Effects of aerobic and resistance training on abdominal fat, apolipoproteins and high-sensitivity C-reactive protein in adolescents with obesity: the HEARTY randomized clinical trial.

OBJECTIVES: To investigate the effects of aerobic training, resistance training, or both on abdominal subcutaneous fat (subcutaneous adipose tissue (SAT)) (deep and superficial), visceral fat (visceral adipose tissue (VAT)), apolipoproteins A-1 and B (ApoA-1, ApoB), ApoB/ApoA-1 ratio and high-sensitivity C-reactive protein (HSCRP) in post-pubertal adolescents with obesity. PARTICIPANTS: After a 4-week supervised moderate-intensity exercise run-in period, 304 postpubertal adolescents with overweight (body mass index (BMI) ⩾85th percentile for age and sex+diabetes risk factor) or obesity (⩾95th BMI percentile) aged 14-18 years were randomized to four groups for 22 weeks (5 months): aerobic training, resistance training, combined training or a non-exercising control. METHODS: This study used a randomized controlled design. All groups received dietary counseling designed to promote healthy eating with a maximum daily energy deficit of 250 kcal. Abdominal fat (SAT and VAT) at the level of the fourth and fifth lumbar vertebrae (L4-L5) was measured by magnetic resonance imaging and ApoA-1, ApoB and HSCRP were measured after a 12-h fast at baseline and after 6 months. RESULTS: Changes in SAT at L4-L5 were -16.2 cm(2) in aerobic (P=0.04 vs control), -22.7 cm(2) in resistance (P=0.009 vs control) and -18.7 cm(2) in combined (P=0.02 vs control). Combined training reduced ApoB levels from 0.81±0.02 to 0.78±0.02 g l(-1) (P=0.04 vs control) and ApoB/ApoA-1 ratio from 0.67±0.02 to 0.64±0.02 (P=0.02 vs control and P=0.04 vs aerobic). There were no significant differences in VAT, ApoA-1 or HSCRP levels between groups. CONCLUSIONS: Aerobic and resistance training and their combination decreased abdominal SAT in adolescents with obesity. Combined training caused greater improvements in ApoB/ApoA-1 ratio compared with aerobic training alone.

Does type 1 diabetes alter post-exercise thermoregulatory and cardiovascular function in young adults?

Recent data demonstrated that individuals with type 1 diabetes mellitus (T1DM) exhibit impaired sweating and increased rectal temperature (i.e., heat storage) during exercise compared with healthy controls. Our purpose in this study was to investigate the consequences of T1DM on post-exercise thermal homeostasis. Sixteen participants (eight controls matched with eight T1DM) performed 90 min of cycling followed by 60 min of seated recovery. Esophageal and rectal temperatures, sweating (forearm, chest, and upper back), skin blood flow [forearm and upper back, presented as cutaneous vascular conductance (CVC)], and blood pressure [mean arterial pressure (MAP)] were measured at baseline and throughout recovery. Esophageal temperature was similar during baseline and recovery between groups (P = 0.88). However, rectal temperature was elevated in our T1DM group throughout recovery (P = 0.05). Sweating and CVC were similar between groups at all sites from 10-min post-exercise until the end of recovery (P ≥ 0.16). While absolute MAP was similar between groups (P = 0.43), the overall decrease in MAP post-exercise was greater in controls from 20 min (T1DM: - 8 ± 5 vs control: - 13 ± 6 mmHg, P = 0.03) until the end of recovery. We conclude that despite increased heat storage during exercise, individuals with T1DM exhibit a suppression in heat loss similar to their healthy counterparts during recovery.

The Alberta Diabetes and Physical Activity Trial (ADAPT): a randomized trial evaluating theory-based interventions to increase physical activity in adults with type 2 diabetes.

BACKGROUND: Physical activity (PA) is associated with reduced morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM); however, most T2DM adults are insufficiently active. PURPOSE: To explore the effectiveness of two innovative/theoretically based behavioral-change strategies to increase PA and reduce hemoglobin A1c (A1c) in T2DM adults. METHODS: Participants (n = 287) were randomly assigned to a control group or an intervention group (i.e., print-based materials/pedometer group or print-based materials/pedometer plus telephone-counseling group). Changes in PA and A1c and other clinical measures were examined by Linear Mixed Model analyses over 18 months, along with moderating effects for gender and age. RESULTS: PA and A1c levels did not significantly change in intervention groups. Step counts significantly increased in the print-based materials and pedometer plus telephone counseling group, for women. CONCLUSIONS: No significant effects were found for PA or A1c levels for T2DM adults. The multi-component strategy including telephone counseling may have potential for women. The trial was registered on ClinicalTrials.gov identifier: NCT00221234.

