DOI: 10.17354/SUR/2016/25 Original Article Hemoglobin A1c in Patients: A Predictor of Healing Rate

R Shashanka1, A Palachandra2

1Assistant Professor, Department of General Surgery, Hassan Institute of Medical Sciences, Hassan, Karnataka, India, 2Associate Professor, Department of General Surgery, Hassan Institute of Medical Sciences, Hassan, Karnataka, India

Abstract

Introduction: as assessed by hemoglobin A1c (HbA1c) may be an important biomarker in predicting healing rate in diabetic patients. Thus, the present study also intended to relate the HbA1c levels to in diabetic patients. Materials and Methods: A total of 100 diabetic patients with foot ulcers of variable sizes were included in the study and were assigned into two groups based on HbA1c levels. Mean area, length, and width of the were measured at baseline and during next subsequent visits in either group. Results: Mean area, length, and width of the ulcer at baseline did not show any signifi cant difference, whereas a statistically signifi cant (p < 0.01) difference was observed in mean measurement change per day between Groups A and B patients. Conclusion: This study suggests that slower wound healing is associated with increased HbA1c levels and can be considered as an independent biomarker in assessing wound healing in patients with diabetic foot ulcer. Keywords: Diabetic foot ulcer, Hemoglobin A1c level, Healing

INTRODUCTION microvascular and perhaps macrovascular complications of .2 A1c (HbA1c) levels are lobally, as the prevalence of diabetes mellitus is considered as a gold standard measurement of patients Gincreasing and so are the long-term complications. glycemic control over the previous 3 months.3 Diabetic foot ulcer is one the most common chronic complications that adds to the morbidity of the patients. Optimization of the wound healing process can be done by The majority of the foot ulcers are unrecognized at identifying modifiable factors that aids in healing. Several initial stages because of associated neuropathy, prognostic factors associated with wound healing in and further progresses rapidly to a stage where limb diabetic patients have been identified in previous studies. salvage might not be possible leading to . However, the majority of the studies have focused on Consequently, this leads to repeated hospitalization, non-modifiable variables such as baseline wound area4-6 economic burden to the patients.1 duration of the wound,7 age,8 and sex.9 Only a few studies have quantified healing rates. In the previous studies, it A strong association is observed between the risk remains unclear whether HbA1c, a standard measure of of diabetic complications and levels of glycemia. glycemia over 2-3 months, is related to wound healing Tighter glycemic control is shown to reduce the risk of rate.6,8,10

Access this article online However, only a few studies have suggested that HbA1c levels can be considered as an important biomarker Month of Submission : 12-2015 in predicting wound healing rate in diabetic patients.1 Month of Peer Review : 01-2016 Thus, this study is intended to find the association of Month of Acceptance : 01-2016 HbA1c levels to wound healing rate in diabetic patients Month of Publishing : 05-2016 www.surgeryijss.com and whether HbA1c level can be used as a predictor of wound healing.

Corresponding Author: Dr. R Shashanka, Department of General Surgery, Hassan Institute of Medical Sciences, Hassan - 573 201, Karnataka, India. Phone: +91-9844577096. E-mail: [email protected]

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MATERIALS AND METHODS RESULTS

