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Three diabetic peritoneal dialysis patients receiving intraperitoneal insulin with dosage adjustment based on capillary glucose levels during peritoneal equilibrium tests
Three Diabetic Peritoneal Dialysis Patients Receiving Intraperitoneal Insulin With Dosage Adjustment Based on Capillary Glucose Levels During Peritoneal Equilibrium Tests Micah L. Thorp, DO, MPH, and Teresa S. Wilks, RN, CNN ● Diabetic patients receiving peritoneal dialysis have vast differences in glucose absorption, significantly affecting glycemic control. Measurement of glucose levels between dialysate exchanges does not adequately reflect these changes. By measuring glucose levels during the peak period of glucose absorption, as determined by a peritoneal equilibrium test, such differences can be measured and accounted for when determining doses of intraperitoneal insulin. In this report, 3 cases in which such an approach was applied are described. Am J Kidney Dis 43:927-929. © 2004 by the National Kidney Foundation, Inc. INDEX WORDS: Peritoneal dialysis (PD); ultrafiltration; glycemic control; peritoneal equilibrium test (PET).
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IABETIC PATIENTS on continuous ambulatory peritoneal dialysis (CAPD) often receive intraperitoneal (IP) insulin. IP insulin offers patients an easy means of insulin administration and can be used to offset IP glucose absorption and control glycemic fluctuations.1 Optimizing the relationships between ultrafiltration, glucose absorption, and insulin administration is key to obtaining both excellent dialysis clearance and tight glycemic control. The means of finding the best balance between these variables is typically accomplished by (1) adjusting dwell times to maximize ultrafiltration while minimizing glucose absorption and (2) adjusting insulin dose based on serum glucose levels measured before dialysate exchanges or before meals. General guidelines regarding IP insulin dosing have been published,2 recommending that CAPD patients receive approximately 2.5 to 3 times the subcutaneous dose over the course of the day, with 85% of the total dose being divided among the diurnal exchanges and 15% at night. These guidelines provide dosing parameters that are subsequently refined based on glucose levels measured before dialysate exchanges or after meals. The many benefits of IP insulin administration in diabetic CAPD patients can be complicated by variation in peritoneal transport characteristics. In general, diabetic patients have higher transport than nondiabetic patients,3 athough, as in nondiabetic patients, there is significant variation. Whereas these measures seem reasonable, they do not adequately account for individual variations in transport characteristics on serum glucose levels. Such variations can lead to sharp rises in serum glucose concentration during dia-
lysate dwell. To improve glycemic control, consideration of individual glucose transport characteristics should be made when designing an IP insulin regimen for patients. One means of accomplishing this is to measure peak blood glucose levels during standard peritoneal equilibrium tests (PETs) and use this measurement to define the timing of subsequent glucose measurements that, in turn, define IP insulin dosages. This report describes 3 cases in which such a protocol has been applied. PATIENT 1 A 53-year-old woman with end-stage renal disease secondary to diabetic nephropathy started CAPD with 4 daily exchanges of 2.5 L of 2.5% dialysate. At the initiation of dialysis, she began using IP insulin, with a sliding scale of regular insulin dosed based on serum glucose levels checked between exchanges. After 3 months of dialysis, her hemoglobin A1C (HgA1C) was 8.6. Her average weekly insulin requirement was 420 units. Her PET results showed a dialysate/plasmal ratio (D/P) of urea of 0.92 at 2 hours and 0.98 at 4 hours with D/P creatinine of 0.70 at 2 hours and 0.81 at 4 hours. Her dialysate glucose concentration to dialysate glucose concentration at time 0 ratio (D/D0) glucose was 0.37 in 2 hours and 0.20 in 4 hours. Her total drain volume was 2,300 mL. Hourly serum glucose levels were checked during the PET and showed a peak serum glucose
From Lake Road Nephrology Center, Kaiser Permanente Kidney Program and Fresenius Medical Care, Portland, OR. Received October 22, 2003; accepted in revised form December 22, 2003. Address reprint requests to Micah L. Thorp, DO, MPH, Nephrologist, Lake Road Nephrology Center, Kaiser Permanente Kidney Program, 6902 SE Lake Rd, Milwaukie, OR 97267. E-mail: [email protected] © 2004 by the National Kidney Foundation, Inc. 0272-6386/04/4305-0020$30.00/0 doi:10.1053/j.ajkd.2003.12.055
American Journal of Kidney Diseases, Vol 43, No 5 (May), 2004: pp 927-929
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Fig 1. PET and blood glucose levels in patient 1. (Diamond) Serum glucose.
level of 343 mg/dL (19 mmol/L) at the first hour (Fig 1). She then was advised to use the same insulin sliding scale but to administer insulin doses based on capillary measurements done an hour into each dwell. The estimated dose then was administered during the subsequent exchange. Using this approach, her average weekly insulin dose fell to 350 units. Three months after initiating this change, her HgA1C level fell to 6.7.