A review of randomized controlled trials of aerobic exercise training on fitness and cardiometabolic risk factors in obese adolescents.

Aerobic training is the most prescribed exercise modality for the management of pediatric obesity. There is strong evidence that it decreases waist circumference, percent body fat and visceral fat, increases cardiorespiratory fitness, and decreases blood pressure in obese adolescents. However, the independent effects of aerobic exercise training on other cardiometabolic risk factors (ie, insulin resistance markers, plasma lipid levels, and inflammatory markers) are limited and yield inconsistent findings. Our article reviews randomized controlled trials evaluating the effects of aerobic exercise training on body composition, fitness, lipid levels, and insulin resistance in obese adolescents (aged 13-18 years) and outlines future research directions for this population.

Comparison of strength development with resistance training and combined exercise training in type 2 diabetes.

Resistance training has been shown to increase strength in type 2 diabetes; however, it is unclear if combining resistance and aerobic training (A + R) impedes strength development compared with resistance training only (R). The purpose of this study was to compare changes in strength with A + R vs R in individuals with type 2 diabetes. We evaluated monthly workload increments in participants from the Diabetes Aerobic and Resistance Exercise clinical trial. Muscular strength was assessed through training volumes and as the eight repetition maximum (8-RM) at 0, 3, and 6 months. Both groups increased their upper and lower body volumes monthly for 6 months. The relative increase in upper body workload in R was significantly greater than A + R at 4 months (161 ± 11% vs 127 ± 11%, P = 0.009) and at 6 months of training (177 ± 11% vs 132 ± 11%, P = 0.008). Both groups had improvements in 8-RM workloads at 3 and 6 months. The resistance training group had a significantly greater improvement in 8-RM on the leg press at 6 months compared with A + R (80 ± 11% vs 58 ± 8%, P = 0.045). Both R and A + R improved strength with a 6-month training program; however, increases in strength may be greater with resistance training alone compared with performing both aerobic and resistance training.

Associations between physical fitness and HbA1(c) in type 2 diabetes mellitus.

AIM/HYPOTHESIS: In people with type 2 diabetes, exercise improves glucose control (as reflected in HbA1(c)) and physical fitness, but it is not clear to what extent these exercise-induced improvements are correlated with one another. We hypothesised that reductions in HbA1(c) would be related: (1) to increases in aerobic fitness and strength respectively in patients performing aerobic training or resistance training; and (2) to changes in strength and aerobic fitness in patients performing aerobic and resistance training. METHODS: We randomly allocated 251 type 2 diabetes patients to aerobic, resistance, or aerobic plus resistance training, or to a sedentary control group. Peak oxygen consumption VO2(peak), workload, treadmill time and ventilatory threshold measurements from maximal treadmill exercise testing were measured at baseline and 6 months. Muscular strength was measured as the maximum weight that could be lifted eight times on the leg press, bench press and seated row exercises. RESULTS: With aerobic training, significant associations were found between changes in both VO2(peak) (p = 0.040) and workload (p = 0.022), and changes in HbA1(c.) With combined training, improvements in VO2(peak) (p = 0.008), workload (p = 0.034) and ventilatory threshold (p = 0.003) were significantly associated with changes in HbA1(c.) Increases in strength on the seated row (p = 0.006) and in mid-thigh muscle cross-sectional area (p = 0.030) were significantly associated with changes in HbA1(c) after resistance exercise, whereas the association between increases in muscle cross-sectional area and HbA1(c) in participants doing aerobic plus resistance exercise (p = 0.059) was of borderline significance. CONCLUSIONS/INTERPRETATION: There appears to be a link between changes in fitness and HbA1(c). The improvements in cardiorespiratory fitness with aerobic training may be a better predictor of changes in HbA1(c) than improvements in strength.

Effects of aerobic exercise, resistance exercise or both, on patient-reported health status and well-being in type 2 diabetes mellitus: a randomised trial.

