Optimizing Important Comorbidities: Diabetes, Rheumatoid Arthritis, Peripheral Vascular Disease, and Cardiac Disease

Diabetes Mellitus

Diabetes mellitus is a chronic disease in which the body’s ability to properly regulate glucose metabolism is impaired, resulting in high blood glucose levels. Diabetes can occur when the pancreas makes little or no insulin (type 1 diabetes) or when insulin resistance develops and the body fails to respond to endogenous insulin appropriately (type 2 diabetes). Patients who have type 1 diabetes are dependent on insulin for blood glucose control, whereas patients who have type 2 diabetes may receive treatment with a variety of oral and injectable medications, including exogenous insulin. Glycemic control is important, as poorly controlled diabetes can contribute to the development of microvascular and macrovascular complications, including retinopathy, nephropathy, neuropathy, peripheral artery disease, coronary artery disease, and stroke.

Diabetes is a well-documented risk factor for postoperative complications after TKA, especially when it is not well controlled. Complications can include superficial infection, deep infection, stroke, deep vein thrombosis, pneumonia, and death. Because TKA is an elective procedure meant to improve patients’ quality of life, a marked amount of research has been devoted to determine the best way to assess and optimize diabetes before arthroplasty to reduce the risk of complications.

The American Diabetes Association provides several criteria by which a diagnosis of diabetes can be made, one of which is a hemoglobin A1c (HbA1c) >6.5% ( Box 3.1 ). The HbA1c test measures glycated hemoglobin and reflects the previous 2 to 3 months of glycemic control in the setting of the usual red blood cell life span of 120 days. HbA1c is used in diagnosing diabetes and monitoring response to antihyperglycemic treatment, so the association between HbA1c and postoperative complications in TKA has been a topic of interest. One study found an increased rate of superficial surgical site infection after TKA in patients who had a preoperative HbA1c ≥8% and/or fasting blood glucose ≥200 mg/dL Another multicenter, retrospective study found that high HbA1c levels were associated with an increased risk of prosthetic joint infection after total joint arthroplasty, and it identified a threshold HbA1c of 7.7%. Other studies, however, have shown a weak or no significant association between HbA1c and the risk of prosthetic knee infection. One study found that even though diabetic patients had a significantly higher risk for infection after TKA compared with nondiabetic patients, HbA1c was not a reliable predictor of infection. Furthermore, many diabetic patients might not be able to achieve a HbA1c ≤7.0% Considering all this, some institutions have adopted a HbA1c target of less than 8%.

Perioperative hyperglycemia has been evaluated in patients undergoing TKA as a predictor of infection and other adverse outcomes. One study found that although HbA1c did not perfectly correlate with the risk of prosthetic joint infection, perioperative hyperglycemia did; patients with a blood glucose level ≥194 mg/dL within the 7 days before surgery were at increased risk of developing a prosthetic joint infection. Although the study did not find HbA1c to be a good predictor for prosthetic joint infection, researchers did observe a significantly higher 2-year mortality in patients with HbA1c >7%. In addition to an increased risk for prosthetic joint infection, preoperative hyperglycemia has also been implicated in increasing the risk of revision for aseptic loosening. The effect of postoperative hyperglycemia has been investigated. One study found a linear relationship between postoperative blood glucose levels and periprosthetic joint infection, further highlighting the importance of blood glucose control not only over the previous 3 months, as reflected in the HbA1c, but also during the perioperative period.

The association between the glycemic marker fructosamine and postoperative complications after total joint arthroplasty has been studied. Fructosamines are molecules formed through the glycation of proteins, and the fructosamine test measures the level of glycated proteins in the serum (mainly albumin). In patients who have diabetes mellitus the level of fructosamine molecules in the serum is elevated due the increased blood glucose levels. Because of the relatively short half-life of serum proteins, fructosamine reflects glycemic control over the previous 2 to 3 weeks. A 2017 study found that patients who had preoperative fructosamine levels of ≥292 mmol/L had a significantly higher risk of developing adverse outcomes, including prosthetic joint infection, readmission, and reoperation. Although the rate of prosthetic joint infection was 3.3-times higher in patients with HbA1c levels of ≥7%, it did not reach statistical significance. A follow-up multicenter prospective study validated fructosamine as a predictor of adverse complications, with a fructosamine level of 293 mmol/L identified as the optimal cutoff associated with adverse outcomes. Patients with elevated fructosamine levels had a 11.2-times higher rate of prosthetic joint infection, 4.2-times higher rate of readmission, and 4.5-times higher rate of reoperation compared with patients who did not have elevated fructosamine levels. HbA1c thresholds of 7% and 7.5%, however, failed to show a significant association with complications. A subset of patients who had elevated fructosamine levels, but a normal HbA1c, were found to have a higher risk of prosthetic joint infection compared with patients with low fructosamine levels and an elevated HbA1c. Because HbA1c reflects the mean blood glucose over the previous 2 to 3 months, spikes in blood glucose levels can be masked if the blood glucose levels are controlled the majority of the time. Because fructosamine reflects the mean blood glucose levels over the previous 2 to 3 weeks, spikes in blood glucose levels are not as easily diluted. Spikes in perioperative blood glucose levels, as some studies have shown, can be a strong predictor of postoperative complications.

In 2018 the International Consensus meeting evaluated the data available at the time and recommended that routine screening for diabetes and glycemic control has the potential to reduce postoperative infections. A study evaluating routine preoperative HbA1c screening in total joint arthroplasty patients found that 33.6% of patients had undiagnosed dysglycemia and 2.6% were undiagnosed diabetics. Similarly, in another study 2.5% of screened patients were found to have undiagnosed diabetes based on HbA1c ≥6.5%. Therefore consideration should be given to screening all patients being considered for TKA. The optimal glycemic marker for preoperative screening continues to be an active area of research, but an HbA1c threshold of 7.5% to 8.0% is a reasonable cutoff based on the data available at this time. Optimization of glycemic control should be multimodal and should be coordinated with the patient’s primary physician or endocrinologist, and it can include pharmacological treatment and dietary modification.

When evaluating a patient who has diabetes mellitus for TKA, it is important to remember the associated comorbidities that are frequently present with diabetes. Patients who have type 2 diabetes are frequently overweight or obese. Obesity has also been identified as a risk factor for postoperative complications after TKA. Weight loss can address obesity and improve glycemic control. The weight loss strategy can include referral to a weight management program, self-directed exercise, and dietary modifications in consultation with a dietician. Bariatric surgery can also be considered, although the utility of bariatric surgery in reducing perioperative complications remains controversial.

Diabetes can result in long-term complications, including peripheral vascular disease and renal insuffiency. The lower extremities should be carefully evaluated preoperatively, with special attention to the peripheral pulses. The presence of decreased or absent pulses, skin changes, hairlessness, or chronic wounds should prompt further evaluation. This can include ankle-brachial indices (ABIs) and referral to a vascular surgeon. With regard to renal insufficiency, modifications might need to be made with regard to perioperative medication dosages to avoid further renal injury.