The effect of rowing ergometry and resistive exercise on skeletal muscle structure and function during bed rest.

Exposure to microgravity causes functional and structural impairment of skeletal muscle. Current exercise regimens are time-consuming and insufficiently effective; an integrated countermeasure is needed that addresses musculoskeletal along with cardiovascular health. High-intensity, short-duration rowing ergometry and supplemental resistive strength exercise may achieve these goals. Twenty-seven healthy volunteers completed 5 wk of head-down-tilt bed rest (HDBR): 18 were randomized to exercise, 9 remained sedentary. Exercise consisted of rowing ergometry 6 days/wk, including interval training, and supplemental strength training 2 days/wk. Measurements before and after HDBR and following reambulation included assessment of strength, skeletal muscle volume (MRI), and muscle metabolism (magnetic resonance spectroscopy); quadriceps muscle biopsies were obtained to assess muscle fiber types, capillarization, and oxidative capacity. Sedentary bed rest (BR) led to decreased muscle volume (quadriceps: -9 ± 4%, P < 0.001; plantar flexors: -19 ± 6%, P < 0.001). Exercise (ExBR) reduced atrophy in the quadriceps (-5 ± 4%, interaction P = 0.018) and calf muscle, although to a lesser degree (-14 ± 6%, interaction P = 0.076). Knee extensor and plantar flexor strength was impaired by BR (-14 ± 15%, P = 0.014 and -22 ± 7%, P = 0.001) but preserved by ExBR (-4 ± 13%, P = 0.238 and +13 ± 28%, P = 0.011). Metabolic capacity, as assessed by maximal O2 consumption, (31)P-MRS, and oxidative chain enzyme activity, was impaired in BR but stable or improved in ExBR. Reambulation reversed the negative impact of BR. High-intensity, short-duration rowing and supplemental strength training effectively preserved skeletal muscle function and structure while partially preventing atrophy in key antigravity muscles. Due to its integrated cardiovascular benefits, rowing ergometry could be a primary component of exercise prescriptions for astronauts or patients suffering from severe deconditioning.

Reduced cardiorespiratory fitness in adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Adult survivors of childhood acute lymphoblastic leukemia (ALL) are at increased cardiovascular risk. Studies of factors including treatment exposures that may modify risk of low cardiorespiratory fitness in this population have been limited. PROCEDURE: To assess cardiorespiratory fitness, maximal oxygen uptake (VO2 max) was measured in 115 ALL survivors (median age, 23.5 years; range 18-37). We compared VO2 max measurements for ALL survivors to those estimated from submaximal testing in a frequency-matched (age, gender, race/ethnicity) 2003-2004 National Health and Nutritional Examination Survey (NHANES) cohort. Multivariable linear regression models were constructed to evaluate the association between therapeutic exposures and outcomes of interest. RESULTS: Compared to NHANES participants, ALL survivors had a substantially lower VO2 max (mean 30.7 vs. 39.9 ml/kg/min; adjusted P < 0.0001). For any given percent total body fat, ALL survivors had an 8.9 ml/kg/min lower VO2 max than NHANES participants. For key treatment exposure groups (cranial radiotherapy [CRT], anthracycline chemotherapy, or neither), ALL survivors had substantially lower VO2 max compared with NHANES participants (all comparisons, P < 0.001). Almost two-thirds (66.7%) of ALL survivors were classified as low cardiorespiratory fitness compared with 26.3% of NHANES participants (adjusted P < 0.0001). In multivariable models including only ALL survivors, treatment exposures were modestly associated with VO2 max. Among females, CRT was associated with low VO2 max (P = 0.02), but anthracycline exposure was not (P = 0.58). In contrast, among males, anthracycline exposure ≥ 100 mg/m(2) was associated with low VO2 max (P = 0.03), but CRT was not (P = 0.54). CONCLUSION: Adult survivors of childhood ALL have substantially lower levels of cardiorespiratory fitness compared with a similarly aged non-cancer population.