PATIENT 2 A 73-year-old man with end-stage renal disease secondary to diabetic nephropathy and hypertension was receiving continuous cycler peritoneal dialysis (CCPD) with 6 cycles of 3L, 2.5% dialysate. He had a single long daytime dwell, also 3L, 2.5% dialysate. His insulin was administered based on a sliding scale of regular IP insulin. His HgA1C was consistently in the low 7s, with a measurement of 7.1 before undergoing a PET. His average weekly insulin requirement was 2,198 units. His PET results showed a D/P creatinine of 0.55 at 2 hours and 0.74 at 4 hours. His D/D0 glucose was 0.49 in 2 hours and 0.33 in 4 hours. Hourly serum glucose levels checked during the PET showed a peak serum glucose level of 346 mg/dL (19 mmol/L) at the second hour (Fig 2). He then was advised to use the same IP insulin sliding scale but to administer insulin doses based on capillary measurements done 2 hours into his nighttime dwell. The estimated dose then was administered during the subsequent night’s treatment. Using this approach, his average weekly insulin dose was 2,240 units. Three months after initiating this change, his HgA1C level fell to 6.4.
Fig 2. PET and blood glucose levels in patient 2. (Diamond) Serum glucose.
then advised to use the same insulin sliding scale but to administer insulin doses based on capillary blood glucose measurements done during the third hour of his daytime dwell. Using this approach, his average weekly insulin dose was 4,116 units. Four months after initiating this change his HgA1C fell to 7.1.
DISCUSSION
Diabetic peritoneal dialysis patients have 2 sources of exogenous glucose, uptake from the gastrointesintal tract and absorption from the peritoneum. Wide variation in glucose uptake from both these sources as well as variation in glucose metabolism makes efforts to idealize intraperitoneal insulin prescription difficult. Optimizing glycemic control has been shown to improve morbidity and mortality among diabetic patients. Balancing increased ultrafiltration and glucose absorption often is a difficult task. Shortened dwell times increase ultrafiltration but often lead to increased glucose absorption. Increased ultrafiltration is thus often achieved at the expense of decreased glycemic control.4 In most IP insulin administration protocols, the dose of IP insulin can be adjusted based on
PATIENT 3 A 66-year-old man with end-stage renal disease caused by diabetic nephropathy and a history of bladder cancer had been treated with CCPD for approximately 1 year. He was receiving 5 nightly exchanges of 2 L of 2.5% dialysate with a single daytime dwell of 2 L, also 2.5%. Before a PET, his hemoglobin A1C was 9.8. His weekly insulin requirement was approximately 4,060 units. His PET showed a D/P creatinine of 0.43 at 2 hours and 0.62 at 4 hours with a D/D0 glucose of 0.55 at 2 hours and 0.74 at 4 hours. His serum glucose levels checked hourly during his PET peaked at 220 mg/dL (12 mmol/L) during the third hour (Fig 3). He was
Fig 3. PET and blood glucose levels in patient 3. (Diamond) Serum glucose.
PERITONEAL DIALYSIS INSULIN DOSING
glucose levels measured at different times (before meals, before exchanges). We have illustrated with these cases that an alternate approach may be to administer a dose of insulin based on the peak blood glucose level during a dialysate dwell, with the precise time determined by hourly capillary blood glucose levels during a standard PET. This approach allows insulin adjustment based not only on glucose uptake from food, but from glucose absorption from dialysate. In addition, it allows for variation in individual differences in transport kinetics, glucose metabolism, and the effects these may have on glycemic control. Although the 3 patients presented used the same dialysate glucose concentrations for all exchanges, many patients may vary these throughout the day. As a result, capillary glucose measurements taken during 1 dwell may be less relevant during the next. Adjustments can likely be made, although this problem clearly compli-
929
cates insulin dosing. Meal schedules will further affect glucose levels. Individual dosing parameters should be refined based on glucose levels measured at the prescribed times. Given the limitations of case reports, it would seem prudent to further study IP insulin dosing strategies via a controlled trial, comparing it to other methods of insulin dosing in achieving glycemic control. REFERENCES 1. Mactier RA, Khanna R: Intraperitoneal insulin in diabetic CAPD patients. Int J Artif Organs 11:9-12, 1988 2. Rutecki GW, Whittier FC: Intraperitoneal insulin in diabetic patients on peritoneal dialysis, in Nissenson AR, Fine RN (eds): Dialysis Therapy. Philadelphia, PA, Hanley and Belfus, 1993, pp 322-324 3. Diaz JA: Peritoneal dialysis prescriptions for diabetic patients, in Khanna R (ed): Advances in Peritoneal Dialysis. Toronto, Peritoneal Dialysis Publications, 1999, pp 91-95 4. Twardowski ZJ, Nolph KD, Khanna R, et al: Daily clearances with continuous ambulatory peritoneal dialysis and nightly peritoneal dialysis. ASAIO Trans 32:575-580, 1986
