Fibrinogen and factor VII levels improve with glycemic control in patients with type 1 diabetes mellitus who have microvascular complications.

To determine whether the hypercoagulable state of patients with complications of diabetes can be reversed toward normal, a group of insulin-dependent individuals with proteinuria was treated with intensive insulin protocols. A statistically significant (P<.001) improvement in control of diabetes was achieved (mean +/- SEM glycosylated hemoglobin, 9.51% +/- 0.35% at baseline to 8.36% +/- 0. 39% at 12 months; and mean +/- SEM advanced glycosylated end products, 14.8 +/- 2.8 U/mL at baseline to 8.4 +/- 1.5 U/mL at 12 months). There were statistically significant decreases in 2 procoagulant factors: mean +/- SEM baseline elevated plasma factor VII, 128.69% +/- 5.63% at baseline to 106.24% +/- 3.43% at 12 months (P =.002); and mean +/- SEM plasma fibrinogen, 12.3 +/- 0.7 micromol/L (417.3 +/- 24.7 mg/dL) at baseline to 10.2 +/- 0.7 micromol/L (348.8 +/- 22.6 mg/dL) at 12 months (P =.04). Throughout the study, lipid fractions did not change significantly. Because plasma factor VII and fibrinogen concentrations were elevated while cholesterol and triglyceride concentrations were not, more attention should be paid to procoagulants as markers for thromboembolic complications in diabetic patients undergoing intensive insulin therapy.

Effects of pulsatile intravenous insulin therapy on the progression of diabetic nephropathy.

The purpose of this study was to assess the effects of pulsatile intravenous insulin therapy (PIVIT) on the progression of diabetic nephropathy in patients with type 1 diabetes mellitus (DM). This 18-month multicenter, prospective, controlled study involved 49 type 1 DM patients with nephropathy who were following the Diabetes Control and Complications Trial (DCCT) intensive therapy (IT) regimen. Of these, 26 patients formed the control group (C), which continued on IT, while 23 patients formed the treatment group (T) and underwent, in addition to IT, weekly PIVIT. Blood pressure in all patients was maintained below 140/90 mm Hg on antihypertensive medication, preferentially using angiotensin-converting enzyme (ACE) inhibitors. All study patients were seen in the clinic weekly for 18 months, had monthly glycohemoglobin (HbA1c), and every 3 months, 24-hour urinary protein excretion and creatinine clearance (CrCl) determinations. The HbA1c levels declined from 8.61% +/- 0.33% to 7.68% +/- 0.31% (P = .0028) in the T group and from 9.13% +/- 0.36% to 8.19% +/- 0.33% (P = .0015) in the C group during the study period. CrCl declined significantly in both groups, as expected, but the rate of CrCl decline in the T group (2.21 +/- 1.62 mL/min/yr) was significantly less than in the C group (7.69 +/- 1.88 mL/min/yr, P = .0343). We conclude that when PIVIT is added to IT in type 1 DM patients with overt nephropathy, it appears to markedly reduce the progression of diabetic nephropathy. The effect appears independent of ACE inhibitor therapy, blood pressure, or glycemic control.

Improved glycemic control and platelet function abnormalities in diabetic patients with microvascular disease.