A prospective study was conducted in the Hassan Institute Lower extremity amputation is a long-term major concern of Medical Sciences, Hassan, Karnataka between August in patients suffering from diabetes mellitus and is often 2013 and August 2015. preceded by neglected and untreated foot ulcers. This study aimed to identify the association of HbA1c levels in A total of 100 diabetic patients with foot ulcers of variable diabetic foot ulcer healing rate and also to find whether sizes were included in the study and were divided into it can be used as the predictor of wound healing. two groups after HbA1c level was recorded. This study included 100 diabetic patients with the Group A: Diabetic patients with HbA1c level >7% foot ulcer and was divided into two groups. Group A Group B: Diabetic patients with HbA1c level <7%. comprised 50 individuals with HbA1c levels <7% and Group B with HbA1c >7%. Inclusion Criteria All diagnosed diabetic patients with foot ulceration. Group A individuals showed mean HbA1c levels of 6.50 ± 0.441 and Group B with the mean value of 10.40 ± 1.550. Exclusion Criteria The mean ulcer size at baseline in Group A was 5.08 ± Diabetic patients with gangrenous foot associated 9.08 and the mean ulcer size in Group B individuals was venous disease, autoimmune, rheumatic disease, and 6.01 ± 10.2, and the difference in baseline ulcer area malignancy. between the two groups was not statistically significant (p = 0.631) (Table 1). When wound length was considered at baseline, Group A patients showed a mean A written informed consent was obtained from all the length of 2.01 ± 2.9 and in Group B 2.23 ± 2.86, and participants who were included in the study. Ethical difference in mean wound length between the two groups clearance was obtained from the Institutional Ethics was insignificant with p = 0.703 (Table 2). Baseline mean Committee. wound width in Group A individuals was 2.36 ± 2.74 and in Group B was 2.65±3.02 and was also statistically Detailed history and physical examination were carried insignificant with p = 0.616 (Table 3). out for every subject. Duration, size, site of the ulcer and clinical assessment for signs of were noted in all the individuals. Table 1: Mean ulcer area at baseline in Groups A and B Variable Group Sample Mean±SD t value df P score Area of ulcer was determined by multiplying the size longest and the widest diameter and expressed in Wound HbA1c 50 5.08±9.08 0.481 98 0.631 square centimeter (cm2) after tracing on graph paper. area <7 baseline Wound grading was done according to the University HbA1c 50 6.01±10.2 >7 of Texas wound classification system as Grade I (Superficial wound without involving , capsule, HbA1c: Hemoglobin A1c, SD: Standard deviation or bone), Grade II (Wound penetrating to tendon or capsule), and Grade III (Wound penetrating bone Table 2: Mean ulcer length at baseline in Groups A and B or joint).11 Variable Group Sample Mean±SD t value df P score size Standard treatment was given to all the study subjects, Wound HbA1c 50 2.01±2.9 0.381 98 0.703 which included removal of non-viable tissue, local length <7 dressing, control of blood glucose levels, and offloading baseline HbA1c 50 2.23±2.86 the . >7 HbA1c: Hemoglobin A1c, SD: Standard deviation The change in wound area in cm2 per day was calculated taking into consideration the size of a wound on the first Table 3: Mean ulcer width at baseline in Groups A and B visit and subsequent visits by dividing the number of days Variable Group Sample Mean±SD t value df P score between the two visits. size Wound HbA1c 50 2.36±2.74 0.502 98 0.616 All the data obtained was entered in the master chart and width <7 was subjected to further statistical analysis using unpaired baseline HbA1c 50 2.65±3.02 t-test. All P < 0.01 was considered to be statistically >7 significant. HbA1c: Hemoglobin A1c, SD: Standard deviation

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Subsequently, standard treatment protocols were DISCUSSION followed, and mean reduction in ulcer area, length, and width were measured; a statistically Lower extremity amputation is a long-term major concern significant difference was found between the two in patients suffering from diabetes mellitus and is often groups with P < 0.0001, <0.01, and <0.01 (Tables 4-6, preceded by neglected and untreated foot ulcers. 1-4% Figures 1 and 2). of people develop foot ulcer each year and can result in gangrene/amputation associated with socioeconomic Table 4: Mean ulcer area change per day in Groups A and B impact, and globally 70% of all leg occur in people with diabetes. Variable Group Sample Mean±SD t value df P score size Increased HbA1c level is considered to be a positive Wound area HbA1c 50 0.08±0.02 18.973 98 <0.0001 change per <7 indicator of uncontrolled glucose level in blood. This day HbA1c 50 0.02±0.01 study evaluated the level of HbA1c in diabetic patients >7 and its effect on wound healing rate. The high percentage of significant difference in healing rate may be the HbA1c: Hemoglobin A1c, SD: Standard deviation significant observation in the management of diabetic foot ulcer12 and this finding correlated with our study. Table 5: Mean ulcer length change per day in Groups A and B Variable Group Sample Mean±SD t value df P score Diabetes mellitus being a metabolic disorder causes size the altered protein and lipid metabolism and thereby Wound length HbA1c 50 0.02±0.04 -0.432 98 <0.01 abnormal granulation tissue formation. This is supported change per <7 by the findings of Goldin et al., who observed that day HbA1c 50 0.02±0.12 hyperglycemia in the body leads to the uncontrolled >7 covalent bonding of aldose sugars to a protein or HbA1c: Hemoglobin A1c, SD: Standard deviation lipid without any normal enzymes. The accumulation of these products advanced glycation Table 6: Mean ulcer width change per day in Groups A and B end-product over the surface of cell membranes occurs Variable Group Sample Mean±SD t value df P score on proteins and alters the properties size of matrix proteins such as , , and 13 Wound width HbA1c 50 0.04±0.11 0.518 98 <0.01 laminin. change per <7 day HbA1c 50 0.03±0.08 Hyperglycemia also affects the migration >7 and proliferation in vitro, impaired migration HbA1c: Hemoglobin A1c, SD: Standard deviation and proliferation, and function, angiogenic response and also add to oxidative stress with a production of reactive oxygen .14

CONCLUSION

This study suggests that slower wound healing is associated with increased HbA1c levels and can be considered as an independent biomarker in assessing wound healing in patients with diabetic foot ulcer. Figure 1: Diabetic foot ulcer of Group A at baseline and after healing REFERENCES

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