Strength training is more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Type 2 diabetes in people in the healthy weight BMI category (<25 kg/m2), herein defined as 'normal-weight type 2 diabetes', is associated with sarcopenia (low muscle mass). Given this unique body composition, the optimal exercise regimen for this population is unknown. METHODS: We conducted a parallel-group RCT in individuals with type 2 diabetes (age 18-80 years, HbA1c 47.5-118.56 mmol/mol [6.5-13.0%]) and BMI <25 kg/m2). Participants were recruited in outpatient clinics or through advertisements and randomly assigned to a 9 month exercise programme of strength training alone (ST), aerobic training alone (AER) or both interventions combined (COMB). We used stratified block randomisation with a randomly selected block size. Researchers and caregivers were blinded to participants' treatment group; however, participants themselves were not. Exercise interventions were conducted at community-based fitness centres. The primary outcome was absolute change in HbA1c level within and across the three groups at 3, 6 and 9 months. Secondary outcomes included changes in body composition at 9 months. Per adherence to recommended exercise protocol (PP) analysis included participants who completed at least 50% of the sessions. RESULTS: Among 186 individuals (ST, n=63; AER, n=58; COMB, n=65) analysed, the median (IQR) age was 59 (53-66) years, 60% were men and 83% were Asian. The mean (SD) HbA1c level at baseline was 59.6 (13.1) mmol/mol (7.6% [1.2%]). In intention-to-treat analysis, the ST group showed a significant decrease in HbA1c levels (mean [95% CI] -0.44 percentage points [-0.78, -0.12], p=0.002), while no significant change was observed in either the COMB group (-0.35 percentage points, p=0.13) or the AER group (-0.24 percentage points, p=0.10). The ST group had a greater improvement in HbA1c levels than the AER group (p=0.01). Appendicular lean mass relative to fat mass increased only in the ST group (p=0.0008), which was an independent predictor of HbA1c change (beta coefficient -7.16, p=0.01). Similar results were observed in PP analysis. Only one adverse event, in the COMB group, was considered to be possibly associated with the exercise intervention. CONCLUSIONS/INTERPRETATION: In normal-weight type 2 diabetes, strength training was superior to aerobic training alone, while no significant difference was observed between strength training and combination training for HbA1c reduction. Increased lean mass relative to decreased fat mass was an independent predictor of reduction in HbA1c level. TRIAL REGISTRATION: ClinicalTrials.gov NCT02448498. FUNDING: This study was funded by the National Institutes of Health (NIH; R01DK081371).

Associations between accurate measures of adiposity and fitness, blood proteins, and insulin sensitivity among South Asians and Europeans.

Objective: South Asians (SAs) may possess a unique predisposition to insulin resistance (IR). We explored this possibility by investigating the relationship between 'gold standard' measures of adiposity, fitness, selected proteomic biomarkers, and insulin sensitivity among a cohort of SAs and Europeans (EURs). Methods: A total of 46 SAs and 41 EURs completed 'conventional' (lifestyle questionnaires, standard physical exam) as well as 'gold standard' (dual energy X-ray absorptiometry scan, cardiopulmonary exercise test, and insulin suppression test) assessments of adiposity, fitness, and insulin sensitivity. In a subset of 28 SAs and 36 EURs, we also measured the blood-levels of eleven IR-related proteins. We conducted Spearman correlation to identify correlates of steady-state plasma glucose (SSPG) derived from the insulin suppression test, followed by multivariable linear regression analyses of SSPG, adjusting for age, sex and ancestral group. Results: Sixteen of 30 measures significantly associated with SSPG, including one conventional and eight gold standard measures of adiposity, one conventional and one gold standard measure of fitness, and five proteins. Multivariable regressions revealed that gold standard measures and plasma proteins attenuated ancestral group differences in IR, suggesting their potential utility in assessing IR, especially among SAs. Conclusion: Ancestral group differences in IR may be explained by accurate measures of adiposity and fitness, with specific proteins possibly serving as useful surrogates for these measures, particularly for SAs.

Trabecular Bone Score (TBS) Varies with Correction for Tissue Thickness Versus Body Mass Index: Implications When Using Pediatric Reference Norms.

Trabecular bone score (TBS) derived from secondary analysis of lumbar spine dual-energy X-ray absorptiometry (DXA) scans improves fracture prediction independent of bone mineral density (BMD) in adults. The utility of TBS to assess fracture risk in younger patients has not been established because pediatric norms have been lacking. Robust TBS reference data from the Bone Mineral Density in Childhood Study (BMDCS) have been published. TBS values for the BMDCS study were derived using an algorithm that accounts for tissue thickness (TBSTH ) rather than the commercially available algorithm that adjusts for body mass index (BMI; TBSBMI ). We examined the magnitude of differences in TBSTH and TBSBMI in a cohort of 189 healthy youth. TBS values using both algorithms increased with age and pubertal development in a similar pattern. However, TBSBMI values were systematically and significantly higher than TBSTH (mean = 0.06, p < 0.0001). The difference between calculated TBSBMI and TBSTH was not uniform. Differences were greater at lower TBS values, in males, in older individuals, in those at later Tanner stages, and in those with a greater BMI Z-score. These systematic differences preclude the development of a simple formula to allow conversion of TBSBMI to TBSTH "equivalents." Because of these systematic differences in these two algorithms, using an individual's TBSBMI to calculate a Z-score using the BMDCS TBSTH reference values results in a falsely higher TBS Z-score (differences mean = 0.73, interquartile range [IQR] = 0.3 to 1.6). Until TBSTH software for Hologic DXA equipment becomes commercially available, BMDCS TBS reference norms should not be used. © 2023 American Society for Bone and Mineral Research (ASBMR).