Effect of rowing ergometry and oral volume loading on cardiovascular structure and function during bed rest.

This study examined the effectiveness of a short-duration but high-intensity exercise countermeasure in combination with a novel oral volume load in preventing bed rest deconditioning and orthostatic intolerance. Bed rest reduces work capacity and orthostatic tolerance due in part to cardiac atrophy and decreased stroke volume. Twenty seven healthy subjects completed 5 wk of -6 degree head down bed rest. Eighteen were randomized to daily rowing ergometry and biweekly strength training while nine remained sedentary. Measurements included cardiac mass, invasive pressure-volume relations, maximal upright exercise capacity, and orthostatic tolerance. Before post-bed rest orthostatic tolerance and exercise testing, nine exercise subjects were given 2 days of fludrocortisone and increased salt. Sedentary bed rest led to cardiac atrophy (125 ± 23 vs. 115 ± 20 g; P < 0.001); however, exercise preserved cardiac mass (128 ± 38 vs. 137 ± 34 g; P = 0.002). Exercise training preserved left ventricular chamber compliance, whereas sedentary bed rest increased stiffness (180 ± 170%, P = 0.032). Orthostatic tolerance was preserved only when exercise was combined with volume loading (-10 ± 22%, P = 0.169) but not with exercise (-14 ± 43%, P = 0.047) or sedentary bed rest (-24 ± 26%, P = 0.035) alone. Rowing and supplemental strength training prevent cardiovascular deconditioning during prolonged bed rest. When combined with an oral volume load, orthostatic tolerance is also preserved. This combined countermeasure may be an ideal strategy for prolonged spaceflight, or patients with orthostatic intolerance.

Accuracy of estimating resting oxygen uptake and implications for hemodynamic assessment.

The Fick principle (cardiac output [Q(c)] = oxygen uptake [Vo(2)]/arteriovenous oxygen difference) can be used to calculate Q(c), with VO(2) frequently estimated by derived equations. To compare the accuracy of measured versus estimated VO(2), data were analyzed from 2 studies in which VO(2) at rest was measured using the Douglas bag technique. One study comprised adults with diabetes, and the other was an exercise study of healthy adults. VO(2) at rest was estimated as VO(2) (ml/min) = 125 ml/min/m(2) × body surface area (m(2)), with sensitivity analyses evaluating 2 other commonly used equations. Mean absolute difference (milliliters per minute) and ordinary least products regression were used to assess agreement between measured and estimated VO(2). Overall, mean measured versus estimated VO(2) differed significantly (307.2 ± 75.2 vs 259.9 ± 36.7 ml/min, p <0.0001), with a mean absolute difference of 52.9 ± 43.2 ml/min (p <0.0001); 20% of the estimates differed by >25% from the measured VO(2). Mean absolute difference increased from 36.7 ml/min in the lowest body mass index group (<25 kg/m(2)) to 91.7 ml/min in the highest group (≥40 kg/m(2)) (p for trend = 0.001) and was significantly higher in men than in women (65.6 vs 33.9 ml/min, p = 0.001); error was similar by median-split age (p = 0.65) and race (p = 0.34). Similar results were obtained when evaluating each of the other 2 estimating equations. Estimation of VO(2) at rest is inaccurate, especially in men and with increasing adiposity. In conclusion, when clinical hemodynamic assessment is performed, VO(2) should be measured, not estimated.

High-volume exercise program in obese bariatric surgery patients: a randomized, controlled trial.

