Diabetes-Induced Osteoarthritis Proposed as Possible Phenotype

Strong signals for a correlation between diabetes and osteoarthritis in several epidemiological and experimental studies have led to the concept of a diabetes-induced OA phenotype. If confirmed, knowledge of the phenotype could have a dramatic impact on the prevention and progression of the musculoskeletal disease, according to Dr. Francis Berenbaum, head of the department of rheumatology at Pierre and Marie Curie University in Paris.

An association between diabetes and OA was first noted in the literature in 1961 in a paper that assessed the occurrence of definite radiological OA in 6 anatomical areas of 30 patients with diabetes and 30 matched controls, which showed a statistically significant correlation between diabetes and OA of the feet and knees (Tufts Folia Med. 1961;7:13-9 Dr. Berenbaum reported online ahead of print in the Annals of Rheumatic Diseases.

Since that time, multiple cross-sectional studies have been published, including one that looked at OA patterns in 809 patients with knee or hip-joint replacement and found that bilateral OA occurred more frequently in patients with non-insulin-dependent diabetes (Scand. J. Rheumatol. 2001;30:169-71).

Most recently, a study designed to test the hypothesis that vascular cell adhesion molecule 1 predicts severe knee or hip OA showed an increased prevalence of non-insulin-dependent diabetes among the 60 patients who underwent joint replacement surgery relative to the 852 patients who did not (Arthritis Rheum. 2009;60:2381-9).

Although it cannot be definitively concluded from the collective case-control studies that diabetes is an independent risk factor for OA given the potential for interference with the results by such confounders as age, weight, and level of activity, "taken together, there may be a positive signal for an independent correlation between OA and diabetes," Dr. Berenbaum wrote (Ann Rheum Dis. 2011 [Epub. Doi:10.1136/ard.2010.146399]).

In vitro, in vivo, and human experimental data also point toward an independent association. For example, advanced glycation end products (AGEs) accumulate in diabetic tissues as a result of hyperglycemia and research data have suggested that AGE modification may contribute to the pathogenesis of OA, Dr. Berenbaum noted. "To the best of my knowledge, to date no experimental studies have assessed the level of AGE formation in diabetic cartilage compared to normal cartilage, either in human or animal cartilage," he stated. "However, it seems realistic to consider that an increased concentration of glucose in the diabetic cartilage–matrix environment would lead to the same deleterious result."

With respect to in vivo data, in the streptozotocin-induced diabetes rat model that mimics type I diabetes, "cartilage becomes resistant to the anabolic action of insulin-like growth factor 1 [IGF-1], a condition that is correctable by hypophysectomy, suggesting a metabolic impairment at the tissue level," Dr. Berenbaum wrote.

Diabetes-induced peripheral nerve impairment, which has been described in human experimental data, "could be an added risk factor for OA in patients with diabetes," Dr. Berenbaum hypothesized, given the presence of local and systemic neurological dysfunction in some patients with OA. Similarly, low-grade systemic inflammation has been associated with both cartilage loss and hyperglycemia. As such, he stated, "I propose that an independent hyperglycemia-induced systemic inflammation may also have an impact on the progression of OA."

Given the multiple signs pointing to a correlation between diabetes and OA, "it is time to encourage the scientific community to perform prospective studies devoted to confirm or invalidate this hypothesis," Dr. Berenbaum wrote. Such studies should be designed to provide insight into the mechanisms underlying the interactions between both diseases, he said, noting that "a better knowledge of the specificities of a diabetes-induced OA phenotype compared to the others should lead to a personalized approach of preventive and curative treatments for OA."

Dr. Berenbaum reported having no competing interests to disclose.

Strong signals for a correlation between diabetes and osteoarthritis in several epidemiological and experimental studies have led to the concept of a diabetes-induced OA phenotype. If confirmed, knowledge of the phenotype could have a dramatic impact on the prevention and progression of the musculoskeletal disease, according to Dr. Francis Berenbaum, head of the department of rheumatology at Pierre and Marie Curie University in Paris.

An association between diabetes and OA was first noted in the literature in 1961 in a paper that assessed the occurrence of definite radiological OA in 6 anatomical areas of 30 patients with diabetes and 30 matched controls, which showed a statistically significant correlation between diabetes and OA of the feet and knees (Tufts Folia Med. 1961;7:13-9 Dr. Berenbaum reported online ahead of print in the Annals of Rheumatic Diseases.

Since that time, multiple cross-sectional studies have been published, including one that looked at OA patterns in 809 patients with knee or hip-joint replacement and found that bilateral OA occurred more frequently in patients with non-insulin-dependent diabetes (Scand. J. Rheumatol. 2001;30:169-71).

Most recently, a study designed to test the hypothesis that vascular cell adhesion molecule 1 predicts severe knee or hip OA showed an increased prevalence of non-insulin-dependent diabetes among the 60 patients who underwent joint replacement surgery relative to the 852 patients who did not (Arthritis Rheum. 2009;60:2381-9).

Although it cannot be definitively concluded from the collective case-control studies that diabetes is an independent risk factor for OA given the potential for interference with the results by such confounders as age, weight, and level of activity, "taken together, there may be a positive signal for an independent correlation between OA and diabetes," Dr. Berenbaum wrote (Ann Rheum Dis. 2011 [Epub. Doi:10.1136/ard.2010.146399]).

In vitro, in vivo, and human experimental data also point toward an independent association. For example, advanced glycation end products (AGEs) accumulate in diabetic tissues as a result of hyperglycemia and research data have suggested that AGE modification may contribute to the pathogenesis of OA, Dr. Berenbaum noted. "To the best of my knowledge, to date no experimental studies have assessed the level of AGE formation in diabetic cartilage compared to normal cartilage, either in human or animal cartilage," he stated. "However, it seems realistic to consider that an increased concentration of glucose in the diabetic cartilage–matrix environment would lead to the same deleterious result."

With respect to in vivo data, in the streptozotocin-induced diabetes rat model that mimics type I diabetes, "cartilage becomes resistant to the anabolic action of insulin-like growth factor 1 [IGF-1], a condition that is correctable by hypophysectomy, suggesting a metabolic impairment at the tissue level," Dr. Berenbaum wrote.

Diabetes-induced peripheral nerve impairment, which has been described in human experimental data, "could be an added risk factor for OA in patients with diabetes," Dr. Berenbaum hypothesized, given the presence of local and systemic neurological dysfunction in some patients with OA. Similarly, low-grade systemic inflammation has been associated with both cartilage loss and hyperglycemia. As such, he stated, "I propose that an independent hyperglycemia-induced systemic inflammation may also have an impact on the progression of OA."

Given the multiple signs pointing to a correlation between diabetes and OA, "it is time to encourage the scientific community to perform prospective studies devoted to confirm or invalidate this hypothesis," Dr. Berenbaum wrote. Such studies should be designed to provide insight into the mechanisms underlying the interactions between both diseases, he said, noting that "a better knowledge of the specificities of a diabetes-induced OA phenotype compared to the others should lead to a personalized approach of preventive and curative treatments for OA."

Dr. Berenbaum reported having no competing interests to disclose.

Strong signals for a correlation between diabetes and osteoarthritis in several epidemiological and experimental studies have led to the concept of a diabetes-induced OA phenotype. If confirmed, knowledge of the phenotype could have a dramatic impact on the prevention and progression of the musculoskeletal disease, according to Dr. Francis Berenbaum, head of the department of rheumatology at Pierre and Marie Curie University in Paris.

An association between diabetes and OA was first noted in the literature in 1961 in a paper that assessed the occurrence of definite radiological OA in 6 anatomical areas of 30 patients with diabetes and 30 matched controls, which showed a statistically significant correlation between diabetes and OA of the feet and knees (Tufts Folia Med. 1961;7:13-9 Dr. Berenbaum reported online ahead of print in the Annals of Rheumatic Diseases.

Since that time, multiple cross-sectional studies have been published, including one that looked at OA patterns in 809 patients with knee or hip-joint replacement and found that bilateral OA occurred more frequently in patients with non-insulin-dependent diabetes (Scand. J. Rheumatol. 2001;30:169-71).

Most recently, a study designed to test the hypothesis that vascular cell adhesion molecule 1 predicts severe knee or hip OA showed an increased prevalence of non-insulin-dependent diabetes among the 60 patients who underwent joint replacement surgery relative to the 852 patients who did not (Arthritis Rheum. 2009;60:2381-9).

Although it cannot be definitively concluded from the collective case-control studies that diabetes is an independent risk factor for OA given the potential for interference with the results by such confounders as age, weight, and level of activity, "taken together, there may be a positive signal for an independent correlation between OA and diabetes," Dr. Berenbaum wrote (Ann Rheum Dis. 2011 [Epub. Doi:10.1136/ard.2010.146399]).

In vitro, in vivo, and human experimental data also point toward an independent association. For example, advanced glycation end products (AGEs) accumulate in diabetic tissues as a result of hyperglycemia and research data have suggested that AGE modification may contribute to the pathogenesis of OA, Dr. Berenbaum noted. "To the best of my knowledge, to date no experimental studies have assessed the level of AGE formation in diabetic cartilage compared to normal cartilage, either in human or animal cartilage," he stated. "However, it seems realistic to consider that an increased concentration of glucose in the diabetic cartilage–matrix environment would lead to the same deleterious result."

With respect to in vivo data, in the streptozotocin-induced diabetes rat model that mimics type I diabetes, "cartilage becomes resistant to the anabolic action of insulin-like growth factor 1 [IGF-1], a condition that is correctable by hypophysectomy, suggesting a metabolic impairment at the tissue level," Dr. Berenbaum wrote.

Diabetes-induced peripheral nerve impairment, which has been described in human experimental data, "could be an added risk factor for OA in patients with diabetes," Dr. Berenbaum hypothesized, given the presence of local and systemic neurological dysfunction in some patients with OA. Similarly, low-grade systemic inflammation has been associated with both cartilage loss and hyperglycemia. As such, he stated, "I propose that an independent hyperglycemia-induced systemic inflammation may also have an impact on the progression of OA."

Given the multiple signs pointing to a correlation between diabetes and OA, "it is time to encourage the scientific community to perform prospective studies devoted to confirm or invalidate this hypothesis," Dr. Berenbaum wrote. Such studies should be designed to provide insight into the mechanisms underlying the interactions between both diseases, he said, noting that "a better knowledge of the specificities of a diabetes-induced OA phenotype compared to the others should lead to a personalized approach of preventive and curative treatments for OA."

Dr. Berenbaum reported having no competing interests to disclose.