Patients with diabetes mellitus have a variety of platelet and coagulation system dysfunctions. At least theoretically, these can contribute to microvascular complications. Intensive glycemic control has been demonstrated to decrease microvascular complications in type 1 diabetics. We studied 16 patients with type 1 diabetes mellitus (11 men and five women; mean age, 39 years) with albuminuria greater than 0.1 g/d and/or proteinuria greater than 0.3 g/d and a creatinine clearance rate higher than 30 mL/min. They received a regimen including three to four injections of insulin per day with or without a weekly infusion of intravenous insulin, and were evaluated for 6 months. We compared the plasma level of von Willebrand factor, platelet aggregation responses to adenosine diphosphate (ADP), epinephrine, and collagen, and platelet adhesion at the beginning of the study and at follow-up intervals. Glycemic control improved significantly. There were no significant differences in the platelet aggregation responses to ADP (1.59 +/- 0.34 v 1.88 +/- 0.23 mmol/L, P = .3; normal, 4.6 +/- 0.2), epinephrine (0.50 +/- 0.20 v 1.11 +/- 0.31 mmol/L, P = .06; normal, 7.6 +/- 1.5), or collagen (92.4 +/- 6.61 v 82.60 +/- 3.78 seconds, P = .6; normal, 79.1 +/- 3.1) or in platelet adhesion (126.31 +/- 16.95 v 195.08 +/- 30.2 platelets, P = .34; normal, 68.6 +/- 1.4). Baseline von Willebrand factor increased, but not significantly (166.38% +/- 10.6% v 142.72% +/- 14.73%, P = .21; normal, 102.0% +/- 6.0%). In type 1 diabetic patients with established microvascular complications of nephropathy, a statistically significant improvement in glycemic control did not improve the in vitro platelet function abnormalities. Improved glycemic control delays the progression of microvascular disease through mechanisms not measured by tests of platelet function.

Prospective evaluation of autonomic dysfunction in aggressive management of diabetic microangiopathy.

Twenty-six type I diabetic nephropathy patients in a rigorous schedule for glucose control to preserve kidney function were studied to determine autonomic functional changes during 18 months. Intercurrent and nonrelated acute illness, withdrawal from the study for personal reasons, or failure to undergo testing on schedule resulted in complete data at 1 year for 26 of the original 41 patients enrolled, 24 patients completing a further 6 months. Glycohemoglobin A1c dropped for the total group from 9.0 to 7.9 at 6 months, 8.0 at 12 months, and 8.1 at 18 months (P<.01). Autonomic function tests revealed baseline results that were below the anticipated normals for age in 38% to 56% of patients. Timed ventilatory heart rate variations measured for the total group were 1.11, 1.13, 1.10, and 1.09 (normal > or =1.20). Valsalva heart rate variations for the total group were 1.27, 1.30, 1.255, and 1.35 (normal > or =1.50). Assumption of upright posture-related heart rate variations for the total group were 1.10, 1.07, 1.07, and 1.06 (normal > or =1.20). Mean arterial pressure day/night ratios for the total group were 1.04, 1.05, 1.05, and 1.08 (normal > or =1.10). Group analysis based on differences in insulin treatment programs, levels of blood pressure, and levels of renal function revealed no significant differences from the total group or companion groups during 18 months. Patients with a glycohemoglobin A1c of <8.0% were more likely to normalize mean arterial pressure day/night ratios than those with glycohemoglobin A1c > or =8.0%. We conclude that aggressive glucose control in diabetic patients with proteinuria for a period of 18 months resulted in a reproducible pattern of autonomic function tests during that period of time with neither worsening nor improvement. The restoration of day/night mean arterial pressure variation in a minority of patients should be studied with a larger cohort.

Circadian patterns of heart rate variability, fibrinolytic activity, and hemostatic factors in type I diabetes mellitus with cardiac autonomic neuropathy.

