Novel resistin promoter polymorphisms: association with serum resistin level in Japanese obese individuals.

OBJECTIVES: Resistin, an adipocyte-secreted cytokine recently discovered in mice, has been proposed as a link between obesity and diabetes. We analyzed resistin gene polymorphisms and examined their association with serum resistin level and obesity phenotypes in humans. SUBJECTS AND METHODS: Sixty young, obese, non-diabetic subjects taking no medication were studied. DNA sequencing and genotyping of identified single nucleotide polymorphisms were performed. Associations between polymorphisms and serum resistin level, BMI, body composition, fat distribution, and several indices of insulin sensitivity were examined. Moreover, single nucleotide polymorphisms in the promoter region were examined for their influence on resistin gene transcriptional activity using luciferase reporter vectors. RESULTS: Ten non-coding single nucleotide polymorphisms were found. The -638G>A, -420C>G, and -358G>A polymorphisms in the promoter region showed marked linkage disequilibrium with each other, and were associated with serum resistin level; however, there was no association between these polymorphisms and parameters related to adiposity or insulin resistance. The results of luciferase assay revealed that -638G>A together with the -420C>G polymorphism influenced resistin gene transcriptional activity. CONCLUSION: We found that variability in the serum resistin level might be related to polymorphic variants of the promoter region of the gene.

Ethnic differences in abdominal visceral fat accumulation between Japanese, African-Americans, and Caucasians: a meta-analysis.

A meta-analysis was performed in order to test the hypothesis that Japanese have a greater amount of abdominal visceral fat (AVF) relative to abdominal subcutaneous fat (ASF) than Caucasians. Data were derived from published studies that included mean values for AVF and ASF areas, measured using computed tomography, and age for native Japanese, African-Americans, and Caucasians of both genders. Mean values from each study were used as single data points. A significant difference in AVF was observed between Japanese and Caucasian populations after adjusting for ASF, age, and sex ( p<0.05). However, the difference in AVF between Japanese and Caucasian females was lower than that between African-American and Caucasian females.

Recognition of left ventricular hypertrophy in new recruits of professional sumo wrestling.

The efficacy of electrocardiography (ECG) in the diagnosis of left ventricular (LV) hypertrophy in 890 males, newly recruited to Japanese professional sumo wrestling (15.9 +/- 1.8 years of age, 177.8 +/- 4.7cm, 107.3 +/- 4.7kg), was tested by comparing simple, widely employed ECG criteria (Sokolow-Lyon chest and limb lead voltages and Cornell voltage with repolarisation criteria) with echocardiographic evaluations of LV mass indexed to body surface area. LV hypertrophy was defined as a LV mass index > 2 SD above the mean value obtained from 115 age-matched, normotensive, sedentary, male controls. The prevalence of LV hypertrophy as determined by echocardiography was 9.0% the entire group and was 8.3% among the 484 normotensives. The sensitivities of the three ECG criteria were < or = 36.0%, and their specificities were 70.0-99.0%. In contrast to the Sokolow-Lyon chest lead criteria, the diagnostic performance of the Cornell criteria was little affected by body mass index (BMI), and stepwise regression revealed that BMI did not significantly correlate with Cornell voltage. Still, the diagnostic efficacy of ECG was not sufficient to merit its use for primary recognition of LV hypertrophy among professional sumo wrestlers. Indeed, LV hypertrophy will likely go undetected by ECG in most overweight muscular athletes.

Fortuitously discovered persistent left superior vena cava in young competitive athletes. Clinical implications of sports physicians.

This report describes two athletes with persistent left superior vena cava (PLSVC) accidentally identified during preparticipation medical evaluation. The clinical implications of PLSVC for sports physicians are also discussed. A 16-year-old male ice hockey player and an 18-year-old male high-level field hockey player visited our institute for medical evaluation prior to participating in competition. Neither complained of palpitation, faintness or syncope, which would have suggested a possible cardiac rhythm disturbance, or had been informed of any abnormalities in previous physical examinations. Nonetheless, echocardiography revealed dilated coronary sinuses, and venography confirmed PLSVC and, in one case, showed the absence of the right superior vena cava. Electrocardiograms showed the field hockey player to have an ectopic atrial rhythm with left axis deviation of the frontal plane P-wave and the ice hockey player to have normal sinus rhythm. Symptom-limited treadmill testing revealed nothing abnormal, and after explaining the possible rhythm instability and the potential risk associated with cardiac surgery, the subjects were permitted full participation in competitive sports. Although information is scarce, available data on PLSVC suggest it is benign for competitive athletes. Nevertheless, complications arising from other cardiovascular anomalies, from potential cardiac rhythm disturbances, and from cardiac surgery necessitated by major injuries should be considered prior to participation in competitive sports.

