a heart attack, stroke, or diabetes) went up significantly with increasing smoking levels and from BMI levels of 26 kg/m2 or higher, and decreased significantly with increasing levels of physical activity up to levels of moderate activity with no further benefit thereafter (heavy smoking vs never: relative risk [RR] [odds], 2.50; 95% confidence interval [CI], 2.12-2.94; BMI > or = 30 vs 20-21.9 kg/m2: RR, 2.11; 95% CI, 1.71-2.62; moderate vs inactive: RR, 0.60; 95% CI, 0.50-0.72). Light drinking (vs occasional) showed a relatively small but significant reduction in risk (RR, 0.84; 95% CI, 0.74-0.96). Using Cox predictive survival models, the estimated probability of surviving 15 years free of cardiovascular events and diabetes in a man aged 50 years ranged from 89% in a moderately active man at BMI levels of 20 to 24.0 kg/m2 who had never smoked to 42% in an inactive smoker with BMI level of 30 kg/m2 or higher. CONCLUSIONS: Modifiable lifestyles (smoking, physical activity, and BMI) in middle-aged men play an important role in long-term survival free of cardiovascular disease and diabetes. These findings should provide encouragement for public health promotion directed toward middle-aged men.

Weight change and duration of overweight and obesity in the incidence of type 2 diabetes.

OBJECTIVE: To examine the relationship between weight change and duration of overweight and obesity and the incidence of type 2 diabetes in a cohort of middle-aged British men. RESEARCH DESIGN AND METHODS: We carried out a prospective study of cardiovascular disease in men aged 40-59 years at screening (1978-1980), drawn from one general practice in 24 British towns, who completed a postal questionnaire 5 years later (Q5) and for whom data on BMI at year 1 (Q1) and Q5 were available (n = 7,100). Men with diabetes at Q1 or Q5 and men with hyperglycemia at Q1 were excluded from the study (n = 184). The main outcome measure was type 2 diabetes (physician-diagnosed) during a mean follow-up period of 12 years starting at Q5 (1983-1985). RESULTS: In the 6,916 men with no history or evidence of diabetes, there were 237 incident cases of type 2 diabetes during the mean follow-up period of 12 years, a rate of 3.2/1,000 person-years. Substantial weight gain (>10%) was associated with a significant increase in risk of type 2 diabetes compared with that in men with stable weight (relative risk [RR] 1.61 [95% CI 1.01-2.56]) after adjustment for age, initial BMI, and other risk factors. Excluding men who developed diabetes within 4 years after the period of weight change increased the risk further (1.81 [1.09-3.00]). After adjustment and exclusion of men who developed diabetes early in the follow-up, weight loss (> or =4%) was associated with a reduction in the risk of type 2 diabetes, compared with that in the stable group, that reached marginal significance (0.65 [0.42-1.03], P = 0.07). A test for trend that fitted weight change as a continuous covariate showed the risk of diabetes to increase significantly from maximum weight loss to maximum weight gain (P = 0.0009). The lower risk associated with weight loss was seen in obese (> or =28 kg/m2) and nonobese subjects and in men with normal (<6.1 mmol/l) and high (> or =6.1 mmol/l) nonfasting blood glucose levels. Although not statistically significant, this is consistent with a benefit from weight loss. Risk of type 2 diabetes increased progressively and significantly with increasing levels of initial BMI and also with the duration of overweight and obesity (P<0.0001). CONCLUSIONS: This study confirms the critical importance of overweight and obesity, particularly of long duration, in the development of type 2 diabetes. The data support current public health recommendations to reduce the risk of type 2 diabetes by preventing weight gain in middle-aged men who are not overweight and by encouraging weight loss in overweight and obese men.

Prospective study of serum gamma-glutamyltransferase and risk of NIDDM.

OBJECTIVE: Serum gamma-glutamyltransferase (GGT) levels are raised in obese individuals, and a particularly strong association with central obesity has been described. We hypothesized that elevated GGT levels are a marker for visceral fat, and specifically for hepatic steatosis (fatty liver), and that hepatic steatosis leads to hepatic insulin resistance. To test this hypothesis, we examined the association between GGT levels and risk of NIDDM. RESEARCH DESIGN AND METHODS: We carried out a prospective cohort study of incident cases of doctor-diagnosed NIDDM in a group of 7,458 nondiabetic men (aged 40-59 years) followed for a mean of 12.8 years (range 11.5-13.0). The men were randomly selected from general practice lists in 24 British towns. Cases of NIDDM were ascertained by repeated postal questionnaires to the men and by regular systematic review of primary care records. RESULTS: A total of 194 men developed NIDDM during follow-up. Mean serum GGT at baseline (geometric mean [95% CI]) was significantly higher in the NIDDM patients than in the rest of the cohort (20.9 [19.3-22.6] vs. 15.3 U/l [15.0-15.6], P < 0.0001). There was a smooth, graded increase in the age-adjusted risk of NIDDM with increasing GGT levels, with a relative risk in the top fifth of the distribution of 6.8 (3.5-12.9) relative to the bottom fifth (trend P < 0.0001). This association was independent of serum glucose and BMI and of other predictors of NIDDM with which GGT is associated, including alcohol intake and physical activity level (adjusted upper to lower fifth relative risk: 4.8 [2.0-11.8], trend P < 0.0001]). CONCLUSIONS: These findings suggest that a raised serum GGT level is an independent risk factor for NIDDM. Serum GGT level may be a simple and reliable marker of visceral and hepatic fat and, by inference, of hepatic insulin resistance.