Diabetes mellitus is associated with a marked increase in the risk of coronary events but with an altered circadian distribution that demonstrates an absent morning peak and higher infarction rate during the evening hours. To elucidate the mechanism of this phenomenon, the circadian pattern of heart rate variability was evaluated in 22 type I diabetic patients with diabetic autonomic neuropathy in conjunction with circadian changes of fibrinolytic and hemostatic factors. The circadian pattern (6 A.M. to 10 P.M. vs 10 P.M. to 6 A.M.) of 3 indexes of parasympathetic tone was evaluated using 24-hour heart rate variability analysis. The high-frequency power (3.0 +/- 0.2 vs 3.3 +/- 0.2 ms2, p = 0.08) and the percentage of RR intervals with >50 ms variation (0.47 +/- 0.18 vs 0.69 +/- 0.33 ms, p = 0.52) demonstrated no significant circadian variation. The square root of mean squared differences of successive RR intervals showed a small but significant increase during nighttime (8.5 +/- 0.7 vs 9.7 +/- 1.1 ms, p = 0.02). Fibrinolytic activity was significantly lower at 8 A.M. than at 4 P.M. (166.4 +/- 12.5 to 200.2 +/- 9.3 mm2, p = 0.0003), but with a low amplitude. Plasminogen activator inhibitor 1 showed no circadian variation. Factor VII and fibrinogen demonstrated a significant reduction from 8 A.M. to 4 P.M., but both peak and nadir values were elevated. The von Willebrand factor was markedly elevated with no circadian variation. Thus, diabetic autonomic neuropathy is associated with a loss of both the nocturnal predominance of parasympathetic activity and a prothrombotic state that persists throughout the day. These abnormalities may attenuate the relative protection from coronary events during the afternoon and nighttime.

Effect of glycemic control on heart rate variability in type I diabetic patients with cardiac autonomic neuropathy.

Diabetic cardiac autonomic neuropathy (CAN) is associated with a high risk of cardiovascular events. Previous studies have shown that strict glycemic control slows the deterioration of CAN as assessed by standard autonomic function tests but fails to show reversibility. The aim of this study was to evaluate the effect of glycemic control on early and advanced CAN in type I diabetic patients using power spectral analysis of heart rate variability (HRV). Ten patients with early and 13 patients with advanced CAN were enrolled in a program of intensified insulin treatment. Standard autonomic function tests and 24-hour time and frequency domain HRV parameters were obtained at baseline, 3, 6, and 12 months. Hemoglobin A1C decreased from 9.5 +/- 0.4% to 8.4 +/- 0.5% (p = 0.02) in the early CAN group, and from 9.3 +/- 0.4% to 8.2 +/- 0.5% (p = 0.006) in the advanced CAN group. In general, both time and frequency domain HRV indexes tended to improve in patients with early CAN but continued to deteriorate in patients with advanced CAN. The low- and high-frequency power increased in patients with early CAN (229 +/- 95 to 626 +/- 563 ms2 and 62 +/- 30 to 183 +/- 168 ms2, respectively). The high-frequency power significantly improved at 12 months over baseline (p = 0.04), indicating increased parasympathetic tone. By contrast, these parameters continued to deteriorate in patients with advanced CAN (65 +/- 32 to 46 +/- 8 ms2 and 193 +/- 75 to 144 +/- 33 ms2, respectively). Autonomic function tests showed no significant change in both groups. These data show that a reversible metabolic component of CAN exists in patients with early CAN. Power spectral analysis of HRV allows early identification of potential reversibility as early as 1 year after the institution of strict glycemic control.

Odynophagia in a woman with known coronary artery disease and ischemia on electrocardiogram.

Esophageal intramural hematoma can mimic other causes of chest pain. When the patient is known to have coronary artery disease, the diagnosis may be difficult. Moreover, the course may be complicated and may harm the patient if antiplatelet drugs, thrombolytics, and anticoagulants are used. The presence of odynophagia should alert the clinician to the possibility of an esophageal origin, even in a patient with known coronary artery disease. We present a case in which early recognition of the clinical presentation prevented potential iatrogenic complications.

A population-based study of appetite-suppressant drugs and the risk of cardiac-valve regurgitation.