Peak aerobic performance and left ventricular morphological characteristics in university students.

OBJECTIVE: To determine whether a relationship exists between left ventricular morphology and aerobic capacity in large numbers of male university students with a physically inactive and active life style. DESIGN: A prospective study. SETTING: Sports medicine research center. PARTICIPANTS: Eleven sedentary normal-weight university students, 17 sedentary overweight university students, and 215 university athletes. MAIN OUTCOME MEASURES: After the echocardiographic examination, an incremental treadmill exercise test until exhaustion was performed to measure peak oxygen uptake (VO2). RESULTS: In sedentary students, absolute peak VO2 in the overweight students was slightly higher than that in normal-weight students (3,024 vs. 2.912 ml/min). Relative peak VO2 (ml/min/kg) was highly negatively correlated with body mass index (kg/m2) in a total of 28 sedentary students. The correlation between absolute peak VO2 and left ventricular dimension was weak in the sedentary overweight students; however, a correlation coefficient of 0.55 was obtained in athletic students. A stepwise multiple regression showed significant determinants of absolute peak VO2 in athletic students for body surface area (45%), left ventricular dimension (7%), and certain sports (6%). CONCLUSIONS: A physically active life style plays a role in increasing both aerobic capacity and left ventricular enlargement. Body size appeared to be a potent stimulus to left ventricular enlargement.

Physiological profile of middle-aged and older climbers who ascended Gasherbrum II, an 8035-m Himalayan peak.

BACKGROUND: The purpose of this study was to investigate the physiological characteristics of a group of middle-aged and older Japanese climbers who ascended Gasherbrum II, an 8035-m peak in the Karakoram Range of the Himalayas. METHODS: Body composition, cardiac structure, and respiratory gas exchange during exercise were estimated in eight climbers with differing levels of experience (seven men and one woman, aged 54 to 63 years) 6 months before their expedition. RESULTS: Using supplementary O2, the four experienced climbers ascended beyond Camp 4 (7400 m) without showing any health problems and were able to attempt the summit. In contrast, the others, who had minimal experience at extreme altitude, suffered from altitude sickness on the way to Camp 4. Body mass index values were relatively high, but their low percentage of body fat (14.9%-21.4%) was indicative of the climbers' substantial lean body weight. Cardiac structures were generally normal, although three experienced male climbers had borderline hypertension and eccentric hypertrophy of the left ventricle. Peak VO2 ranged from 30.9 to 45.6 ml/kg/min, and no significant relationship between fitness level and the success or failure of the ascent was evident. CONCLUSIONS: Even sexagenarians are capable of safely climbing 8000-m peaks with supplementary O2. An exceptionally high fitness level, as is seen in elite older athletes, does not appear to be required. What is essential, however, is moderate fitness, good health, and extensive experience.

Aortic root dilatation among young competitive athletes: echocardiographic screening of 1929 athletes between 15 and 34 years of age.

BACKGROUND: Aortic dilatation can be lethal for young competitive athletes. The prevalence among athletes is not known, however, and thus a reasonable approach to early recognition remains uncertain. METHODS AND RESULTS: Echocardiograms of 1929 normotensive athletes 15 to 34 years of age were analyzed. Five (0.26%) athletes had aortic dilatation; 4 of the 5 played basketball. This made the prevalence of aortic dilatation 0.96% (4 of 415) among basketball and volleyball players, who represented a population of especially tall athletes. Tallness aside, only 2 of the 5 athletes had features of Marfan syndrome. Among the athletes without aortic dilatation, the relation between body surface area and aortic root dimension was nonlinear and best described with a quadratic regression model. Athletes with aortic dilatation fell well outside the 95% confidence interval. CONCLUSION: Because a higher incidence of aortic dilatation is to be anticipated among very tall athletes, inclusion of echocardiography in screening before participation in certain sports should be considered.

Effects of troglitazone on fat distribution in the treatment of male type 2 diabetes.