AIMS/HYPOTHESIS: The Diabetes Aerobic and Resistance Exercise (DARE) study showed that aerobic and resistance exercise training each improved glycaemic control and that a combination of both was superior to either type alone in patients with type 2 diabetes mellitus. Here we report effects on patient-reported health status and well-being in the DARE Trial. METHODS: We randomised 218 inactive participants with type 2 diabetes mellitus in parallel to 22 weeks of aerobic exercise (n = 51), resistance exercise (n = 58), combined aerobic and resistance exercise (n = 57) or no exercise (control; n = 52). Intervention allocation was managed by a central office. Outcomes included health status as assessed by the physical and mental component scores of the Medical Outcomes Trust Short-Form 36-item version (SF-36) and well-being as measured by the Well-Being Questionnaire 12-item version (WBQ-12); these were measured at the Ottawa Hospital. RESULTS: Using a p value of 0.0125 for statistical significance due to multiple comparisons, mixed model analyses indicated that resistance exercise led to clinically but not statistically significant improvements in the SF-36 physical component score compared with aerobic exercise (Delta = 2.7 points; p = 0.048) and control (i.e. no exercise; Delta = 3.3 points; p = 0.015). For mental component scores, there were clinically important improvements favouring no (control) compared with resistance (Delta = 7.6 points; p < 0.001) and combined (Delta = 7.2 points; p < 0.001) exercise. No effects on WBQ-12 scores were noted. Overall, 59/218 (27%) of participants included in this analysis sustained an adverse event during the course of the study, including 16 participants in the combined exercise group, 19 participants in the resistance exercise group, 16 participants in the aerobic exercise group, and eight participants in the control group. All participants were included in the intent-to-treat analyses. The trial is now closed to follow-up. CONCLUSIONS/INTERPRETATION: Resistance exercise was better than aerobic or no exercise for improving physical health status in these patients. No exercise was superior to resistance or combined exercise for improving mental health status. Well-being was unchanged by intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00195884 FUNDING: This study was funded by the Canadian Institutes of Health Research (grant MCT-44155) and the Canadian Diabetes Association (The Lillian Hollefriend Grant).

Multicomponent, home-based resistance training for obese adults with type 2 diabetes: a randomized controlled trial.

PURPOSE: To investigate whether a home-based resistance training (RT) program that supplied high-quality equipment and qualified exercise specialists could provide benefits to obese patients with type 2 diabetes. METHODS: A total of 48 obese individuals with type 2 diabetes were randomly assigned to either an RT (n=27) or a control group (n=21). Those in the RT group received a multigym and dumbbells and performed RT 3 days per week for 16 weeks at home. A qualified exercise specialist supervised training, with supervision being gradually decreased throughout the study. Primary outcome measures included strength and hemoglobin-A1C, whereas secondary outcome measures included other cardiovascular risk markers, key social-cognitive constructs and health-related quality of life. RESULTS: Intention-to-treat analyses indicated a significant increase in upper and lower body strength for the RT group compared with controls (20-37% mean increases in the RT group). No significant reduction in A1C levels was observed. The RT group had unchanged high-density lipoprotein cholesterol levels in comparison to declines in the control group. Significant reductions in fasting insulin, and increases in RT-related self-efficacy and intentions, were also observed in the RT group. CONCLUSIONS: Supervised home-based RT with high-quality equipment was effective for improving strength, along with other secondary outcomes in obese patients with type 2 diabetes.

Fetal macrosomia and adolescence obesity: results from a longitudinal cohort study.

OBJECTIVE: To assess the association between fetal macrosomia and adolescent obesity. DESIGN: Longitudinal cohort study of the association between macrosomia and adolescent obesity. SUBJECTS: Between 1 October 2005 and 1 February 2007, a follow-up study of live-born infants born in 1993-1995 in Wuxi, a suburban area of Shanghai, was conducted. Subjects with birth weight > 4000 g were selected as the exposed. For each exposed subject, one subject with a birth weight of 2500-4000 g, matched by year of birth, sex of infant, and type of institute at birth, was chosen as non-exposed. Clinical data were collected by structured interview and physical examination. Obesity was defined as body mass index (weight (kg)/height (m(2))) higher than the sex-age-specific criteria by the working group on obesity in China. Distribution of baseline characteristics and adolescent obesity rate between the exposed and non-exposed groups was compared. RESULTS: A total of 1435 pairs of exposed and non-exposed subjects were included in the final analysis. No major difference in baseline characteristics (other than birth weight) was found between the exposed and non-exposed groups. Obesity rate was significantly higher in the exposed group (2.9%) than in the non-exposed group (1.6%). Adolescent obesity rates were 1.4, 1.9, 2.6, and 5.6%, respectively, in study subjects with a birth weight of 2500-3499, 3500-3999, 4000-4499, and > or =4500 g. The association between birth weight and adolescent obesity remained essentially the same when mother's demographic and anthropometric factors, breast feeding, and adolescent life-style factors were adjusted. CONCLUSION: Compared with infants of normal birth weight, infants with birth weight >4000 g, especially those >4500 g, are at increased risk of adolescent obesity.

Edmonton Obesity Staging System for Pediatrics, quality of life and fitness in adolescents with obesity.

BACKGROUND: Body mass index (BMI) is often used to diagnose obesity in childhood and adolescence but has limitations as an index of obesity-related morbidity. The Edmonton Obesity Staging System for Pediatrics (EOSS-P) is a clinical staging system that uses weight-related comorbidities to determine health risk in paediatric populations. The purpose of this study was to investigate the associations of EOSS-P and BMI percentile with quality of life (QOL), cardiorespiratory fitness (CRF) and muscular strength in adolescents with obesity. METHODS: Participants were enrolled at baseline in the Healthy Eating, Aerobic and Resistance Training in Youth trial (BMI = 34.6 ± 4.5 kg m-2, age = 15.6 ± 1.4 years, N = 299). QOL, CRF (peak oxygen uptake, VO2peak) and muscular strength were assessed by the Pediatric QOL Inventory (PedsQL), indirect calorimetry during a maximal treadmill test and eight-repetition maximum bench and leg press tests, respectively. Participants were staged from 0 to 3 (absent to severe health risk) according to EOSS-P. Associations were assessed using age-adjusted and sex-adjusted general linear models. RESULTS: Quality of life decreased with increasing EOSS-P stages (p < 0.001). QOL was 75.7 ± 11.4 in stage 0/1, 69.1 ± 13.1 in stage 2 and 55.4 ± 13.0 in stage 3. BMI percentile was associated with VO2peak (ß = -0.044 mlO2 kg-1 min-1 per unit increase in BMI percentile, p < 0.001), bench press (ß = 0.832 kg per unit increase in BMI percentile, p = 0.029) and leg press (ß = 3.992 kg, p = 0.003). There were no significant differences in treadmill time or VO2peak between EOSS-P stages (p > 0.05). CONCLUSION: As EOSS-P stages increase, QOL decreases. BMI percentile was negatively associated with CRF and positively associated with muscular strength.

Understanding low adherence to an exercise program for adolescents with obesity: the HEARTY trial.

INTRODUCTION: Despite efforts to improve adherence to physical activity interventions in youth with obesity, low adherence and attrition remain areas of great concern. OBJECTIVE: The study was designed to determine which physiological and/or psychological factors predicted low adherence in adolescents with obesity enrolled in a 6-month exercise intervention study aimed to improve body composition. METHODS: Three hundred four adolescents with obesity aged 14-18 years who volunteered for the HEARTY (Healthy Eating Aerobic and Resistance Training in Youth) randomized controlled trial completed physiological (body mass index, waist circumference, per cent body fat, resting metabolic rate and aerobic fitness) and psychological (body image, mood, self-esteem and self-efficacy) measures. RESULTS: One hundred forty-one out of 228 (62%) randomized to exercise groups had low adherence (completed <70% of the prescribed four exercise sessions per week) to the intervention protocol. Logistic regression revealed that there were no baseline demographic or physiological variables that predicted low adherence in the participants. Appearance concern (a subscale of body image) (odds ratio [OR] 1.46, 95% confidence interval [CI]: 1.01, 2.1, P = 0.04), depressive mood (OR 1.12, 95% CI: 1.01, 1.23, P = 0.03) and confused mood (OR 1.16, 95% CI: 1.05, 1.27, P = 0.003) (two subscales of mood) were significant predictors of low adherence. CONCLUSIONS: Adolescents with obesity who had higher appearance concerns and depressive and confused moods were less likely to adhere to exercise. Body image and mood should be screened to identify adolescents who may be at high risk of poor adherence and who may need concurrent or treatment support to address these psychological issues to derive maximal health benefits from an exercise programme.