BACKGROUND: Recent case reports suggest that a combination of the appetite suppressants fenfluramine and phentermine is associated with an increased risk of cardiac-valve regurgitation. There are also reports of valvular disorders in persons taking fenfluramine or dexfenfluramine alone, particularly for more than three months. METHODS: We conducted a population-based follow-up study and a nested case-control analysis of 6532 subjects who received dexfenfluramine, 2371 who received fenfluramine, and 862 who received phentermine to assess the risk of a subsequent clinical diagnosis of a valvular disorder of uncertain origin. For comparison, we identified a group of 9281 obese subjects who had not taken appetite suppressants who were matched to the treated subjects for age, sex, and weight. All subjects were free of diagnosed cardiovascular disease at the start of follow-up. The average duration of follow-up for all subjects was about four years. RESULTS: There were 11 cases of newly diagnosed idiopathic valvular disorders, 5 after the use of dexfenfluramine and 6 after the use of fenfluramine. There were six cases of aortic regurgitation, two cases of mitral regurgitation, and three cases of combined aortic and mitral regurgitation. There were no cases of idiopathic cardiac-valve abnormalities among the subjects who had not taken appetite suppressants or among those who took only phentermine. The five-year cumulative incidence of idiopathic cardiac-valve disorders was 0 per 10,000 subjects among those who had not taken appetite suppressants (95 percent confidence interval, 0 to 15.4) and among those who took phentermine alone (95 percent confidence interval, 0 to 76.6), 7.1 per 10,000 subjects among those who took either fenfluramine or dexfenfluramine for less than four months (95 percent confidence interval, 3.6 to 17.8; P=0.02 for the comparison with subjects who had not taken appetite suppressants), and 35.0 per 10,000 subjects among those who received either of these medications for four or more months (95 percent confidence interval, 16.4 to 76.2; P<0.001). CONCLUSIONS: The use of fenfluramine or dexfenfluramine, particularly for four months or longer, is associated with an increased risk of newly diagnosed cardiac-valve disorders, particularly aortic regurgitation.

Relation of heart rate variability and serum lipoproteins in type 1 diabetes mellitus and chronic stable angina pectoris.

This investigation examines whether serum lipoprotein levels in patients with diabetes mellitus and in those with coronary artery disease are associated with lower heart rate variability (HRV). The study group consisted of 58 subjects divided into 3 groups: normal subjects, chronic stable angina, and type 1 diabetes. Twenty-four-hour ambulatory electrocardiographic recordings were analyzed in the time and frequency domains; standard instantaneous autonomic testing was also performed. On 24-hour ambulatory recordings, patients with chronic stable angina had significantly lower HRV than normals, and diabetics had a more marked reduction in HRV than both normals and anginal patients. When anginal patients and diabetics were stratified by total serum and low-density lipoprotein (LDL) cholesterol levels, diabetics with elevated total and LDL cholesterol had an additional, significant decrease in HRV parameters. No such difference was demonstrated in patients with stable angina. No significant correlations were noted for high-density lipoprotein (HDL) cholesterol, triglycerides, or total cholesterol/HDL ratio and HRV in diabetics or patient with angina. Diabetics with markedly abnormal peripheral reflexes had significantly higher triglycerides and total cholesterol/HDL ratios. Finally, standard tests of autonomic function did not correlate with total, LDL, HDL cholesterol levels, total cholesterol/HDL ratio, or triglycerides. Thus, we found a relation between atherogenic lipid levels and reduced HRV in diabetic patients that has not been previously identified.

Relationship between autonomic function and progression of renal disease in diabetic proteinuria: clinical correlations and implications for blood pressure control.