Weight regain is a problem among many bariatric surgery patients. Whether a high-volume exercise program (HVEP), a strategy to limit weight regain, is feasible in these patients is unknown. The feasibility of an HVEP in obese post-bariatric-surgery patients was determined by randomizing 33 Roux-en-Y gastric bypass (RYGB) and gastric banding (GB) surgery patients with a mean BMI of 41 ± 6 kg/m2 to an HVEP or control group for 12 weeks. The HVEP group was instructed to expend ≥ 2,000 kcal/week in moderate-intensity exercise. All patients were counseled to limit energy intake. Treatment effect was assessed by repeated measures analysis. During the last 4 weeks of the study, 53% of the HVEP group expended ≥ 2,000 kcal/week and 82% expended ≥ 1,500 kcal/week. Step count, reported time spent and energy expended during moderate physical activity, maximal oxygen consumption relative to weight, and incremental area under the postprandial blood glucose curve were significantly improved over 12 weeks in the HVEP group compared to controls (group-by-week effect: P = 0.009-0.03). Both groups reported significant improvement in some quality-of-life scales. Changes in weight, energy and macronutrient intake, resting energy expenditure (REE), fasting lipids and glucose, and fasting and postprandial insulin concentrations were not different between the two groups. HVEP is feasible in about 50% of the patients and enhances physical fitness and reduces postprandial blood glucose in bariatric surgery patients.

Assessment of cardiac structure and function in patients without and with peripheral oedema during rosiglitazone treatment.

BACKGROUND: Thiazolidinediones cause peripheral oedema, the aetiology of which remains poorly understood. METHODS: In a sub-study of a 6-month trial comparing rosiglitazone (Rsg) versus placebo, we compared those with versus without oedema among the 74 subjects treated with Rsg with respect to peak oxygen consumption indexed to fat-free mass (VO(2peak-FFM) ), cardiac MRI and markers of plasma volume expansion. RESULTS: Almost half (49%) of the Rsg-treated patients developed oedema. Baseline VO(2peak-FFM) was not different between those with versus without oedema (25.8 versus 28.2 ml/kg/min; p = 0.22) and declined 5% in the oedema group (Δ -1.3 ml/min/kg; p = 0.005) with no change in those without oedema. Stroke volume increased in both groups (Δ 8.7 and 8.8 ml; p < 0.001 for each); end-diastolic volume increased only in those with oedema (+13.1 ml; p = 0.001). No other cardiac function changes were observed. In both groups, weight increased (3.6 and 2.2 kg) and haematocrit decreased (-3.2% and -2.1%; p < 0.001 for each). In those with oedema, albumin decreased (-0.2 g/dl) and brain natriuretic peptide increased (11.9 pg/ml; p < 0.03 for each). CONCLUSIONS: Oedema was associated with a small decline in VO(2peak FFM), no adverse effects on cardiac function, and changes in selected measures suggesting that volume expansion underpins Rsg oedema.

Antenatal depression: a rationale for studying exercise.

BACKGROUND: Major depressive disorder (MDD) in pregnancy or antenatal depression poses unique treatment challenges and has serious consequences for mothers, unborn babies, and families when untreated. This review presents current knowledge on exercise during pregnancy, antidepressant effects of exercise, and the rationale for the specific study of exercise for antenatal depression. METHOD: A systematic literature review was performed using English language articles published in Medline, PsycINFO, CINAHL, and the Cochrane Library from 1985 to January 2010. RESULTS: There is a broad literature supporting the antidepressant effects of exercise, but a paucity of studies specifically for antenatal depression. A small number of observational studies have reported that regular physical activities improve self-esteem and reduce symptoms of anxiety and depression during pregnancy. To date, there have not been randomized controlled studies of exercise for the treatment of MDD in pregnant women. CONCLUSIONS: Systematic studies are needed to assess exercise as a treatment alternative for MDD during pregnancy. In consideration of the benefits of exercise for the mother and baby, and the burden of depression, studies are needed to determine the role of exercise for pregnant women with depression.

Comparative effects of selected non-caffeinated rehydration sports drinks on short-term performance following moderate dehydration.