We investigated the efficacy of additional administration of 400 mg troglitazone (+T), which became available as a treatment for type 2 diabetes following the demonstration of its ability to reduce insulin resistance, in combination with diet (D + T) or sulfonylurea (S + T) therapy. Body fat area as determined by computed tomographic (CT) scanning at the umbilical level, as well as several clinical and biochemical parameters of glycemic control and lipid metabolism, were compared before and after 3 months of additional treatment with troglitazone. The body mass index (BMI) tended to increase in both groups (22.7 +/- 0.6 v 23.2 +/- 0.6 kg/m2 in D + T, nonsignificant [NS]; 22.2 +/- 0.5 v 22.3 +/- 0.5 kg/m2 in S + T, NS), while it tended to decrease in the control group (only diet therapy, 23.6 +/- 0.6 v 23.1 +/- 0.8 kg/m2, NS). Mean blood pressure ([BP] 96 +/- 3 v 89 +/- 4 mm Hg, P < .05) decreased significantly in the D + T group. Changes in the glycemic and lipid profile and leptin did not reach statistical significance. The D + T group showed a significant decline in immunoreactive insulin ([IRI] 12.4 +/- 1.2 v 8.0 +/- 1.0 microU/mL, P < .05), reflecting markedly reduced insulin resistance, as well as a significant increase in plasma insulin-like growth factor-1 ([IGF-1] 175.7 +/- 14.2 v 189.8 +/- 12.6 ng/mL, P < .05). A slight weight gain was associated with a tendency for subcutaneous fat to increase, while visceral fat decreased in both troglitazone-treated groups. The decrease in the visceral to subcutaneous fat ratio (V/S ratio) was statistically significant in the D + T group (1.09 +/- 0.11 v 0.94 +/- 0.09, P < .05), while the V/S ratio in the control group did not change. A notable finding of this study is the difference in the response to troglitazone between subcutaneous and visceral adipose tissue. It is suggested that troglitazone may exert beneficial effects by reducing visceral fat.

Effect of insulin therapy on body fat distribution in NIDDM patients with secondary sulfonylurea failure: a preliminary report.

OBJECTIVE: To clarify the influence of insulin therapy on body weight and fat distribution, we compared these parameters in five non-insulin dependent diabetes mellitus (NIDDM) patients, with secondary sulfonylurea failure, before and after insulin therapy. Body weight increased significantly after instituting insulin treatment. However, the visceral to subcutaneous fat (V/S) ratio decreased significantly due to a marked increase in S-fat without a change in V-fat. Insulin therapy necessitated by sulfonylurea failure does not appear to accelerate the atherogenic process in NIDDM patients as there is no increase in visceral fat.

Depression of dehydroepiandrosterone in Japanese diabetic men--comparison between non-insulin-dependent diabetes mellitus and impaired glucose tolerance.

Hyperglycemia is known to reduce dehydroepiandrosterone (DHEA) circulating levels; however, the mechanism by which hyperglycemia decreases DHEA is not elucidated. In this study, serum DHEA and DHEA sulfate (DHEA-S) levels were compared in 50 men with non-insulin-dependent diabetes mellitus (NIDDM) and 50 age-matched men with impaired glucose tolerance (IGT) receiving only diet therapy. Serum concentrations of DHEA and DHEA-S in the NIDDM group were significantly lower than in the IGT group (7.8 and 9.7 nmol/l vs 3.4 and 4.9 mumol/l, respectively; p < 0.01) but there was no significant difference in immunoreactive insulin between the two groups. When the results from both groups were combined, HbA1C was significantly inversely related to DHEA (r = -0.243, p < 0.01) and DHEA-S (r = -0.305, p < 0.01). Immunoreactive insulin showed no correlation with DHEA and DHEA-S. Multiple regression analysis showed that HbA1C was independently negatively related to both DHEA and DHEA-S. We conclude that hyperglycemia may decrease serum DHEA and DHEA-S in Japanese men with NIDDM, but the depression of DHEA(-S) is independent of serum insulin level.

Hyperglycemia decreases dehydroepiandrosterone in Japanese male with impaired glucose tolerance and low insulin response.

Recent studies indicate that experimentally induced hyperinsulinemia may reduce serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S). Serum DHEA and DHEA-S decrease in diabetic patients, but the mechanism by which hyperglycemia decreases DHEA and DHEA-S is unknown. In this study, we investigated the effect of hyperglycemia on DHEA and DHEA-S in impaired glucose tolerance (IGT) by means of the 75g-oral glucose tolerance test (OGTT). We selected 30 male IGT patients receiving diet therapy only, whose insulinogenic Index was under 0.3. Oral glucose challenge significantly reduced DHEA (P = 0.0001) and DHEA-S (P < 0.05) at 60 and 120 min after OGTT. Setting the value of DHEA and DHEA-S at time zero as 100%, we calculated the DHEA and DHEA-S values at 60 and 120 min after OGTT as %DHEA(-S) 60 min and %DHEA(-S) 120 min, respectively. DHEA and DHEA-S at time zero showed no correlation with BMI, HbA1c, the sum of insulin values (sigma IRI) or the area under the curve of plasma glucose (AUC). We found decreases in %DHEA 60 min (r = -0.411, P < 0.05), %DHEA-S 60 min (r = -0.508, P < 0.01) and %DHEA-S 120 min (r = -0.393, P < 0.05) as AUC increased, but sigma IRI showed no correlation with %DHEA(-S) 60 min or %DHEA(-S)120 min. We conclude that the depression of DHEA and DHEA-S after OGTT is attributable to hyperglycemia in male Japanese IGT with low insulin response.

Relation between grip strength and radial bone mineral density in young athletes.

In this study, we evaluated the relationship between bone mineral density (BMD) and muscle strength in young athletes who had not yet experienced age-related bone loss. Radial BMD and grip strength were measured in 10 male college wrestlers, 16 female college basketball players, and 12 female college tennis players. Radial BMD was measured in the distal and middle radius by dual energy x-ray absorptiometry (DEXA). Isometric grip strength was assessed with a hand-held dynamometer. The dominant forearm was examined in the amateur wrestlers and basketball players for grip strength and BMD. Both forearms were examined in the tennis players. A significant positive correlation was found between radial BMD and grip strength in the dominant forearm, and between radial BMD and body weight. Moreover, to eliminate a possible effect of body weight on radial BMD, we compared radial BMD with grip strength in both the dominant and nondominant arm of 12 college tennis players. Grip strength in the dominant forearm was significantly greater than in the nondominant forearm. The midradial BMD of the dominant forearm was also significantly higher than in the nondominant forearm. Based on these findings, we conclude that grip strength is one of the determinant factors of radial BMD in the dominant forearm of young college athletes.

Prolonged QT interval in alcoholic autonomic nervous dysfunction.

QT prolongation on electrocardiography is related to sudden cardiac death and is frequently found in alcoholics. We studied QT prolongation in relation to the function of cardiac autonomic nerves assessed by the coefficient of variation of the R-R interval (CVRR) in three age-matched groups of men: 32 alcoholics with autonomic nervous dysfunction (AN), 32 alcoholics without AN, and 32 healthy controls. The QTc interval and CVRR were measured at rest on the 30th day of abstinence, when electrolyte imbalance had disappeared. Subjects with arrhythmia, conduction abnormality, cardiomegaly, ischemic heart disease or diabetes mellitus were excluded. A CVRR of less than 80% of standard predicted value was judged to represent AN. In alcoholics, QTc correlated negatively with the ratio of CVRR to its standard value (r = -0.49, p < 0.0001). The incidence of QTc prolongation was higher in alcoholics with AN (46.9%) than in alcoholics without AN (21.9%, p < 0.05). QTc prolongation was not observed in healthy controls. The QTc interval was significantly (p < 0.01) longer in alcoholics with AN (444 +/- 20 msec) than in alcoholics without AN (426 +/- 17) and in healthy controls (398 +/- 18). These results suggest that alcoholism causes dysfunction of the autonomic nerves as well as worsening QT prolongation, and this may predispose such patients to sudden cardiac death.

Influence of glycemic control and hypertension on urinary microprotein excretion in non-insulin-dependent diabetes mellitus.

In order to evaluate the influence of glycemic control and hypertension on the development of diabetic nephropathy, we measured urinary excretion of albumin (AER) and other microproteins in non-insulin-dependent diabetes mellitus (NIDDM), and reexamined the 103 patients who had had AER less than 300 micrograms/min at the initial study 12-18 months later. AER in the patients with HbA1c greater than or equal to 7.5% increased significantly in both the normoalbuminuric (AER less than 30 micrograms/min) and microalbuminuric (30-300 micrograms/min) groups, whereas no significant change in AER was observed in the patients with HbA1c less than 7.5%. In the microalbuminuric group, AER in both hypertensive and normotensive patients increased significantly. In this group, the change in AER correlated positively with the change in alpha 1-microglobulin (alpha 1M). These results indicate that glycemic control has a greater influence on the development of nephropathy in its early stage than hypertension and that alpha 1M is as a good predictor of nephropathy as albumin.