Tedd L. Mitchell

The Association between Cardiorespiratory Fitness and Impaired Fasting Glucose and Type 2 Diabetes Mellitus in Men

Type 2 diabetes is a common disease in industrialized countries. It is a major cause of cardiovascular disease and all-cause mortality (1-6), and its prevalence has increased continuously over the past few decades (1). The American Diabetes Association currently defines impaired fasting glucose as a fasting plasma glucose level from 6.1 to 6.9 mmol/L (110 to 125 mg/dL) and type 2 diabetes as a fasting plasma glucose level of 7.0 mmol/L (126 mg/dL) or more (1). Data from several prospective studies show an inverse association between physical activity and diabetes (7-13). However, these studies are limited by the use of self-reporting of physical activity and presence of type 2 diabetes (7-12). Self-reporting of physical activity tends to be imprecise, and type 2 diabetes is undiagnosed in about 50% of the prevalent cases (14). This leads to misclassification on both exposure and outcome measures (15). These limitations may result in underestimation of the true association between sedentary habits and risk for type 2 diabetes. Impaired fasting glucose is a strong predictor of type 2 diabetes, cardiovascular disease, and other diabetic complications (6, 16-18). The underlying cause of impaired fasting glucose is unknown, and no prospective study of the association between physical activity and impaired fasting glucose has been published. We examined the relation of cardiorespiratory fitness, objectively determined by a maximal exercise test on a treadmill, to the incidence of impaired fasting glucose and type 2 diabetes. Cases of impaired fasting glucose and diabetes at baseline and follow-up were determined by using the American Diabetes Associations current guidelines (1). Methods Patients In our population-based prospective study, we included 8633 men 30 to 79 years of age at baseline (mean, 43.5 years) who completed at least two medical evaluations at the Cooper Clinic in Dallas, Texas, from 1970 to 1995. Patients come to the Cooper Clinic for preventive medical examinations and health promotion counseling. Many are sent by their employers for these services, some are referred by their personal physicians, and others are self-referred. More than 97% of the patients are white, and most are employed in executive or professional occupations. More than 75% are college graduates. Although study participants came from middle and upper socioeconomic strata, they were similar to other well-characterized population-based cohorts in terms of blood pressure, cholesterol level, body weight, and cardiorespiratory fitness (19). The study was reviewed and approved annually by the institutional review board at the Cooper Institute for Aerobics Research. Additional details of the study methods and population characteristics of the cohort have been published elsewhere (20, 21). Because clinical or subclinical heart disease and other conditions associated with type 2 diabetes may alter the level of physical activity and thus cardiorespiratory fitness, we excluded men with an abnormal resting or exercise electrocardiogram or a history of heart attack, stroke, or cancer at the baseline clinical examination (n=2350). The baseline evaluation was performed after participants gave written informed consent for the initial medical examination and registration in the follow-up study. Examinations were done after patients had fasted for at least 12 hours and included personal and family health histories, a questionnaire on demographic characteristics and health habits, a physical examination, an exercise test, anthropometric measurement, electrocardiography, blood chemistry analyses, and blood pressure measurement. Technicians who followed a standard manual of operations administered all procedures. Impaired fasting glucose and type 2 diabetes were diagnosed according to American Diabetes Association criteria that define impaired fasting glucose as a fasting plasma glucose level of 6.1 to 6.9 mmol/L (110 mg/dL to 125 mg/dL) and diabetes as a fasting plasma glucose level of 7.0 mmol/L (126 mg/dL) or more (1). Patients who did not meet these criteria but who reported a history of diabetes or current therapy with oral antidiabetic agents or insulin were also considered to have diabetes. We excluded patients who had diabetes at baseline according to any of these criteria (n=377). Cardiorespiratory fitness was assessed with a maximal exercise test that followed a modified Balke protocol (22). Details of treadmill speed and elevation have been described elsewhere (20, 21). Briefly, the test began with the patient walking on a horizontal treadmill at 88 m/min. After the first minute, the elevation increased to 2%; the elevation then increased 1% each minute up to 25 minutes. For the few patients who were still able to continue, the elevation was held constant after 25 minutes and the speed was increased by 5.4 m/min until the patient reached volitional fatigue. Use of this protocol for the exercise test correlates highly (r=0.92) with measured maximal oxygen uptake (23). All patients in our study achieved at least 85% of their age-predicted maximal heart rate; average maximal heart rates ( SD) in each age group were 186 11 beats/min for patients 30 to 39 years of age, 179 12 beats/min for those 40 to 49 years of age, 172 13 beats/min for those 50 to 59 years of age, and 162 17 beats/min for those 60 years of age or older. Average maximal heart rates in each age group exceeded the age-predicted rate (220 beats/min age in years), which indicates that the exercise test can be considered maximal performance. We defined level of fitness by total time on the treadmill at the baseline examination, as in our previous studies (20, 21). Treadmill times were placed in frequency distributions for specific age groups (30 to 39, 40 to 49, 50 to 59, or 60 or more years of age). The least fit 20% of the participants in each age group were classified as low fitness, the next 40% as moderate fitness, and the remaining 40% as high fitness. The respective cut-points for total treadmill time in the low-, moderate-, and high-fitness groups were 945 seconds or less, 946 to 1259 seconds, and 1260 seconds or more for patients 30 to 39 years of age; 849 seconds or less, 850 to 1020 seconds, and 1021 seconds or more for patients 40 to 49 years of age; 750 seconds or less, 751 to 1035 seconds, and 1036 seconds or more for patients 50 to 59 years of age; and 644 seconds or less, 645 to 953 seconds, and 954 seconds or more for patients 60 years of age or older. These cut-points at the 20th and 60th percentiles to define fitness levels were used in previous studies (20, 21) and were selected before analysis for our investigation. However, we calculated these cut-points with patients in the current study, from which unhealthy persons were excluded. Therefore, they differ somewhat from the cut-points derived from the entire cohort of the Aerobics Center Longitudinal Study (21). For some analyses, such as the models that included change in fitness from baseline to follow-up, cardiorespiratory fitness was expressed as maximal metabolic units (metabolic equivalents [METs], calculated as the working metabolic rate/resting metabolic rate; 1 MET is equivalent to an oxygen uptake of 3.5 mL1 kg1) achieved on the exercise test. In other analyses, time on the treadmill was used as a continuous variable. Serum samples were analyzed by using automated techniques in a laboratory that participates in the Centers for Disease Control and Prevention Lipid Standardization Program. Blood pressure was measured by using auscultatory methods with a mercury sphygmomanometer. We defined high blood pressure as systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or a history of hypertension. Height and weight were measured with a standard physicians scale and stadiometer, and body mass index was calculated as weight in kg/height in m2. Waist circumference was measured with a standard anthropometric tape. Statistical Analysis We used SAS statistical software for data analyses (24). The incidence of impaired fasting glucose was calculated for men with normal fasting glucose at baseline, and the incidence of diabetes was based on data from all 8633 patients. For analyses with impaired fasting glucose as the outcome, we excluded 1122 men who had impaired fasting glucose at baseline and an additional 69 men who had normal fasting plasma glucose at baseline but developed diabetes during follow-up. Rates of impaired fasting glucose or diabetes were calculated by dividing the number of incident cases during the study period by the number of person-years over the same period. We defined the study period as the interval between the baseline examination and the last follow-up visit. We used logistic regression to estimate the association between dependent variables and independent variables after adjustment for possible confounding factors. We used general linear models to study the cross-sectional association of fitness level and parental history of diabetes (24, 25). To account for the possible cohort effect of baseline year, we examined the relation between incident cases and baseline year and found no association. We used tests for ordinal linear trend to evaluate the possible relation of higher treadmill time with risk for impaired fasting glucose or diabetes after dividing the sample into the three fitness groups. All P values are two-sided, and those less than 0.05 were considered statistically significant. Role of the Funding Source The funding agencies did not participate in the collection, analysis, or interpretation of data presented in this report or in the decision to submit the manuscript for publication. Results During an average follow-up of 6.1 4.8 years (range, 1 to 24.8 years) that included 52 588 person-years, 593 men developed impaired fasting glucose and 149 developed diabetes. Of the men with incident diabetes, 139 (93%) were not aware of their

Maximal exercise test as a predictor of risk for mortality from coronary heart disease in asymptomatic men