BACKGROUND: The effect of moderate dehydration and consequent fluid replenishment on short-duration maximal treadmill performance was studied in eight healthy, fit (VO2max = 49.7 +/- 8.7 mL kg-1 min-1) males aged 28 +/- 7.5 yrs. METHODS: The study involved a within subject, blinded, crossover, placebo design. Initially, all subjects performed a baseline exercise test using an individualized treadmill protocol structured to induce exhaustion in 7 to 10 min. On each of the three subsequent testing days, the subjects exercised at 70-75% VO2max for 60 min at 29-33 degrees C, resulting in a dehydration weight loss of 1.8-2.1% body weight. After 60 min of rest and recovery at 22 C, subjects performed the same treadmill test to voluntary exhaustion, which resulted in a small reduction in VO2max and a decline in treadmill performance by 3% relative to the baseline results. Following another 60 min rest and recovery, subjects ingested the same amount of fluid lost in the form of one of three lemon-flavored, randomly assigned commercial drinks, namely Crystal Light (placebo control), Gatorade(R) and Rehydrate Electrolyte Replacement Drink, and then repeated the treadmill test to voluntary exhaustion. RESULTS: VO2max returned to baseline levels with Rehydrate, while there was only a slight improvement with Gatorade and Crystal Light. There were no changes in heart rate or ventilation with all three different replacement drinks. Relative to the dehydrated state, a 6.5% decrease in treadmill performance time occurred with Crystal Light, while replenishment with Gatorade, which contains fructose, glucose, sodium and potassium, resulted in a 2.1% decrease. In contrast, treatment with Rehydrate, which comprises fructose, glucose polymer, calcium, magnesium, sodium, potassium, amino acids, thiols and vitamins, resulted in a 7.3% increase in treadmill time relative to that of the dehydrated state. CONCLUSIONS: The results indicate that constituents other than water, simple transportable monosaccharides and sodium are important for maximal exercise performance and effective recovery associated with endurance exercise-induced dehydration.

Randomized comparison of the effects of rosiglitazone vs. placebo on peak integrated cardiovascular performance, cardiac structure, and function.

AIMS: To assess the effect of rosiglitazone on cardiovascular performance and cardiac function. METHODS AND RESULTS: One hundred and fifty type 2 diabetes patients with cardiovascular disease (CVD) or ≥ 1 other CVD risk factor were randomized to receive rosiglitazone vs. placebo for 6 months. The primary outcome was peak oxygen uptake indexed to fat-free mass (VO(2peak)-FFM) during maximum exercise. A subset of 102 subjects underwent cardiac magnetic resonance imaging (cMRI). On hundred and eight subjects completed the study, including 75 completing the cMRI substudy. No significant differences were observed in mean VO(2peak)-FFM between rosiglitazone and placebo (26.1 ± 7.0 vs. 27.6 ± 6.6 mL/kg-FFM/min; P = 0.26). Compared with placebo, the rosiglitazone group had lower hematocrit (38 vs. 41%; P < 0.001) and more peripheral oedema (53.7 vs. 33.3%; P = 0.03). In the cMRI substudy, compared with placebo, the rosiglitazone group had larger end-diastolic volume (128.1 vs. 112.0 mL; P = 0.01) and stroke volume (83.7 vs. 72.9 mL; P = 0.01), and a trend toward increased peak ventricular filling rate (79.4 vs. 60.5; P = 0.07). CONCLUSION: Rosiglitazone increased peripheral oedema but had no pernicious effects on cardiovascular performance or cardiac function, with modest improvement in selected cMRI measures. Changes in indirect markers of plasma volume suggest expansion with rosiglitazone. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00424762.

Insulin resistance and risk factors for cardiovascular disease in young adult survivors of childhood acute lymphoblastic leukemia.