Correlates of low bone mass in children with generalized forms of epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is a family of rare, heterogeneous, genetic disorders characterized by fragility of the skin and mucous membranes. Reduced bone mass and fractures have been recognized as complications of generalized forms of EB. OBJECTIVES: We sought to describe the range and to estimate the prevalence of low bone mass in children with generalized EB, and to identify correlates of low bone mass in this population. METHODS: This was a prospective, observational study of 24 patients with generalized EB. Each patient completed a history, physical examination, laboratory studies, bone age, and x-rays of the lumbar spine. Those aged 6 years and older underwent dual energy x-ray absorptiometry scans of the lumbar spine. Primary outcomes were areal bone mineral density (aBMD) based on chronologic age, bone age, and adjusted for height Z-score. Descriptive statistics were used to summarize results, and linear regression was used to determine factors associated with low aBMD. RESULTS: Mean lumbar spine aBMD Z-scores ± SD were: -2.6 ± 1.4 for chronologic age, -1.7 ± 1.3 for bone age, and -1.0 ± 1.2 after adjusting for height Z-score. aBMD Z-scores were less than or equal to -2 in 64% for chronologic age, 50% for bone age, and 28% after adjusting for height Z-score. aBMD correlated with height Z-score, weight Z-score, extensive blistering, immobility, albumin, hemoglobin, iron, erythrocyte sedimentation rate, and c-reactive protein values. LIMITATIONS: Small sample size was a limitation. CONCLUSIONS: Children with severe, generalized recessive dystrophic EB have low aBMD for age. Deficits in aBMD were reduced after adjusting for delayed skeletal maturation and small body size.

Effect of oral contraceptives on weight and body composition in young female runners.

PURPOSE: To examine the effect of oral contraceptives (OC) on body weight, fat mass, percent body fat, and lean mass in young female distance runners. METHODS: The study population consisted of 150 female competitive distance runners aged 18-26 yr who had participated in a 2-yr randomized trial of the effect of the OC Lo/Ovral (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) on bone health. Weight and body composition were measured approximately yearly by balance beam scales and dual-energy x-ray absorptiometry, respectively. RESULTS: Women randomized to the OC group tended to gain slightly less weight (adjusted mean difference (AMD) = -0.54 +/- 0.31 kg.yr, P = 0.09) and less fat (AMD = -0.35 +/- 0.25 kg.yr, P = 0.16) than those randomized to the control group. OC assignment was associated with a significant gain in lean mass relative to controls among eumenorrheic women (those who had 10 or more menstrual cycles in the year before baseline; AMD = 0.77 +/- 0.17 kg.yr, P < 0.0001) but not among women with fewer than 10 menstrual cycles in that year (AMD = 0.02 +/- 0.35 kg.yr, P = 0.96). Treatment-received analyses yielded similar results. CONCLUSION: This randomized trial confirms previous findings that OC use does not cause weight or fat mass gain, at least among young female runners. Our finding that this OC is associated with lean mass gain in eumenorrheic runners, but not in those with irregular menses, warrants examination in other studies.

The effect of oral contraceptives on bone mass and stress fractures in female runners.

PURPOSE: To determine the effect of oral contraceptives (OC) on bone mass and stress fracture incidence in young female distance runners. METHODS: One hundred fifty competitive female runners ages 18-26 yr were randomly assigned to OC (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) or control (no intervention) for 2 yr. Bone mineral density (BMD) and content (BMC) were measured yearly by dual x-ray absorptiometry. Stress fractures were confirmed by x-ray, magnetic resonance imaging, or bone scan. RESULTS: Randomization to OC was unrelated to changes in BMD or BMC in oligo/amenorrheic (N=50) or eumenorrheic runners (N=100). However, treatment-received analyses (which considered actual OC use) showed that oligo/amenorrheic runners who used OC gained about 1% per year in spine BMD (P<0.005) and whole-body BMC (P<0.005), amounts similar to those for runners who regained periods spontaneously and significantly greater than those for runners who remained oligo/amenorrheic (P<0.05). Dietary calcium intake and weight gain independently predicted bone mass gains in oligo/amenorrheic runners. Randomization to OC was not significantly related to stress fracture incidence, but the direction of the effect was protective in both menstrual groups (hazard ratio [95% CI]: 0.57 [0.18, 1.83]), and the effect became stronger in treatment-received analyses. The trial's statistical power was reduced by higher-than-anticipated noncompliance. CONCLUSION: OC may reduce the risk for stress fractures in female runners, but our data are inconclusive. Oligo/amenorrheic athletes with low bone mass should be advised to increase dietary calcium and take steps to resume normal menses, including weight gain; they may benefit from OC, but the evidence is inconclusive.