Exercise testing in asymptomatic persons has been criticized for failing to accurately predict those at risk for coronary heart disease (CHD). Previous studies on asymptomatic subjects, however, may not have been large enough or long enough to provide reliable outcome measures. This study examines the ability of a maximal exercise test to predict death from CHD and death from any cause in a population of asymptomatic men. This is a prospective longitudinal study performed between 1970 and 1989, with an average follow-up of 8.4 years. The subjects are 25,927 healthy men, 20 to 82 years of age at baseline (mean 42.9 years) who were free of cardiovascular disease and who were evaluated in a preventive medicine clinic. The main outcome measures are CHD mortality and all-cause mortality. During follow-up there were 612 deaths from all causes and 158 deaths from CHD. The sensitivity of an abnormal exercise test to predict coronary death was 61%. The age-adjusted relative risk of an abnormal exercise test for CHD death was 21 (6.9 to 63.3) in those with no risk factors, 27 (10.7 to 68.8) in those with 1 risk factor, 54 (21.5 to 133.7) in those with 2 risk factors, and 80 (30.0 to 212. 5) in those with >/=3 factors. A maximal exercise test performed in asymptomatic men free of cardiovascular disease does appear to be a worthwhile tool in predicting future risk of CHD death. An abnormal exercise test is a more powerful predictor of risk in those with than without conventional risk factors.

Low Fasting Plasma Glucose Level as a Predictor of Cardiovascular Disease and All-Cause Mortality

BACKGROUND Although medical textbooks usually classify fasting plasma glucose <70 or 80 mg/dL (<3.89 or 4.44 mmol/L) as abnormal, the prognosis for patients with low fasting plasma glucose is unclear. METHODS AND RESULTS We conducted prospective cohort studies among 40 069 men and women to investigate the association between fasting plasma glucose levels and cardiovascular disease and all-cause mortality. We documented a U-shaped relation between fasting plasma glucose and mortality. In addition to diabetes and impaired fasting glucose levels, low fasting plasma glucose levels were also associated with high mortality. After multivariate adjustment for age, sex, study population, ethnicity, current smoking status, high blood pressure, total cholesterol, body mass index, triglycerides, history of cardiovascular disease and cancer, and a family history of cardiovascular disease, patients with fasting plasma glucose <70 mg/dL (<3.89 mmol/L) had a 3.3-fold increased risk of cardiovascular disease mortality, and patients with fasting plasma glucose 70 to 79 mg/dL (3.89 to 4.43 mmol/L) had a 2.4-fold increased risk compared with the risk in patients with fasting plasma glucose 80 to 109 mg/dL (4.44 to 6.05 mmol/L) (tests for trend P<0.0001). Participants with low fasting plasma glucose levels also had increased risk of all-cause mortality (test for trend P<0.0001). CONCLUSIONS Participants with low fasting plasma glucose levels had a high risk of cardiovascular disease and all-cause mortality.

Relation of the Number of Metabolic Syndrome Risk Factors With All-Cause and Cardiovascular Mortality

The metabolic syndrome (MS) is a constellation of risk factors associated with diabetes and cardiovascular disease. This syndrome consists of at least 3 parameters assessing central obesity, hypertension, high-density lipoprotein cholesterol, triglycerides, and impaired glucose metabolism. Whether persons with 4 or 5 risk factors are at higher risk than those with 3 risk factors is unclear. Also unclear is whether those without the MS but with 1 or 2 risk factors warrant therapy. We assessed cardiovascular and all-cause mortality as a function of the number of these risk factors. We followed 30,365 men for a median follow-up of 13.6 years. During follow-up, 1,449 participants died, 527 from cardiovascular causes. All of the individual parameters defining the MS were significantly associated with both all-cause and cardiovascular mortality (p <0.001). After adjustment for age and the other MS variables, hypertension was the most potent risk factor whereas central obesity and hypertriglyceridemia remained associated with both all-cause and cardiovascular mortality. A highly significant trend was also noted between both all-cause or cardiovascular mortality and the number of risk factors (p <0.001 for trend). Risk increased incrementally, beginning at 1 risk factor for cardiovascular mortality and at 2 risk factors for all-cause mortality. In conclusion, there is a continuum of risk as the number of metabolic syndrome risk factors increases. These findings add to the growing evidence that central obesity can independently and adversely affect health.

