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NOS1AP genetic variation is associated with impaired healing of diabetic foot ulcers and diminished response to healing of circulating stem/progenitor cells.

ABSTRACT: It is unclear why many with diabetes develop foot ulcers (DFU) and why some do not heal. It could be associated with genetic variation. We have previously shown that NOS1AP variation is associated with lower extremity amputation in those with diabetes and that circulating stem progenitor cell concentration (SPC) is associated with impaired foot ulcer healing in those with diabetes. The goal of this study was to determine if NOS1AP variation is associated with impaired wound healing and with SPC mobilization in those with DFU. In longitudinal cohort study we demonstrate that NOS1AP variants rs16849113 and rs19649113 are associated with impaired wound healing and with SPC mobilization in those with DFU. We believe that further study of NOS1AP is merited and that it NOS1AP might be associated with a functional impairment.

SUBMITTER: Margolis DJ

PROVIDER: S-EPMC5747323 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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NOS1AP genetic variation is associated with impaired healing of diabetic foot ulcers and diminished response to healing of circulating stem/progenitor cells.

Margolis David J DJ Hampton Michelle M Hoffstad Ole O Mala D Scot DS Mirza Ziad Z Woltereck Diana D Shannon Steven S Troiano Michael A MA Mitra Nandita N Yang Ming M Bhopale Veena M VM Thom Stephen R SR

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 20170814 4

It is unclear why many with diabetes develop foot ulcers (DFU) and why some do not heal. It could be associated with genetic variation. We have previously shown that NOS1AP variation is associated with lower extremity amputation in those with diabetes and that circulating stem progenitor cell concentration (SPC) is associated with impaired foot ulcer healing in those with diabetes. The goal of this study was to determine if NOS1AP variation is associated with impaired wound healing and with SPC ...[more]

PMID: 28755516

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Project description:INTRODUCTION:One in four diabetes patients will develop a foot ulcer over their lifetime. The role of glycaemic control in the healing of foot ulcers in diabetes patients is not supported by randomised controlled trial (RCT) data. OBJECTIVES:To determine the feasibility of an RCT of glycaemic control with intensive insulin therapy in diabetic foot ulcer, by assessing: entry criteria, fasting capillary blood glucose (FCBG) medication satisfaction and sensitivity of different ulcer-healing endpoints to glycaemic control. DESIGN:Two substudies: one cross-sectional and one single-arm prospective. SETTING:Single-centre secondary care diabetic foot clinic in New Zealand. PARTICIPANTS:Substudy 1: 78 participants consisting of all people ?18 years with a diabetic foot ulcer presenting to the clinic over 35 weeks in 2015.Substudy 2: 15 participants from Substudy 1 consenting to intensive insulin therapy. INTERVENTION:Substudy 1: None.Substudy 2: Intensive insulin therapy with standard podiatry care over 24 weeks. OUTCOME:Substudy 1: Proportion of participants satisfying potential RCT entry criteria; medication satisfaction (Diabetes Medication Satisfaction).Substudy 2: FCBG, index ulcer healing time, index ulcer size, health-related quality of life (HRQoL; EuroQol 5 Dimensions 5 Levels and Diabetic Foot Ulcer Scale-Short Form). RESULTS:Proportion in Substudy 1 satisfying all entry criteria was 31% (95% CI 21 to 42). FCBG values decreased between baseline and study end (difference -3.7 mmol/L, 95% CI -6.5 to -0.8); 83% (95% CI 44 to 95) of ulcers healed by 24 weeks. FCBG correlated negatively with medication satisfaction. Ulcer area logarithm was most sensitive to FCBG changes, displaying significant negative correlation with HRQoL outcomes. Detecting a 30% between-group difference in this outcome (80% power, ?=5%) requires 220 participants per arm, achievable within 1 year with 15 centres similar to study setting. CONCLUSIONS:An adequately powered RCT requires cooperation between a large number of centres. Ulcer area logarithm should be primary endpoint. TRIAL REGISTRATION NUMBER:ANZCTR ACTRN12617001414303.

Dataset Information

NOS1AP genetic variation is associated with impaired healing of diabetic foot ulcers and diminished response to healing of circulating stem/progenitor cells.

Publications

NOS1AP genetic variation is associated with impaired healing of diabetic foot ulcers and diminished response to healing of circulating stem/progenitor cells.

Similar Datasets

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