The objective of this study was to test the relationship between neurologic and microvascular complications of type 1 diabetes mellitus. It was hypothesized that the mechanisms operative in autonomic dysfunction seen in diabetic patients with microangiopathy play a role in the rapidity of progression to renal failure. Twenty-six type 1 diabetic patients with proteinuria were studied with computerized monitoring of heart rate variation during timed ventilation, assumption of upright posture, and Valsalva maneuver and with 24-h ambulatory blood pressure monitoring at baseline. Renal function was evaluated over the ensuing 12 months of intensive insulin therapy. Blood pressure was treated so as to achieve consistent 24-h readings < 140/90 mm Hg. Angiotensin converting enzyme inhibitors were the preferred antihypertensive agents. Serial serum creatinine concentrations were compared using repeated measures analysis of variance. Over 12 months there were no significant serum creatinine changes for any autonomic test group with normal results at baseline. Groups with abnormal autonomic results at baseline demonstrated statistically significant increases in serum creatinine over 12 months compared to their baseline. Of the tests, Valsalva separated groups of patients with similar degrees of baseline renal impairment. Each of the sympathetic plus Valsalva combinations demonstrated a significant difference in progression of serum creatinine increase over 12 months. In each instance, if both sympathetic and Valsalva results were abnormal, there was a statistically significant increase in serum creatinine over 12 months when compared to groups in which one or both test results were normal. There is a relationship between autonomic function and the progression of renal dysfunction. The inability to vary the heart rate to a Valsalva maneuver identifies a degree of parasympathetic dysfunction that permits unopposed sympathetic tone, heralding more rapid renal destruction. A simple inexpensive bedside laboratory test discerned a relatively low-risk group of diabetic patients with proteinuria that demonstrated no deterioration in renal function over 12 months. When the Valsalva maneuver was markedly abnormal the presence of a mean arterial pressure > 100 mm Hg was associated with a greater likelihood of rapid renal deterioration. This group at higher risk of renal deterioration should undergo aggressive lowering of mean arterial blood pressure to < 95 mm Hg.

Short- and long-term reproducibility of heart rate variability in patients with long-standing type I diabetes mellitus.

Heart rate variability (HRV) has been used to assess cardiac autonomic function noninvasively, understand the pathophysiologic mechanisms of heart disease, evaluate therapy, and assess long-term prognosis. We examined both the short- and long-term reproducibility of the time and frequency domain HRV parameters in 23 type I diabetics over a 12-month interval. Entry criteria included juvenile onset diabetes before age 35 years, >24-year duration of diabetes, diabetes difficult to control, and albuminuria. Standardized noninvasive autonomic testing and 24-hour ambulatory electrocardiographic recordings were obtained. Fifteen men and 8 women (mean age 36.7 years) were enrolled. Fifty-three percent of the men and 75% of the women were smokers, and women had higher cholesterol than men. All HRV parameters were markedly decreased when compared with normal persons. Using Pearson correlation, the time domain indicators of parasympathetic activity demonstrated very strong correlations at 3 and 6 months compared with baseline, with good correlations at 1 year. The average SD of all 5-minute RR intervals maintained a very strong correlation for the entire year (r >0.94). In the frequency domain, the measures of parasympathetic and sympathetic activity maintained a solid correlation for the entire study period. Reproducibility of HRV was also examined using repeated-measures analysis of variance. The time and frequency domain parameters demonstrated very little variation over the study period of 12 months. Thus, our investigation demonstrated that HRV in long-term diabetics using 24-hour ambulatory recordings is abnormal and reproducible over a 12-month interval; very little variation in all HRV parameters, especially in parameters of parasympathetic activity, occurred during the study period.

Relationship between autonomic function and plasma fibrinogen, viscosity, and elements of fibrinolytic activity in diabetic nephropathy.

