Browsing by Subject "Metabolic"

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    The human preference for symmetric walking often disappears when one leg is constrained
    (The Physiological Society, 2021) Browne, Michael G.; Smock, Cameron S.; Roemmich, Ryan T.; Medicine, School of Medicine
    We hypothesized that minimization of metabolic power could drive people to walk asymmetrically when one leg is constrained We studied healthy young adults and independently constrained one or both step lengths to be markedly shorter or longer than preferred using visual feedback When one leg was constrained to take a shorter or longer step than preferred, asymmetric walking patterns were less metabolically costly than symmetric walking patterns When one leg was constrained to take a shorter or longer step than preferred and the other leg was allowed to move freely, most participants naturally adopted an asymmetric gait People may prefer to walk asymmetrically to minimize metabolic power when the function of one leg is constrained during fixed-speed treadmill walking ABSTRACT: The bilateral symmetry inherent in healthy human walking is often disrupted in clinical conditions that primarily affect one leg (e.g. stroke). This seems intuitive: with one leg constrained, gait becomes asymmetric. However, the emergence of asymmetry is not inevitable. Consider that symmetric walking could be preserved by matching the movement of the unconstrained leg to that of the constrained leg. While this is theoretically possible, it is rarely observed in clinical populations. Here, we hypothesized that minimization of metabolic power could drive people to walk asymmetrically when one leg is constrained, even when symmetric walking remains possible. We tested this hypothesis by performing two experiments in healthy adults. In Experiment 1, we constrained one step to be markedly shorter or longer than preferred. We observed that participants could significantly reduce metabolic power by adopting an asymmetric gait (one short/long step, one preferred step) rather than maintaining a symmetric gait (bilateral short/long steps). Indeed, when allowed to walk freely in this situation, participants naturally adopted a less effortful asymmetric gait. In Experiment 2, we applied a milder constraint that more closely approximated magnitudes of step length asymmetry that are observed in clinical populations. Responses in this experiment were more heterogeneous, though most participants adopted an asymmetric gait. These findings support two central conclusions: (1) symmetry is not necessarily energetically optimal in constrained human walking, and (2) people may prefer to walk asymmetrically to minimize metabolic power when one leg is constrained during fixed-speed treadmill walking, especially when the constraint is large.
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    Index60 Is Superior to HbA1c for Identifying Individuals at High Risk for Type 1 Diabetes
    (Oxford University Press, 2022) Jacobsen, Laura M.; Bundy, Brian N.; Ismail, Heba M.; Clements, Mark; Warnock, Megan; Geyer, Susan; Schatz, Desmond A.; Sosenko, Jay M.; Pediatrics, School of Medicine
    Context: HbA1c from ≥ 5.7% to < 6.5% (39-46 mmol/mol) indicates prediabetes according to American Diabetes Association guidelines, yet its identification of prediabetes specific for type 1 diabetes has not been assessed. A composite glucose and C-peptide measure, Index60, identifies individuals at high risk for type 1 diabetes. Objective: We compared Index60 and HbA1c thresholds as markers for type 1 diabetes risk. Methods: TrialNet Pathway to Prevention study participants with ≥ 2 autoantibodies (GADA, IAA, IA-2A, or ZnT8A) who had oral glucose tolerance tests and HbA1c measurements underwent 1) predictive time-dependent modeling of type 1 diabetes risk (n = 2776); and 2) baseline comparisons between high-risk mutually exclusive groups: Index60 ≥ 2.04 (n = 268) vs HbA1c ≥ 5.7% (n = 268). The Index60 ≥ 2.04 threshold was commensurate in ordinal ranking with the standard prediabetes threshold of HbA1c ≥ 5.7%. Results: In mutually exclusive groups, individuals exceeding Index60 ≥ 2.04 had a higher cumulative incidence of type 1 diabetes than those exceeding HbA1c ≥ 5.7% (P < 0.0001). Appreciably more individuals with Index60 ≥ 2.04 were at stage 2, and among those at stage 2, the cumulative incidence was higher for those with Index60 ≥ 2.04 (P = 0.02). Those with Index60 ≥ 2.04 were younger, with lower BMI, greater autoantibody number, and lower C-peptide than those with HbA1c ≥ 5.7% (P < 0.0001 for all comparisons). Conclusion: Individuals with Index60 ≥ 2.04 are at greater risk for type 1 diabetes with features more characteristic of the disorder than those with HbA1c ≥ 5.7%. Index60 ≥ 2.04 is superior to the standard HbA1c ≥ 5.7% threshold for identifying prediabetes in autoantibody-positive individuals. These findings appear to justify using Index60 ≥ 2.04 as a prediabetes criterion in this population.
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    The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening
    (Springer Verlag, 2020-03) Jacobsen, Laura M.; Bocchino, Laura; Evans-Molina, Carmella; DiMeglio, Linda; Goland, Robin; Wilson, Darrell M.; Atkinson, Mark A.; Aye, Tandy; Russell, William E.; Wentworth, John M.; Boulware, David; Geyer, Susan; Sosenko, Jay M.; Medicine, School of Medicine
    Aims/hypothesis: Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. Methods: Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1-49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. Results: Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%. Conclusions/interpretation: Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress.