Title: The Effects of Local Insulin Delivery on Diabetic Fracture Healing
Authors: Gandhi A, Beam HA, O’Connor JP, Parsons R and Sheldon SL
Source: Bone 2005; 37: 482-490
PODIATRIC RELEVANCE:
Healing in diabetics is not a trivial problem. Decreased wound closure and fracture healing is significant variable in the surgical equation. In relation to fracture healing, experimenters have reported that fractures in diabetic patients take twice as long to complete healing. In order to promote adequate local milieu for proper bone healing, this paper evaluates the use of an intra-medullary insulin delivery system in a diabetic rat model.
METHODS:
In this paper, authors used 3 groups of experimental rats i) control non-diabetic rats that received a sham (no insulin) subcutaneous and intra-medullary implant ii) diabetic rats that received a insulin releasing subcutaneous implant and a sham (no insulin) intra-medullary implant and iii) diabetic rats that received insulin releasing subcutaneous implant and an insulin releasing intra-medullary implant. From these animals, blood insulin levels and HbA1c were evaluated. Additionally, femoral fractures were induced and several parameters were examined. These included cellular proliferation, early (days 2, 4 and 7 days post fractures) and late (6-8 weeks post-fracture) histomorphometry and mechanical testing (6-8 weeks post fracture). Significance was considered at P<.05.
RESULTS:
Blood glucose and HbA1c were significantly lower for non-diabetic rats, when compared to either diabetic rat group. However, there was no significance in blood glucose levels and HbA1c between the diabetic groups (intra-medullary sham rod vs. intra-medullary insulin releasing rod). The authors state the importance of this finding is that the intra-medullary insulin releasing rod does not release insulin systemically. Additional data to support this hypothesis is that insulin levels between diabetic groups (intra-medullary sham rod vs. intra-medullary insulin releasing rod) were not significant. Interestingly, isolated rat femora that had the insulin releasing rods inserted, had five fold increases in insulin levels (total protein).
Examining post-fracture cellular proliferation revealed that at day 2 and 4, there was significantly less periosteal and gap callus formation in the diabetic( non-insulin releasing rod) group, when compared to non-diabetic (non-insulin releasing intra-medullary rod) and diabetic rats with insulin releasing intra-medullary rod. There was no significance between the 3 groups at day 7 post-fracture. Early histomorphometry showed no significance amongst the 3 groups in gap callus formation at day 2 and 4. However, at day 7, the gap callus in the non-diabetic and diabetic with insulin releasing intra-medullary rod contained an increase in percent cartilage, when compared to diabetic rat with non-insulin releasing intra-medullary rod. At week 6, non-diabetic and diabetic with insulin releasing intra-medullary rod exhibited bridging of the cortice/fracture callus, when compared to diabetic rat with non-insulin releasing intra-medullary rod. Moreover, at week 8, non-diabetic and diabetic with insulin releasing intra-medullary rod exhibited full bridging of the cortice/fracture callus, when compared to diabetic rat with non-insulin releasing intra-medullary rod. At week 8, diabetic rats with non-insulin releasing intra-medullary rod still showed signs of delayed healing and fibrous tissue containing callus. At week 6 and 8 post fracture, mechanical studies demonstrated diabetic and diabetic with insulin releasing intra-medullary rod femora exhibited significant increase in torque to failure and maximum shear stress, when compared to diabetic rat with non-insulin releasing intra-medullary rod femora.
COMMENTS:
As surgeons, molecular processes can sometimes be overlooked, or trivialized. This article has shown that the surgeon must take into consideration the whole organism, and the local processes that take place at the surgical site. Additionally, the authors have shown that local processes that take place at the surgical site may be exposed to a milieu that does not interact systemically. The authors have illustrated that diabetic rats with subcutaneous insulin release and without intra-medullary rod insulin release had overall delayed fracture healing characteristics and post-fracture mechanics, when compared to diabetic rats with similar subcutaneous insulin release and intra-medullary rod insulin release and non-diabetic rats. Furthermore, regarding systemic evaluation, both diabetic groups were not significant, but fracture healing characteristics were significant; with diabetic rats containing insulin releasing femoral rods being relatively equivalent to non-diabetic rats.
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Disclaimer:
Scientific Abstract Monthly postings are submitted by podiatric surgical residents. The ideas presented are not the opinions of the American College of Foot and Ankle Surgeons (ACFAS), nor are they presented as facts. ACFAS presents this information without any warranty of any kind, expressed or implied, and is not liable for its accuracy nor for any loss or damage caused by the user's reliance on information obtained in these areas.