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Objective: To determine how much physical activity (PA) is needed to protect against diabetes onset in older adults, whether protection is greater among overweight individuals, and whether taking up moderate activity in later life is beneficial.Research Design and Methods: Men (4,252) from a U.K. population-based cohort self-reported usual PA (regular walking and cycling, recreational activity, and sport) in 1996 and in 1998-2000, alongside other health behaviors and medical history. Fasting blood lipids were measured. Median follow-up was 7.1 years, during which 135 cases of type 2 diabetes (validated self-report) occurred.Results: Among 3,012 men free from cardiovascular disease and diabetes in 1998-2000, 9% reported no usual leisure-time PA, 23% occasional PA, and 15% vigorous PA. Compared with men reporting no activity, men reporting occasional, light, moderate, moderately vigorous, and vigorous PA had lower diabetes risks: hazard ratio (HR) 0.58 (95% CI 0.33-1.02), 0.39 (0.20-0.74), 0.38 (0.19-0.73), 0.39 (0.20-0.77), and 0.33 (0.16-0.70), respectively; P (trend) = 0.002, adjusted for age, social class, tobacco, alcohol, diet, and blood lipids. Adjustment for BMI, waist circumference, or fasting insulin attenuated HRs. HRs were stronger in men with BMI ≥28 vs. <28 kg/m(2) (interaction P = 0.02). Compared with men reporting light activity or less in 1996 and 2000, men who became at least moderately active by 2000 or remained at least moderately active at both times had adjusted HRs of 0.62 (0.34-1.12) and 0.51 (0.31-0.82), respectively.Conclusions: Even light PA markedly reduced diabetes risk in older men, especially among the overweight or obese. Taking up or maintaining at least moderate PA in older adulthood strongly protected against diabetes. [ABSTRACT FROM AUTHOR]

Objective: To estimate the extent to which increasing BMI may explain the rise in type 2 diabetes incidence in British men from 1984 to 2007.Research Design and Methods: A representative cohort ratio of 6,460 British men was followed-up for type 2 diabetes incidence between 1984 (aged 45-65 years) and 2007 (aged 67-89 years). BMI was ascertained at regular intervals before and during the follow-up.Results: Between 1984-1992 and 1999-2007, the age-adjusted hazard of type 2 diabetes more than doubled (hazard ratio 2.33 [95% CI 1.75-3.10]). Mean BMI rose by 1.42 kg/m(2) (95% CI 1.10-1.74) between 1984 and 1999; this could explain 26% (95% CI 17-38) of the type 2 diabetes increase.Conclusions: An appreciable portion of the rise in type 2 diabetes can be attributed to BMI changes. A substantial portion remains unexplained, possibly associated with other determinants such as physical activity. This merits further research. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between dietary fiber and the risk of type 2 diabetes in older men and the role of hepatic and inflammatory markers.Research Design and Methods: The study was performed prospectively and included 3,428 nondiabetic men (age 60-79 years) followed up for 7 years, during which there were 162 incident cases of type 2 diabetes.Results: Low total dietary fiber (lowest quartile < or =20 g/day) was associated with increased risk of diabetes after adjustment for total calorie intake and potential confounders (relative risk -1.47 [95% CI 1.03-2.11]). This increased risk was seen separately for both low cereal and low vegetable fiber intake. Dietary fiber was inversely associated with inflammatory markers (C-reactive protein, interleukin-6) and with tissue plasminogen activator and gamma-glutamyl transferase. Adjustment for these markers attenuated the increased risk (1.28 [0.88-1.86]).Conclusions: Dietary fiber is associated with reduced diabetes risk, which may be partly explained by inflammatory markers and hepatic fat deposition. [ABSTRACT FROM AUTHOR]

Objective: To examine whether adult social class and childhood social class are related to metabolic syndrome in later life, independent of adult behavioral factors.Research Design and Methods: This was a population-based cross-sectional study comprising 2,968 men aged 60-79 years.Results: Adult social class and childhood social class were both inversely related to metabolic syndrome. Mutual adjustment attenuated the relation of metabolic syndrome with childhood social class; that with adult social class was little affected. However, the relation with adult social class was markedly attenuated by adjustment for smoking status, physical activity, and alcohol consumption. High waist circumference was independently associated with adult social class.Conclusions: The association between adult social class and metabolic syndrome was largely explained by behavioral factors. In addition, central adiposity, a component of metabolic syndrome, was associated with adult social class. Focusing on healthier behaviors and obesity, rather than specific efforts to reduce social inequalities surrounding metabolic syndrome, is likely to be particularly important in reducing social inequalities that affect people with coronary disease. [ABSTRACT FROM AUTHOR]