D
IABETIC PATIENTS on continuous ambulatory peritoneal dialysis (CAPD) often receive intraperitoneal (IP) insulin. IP insulin offers patients an easy means of insulin administration and can be used to offset IP glucose absorption and control glycemic fluctuations.1 Optimizing the relationships between ultrafiltration, glucose absorption, and insulin administration is key to obtaining both excellent dialysis clearance and tight glycemic control. The means of finding the best balance between these variables is typically accomplished by (1) adjusting dwell times to maximize ultrafiltration while minimizing glucose absorption and (2) adjusting insulin dose based on serum glucose levels measured before dialysate exchanges or before meals. General guidelines regarding IP insulin dosing have been published,2 recommending that CAPD patients receive approximately 2.5 to 3 times the subcutaneous dose over the course of the day, with 85% of the total dose being divided among the diurnal exchanges and 15% at night. These guidelines provide dosing parameters that are subsequently refined based on glucose levels measured before dialysate exchanges or after meals. The many benefits of IP insulin administration in diabetic CAPD patients can be complicated by variation in peritoneal transport characteristics. In general, diabetic patients have higher transport than nondiabetic patients,3 athough, as in nondiabetic patients, there is significant variation. Whereas these measures seem reasonable, they do not adequately account for individual variations in transport characteristics on serum glucose levels. Such variations can lead to sharp rises in serum glucose concentration during dia-
lysate dwell. To improve glycemic control, consideration of individual glucose transport characteristics should be made when designing an IP insulin regimen for patients. One means of accomplishing this is to measure peak blood glucose levels during standard peritoneal equilibrium tests (PETs) and use this measurement to define the timing of subsequent glucose measurements that, in turn, define IP insulin dosages. This report describes 3 cases in which such a protocol has been applied. PATIENT 1 A 53-year-old woman with end-stage renal disease secondary to diabetic nephropathy started CAPD with 4 daily exchanges of 2.5 L of 2.5% dialysate. At the initiation of dialysis, she began using IP insulin, with a sliding scale of regular insulin dosed based on serum glucose levels checked between exchanges. After 3 months of dialysis, her hemoglobin A1C (HgA1C) was 8.6. Her average weekly insulin requirement was 420 units. Her PET results showed a dialysate/plasmal ratio (D/P) of urea of 0.92 at 2 hours and 0.98 at 4 hours with D/P creatinine of 0.70 at 2 hours and 0.81 at 4 hours. Her dialysate glucose concentration to dialysate glucose concentration at time 0 ratio (D/D0) glucose was 0.37 in 2 hours and 0.20 in 4 hours. Her total drain volume was 2,300 mL. Hourly serum glucose levels were checked during the PET and showed a peak serum glucose
From Lake Road Nephrology Center, Kaiser Permanente Kidney Program and Fresenius Medical Care, Portland, OR. Received October 22, 2003; accepted in revised form December 22, 2003. Address reprint requests to Micah L. Thorp, DO, MPH, Nephrologist, Lake Road Nephrology Center, Kaiser Permanente Kidney Program, 6902 SE Lake Rd, Milwaukie, OR 97267. E-mail: [email protected] © 2004 by the National Kidney Foundation, Inc. 0272-6386/04/4305-0020$30.00/0 doi:10.1053/j.ajkd.2003.12.055
American Journal of Kidney Diseases, Vol 43, No 5 (May), 2004: pp 927-929
927
928
THORP AND WILKS
Fig 1. PET and blood glucose levels in patient 1. (Diamond) Serum glucose.
level of 343 mg/dL (19 mmol/L) at the first hour (Fig 1). She then was advised to use the same insulin sliding scale but to administer insulin doses based on capillary measurements done an hour into each dwell. The estimated dose then was administered during the subsequent exchange. Using this approach, her average weekly insulin dose fell to 350 units. Three months after initiating this change, her HgA1C level fell to 6.7.