Normalization of bone density in a previously amenorrheic runner with osteoporosis.

PURPOSE: To examine changes in bone mineral density (BMD) and bone mineral content (BMC) in relation to pharmacological and nutritional interventions in a distance runner diagnosed with the female athlete triad of disordered eating, amenorrhea, and osteoporosis. METHODS: BMD of the lumbar spine (L2-L4) and total proximal femur were measured from ages 22.9 to 30.8 yr using dual x-ray absorptiometry (DXA). RESULTS: At age 22.9, the patient presented with primary amenorrhea, low body weight (BMI: 15.8 kg.m(-2)), and low BMD in the spine (74% of normal, T score: -2.50) and hip (80% of normal, T score: -1.54). For the next 2 yr, the patient took oral contraceptives to induce menses, but continued to maintain a low weight. Her BMD remained unchanged. At age 25.1 yr, she decided to gain weight and improve her nutrition, resulting in small increases in spinal BMD (+1.1%), hip BMD (+1.6%), and total body BMC (+7.6%) in 4 months. From ages 25.4 to 30.8 yr, the patient continued to gain weight, eventually reaching a healthy BMI of 21.3 kg.m(-2); correspondingly, since baseline, her BMD had increased 25.5% in the spine and 19.5% in the hip, bringing her BMD to within normal values (spine: 94% of normal, hip: 96% of normal). CONCLUSION: This case illustrates that even if skeletal development is interrupted in adolescence, there is still the potential for "catch-up" in BMD well into the third decade of life. Reversal of large bone density deficits in this patient can be attributed to improved nutrition and weight gain but not to hormone replacement.

Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women.

Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicory oligofructose and long-chain inulin (Synergy1; SYN1) would increase the absorption of both Ca and Mg and alter markers of bone turnover. Fifteen postmenopausal women (72.2 (SD 6.4) years) were treated with SYN1 or placebo for 6 weeks using a double-blind, placebo-controlled, cross-over design. Fractional Ca and Mg absorption were measured using dual-tracer stable isotopes before and after treatment. Bone turnover markers were measured at baseline, 3 and 6 weeks. Fractional absorption of Ca and Mg increased following SYN1 compared with placebo (P < 0.05). Bone resorption (by urinary deoxypyridinoline cross-links) was greater than baseline at 6 weeks of active treatment (P < 0.05). Bone formation (by serum osteocalcin) showed an upward trend at 3 weeks and an increase following 6 weeks of SYN1 (P < 0.05). Closer examination revealed a variation in response, with two-thirds of the subjects showing increased absorption with SYN1. Post hoc analyses demonstrated that positive responders had significantly lower lumbar spine bone mineral density than non-responders (dual X-ray absorptiometry 0.887 +/- 0.102 v. 1.104 +/- 0.121 g/cm2; P < 0.01), and changes in bone turnover markers occurred only in responders. These results suggest that 6 weeks of SYN1 can improve mineral absorption and impact markers of bone turnover in postmenopausal women. Further research is needed to determine why a greater response was found in women with lower initial spine bone mineral density.

Novel, high-frequency, low-strain mechanical loading for premenopausal women with low bone mass: early findings.

Universally safe and effective methods of mechanically loading the skeleton to improve strength and prevent fracture have yet to be identified. To be osteogenic, mechanical strains must either be of substantial magnitude or applied at high frequency (>15 Hz). High-magnitude loads place frail bones at risk of fracture. Active loading can rarely be achieved at a frequency faster than 2-3 Hz. A 12-month, uncontrolled, prospective, pilot intervention trial was conducted with five premenopausal Caucasian women with low bone mass. Subjects stood on a vibrating platform (Optimass model 1000 Mechanical Strain Device) and received a 0.2-g stimulus at 30 Hz, 2 x 10 min/day, for 12 months. Bone mineral density (BMD) was measured at the whole body, lumbar spine, proximal femora (PF), and distal radius at baseline and 6 and 12 months by DXA (Hologic QDR-1000/W). Blood and urine were collected at baseline and 3, 6, 9 and 12 months for markers of bone resorption and formation. A mean percent BMD increase of 2.03% +/- 0.33% (P < 0.02) was detected at the non-dominant PF after 12 months. Trends for increases were observed at all other sites with the exception of the dominant PF. No uniform trends were observed in bone resorption and formation markers. One subject, on Fosamax, increased BMD by 6% at the lumbar spine and 4.4% at the distal radius. Preliminary findings provide evidence of a possible positive response of regions of low bone mass to brief daily bouts of in-home, passive, noninvasive, low-strain, high-frequency, mechanical loading.