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Part 5: PD in Pediatric, Elderly, and Diabetic Patients |
Division of Nephrology, Department of Medicine, China Medical University Hospital, Taichung, Taiwan
Correspondence to: C.C. Huang, Department of Medicine, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung, Taiwan. cch{at}www.cmuh.org.tw
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ABSTRACT |
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Diabetic patients are often affected by comorbid conditions that
influence clinical outcome. Taking care of diabetic peritoneal dialysis (PD)
patients is a challenge for nephrologists, not only because these patients
have more complications and comorbidities, but also because of their
difficulties in maintaining glycemic control with the use of current
glucose-containing dialysis solutions. In addition, the increased transport of
small molecules and proteins by the peritoneal membrane in diabetic patients
adds the further problems of ultrafiltration deficit and malnutrition. The
present article reviews pertinent evidence toward establishing the best
strategy for the care of diabetic PD patients. With better glycemic control,
improved nutrition, improved fluid balance, and optimal preservation of
residual renal function, there is hope for improving the survival of diabetic
PD patients.
KEY WORDS: Diabetes mellitus; glycemic control.
Diabetes mellitus is the leading cause of end-stage renal disease (ESRD) in many countries. Compared with nondiabetic patients, patients with diabetes generally have poorer survival because of a higher incidence of complications and comorbidities. Strategies for managing diabetic patients on peritoneal dialysis (PD) include proper control of glycemia, ultrafiltration, blood pressure, and metabolic status. In addition, prevention of cardiovascular complications, nutrition optimization, and preservation of residual renal function (RRF) are also important.
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GLYCEMIC CONTROL |
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No study specifically addresses glycemic control targets for diabetic PD patients. However, the most recent recommendations from the American Diabetes Association suggest these targets for diabetic patients (3):
Good glycemic control is often difficult to maintain in diabetic patients treated with PD because they are continuously exposed to high concentrations of glucose in peritoneal dialysate. The continuous blood glucose monitor (CGMS) has recently offered an opportunity to monitor blood glucose at 5-minute intervals for 72 continuous hours in diabetic patients. The CGMS patterns revealed blood glucose tracings well above the recommended standards of control in most of the diabetic PD patients tracked (4). Most of the patients in the study had HbA1c readings above 7% despite the recommendation to keep the reading below 7%. However, reaching that target is not easy.
Reaching targets for glycemic control requires a combination of insulin (subcutaneous or intraperitoneal) and oral hypoglycemic agents (OHAs—for example, rosiglitazone, glimepiride, mitiglinide). Use of non-glucose-based dialysis solutions (for example, those with icodextrin or amino acids) may be a helpful addition. Notably, 60%–80% of glucose PD solution instilled into the peritoneal cavity is absorbed, corresponding to a daily intake of 100–300 g glucose. The use of 1 bag of icodextrin or amino-acid solution daily may reduce the glucose load by 15%–30%.
Insulin: Insulin administered either intraperitoneally (IP) or subcutaneously (SC) is acceptable therapy for diabetic PD patients. Insulin instilled IP directly into the empty abdominal cavity is absorbed more rapidly than is SC-administered insulin, because the hormone passes directly into the portal vein system. As compared with the SC route, IP administration into the empty abdomen was observed to require 26% less insulin and to produce a 2.3% decline in mean HbA1c (5). Administration of insulin by the IP route also minimizes the fluctuations in blood glucose observed with SC administration, and plasma lipids such as LDL also decrease (6).
Unfortunately, as compared with SC administration, IP instillation of insulin directly into the empty abdomen increases the risk of peritonitis (1 episode in 32.9 patient–months vs. 26.4 patient–months, p < 0.05) in diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). But if IP insulin is added to the dialysis solution before an exchange, the insulin requirement rises significantly.
A study found that 65% of insulin added to dialysate was adsorbed into the delivery system, and only 35% passed into the abdomen. Also, peritoneal insulin absorption from dialysate varied markedly. Differences in membrane transport status did not account for this variation in absorption (7). The mean absorption of insulin depends on dwell time: 21% is absorbed in a 2-hour dwell, and 46% is absorbed in an 8-hour dwell (8).
Two elegant studies showed lower HbA1c levels and increased glucose disposal rates after patients were switched from SC to IP insulin (9,10). In contrast to IP instillation of insulin into the empty abdomen, IP administration via the dialysate leads to an increase in total cholesterol and triglycerides and to a significant decline in high-density lipoprotein cholesterol. In addition, hepatic subcapsular and intrahepatic steatosis are observed in CAPD patients receiving IP insulin—especially in those who are high transporters (11).
To summarize, IP insulin may have advantages such as direct delivery of insulin to the liver, better insulin sensitivity, prevention of insulin antibody formation, and prevention of major fluctuations in blood sugar. Possible disadvantages include the need for a larger dose of insulin (and thus higher costs), an increased peritonitis rate, induction of subcapsular steatosis, and an aggravated lipid profile. The choice of SC or IP insulin therefore depends on physician and patient preference and can be tailored accordingly.
OHAs: As newer generations of OHAs with fewer adverse effects—for example, thiazolidinediones, glimepiride, and mitiglinide—enter the market, the hope is that they can be used as monotherapy or in combination to reach glycemic control targets. However, few data are available about the safety and efficacy of these OHAs in PD patients.