Role of exercise training in polycystic ovary syndrome: a systematic review and meta-analysis.

Preliminary evidence suggests exercise in polycystic ovary syndrome (PCOS) may improve reproductive and cardiometabolic parameters. Our primary aim was to determine the impact of exercise training on reproductive health in women with PCOS. Our secondary aim was to determine the effect of exercise training on cardiometabolic indices. A systematic review of published literature was conducted using MEDLINE and EMBASE based on a pre-published protocol (PROSPERO CRD42017065324). The search was not limited by year. Randomized controlled trials, non-randomized controlled trials and uncontrolled trials that evaluated an exercise intervention in women with PCOS and reported reproductive outcomes were included. Reproductive outcomes were analysed semi-quantitatively and a meta-analysis was conducted for reported cardiometabolic outcomes. Of 517 screened abstracts, 14 studies involving 617 women with PCOS were included: seven randomized controlled trials, one non-randomized controlled trial and six uncontrolled trials. There were insufficient published data to describe the effect of exercise interventions on ovulation quantitatively, but semi-quantitative analysis suggested that exercise interventions may improve menstrual regularity, pregnancy and ovulation rates. Our meta-analysis found that exercise improved lipid profiles and decreased waist circumference, systolic blood pressure and fasting insulin. The impact of exercise interventions on reproductive function remains unclear. However, our meta-analysis suggests that exercise interventions may improve cardiometabolic profiles in women with PCOS.

Impacts of diabetes and hypertension on the risk of hospitalization among less educated people.

Coexisting hypertension increases the morbidity and mortality associated with diabetes, and may be more so in less educated people. We analysed data from 49 904 Canadians 40-64 years of age who participated in the Canadian Community Health Survey, 2000-2001. Multiple classification analysis was used to adjust for covariates. Population weight and design effect of the survey were taken into account in the analysis. The association between hypertension and hospitalization varied according to diabetes and education. The adjusted difference in hospitalization incidence attributable to hypertension was significantly higher for the lower education group than the higher education group, and such a pattern tended to be more pronounced among diabetic people. The adjusted incidence difference attributable to hypertension was higher in the diabetic group (8.8, 95% confidence interval (CI): 4.6, 13.0%) than in the non-diabetic group (4.6, 95% CI: 3.6, 5.6%) for people with low education, but was similar for those with well-educated people. Possible reasons for the modifying effect of education on the relationship among hypertension, diabetes and hospitalization were discussed.

The roles of catecholamines in glucoregulation in intense exercise as defined by the islet cell clamp technique.

Exercise at > 85% VO2max causes the greatest known physiological increases in glucose production rates (Ra). To define the relative roles of catecholamine versus glucagon/insulin responses in stimulating Ra, normal subjects in the postabsorptive state exercised at 87 +/- 2% VO2max during an islet cell clamp (IC): intravenous octreotide (somatostatin analog), 30 ng.kg-1.min-1; glucagon, 0.8 ng.kg-1.min-1; growth hormone, 10 ng.kg-1.min-1; and insulin adjusted to achieve euglycemia, then constant 56 +/- 7 min before exercise. Seven control subjects exercised without an IC. In four subjects (IC-1) with hormone infusions held constant during exercise, plasma insulin rose 76% and glucagon 35%, perhaps because of altered hemodynamics. In seven subjects (IC-2), hormone infusions were decreased stepwise during exercise and returned stepwise to initial rates during early recovery. Ra increased sixfold in control and both IC groups. Plasma norepinephrine and epinephrine likewise increased > 12-fold with no differences among groups; both catecholamines correlated closely with Ra. Because mixed venous blood plasma insulin declined and glucagon did not change in control subjects, the glucagon-to-insulin ratio increased from 0.20 to 0.26 (P = 0.02). In IC subjects, plasma insulin increased and glucagon was either constant (IC-2) or increased less than insulin, resulting in nonsignificant declines in the immunoreactive glucose-to-immunoreactive insulin ratio. Although a rise in insulin would have been expected to attenuate the Ra increment, this effect was overridden. The strong correlations of Ra with catecholamines and the similar Ra responses despite divergent glucagon-to-insulin responses are consistent with the primacy of catecholamines in regulation of Ra in intense exercise.