Objective: We prospectively examined the relationship between lung function and risk of type-2 diabetes and fatal and nonfatal coronary heart disease (CHD) events and investigated the hypothesis that inflammation may underlie these associations., Research Design and Methods: A prospective study of 4,434 men aged 40-59 years with no history of cardiovascular disease (CHD or stroke) or diabetes drawn from general practices in 24 British towns and followed up for 20 years., Results: There were 680 major CHD events (276 fatal, 404 nonfatal) and 256 incident type 2 diabetes during the 20 years follow-up. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) but not FEV(1)-to-FVC ratio were significantly and inversely associated with incident type 2 diabetes and fatal CHD events (not nonfatal events) after adjustment for age, potential confounders, and metabolic risk factors. The adjusted relative risk (RR) for type 2 diabetes (Quartile 1 vs. Quartile 4) were 1.59 (1.07-2.56) and 1.74 (1.16-2.61) for FVC and FEV(1), respectively (P = 0.03 and P = 0.04 for trend). The corresponding RR for fatal CHD were 1.48 (1.00-2.21) and 1.81 (1.19-2.76) (P = 0.002 and P = 0.0003 for trend). Lung function was significantly and inversely associated with C-reactive protein and interleukin-6; the inverse associations with type 2 diabetes for FVC and FEV(1) were attenuated after further adjustment for these factors (P = 0.14 and P = 0.11 for trend) but remained significant for fatal CHD (P = 0.03 and P = 0.01, respectively)., Conclusions: Restrictive rather than obstructive impairment of lung function is associated with incident type 2 diabetes (and fatal CHD) with both associations partially explained by traditional and metabolic risk factors and inflammation.

Objective: The objective of this study was to assess the relationship between putative markers of endothelial dysfunction (tissue plasminogen activator [t-PA] antigen and von Willebrand factor [vWF] antigen) and development of type 2 diabetes, as well as the role of inflammation, adipokines, hepatic function, and insulin resistance in modifying these relationships., Research Design and Methods: This was a prospective study of 3,562 nondiabetic men aged 60-79 years followed up for an average of 7 years during which there were 162 incident cases of type 2 diabetes., Results: Elevated t-PA (top third) was associated with a near threefold increase in risk of diabetes compared with the risk in those in the bottom third after adjustment for lifestyle factors and waist circumference (relative risk [RR] 2.98 [95%CI 1.79-5.00]; P(trend) < 0.0001); weaker but significant (marginal) associations were seen with vWF (1.24 [0.83-1.85]; P = 0.05 for trend). Both biomarkers of endothelial dysfunction correlated significantly with markers of inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]), hepatic function (gamma-glutamyl transferase [GGT]), and insulin resistance, with t-PA showing stronger associations with adiposity, hepatic function, and insulin resistance than vWF. t-PA was also significantly and inversely associated with adiponectin. Adjustment for IL-6, adiponectin, and GGT attenuated the association of incident diabetes with vWF (1.06 [0.71-1.60]), but the relationship seen with t-PA remained significant (adjusted RR 2.19 [1.29-3.70]). Subsequent adjustment for insulin attenuated the association further, but t-PA was still associated with a significant increase in risk (1.66 [0.96-2.85]; P(trend) = 0.02)., Conclusion: t-PA antigen, but not vWF antigen, is independently associated with risk of type 2 diabetes.

Objective: The aim was to assess the relationship between adipokines, including interleukin (IL)-6, leptin, and adiponectin, with development of type 2 diabetes and assess the role of obesity and insulin resistance in these relationships., Research Design and Methods: We conducted a prospective study of 3,599 nondiabetic men aged 60-79 years and followed up for a mean period of 5 years, during which time there were 108 incident cases of type 2 diabetes., Results: Elevated IL-6, leptin, and low adiponectin were associated with increased risk of type 2 diabetes even after adjustment for BMI, lifestyle factors, preexisting cardiovascular disease, and systolic blood pressure. The relative risks (RRs) (top vs. bottom third) were 2.02 (95% CI 1.14-3.58) for IL-6, 1.91 (0.97-3.76) for leptin, and 0.40 (0.23-0.70) for adiponectin. Further adjustment for insulin resistance made minor differences to the IL-6 diabetes relationship (adjusted RR 2.12 [1.18-3.81]), weakened the associations with adiponectin (0.59 [0.33-1.04]), and abolished the association between leptin and diabetes (1.12 [0.55-2.26]). The inverse relation between low adiponectin and diabetes was significantly stronger in men who were obese (waist circumference > 102 cm or BMI > or = 30 kg/m2) (0.30 [0.11-0.79]) relative to leaner men (0.93 [0.44-1.96]) (test for interaction P = 0.04)., Conclusions: The association between leptin and incident diabetes is mediated by insulin resistance. By contrast, the positive association between IL-6 and diabetes appeared to be independent of obesity and insulin resistance. Finally, the association between low adiponectin and increased risk of diabetes appears to be significantly stronger in obese men than in leaner counterparts.