Twenty-three insulin-dependent diabetics with proteinuria (3.3 g/day: range 0.3 to 8.9) and azotemia (creatinine clearance: 58 mL/min, range 30 to 112) were tested for 24-h mean arterial blood pressure; instantaneous heart rate variations to a computerized protocol involving timed ventilation, assumption of upright posture, and Valsalva maneuver; plasma fibrinogen, viscosity, fibrinolytic activity, and plasminogen activator inhibitor. These were to test the hypothesis that autonomic dysfunction is associated with altered concentrations of plasma fibrinogen, fibrinolytic activity, viscosity, and plasminogen activator inhibitor. We have previously shown the absence of a correlation between level of blood pressure, clinical and standard laboratory testing, and the results of the autonomic function testing protocol used in this study. In this group of patients, plasma fibrinogen concentration was correlated (positively) with mean arterial pressure and (negatively) with heart rate variation in response to the Valsalva maneuver. The greater the mean arterial pressure or the worse the Valsalva results, the higher the plasma fibrinogen concentration. In addition, patients with one or no abnormal autonomic function tests had a mean fibrinogen of less than 400 mg/dL compared to the group of patients with two or more abnormal tests who had a mean fibrinogen of 500 mg/dL. In patients with demonstrated parasympathetic abnormalities, postural heart rate variation testing also discerned a differential in plasma fibrinogen. Lower concentration of plasminogen activator inhibitor throughout the day, and greater fibrinolytic activity in the morning were also noted to be present in patients with abnormal heart rate response to the Valsalva maneuver. We conclude that there are relationships between high blood pressure, autonomic function, and hemostatic factors favoring thrombogenesis that may be related by common mechanisms and treatments in the diabetic with kidney disease.

Role of calcium channel blockers in diabetic renal transplant patients: preliminary observations on protection from sepsis.

BACKGROUND: Diabetic recipients of kidney transplants have an excessively high risk of allograft loss, infectious complications with sepsis, cardiovascular events and early death. This study was designed in order to determine whether post-transplantation medical management influenced long-term results. METHODS: Seventy consecutive diabetic recipients of cadaveric renal allografts were followed from the time of transplant. Treatment regimens were based on the clinical judgement of transplant nephrologists and surgeons, not by the study team. Patients were followed for 2 to 9 years (mean follow-up of 50.85 months, one lost to follow-up). Groups were classified by HLA match, type of immunosuppression, prior cardiovascular history, type of antihypertensives (36 on calcium channel blockers, 32 on beta blockers, 8 ACE inhibitors). Events were defined as myocardial infarction, CVA, graft loss with return to dialysis, life-threatening sepsis, or death. RESULTS: Twenty allografts failed during the study, 24 patients died. Potentially cardioprotective drugs did not impact significantly on cardiac death, MI or CVA. Survivals were better when calcium channel blockers were used (mean 71.7 vs 38.6 months, p < 0.05; 4-year survival 84 vs 58%). When both beta and calcium channel blockers were used (n = 20), patients mean survival was 72.5 months vs 36.8 months for 21 patients who were not treated with blockers (p < 0.005). There was a lower incidence of graft loss when beta blockers and calcium channel blockers were used: at mean patient survival of 36.8 months, the no-blockers group had a mean graft survival of 19.3 months vs 72.5 months for blocker-treated patients (p < 0.002). Reinstitution of dialysis occurred less often with calcium channel blockers (17 vs 42%) or beta blockers (19 vs 38%) used either individually or together (5 vs 42%), all p < 0.05. Calcium channel blocker treated patients had 1/9 the number of septic deaths, fewer patients had multiple septic episodes, all p < 0.02. CONCLUSION: Allograft success and patient survivals may be improved and sepsis related events diminished when diabetic renal allograft recipients are treated with calcium channel blocking agents, plus or minus beta blockers. Considerable savings can be accomplished and graft results with these drugs can approach non-diabetic and live-related transplant results.

Autonomic function in type I diabetes mellitus complicated by nephropathy. A cross-sectional analysis in the presymptomatic phase.