Acute postchallenge hyperinsulinemia predicts weight gain: a prospective study.

The relationships of insulin secretion and insulin action to body weight are incompletely understood. Obesity is associated with reduced sensitivity to insulin and high fasting and postprandial serum insulin levels. However, it is unknown whether insulin secretion rises to compensate for insulin resistance or high insulin secretion promotes body weight gain and the development of insulin resistance. To shed light on this question, we examined weight gain over an interval of 16.7 +/- 3.9 years (mean +/- SD) in 107 glucose-tolerant offspring (48 men, 59 women) of two parents with NIDDM. The offspring had a baseline intravenous glucose tolerance test, at which time they were aged 32.9 +/- 9.7 years, and only those who did not develop diabetes during the follow-up period were included. We estimated insulin sensitivity with the insulin sensitivity index from Bergman's minimal model of glucose disposal and acute insulin secretion from the incremental area under the insulin curve in the first 10 min of the intravenous glucose tolerance test. Weight-gain rate (g/year) was defined as the regression slope of each subject's body weight over time. High acute insulin secretion, young age, and low baseline percent ideal body weight (IBW) were each associated with a high rate of weight gain. After adjustment for differences in age and IBW, statistically significant effects of insulin sensitivity (P = 0.05) as well as acute insulin secretion (P = 0.001) were obtained. To estimate the effects of acute insulin secretion and insulin sensitivity on the average rate of weight gain (adjusting for age and IBW), the study group was stratified into four subgroups by dividing it at the medians of these two variables. Among those with low acute insulin secretion, weight-gain rate was the same regardless of whether insulin sensitivity was low or high (176 and 152 g/year, respectively). Among those with high acute insulin secretion, mean weight-gain rate was still rather low in those with low insulin sensitivity (271 g/year), but it was quite high in those with high insulin sensitivity (672 g/year; significantly higher than in all other subgroups). Therefore a high first-phase insulin response to intravenous glucose is a risk factor for long-term weight gain, and this effect is particularly manifested in insulin-sensitive individuals.

Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus.

Because of the role of insulin receptor substrate-1 in insulin action, the insulin receptor substrate-1 gene is a candidate gene for noninsulin-dependent diabetes mellitus (NIDDM). Modest associations between NIDDM and a GGG-->AGG single base substitution (corresponding to a glycine-->arginine amino acid substitution) in codon 972 of the gene have been found, but none reached statistical significance. To examine further how large a proportion of NIDDM cases could be caused by the mutation, we performed a stratified analysis combining the results from the 6 earlier studies and those from our panel of 192 unrelated NIDDM subjects and 104 healthy controls. In addition, we looked for a possibility that the codon 972 mutation plays a role only in the presence of certain conditions. Genomic DNA samples obtained from NIDDM cases and healthy controls were genotyped using a PCR-restriction fragment length polymorphism protocol modified for genomic DNA. The GGG-->AGG substitution was found in 5.7% of the diabetic subjects (11 of 192) and 6.9% of the controls (7 of 104). The difference between groups was not statistically significant, and it was not different from the results of other studies. The Mantel-Haenszel summary odds ratio across all studies was 1.49 (P < 0.05; 95% confidence intervals, 1.01-2.2). This summary odds ratio is consistent with a small proportion of NIDDM cases (approximately 3%) being caused by the mutation. Exploratory subgroup analyses on our panel suggested a clustering of NIDDM, the codon 972 mutation, and overweight, raising the hypothesis that the mutation may predispose to NIDDM only in the presence of excess body weight.

Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects.