Objective: We have examined the relationship between hepatic enzymes, the metabolic syndrome, insulin resistance, and type 2 diabetes and assessed the potential of hepatic enzyme measurements in determining diabetes risk., Research Design and Methods: We conducted a prospective study of 3,500 nondiabetic men aged 60-79 years who were followed-up for a mean period of 5 years and in whom there were 100 incident type 2 diabetes cases., Results: In cross-sectional analyses, alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were strongly associated with obesity, insulin resistance, and the metabolic syndrome. Prospectively, the risk of type 2 diabetes significantly increased with increasing levels of ALT and GGT even after adjustment for confounders including BMI (top versus bottom quarter ALT: relative risk 2.72 [95% CI 1.47-5.02]; GGT: 3.68 [1.68-8.04]). Additional adjustment for insulin resistance attenuated the effects, but the relationships with ALT and GGT remained significant (1.91 [1.01-3.60] and 2.69 [1.21-5.97], respectively). Further adjustment for inflammatory markers (C-reactive protein) made minor differences. Among high-risk subjects (obese men or those with the metabolic syndrome), elevated GGT and ALT enhanced the prediction of diabetes risk., Conclusions: Elevated levels of ALT and GGT within the normal range are independent predictors of type 2 diabetes in older men and are useful additional measures in identifying those at high risk of diabetes.

Objective: To examine the effects of cigarette smoking, giving up smoking, and primary or secondary pipe or cigar smoking on the risk of type 2 diabetes., Research Design and Methods: A prospective study followed 7,735 men aged 40-59 years from general practices in 24 British towns for an average of 16.8 years. Incident cases of physician-diagnosed diabetes were ascertained by repeated postal questionnaires and systematic reviews of primary care records., Results: A total of 290 incident cases of diabetes were found in 7,124 men with no history of diabetes, coronary heart disease, or stroke. Cigarette smoking was associated with a significant increase in risk of diabetes, even after adjustment for age, BMI, and other potential confounders. The benefit of giving up smoking was only apparent after 5 years of smoking cessation, and risk reverted to that of never-smokers only after 20 years. The risk of diabetes in those who switched from smoking cigarettes to pipe or cigars remained equal to the risk in continuing cigarette smokers. Men who gave up smoking during the first 5 years of follow-up showed significant weight gain and subsequently higher risk of diabetes than continuing smokers., Conclusions: Cigarette smoking is an independent and modifiable risk factor for type 2 diabetes. Smoking cessation is associated with weight gain and a subsequent increase in risk of diabetes, but in the long term, the benefits of giving up smoking outweigh the adverse effects of early weight gain.

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.

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.

Objective: To assess the relationship between self-reported frequency of participation in sporting activity and the prevalence of hyperglycemia (nonfasting glucose level > or = 7.8 mM) in middle-aged men., Research Design and Methods: We used a cross-sectional study of 7617 British middle-aged men, drawn from 24 general practices in England, Wales, and Scotland, who were participants in the British Regional Heart Study. The response rate was 78%. Patients with diabetes (physician-diagnosed) were excluded from our analysis. Frequency of participation in sporting activity was determined by the respondents and reported as none (61%), occasionally (12%), or frequently (27%)., Results: The age-adjusted prevalence odds ratio for hyperglycemia was 0.86 (95% confidence interval, 0.6-1.2) in those reporting occasional, and 0.62 (95% confidence interval, 0.4-0.85) in those reporting frequent sporting activity, compared with those reporting none. This effect of frequent sporting activity on the prevalence of hyperglycemia was independent of body mass index, occupational status, smoking status, systolic blood pressure, use of antihypertensive therapy, and time of sampling., Conclusions: Frequent sporting activity in middle-aged men is associated with a reduced prevalence of hyperglycemia and may reduce the risk of NIDDM.