In patients with type 2 diabetes, selection of an OHA must be individualized. Glimepiride or mitiglinide can be considered for patients with existing beta-cell function (12). Patients should receive instruction in how to treat hypoglycemia. Prescription of metformin and glyburide should be avoided because of the adverse effects of lactic acidosis and hypoglycemia. Thiazolidinediones [TZDs, which are peroxisome proliferator-activated receptor gamma (PPARG) agonists], improve insulin sensitivity and peripheral glucose utilization, and reduce hepatic glucose production.
For patients with loss of beta-cell function, a combination of insulin-sensitizing agents (TZDs) and insulin treatment for blood sugar control may be prescribed. At the time of writing, only two studies of rosiglitazone in PD patients had been published. Lin et al. found that rosiglitazone improved insulin resistance in CAPD patients without diabetes (13). After 12 weeks of rosiglitazone therapy, fasting glucose and fasting insulin levels declined significantly, the homeostasis model of insulin resistance assessment declined, and the whole-body insulin sensitivity index increased significantly. Wong et al. randomized 52 PD patients with type 2 diabetes to SC insulin either alone or with rosiglitazone for 24 weeks (14). In the SC insulin plus rosiglitazone group, a significantly reduced requirement for insulin and lower levels of C-reactive protein were found. This study suggests that rosiglitazone may be useful as first-line treatment for glycemic control in ESRD patients with diabetes. Adverse effects of rosiglitazone, including fluid overload, weight gain, and liver function impairment, were not common but need to be monitored closely. New treatment regimes with insulin glargine (Lantus: Aventis Pharma, Bridgewater, NJ, U.S.A.) and OHAs are under investigation.
Non-Glucose-Based Dialysis Solutions: The use of newly introduced non-glucose-based dialysis solutions is anticipated to improve glycemic control in diabetic patients because mean carbohydrate absorption decreases (62 ± 5 g vs. 29 ± 5 g) when these patients are switched from 3.86% glucose solution to icodextrin solution.
Marshall et al. studied glycemic control in 8 insulin-treated diabetic CAPD patients assessed by CGMS for a 72-hour period (15). All patients completed a 3-phase study involving various combinations of dialysis solution. Combinations that contained the more biocompatible and non-glucose-containing dialysis solutions [1 icodextrin solution exchange, 1 amino-acid solution exchange, and 2 exchanges of 1.36% Physioneal solution (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.)] were associated with improvements in glycemic control.
Use of biocompatible glucose-containing dialysis solution alone did not have an impact on glycemic control. Johnson et al. reported a 1% lowering of HbA1c leading to a reduction in insulin dose in 7 of 12 patients (16). However, Gradden et al. (17) and Hithaishi et al. (18) found no significant alteration in mean HbA1c level after using 1 long-dwell exchange of icodextrin for 3–12 months in diabetic patients.
All of the foregoing studies were small-scale trials, and so further studies with larger numbers of patients and longer treatment durations are necessary.
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OTHER SPECIFIC PROBLEMS OF DIABETIC PATIENTS TREATED WITH PD |
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Protein–energy malnutrition is not uncommon in diabetic PD patients, particularly if inadequate intake of protein and calories because of anorexia is added on top of protein loss. Captopril therapy has been reported to significantly lower both peritoneal and urinary protein excretion in 12 diabetic patients (21). Further studies are necessary to assess the potential benefits of angiotensin converting-enzyme inhibitors (ACEIs) or angiotensin II receptor-blockers (ARBs) on peritoneal protein permeability. For malnourished diabetic PD patients, use of 1.1% amino-acid dialysis solution is beneficial as nutritional support (22).
Transport Characteristics: Studies reporting on peritoneal transport of small solutes and water in diabetic PD patients have produced inconsistent results. In an animal study, increased peritoneal permeability to small solutes was resolved after glycemic control was established (23). In human studies, results are controversial. Transport of small solutes in diabetic patients has been reported to be either higher than or similar to that seen in patients without diabetes, and ultrafiltration is reported to be either similar or lower. These conflicting results all come from cross-sectional studies.
The discrepancies may possibly be attributable to wide variation in the duration of exposure to glucose-containing dialysis solutions in different patient populations. Smit et al. (24) compared peritoneal function tests between 10 patients with diabetes and 10 nondiabetic patients. All patients were newly started on PD (<4 months). The authors found no differences in the net ultrafiltration rate, transcapillary ultrafiltration rate, lymphatic absorption profile, free water transport, or small-solute transport between the two groups. With long-term exposure to glucose-containing dialysis solutions in PD, peritoneal small-solute transport increases and ultrafiltration declines in diabetic patients (25).
RRF and Blood Pressure: Residual renal function and blood pressure control both contribute to survival in PD patients. Maintenance of RRF is an important task in the care of any dialysis patient, but especially in diabetic PD patients. The use of either ACEIs or ARBs has been shown to better preserve RRF than control treatment does and consequently to help maintain weekly creatinine clearance and Kt/V, which are the factors that make the major contribution to avoidance of mortality and morbidity in PD patients (26,27).
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CONCLUSIONS |
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