Hyperglycemia with accompanying hyperinsulinemia occurs after brief, greater than 85% maximum oxygen consumption exercise to exhaustion in normal subjects and persists up to 60 min of recovery. To determine the importance of endogenous insulin secretion during and after intense exercise, responses to exercise of lean fit male post-absorptive insulin-dependent diabetes mellitus (IDDM) subjects, aged 18-34 yr, were compared with those of control subjects (C; n = 6). Three iv insulin protocols were employed: hyperglycemic (HG; n = 7) and euglycemic (EG1; n = 6) with constant insulin infusion, and euglycemic with doubled insulin infusion during recovery (EG2; n = 6). Overnight iv insulin was adjusted to achieve prolonged euglycemia (5.4 +/- 0.3 mmol/L) or hyperglycemia (8.6 +/- 0.3 mmol/L) before exercise. This allowed for comparisons between HG and EG1 (constant infusion) and between C and EG2 (to approximate physiological hyperinsulinemia by doubling the infusion rates at exhaustion for 56 +/- 7 min during recovery). Subjects exercised to 89-98% of their individual maximum oxygen consumption for 12.8 +/- 0.3 min. Glycemia increased to maximum values at 6 min of recovery (9.8 +/- 0.5 in HG, 6.9 +/- 0.4 in EG1, 7.3 +/- 0.3 in EG2, and 6.9 +/- 0.4 mmol/L in C). Whereas in EG2 and C, glucose returned to resting values in 50-80 min, it remained elevated at 120 min recovery in HG and EG1. During exercise, [3-3H]-glucose-determined glucose production increased markedly and exceeded disappearance in all groups, but less so in the HG subjects than in the other groups. An early recovery decline in glucose production did not differ among groups, but MCR (rate of glucose disappearance/glycemia) were markedly lower in HG and EG1, in whom plasma free insulin remained unchanged from 15 min of recovery onward (MCR, 1.6-1.9 vs. 2.3-2.8 mL/kg.min in C). Doubling the insulin infusion rate in EG2 restored the MCR response to that of C subjects. In summary, constant insulin infusion is insufficient to prevent prolonged postexercise hyperglycemia in IDDM subjects, even when provided at a rate sufficient to maintain normal resting glycemia and glucose turnover. The finding that increasing the rate of insulin infusion restored plasma glucose to normal in IDDM subjects suggests that the postexercise increase in insulin levels observed in normal subjects is essential to return plasma glucose to resting levels. Therefore, special strategies, differing from those for less strenuous exercise, are required for the management of insulin therapy in IDDM during and after intense exercise.

Glucoregulation during and after intense exercise: effects of beta-blockade.

To define the roles of beta- and alpha-adrenergic receptors in intense exercise, 17 lean healthy fit young males underwent 13.6 +/- 0.2 (+/-SE) min of cycle ergometer exercise: 6 at 100% maximum oxygen uptake (VO2max; MAX), 7 at their maximum possible (87 +/- 2.3%) during iv propranolol (P; 150 micrograms/kg bolus 30 min preexercise, then 80 micrograms/kg.min), and 7 (including 3 of the P subjects) at 87% VO2max (C) as controls for P. Plasma glucose increased from similar resting values to a peak in the early recovery period at 7.2 +/- 0.44 in MAX and 6.8 +/- 0.37 in P, but only 5.2 +/- 0.3 mmol/L in C. The rate of glucose appearance (Ra) rose about 8-fold in both MAX and P, but only 4-fold in C (P = 0.001). The rate of glucose disappearance (Rd) increased 4-fold in MAX, 5.5-fold in P, and 3-fold in C (P = 0.001). Plasma insulin declined during exercise (P < 0.05) in MAX and P, but not in C, whereas plasma glucagon increased modestly in all groups. The mean peak plasma norepinephrine level was 36.3 +/- 4.5 in MAX, 20.2 +/- 3.4 in P, and 15.2 +/- 2.9 nmol/L in C (P = 0.002); epinephrine reached 7141 +/- 1790 in MAX and 5605 +/- 1532 in P (P = NS), but only 1715 +/- 344 pmol/L in C (P = 0.03). Therefore, 1) an "unmasked" alpha-adrenergic effect, directly and/or via an altered glucagon/insulin ratio, probably contributed to increased Ra with P treatment; and 2) the marked facilitation of the increase in Rd with P supports a major role for beta-adrenergic restraint of Rd at this exercise intensity.

Glucoregulation during and after intense exercise: effects of beta-adrenergic blockade in subjects with type 1 diabetes mellitus.

