Association between glycaemic control and diabetic foot outcomes: Dark side of the moon?

Several pathogenic abnormalities have been demonstrated in diabetes, notably dysfunctional keratinocytes, abnormal angiogenesis, changes to innate immunity, and irregularities of matrix metalloproteinase turnover.4,5 In in-vitro models, high wound glucose directly impaired epidermal growth factor receptor (EGFR) signalling6 and fibroblast cell migration.7 In line with this, a potential for improved wound healing has been suggested when blood sugar is optimised.8,9 From a patient's perspective, faster wound healing and avoidance of amputation are key outcomes. [...]is there clinical evidence to support the notion that DFU outcomes are linked to stringent diabetes control? From the 47 studies included in the quantitative synthesis (n = 12,604 DFUs), glycated haemoglobin (HbA1c) levels >8% (64 mmol/mol) significantly increased the pooled odds ratio (OR) of LEA (OR: 4.80; 95% confidence interval [CI]: 2.83–8.13).10 Fasting glucose levels >126 mg/dl (7.0 mmol/mol) was also associated with increased risk (pooled OR: 1.46; 95% CI: 1.02–2.09). [...]the authors calculated the pooled means for many studies but did not have access to individual data.10 These unadjusted ORs were combined with studies with adjusted ORs, increasing the probability of bias.10 Third, an association was seen for HbA1c and LEA only when HbA1c was treated as a categorical, not a continuous measure.10 Dichotomising a continuous variable (HbA1c) may only be justified when its distribution is highly skewed, or it has a non-linear functional relationship to wound healing or LEA.