PURPOSE: To determine the prevalence of insulin resistance and other risk factors for cardiovascular disease (CVD) in young adult survivors of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: In this cross-sectional evaluation of 118 survivors of childhood ALL (median age, 23.0 years; range, 18 to 37 years), insulin resistance was estimated using the homeostasis model for assessment of insulin resistance (HOMA-IR). Sex-specific comparisons were made with a cohort of 30- to 37-year-old individuals from the same region participating in the Dallas Heart Study (DHS, N = 782). ALL survivors were stratified by treatment with and without cranial radiotherapy (CRT). RESULTS: Female ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.6, 95% CI, 3.6 to 5.7; no CRT, mean 3.3, 95% CI, 2.8 to 3.8) in comparison with DHS women (mean 2.4, 95% CI, 2.2 to 2.7). Eighty percent of women treated with CRT had at least three of six CVD risk factors, and they were significantly more likely to have three or more risk factors compared with DHS women (odds ratio [OR], 5.96; 95% CI, 2.15 to 16.47). Male ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.0, 95% CI, 2.8 to 5.6; no CRT, mean 3.4, 95% CI, 2.9 to 3.9) in comparison with DHS men (mean 2.3, 95% CI, 2.1 to 2.6), but were not more likely to have multiple CVD risk factors. CONCLUSION: ALL survivors had an increased prevalence of insulin resistance in comparison with a cohort of older individuals from the same community. Importantly, women treated with CRT seem to have an increased prevalence of multiple CVD risk factors, warranting close monitoring and risk-reducing strategies.

A forty-year follow-up of the Dallas Bed Rest and Training study: the effect of age on the cardiovascular response to exercise in men.

BACKGROUND: In 1966, five 20-year-old men underwent a comprehensive physiological evaluation of the capacity for adaptation of the cardiovascular system in response to 3 weeks of bed rest and 8 weeks of heavy endurance training; these same participants were reevaluated before and after training at the age of 50. The aim of the present study was to reexamine these same men 40 years following the original assessments. METHODS AND RESULTS: In all three studies, minute ventilation and expired gases were analyzed during exercise testing with Douglas bag collection. Cardiac output (CO) was determined using the acetylene rebreathing technique. Compared with the original 30-year interval, the decline in maximal oxygen uptake (VO(2max)) (-11% vs -25%), maximal CO (+6% vs -11%), and maximal stroke volume (+10% vs -10%) were greater between 50 and 60 years of age. The annualized decline in VO(2max) (55 mL/min/y) between ages 50 and 60 was approximately fourfold higher than the decline between 20 and 50 years (12 mL/min/y). CONCLUSIONS: In the original five participants of the Dallas Bed Rest and Training Study, VO(2max) declined after 40 years of living due to a balanced decrease in central and peripheral determinants of oxygen uptake. The rate of decline in VO(2max) and its components accelerated after the age of 50 years secondary to age and clinical comorbidities. The net proportional decline in VO(2max) for a period of 40 years of life was comparable with that experienced after 3 weeks of strict bed rest at the age of 20 (27% vs 26%, respectively).

The effect of rosiglitazone on integrated cardiovascular performance, cardiac structure, function and myocardial triglyceride: trial design and rationale.

The thiazolidinedione (TZD) class of medications has been associated with increased risk for peripheral oedema, as well as incident and worsening heart failure (HF). The mechanism of these observed effects remains unclear. Here we present the rationale and study design for a randomised clinical trial designed to evaluate the cardiac effects of rosiglitazone on integrated cardiovascular performance, cardiac structure and function. The study is a randomised, single-centre, double-blind, placebo-controlled, parallel-group clinical trial to evaluate the effect of rosiglitazone on integrated cardiovascular performance in a cohort of patients with type 2 diabetes mellitus (T2DM) at increased risk for developing heart failure (HF). Participants will be randomised to receive rosiglitazone or matching placebo for six months. All subjects will undergo maximal treadmill cardiopulmonary exercise testing at baseline and after six months on study drug, with the primary trial end point of peak oxygen uptake indexed to fat-free mass (VO 2peak-FFM). Approximately two-thirds of the study cohort will undergo cardiac magnetic resonance imaging (MRI) and spectroscopy (MRS) at baseline and after six months of study therapy to assess cardiac structure, function and myocardial triglyceride content. While concerns for peripheral oedema and HF continue to confound clinical use of TZD medications, the direct cardiac effects of these drugs remain poorly understood and the clinical relevance of these clinical observations remains unclear. The present study will combine a series of state-of-the-art assessments to evaluate the cardiac effects of rosiglitazone treatment.

Insulin resistance and body fat distribution in South Asian men compared to Caucasian men.

OBJECTIVE: South Asians are susceptible to insulin resistance even without obesity. We examined the characteristics of body fat content, distribution and function in South Asian men and their relationships to insulin resistance compared to Caucasians. RESEARCH DESIGN AND METHODS: Twenty-nine South Asian and 18 Caucasian non-diabetic men (age 27+/-3 and 27+/-3 years, respectively) underwent euglycemic-hyperinsulinemic clamp for insulin sensitivity, underwater weighing for total body fat, MRI of entire abdomen for intraperitoneal (IP) and subcutaneous abdominal (SA) fat and biopsy of SA fat for adipocyte size. RESULTS: Compared to Caucasians, in spite of similar BMI, South Asians had higher total body fat (22+/-6 and 15+/-4% of body weight; p-value<0.0001), higher SA fat (3.5+/-1.9 and 2.2+/-1.3 kg, respectively; p-value = 0.004), but no differences in IP fat (1.0+/-0.5 and 1.0+/-0.7 kg, respectively; p-value = 0.4). SA adipocyte cell size was significantly higher in South Asians (3491+/-1393 and 1648+/-864 microm2; p-value = 0.0001) and was inversely correlated with both glucose disposal rate (r-value = -0.57; p-value = 0.0008) and plasma adiponectin concentrations (r-value = -0.71; p-value<0.0001). Adipocyte size differences persisted even when SA was matched between South Asians and Caucasians. CONCLUSIONS: Insulin resistance in young South Asian men can be observed even without increase in IP fat mass and is related to large SA adipocytes size. Hence ethnic excess in insulin resistance in South Asians appears to be related more to excess truncal fat and dysfunctional adipose tissue than to excess visceral fat.

Maximal oxygen uptake as a parametric measure of cardiorespiratory capacity.

INTRODUCTION: Maximal oxygen uptake (.VO2max) was defined by Hill and Lupton in 1923 as the oxygen uptake attained during maximal exercise intensity that could not be increased despite further increases in exercise workload, thereby defining the limits of the cardiorespiratory system. This concept has recently been disputed because of the lack of published data reporting an unequivocal plateau in .VO2 during incremental exercise. PURPOSE: The purpose of this investigation was to test the hypothesis that there is no significant difference between the .VO2max obtained during incremental exercise and a subsequent supramaximal exercise test in competitive middle-distance runners. We sought to determine conclusively whether .VO2 attains a maximal value that subsequently plateaus or decreases with further increases in exercise intensity. METHODS: Fifty-two subjects (36 men, 16 women) performed three series of incremental exercise tests while measuring .VO2 using the Douglas bag method. On the day after each incremental test, the subjects returned for a supramaximal test, during which they ran at 8% grade with the speed chosen individually to exhaust the subject between 2 and 4 min. .VO2 at supramaximal exercise intensities (30% above incremental .VO2max) was measured continuously. RESULTS: .VO2max measured during the incremental test (63.3 +/- 6.3 mL.kg(-1).min(-1); mean +/- SD) was indistinguishable from the .VO2max during the supramaximal test (62.9 +/- 6.2, N = 156; P = 0.77) despite a sufficient duration of exercise to demonstrate a plateau in .VO2 during continuous supramaximal exercise. These data provide strong support for the hypothesis that there is indeed a peak and subsequent plateau in .VO2 during maximal exercise intensity. CONCLUSIONS: .VO2max is a valid index measuring the limits of the cardiorespiratory systems' ability to transport oxygen from the air to the tissues at a given level of physical conditioning and oxygen availability.

Regional body fat distribution in HIV-infected patients with lipodystrophy.