In intense exercise (>80% maximum oxygen uptake) a huge, up to 8-fold increase in glucose production (Ra) is tightly correlated to marked increases in plasma norepinephrine (NE) and epinephrine. Both Ra and glucose uptake (Rd) are enhanced, not reduced, during beta-adrenergic blockade in normal subjects. Beta-blockade also caused a greater fall in immunoreactive insulin (IRI) during exercise, which could, in turn, have increased Ra directly or via an increased glucagon/insulin ratio. To control for adrenergic effects on endogenous insulin secretion, we tested type 1 diabetic subjects (DM) made euglycemic by overnight i.v. insulin that was kept constant in rate during and after exercise. Their responses to postabsorptive cycle ergometer exercise at 85-87% maximum oxygen uptake for approximately 14 min were compared to those of similar male control (CP) subjects. Six DM and seven CP subjects received i.v. 150 microg/kg propranolol over 20 min, then 80 microg/kg x min from -30 min, during exercise and for 60 min during recovery. Plasma glucose increased from similar resting values to peaks of 6.8 mmol/L in DM and 6.5 mmol/L in CP, then returned to resting values in CP within 20 min, but in DM, remained higher than in CP from 8-60 min (P = 0.049). Ra rose rapidly until exhaustion, to 13.3 mg/kg x min in CP and 11.6 in DM (P = NS). Ra declined rapidly in recovery, although somewhat more slowly in DM (P = 0.013 from 2-15 min). The Rd increased to 10.6 in CP and 9.2 mg/kg x min in DM (P = NS), then declined similarly in early recovery, but remained higher in CP from 50-100 min (P = 0.05). The rises in plasma glucose during exercise in both groups were thus due to the increments in Rd less than those in Ra. The higher recovery glucose in DM was due to the slower decline in Ra and the lower Rd in later recovery. IRI was higher in DM than in CP before exercise (P = 0.011), and whereas it decreased in CP (P < 0.05), it increased approximately 2-fold in DM, thus being higher throughout exercise (P = 0.003). The glucagon/insulin ratio was unchanged in DM, but increased in CP during exercise (P = 0.002). NE showed a rapid, marked increment during exercise to peak values of 23.7 nmol/L in CP and 25.7 nmol/L in DM (P = NS), and epinephrine showed parallel responses. Both correlated significantly with the Ra responses. In summary, the Ra responses of both DM and CP during exercise were greater than those of control unblocked subjects (previously reported) despite higher IRI (all exogenous) in DM. This suggests an important contribution of direct alpha-adrenergic stimulation to this Ra effect.

Effect of glycemic control on the kinetics of whole-body protein metabolism in obese subjects with non-insulin-dependent diabetes mellitus during iso- and hypoenergetic feeding.

We postulated whether interventions capable of restoring euglycemia would correct whole-body protein metabolism, shown previously to be elevated in hyperglycemic persons with non-insulin-dependent diabetes (NIDDM). The kinetics of protein metabolism were estimated in obese subjects with NIDDM in the hyper- and normoglycemic states during isoenergetic feeding and in the normoglycemic state induced by 4 wk of a very-low-energy diet (VLED) with constant protein intake. Seven NIDDM subjects [three males and four females with a body mass index (in kg/m2) of 39 +/- 2] were given a weight-maintaining, liquid formula providing 95 g protein/d for 15 d, followed in six subjects (two males and four females) for 27 d by a diet providing 1.7 MJ, 93 g protein derived from casein-soy, 13 g carbohydrate, 2 g fat, multivitamins and minerals, and a potassium bicarbonate supplement (32 mmol) per day. Exogenous insulin was given to achieve normoglycemia during the first 8 d of isoenergetic feeding. On days 6-8, 12-14, and 25-27, nitrogen flux rate was calculated from the urine [15N]urea enrichment by using the 60-h oral [15N]glycine method to obtain "integrated" feeding and fasting values. Rates of synthesis and breakdown were calculated from nitrogen flux. During isoenergetic feeding, normoglycemia was associated with more positive nitrogen balance (2.6 +/- 0.5 compared with -0.6 +/- 0.6 g N/d, P < 0.05); 18-23% lower nitrogen flux, and synthesis and breakdown rates (P < 0.05), and a 3% decrease in resting energy expenditure (P < 0.05). During the VLED, euglycemia was achieved but nitrogen balance, although it became less negative with time, never reached equilibrium. This was associated with significant (P < 0.05) decreases in the synthesis rate, resulting in net protein losses. Thus, the altered protein metabolism in moderately hyperglycemic NIDDM subjects was improved with exogenous insulin in doses sufficient to restore normoglycemia in the isoenergetic fed state, but it remained abnormal with a reduced non-protein energy intake. This suggests that protein metabolism is more sensitive to insulinization than was thought previously.