Age- and sex-based nomograms from coronary artery calcium scores as determined by electron beam computed tomography

We present data for 18,785 patients undergoing electron beam computed tomography, dividing them by sex and age (using 5-year age increments) to determine coronary artery calcium scores representing the 50th and 75th percentiles for each group. Because risk stratification is an integral part of determining therapies for coronary artery disease, age- and sex-based scores may be more clinically useful than total coronary artery calcium scores alone.

Review of the role of exercise in improving quality of life in healthy individuals and in those with chronic diseases.

The use of exercise for improving health has been the subject of research for several decades. Studies have shown unequivocally that exercise is beneficial for preventing and/or treating numerous medical conditions. With the U.S. population increasing in age, use of exercise to ameliorate the effect of illnesses related to aging is therefore of great potential value. Despite this information, most members of the population do not incorporate physical activity into their daily routine. Because aging often is associated with diminished quality of life, we reviewed the literature to assess whether exercise is of value in maintaining a persons functional capacity as he or she ages. Available data suggest a positive relationship between higher levels of fitness and higher functional state/improved quality of life, both in healthy individuals and in those experiencing specific ailments commonly seen in an aging population.

Incidental detection of preclinical renal tumors with electron beam computed tomography: report of 26 consecutive operated patients.

Purpose The purpose of this work was to describe the positive predictive value of electron beam CT (EBCT) for diagnosis of solid renal tumors. Method Among 11,932 consecutive patients undergoing screening EBCT, 27 cases met EBCT criteria for solid renal tumors. Twenty-six of 27 patients underwent surgery. Results Surgical pathology identified 25 solid renal tumors and 1 adrenal hemorrhage with thrombus. Twenty tumors were classified as T1N0M0, one was T2N0M0, and one was T3aN0M0. All tumor patients are clinically well at 1–41 months (mean 17 months) postoperatively. None of the patients had clinical signs or symptoms characteristic of renal malignancy. Conclusion EBCT is an effective tool for detection of solid renal tumors in a healthy outpatient population (positive predictive value 0.96). The detection rate is low [0.2% (26/11,932) at our facility] in patients undergoing EBCT for other indications. The cost-effectiveness and sensitivity of this technique for solid renal tumor detection among various populations remain to be determined.

Observations ‐ Fit to lead: is fitness the key to effective executive leadership?

This article describes the importance of fitness (chiefly exercise) for top ranking executive leaders and for their respective organizations. The authors discuss how fitness can contribute to stamina, mental clarity, ability to cope with stress and a variety of other factors that can affect an executive’s ability to lead. The authors support this premise by drawing on key research studies and actual accounts of top executives from a variety of business organizations. The authors feature information obtained from direct interviews with the year 2000 USA presidential candidates, Al Gore and George W. Bush. The authors view them as high profile models of how fitness can be given high priority for maintaining personal effectiveness for even the busiest executive leaders.

Controlling blood lipids part 1: a practical role for diet and exercise.

Dietary measures that can improve blood lipids include limiting consumption of saturated fats, trans fatty acids, simple sugars, and stearic acid and consuming adequate amounts of vitamins C and E and beta-carotene. Eating certain fish once a week may significantly lower the risk of sudden cardiac death. Aerobic exercise three times per week for 20 to 30 minutes at 60% to 80% of the age-predicted maximum heart rate may also improve lipid levels. Research indicates that modest fitness reduces overall mortality, and higher levels benefit those who have abnormally high cholesterol. Moderate alcohol consumption may influence a persons lipid profile favorably but is not recommended for nondrinkers.

Controlling blood lipids : Part 2 : When and how to use medication

Drug treatment for abnormal blood lipids includes bile acid sequestrants, fibric acid derivatives, statins, and niacin. Statins generally offer the best combination of safety and effectiveness. Hormone replacement therapy reduces the risk of coronary artery disease in postmenopausal women. The National Cholesterol Education Program offers clear guidelines as to what levels of low-density lipoprotein cholesterol (LDL-C) should trigger consideration of drug treatment, and the authors suggest what levels of high-density lipoprotein cholesterol should prompt treatment. Measurements of small dense LDL-C and lipoprotein(a) may also be helpful in decisions about drug treatment for selected patients.