PATIENT 2 A 73-year-old man with end-stage renal disease secondary to diabetic nephropathy and hypertension was receiving continuous cycler peritoneal dialysis (CCPD) with 6 cycles of 3L, 2.5% dialysate. He had a single long daytime dwell, also 3L, 2.5% dialysate. His insulin was administered based on a sliding scale of regular IP insulin. His HgA1C was consistently in the low 7s, with a measurement of 7.1 before undergoing a PET. His average weekly insulin requirement was 2,198 units. His PET results showed a D/P creatinine of 0.55 at 2 hours and 0.74 at 4 hours. His D/D0 glucose was 0.49 in 2 hours and 0.33 in 4 hours. Hourly serum glucose levels checked during the PET showed a peak serum glucose level of 346 mg/dL (19 mmol/L) at the second hour (Fig 2). He then was advised to use the same IP insulin sliding scale but to administer insulin doses based on capillary measurements done 2 hours into his nighttime dwell. The estimated dose then was administered during the subsequent night’s treatment. Using this approach, his average weekly insulin dose was 2,240 units. Three months after initiating this change, his HgA1C level fell to 6.4.
Fig 2. PET and blood glucose levels in patient 2. (Diamond) Serum glucose.
then advised to use the same insulin sliding scale but to administer insulin doses based on capillary blood glucose measurements done during the third hour of his daytime dwell. Using this approach, his average weekly insulin dose was 4,116 units. Four months after initiating this change his HgA1C fell to 7.1.
DISCUSSION
Diabetic peritoneal dialysis patients have 2 sources of exogenous glucose, uptake from the gastrointesintal tract and absorption from the peritoneum. Wide variation in glucose uptake from both these sources as well as variation in glucose metabolism makes efforts to idealize intraperitoneal insulin prescription difficult. Optimizing glycemic control has been shown to improve morbidity and mortality among diabetic patients. Balancing increased ultrafiltration and glucose absorption often is a difficult task. Shortened dwell times increase ultrafiltration but often lead to increased glucose absorption. Increased ultrafiltration is thus often achieved at the expense of decreased glycemic control.4 In most IP insulin administration protocols, the dose of IP insulin can be adjusted based on
PATIENT 3 A 66-year-old man with end-stage renal disease caused by diabetic nephropathy and a history of bladder cancer had been treated with CCPD for approximately 1 year. He was receiving 5 nightly exchanges of 2 L of 2.5% dialysate with a single daytime dwell of 2 L, also 2.5%. Before a PET, his hemoglobin A1C was 9.8. His weekly insulin requirement was approximately 4,060 units. His PET showed a D/P creatinine of 0.43 at 2 hours and 0.62 at 4 hours with a D/D0 glucose of 0.55 at 2 hours and 0.74 at 4 hours. His serum glucose levels checked hourly during his PET peaked at 220 mg/dL (12 mmol/L) during the third hour (Fig 3). He was
Fig 3. PET and blood glucose levels in patient 3. (Diamond) Serum glucose.
PERITONEAL DIALYSIS INSULIN DOSING
glucose levels measured at different times (before meals, before exchanges). We have illustrated with these cases that an alternate approach may be to administer a dose of insulin based on the peak blood glucose level during a dialysate dwell, with the precise time determined by hourly capillary blood glucose levels during a standard PET. This approach allows insulin adjustment based not only on glucose uptake from food, but from glucose absorption from dialysate. In addition, it allows for variation in individual differences in transport kinetics, glucose metabolism, and the effects these may have on glycemic control. Although the 3 patients presented used the same dialysate glucose concentrations for all exchanges, many patients may vary these throughout the day. As a result, capillary glucose measurements taken during 1 dwell may be less relevant during the next. Adjustments can likely be made, although this problem clearly compli-
929
cates insulin dosing. Meal schedules will further affect glucose levels. Individual dosing parameters should be refined based on glucose levels measured at the prescribed times. Given the limitations of case reports, it would seem prudent to further study IP insulin dosing strategies via a controlled trial, comparing it to other methods of insulin dosing in achieving glycemic control. REFERENCES 1. Mactier RA, Khanna R: Intraperitoneal insulin in diabetic CAPD patients. Int J Artif Organs 11:9-12, 1988 2. Rutecki GW, Whittier FC: Intraperitoneal insulin in diabetic patients on peritoneal dialysis, in Nissenson AR, Fine RN (eds): Dialysis Therapy. Philadelphia, PA, Hanley and Belfus, 1993, pp 322-324 3. Diaz JA: Peritoneal dialysis prescriptions for diabetic patients, in Khanna R (ed): Advances in Peritoneal Dialysis. Toronto, Peritoneal Dialysis Publications, 1999, pp 91-95 4. Twardowski ZJ, Nolph KD, Khanna R, et al: Daily clearances with continuous ambulatory peritoneal dialysis and nightly peritoneal dialysis. ASAIO Trans 32:575-580, 1986