Obesity Related-Energy Expenditure & Peripheral Neuropathy in Obesity and Type 1 Diabetes

Lim, Jonathan Zhang Ming ORCID: 0000-0003-3682-8910
(2023) Obesity Related-Energy Expenditure & Peripheral Neuropathy in Obesity and Type 1 Diabetes. PhD thesis, University of Liverpool.

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BACKGROUND: Decreased resting energy expenditure (REE), activity energy expenditure, diet-induced thermogenesis, or a combination of all these components, plays an important role in the development of obesity. The positive energy balance and higher respiratory quotient (RQ) from the indirect calorimetry (IC), a proxy for substrate oxidation, subsequently predicts weight gain. The aim was (i) to evaluate the effectiveness of providing IC-guided dietary intervention (INT) versus standard of care (SC) during weight loss intervention in obesity; (ii) to evaluate if the baseline RQ or change in RQ correlates with the observed weight loss. Obesity is an independently associated risk factor for peripheral neuropathy, but its contribution in the development of peripheral neuropathy remains unclear. The aim was (iii) to evaluate the prevalence of obesity-mediated peripheral neuropathy compared to primarily hyperglycaemia-driven neuropathy in type 1 diabetes (T1D); (iv) to investigate the role of corneal confocal microscopy (CCM) in detecting diabetic peripheral neuropathy (DPN) in diabetic neuropathic foot ulcer (DFU) in T1D. METHODS: A randomized controlled trial was performed to evaluate INT vs SC in people with obesity. A systematic review was performed to evaluate current literature to address the question “Does baseline RQ or change in RQ during weight intervention correlate with observed weight loss?” A prospective cross-sectional study was performed to characterize neuropathy phenotype and compare corneal nerve morphology using CCM between people with T1D versus obesity. CCM and other measures of neuropathy were utilized to explore the large and small nerve fibre deficits between people with T1D-DPN and T1D-DFU. RESULTS: The systematic review (ten RCTs included) demonstrated that baseline or change in RQ during weight loss intervention does not correlate with weight loss. IC-guided (INT) group had greater weight loss (P<0.001), reduced fat-mass (p<0.001), decreased REE (p=0.016) and decreased RQ (p=0.018) compared to SC. Greater centripetal adiposity was associated with peripheral neuropathy with 33% prevalence in obesity, compared with 50% prevalence in T1D. However, the RQ did not correlate with small and large fibre deficits in peripheral neuropathy. Greater small and large nerve fibre deficits were observed in a progressive manner from T1D to T1D-DPN to T1D-DFU. For the diagnosis of DFU in T1D, ROC analysis showed that corneal nerve fibre density (CNFD) (AUC of 0.92; SN 0.88; SP 0.72) and corneal nerve branch density (CNBD) (AUC 0.85; SN 0.88; SP 0.72) has high sensitivity and specificity. CONCLUSIONS: Providing EE information improved compliance to dietary intervention. Substrate oxidation alters in response to macronutrient diet composition and degree of energy restriction. Greater centripetal adiposity leads to microvascular dysfunction resulting in peripheral neuropathy. CCM is a useful biomarker to detect small nerve fibre degeneration in people with obesity and T1D, with high diagnostic sensitivity and specificity to detect DFU in T1D.

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 16 Feb 2023 11:37
Last Modified: 16 Feb 2023 11:37
DOI: 10.17638/03167786
  • Wilding, John
  • Alam, Uazman
URI: https://livrepository.liverpool.ac.uk/id/eprint/3167786