BACKGROUND: Objective criteria for the assessment of patients with lipodystrophy syndrome in human immunodeficiency virus infection (LDHIV) have not emerged. METHODS: We compared regional body fat changes in 13 men with severe LDHIV on protease inhibitor-inclusive antiretroviral therapy with 13 control HIV-infected men using anthropometry, dual-energy X-ray absorptiometry (DEXA), and whole-body magnetic resonance imaging (MRI). RESULTS: LDHIV patients, compared with control subjects, had thinner gluteal, suprailiac, and triceps skinfolds (p < .01) and increased waist circumference (98 +/- 5 cm vs 86 +/- 9 cm, respectively; p = .0008). DEXA studies revealed reduced lower extremity fat (12 +/- 5% vs 22 +/- 9%; p = .0006), increased head and neck fat (18 +/- 3% vs 16 +/- 1%; p = .01), and increased proportion of total body fat in the trunk (65 +/- 7% vs 53 +/- 8%; p = .0005). MRI analysis revealed reduced thigh fat (12 +/- 5% vs 22 +/- 12%; p = .01), increased dorsocervical fat depth (47 +/- 24 mm vs 19 +/- 7 mm; p = .0009), and nearly significant increase in intra-abdominal fat (218 +/- 90 cm2 vs 157 +/- 70 cm2; p = .057). Interestingly, control subjects showed a positive relationship between intra-abdominal and dorsocervical fat (r= .57, p = .04), but the LDHIV patients showed a negative relationship (r= -.55, p = .05), suggesting a novel split phenotype among LDHIV patients of either dorsocervical or intra-abdominal fat accumulation. CONCLUSIONS: We conclude that MRI provides the best tools for definition of LDHIV syndrome and reveals variable phenotypes among LDHIV patients.

Adipose tissue metabolites and insulin resistance in nondiabetic Asian Indian men.

Obesity-related insulin resistance is associated with changes in adipose tissue release of leptin, adiponectin, and nonesterified fatty acids (NEFAs). We have previously described that persons originating from the Indian subcontinent (Asian Indians) manifest excessive insulin resistance even in the absence of obesity. Therefore, in this study, we tested the hypothesis that nondiabetic, insulin-resistant Asian Indians differ from less insulin-resistant Caucasians of similar age and body composition in adipose tissue production of leptin and adiponectin, and in suppression of plasma NEFA concentrations during hyperinsulinemia. Seventy-nine Asian Indian men were compared with 61 Caucasian men. Higher plasma NEFAs and leptin in Asian Indians (P < 0.0001 and P = 0.003 for NEFAs and leptin, respectively) and lower plasma concentrations of adiponectin (P = 0.009) were not explained by body fat content and distribution. Oral glucose tolerance test studies revealed that Caucasian men had greater suppression of plasma NEFAs than Asian Indian men. We conclude that plasma concentrations of the adipose tissue metabolites leptin and NEFAs are higher and that of adiponectin is lower in insulin-resistant Asian Indians compared with more insulin-sensitive Caucasians. These differences may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease in nonobese Asian Indians.

Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance.

Genetic susceptibility may be responsible for high prevalence of insulin resistance in Asian Indians. This study was carried out in samples of local Asian Indians and Caucasians to determine whether plasma cell membrane glycoprotein (PC)-1 K121Q and insulin receptor substrate-1 (IRS-1) G972A polymorphisms contribute significantly to susceptibility to insulin resistance in Asian Indians. The frequency of carrying at least one copy of the PC-1 121Q variant in Asian Indians was significantly higher than that in Caucasians (P = 0.01), but the frequency was similar for IRS-1 972A (6% and 7%). A significantly higher insulin area under the curve during oral glucose tolerance testing (P < 0.0001) and lower insulin sensitivity during hyperinsulinemic-euglycemic clamps (P = 0.04) were found in Asian Indians with PC-1 121Q variant compared with Asian Indians with wild-type PC-1 and with Caucasians with or without the polymorphism. IRS-1 972A was not associated with any change in insulin sensitivity. We conclude that the PC-1 K121Q polymorphism associates with primary insulin resistance in migrant Asian Indians. A relatively high frequency of this polymorphism thus may be one factor contributing to insulin resistance susceptibility in Asian Indians. This finding indicates the need for expanded studies on the association between PC-1 K121Q and insulin resistance in a representative sample of the Asian Indian population.