The purpose of this study was to determine the prevalence of parasympathetic and sympathetic autonomic dysfunction in long-standing type I diabetics with established nephropathy and to correlate autonomic function with cardiac risk factors. We used prospective analysis of heart rate variations to standardized testing and 24-hour blood pressure control prior to enrollment in a study utilizing various methods of intense diabetic control to prevent deterioration of kidney function. The settings were outpatient clinical research units. The patients were 42 type I diabetics with proteinuria (total urinary protein > or = 300 mg/day or urinary albumin > or = 100 mg/day) and creatinine clearance > or = 30 mL/min. Heart rate variation during respiratory cycles with change in posture from supine to upright, and during the Valsalva maneuver was recorded by a computerized method. Mean arterial blood pressure was recorded for 24 h by a computerized method. Heart rate variations in this group were abnormal during timed respiratory cycles in 26 of 40 patients (56%), during changes in posture in 15 of 40 patients (38%), and during Valsalva maneuver in 13 of 34 patients (38%) whose retinal disease permitted Valsalva testing. Blunted day/night mean arterial pressure ratios occurred in 18 of 41 (44%) patients and were more severe in men than in women (1.00 v 1.06, P < or = .05). Absence of deep tendon reflexes was associated with an increased incidence of both parasympathetic (respiratory rate variation) and sympathetic (postural rate variation) abnormalities (both P < or = .05). Loss of vibration sensation was not associated with autonomic functional abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary screening of the relationship of serum lipids to survival of chronic dialysis patients.

To assess the predictive value of serum lipid measurements in dialysis patients once the initial decrease on early dialysis had occurred, we obtained random serum cholesterol and triglyceride levels in stable, chronic dialysis patients who were then followed up to 9 years. Derived LDL (DLDL) was estimated by the Friedewald formula, calculated for all HDL levels between 30 and 45 mg/dL, and evaluated statistically against a panel of vascular disease markers, including clinical assessment for coronary, peripheral, and cerebrovascular disease; ECG, both standard and ambulatory; two-dimensional echocardiogram; and medications. Survival was calculated from entry (not dialysis onset) for 58 hemodialysis and 33 peritoneal dialysis patients. The 91 patients (49 males, 74 diabetics) were divided by cholesterol level (> or = 175 mg/dL = 53, < 175 = 38), triglyceride (> or = 175 mg/dL = 55, < 175 = 36), and DLDL (> or = 75 = 58, < 75 = 24). High total cholesterol was present in a larger proportion of females than low cholesterol, but groups were not different with respect to all vascular determinants, including survival (mean = 33.4 months vs. 43.2, p = NS). High vs. low triglyceride groups were not different with respect to vascular indicators, except for both incidence of abnormal standard ECG (69% vs. 42%, p < 0.05) and survivals (mean = 42.0 vs. 30.7, p < 0.05; 1 year = 80% vs. 56%, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of left ventricular size and function in predicting survival in chronic dialysis patients with diabetes mellitus.

To identify patients at high risk for sudden death, a group of stable patients on maintenance dialysis with diabetes mellitus were studied for up to 135 months to determine if there were clinical, laboratory or echocardiographic predictors of high risk. Eighty-two patients on maintenance dialysis who underwent clinical, laboratory evaluation and echocardiography were enrolled and followed for a mean of 25 months for cardiac and noncardiac complications. Thirty-seven patients with normal wall motion and left ventricular (LV) internal diameter had a mean survival of 35.8 months; 28 patients survived greater than 12 months. Seven patients with normal LV wall motion and dilated LV cavities had a mean survival of 45.7 months; 7 patients survived greater than 12 months. Fifteen patients with abnormal LV wall motion and normal internal LV dimensions had a mean survival of 17 months; 7 patients survived greater than 12 months. Twenty-three patients with both abnormal LV wall motion and dilated LV cavities had a mean survival of 7.8 months; 5 patients survived greater than 12 months. Although echocardiographic abnormalities predicted cardiac mortality at 6 and 12 months, the combination of an abnormal standard electrocardiogram at baseline, clinical history of angina pectoris, and prior documented myocardial infarction or congestive heart failure did not. When the study group was divided by mode or duration of dialysis, presence or absence of diabetes, or use of cardioactive drugs, echocardiographic LV wall motion abnormalities remained the most important determinant of survival.

Preoperative evaluation for diabetic renal transplantation: impact of clinical, laboratory, and echocardiographic parameters on patient and allograft survival.

OBJECTIVE: To assess the impact on renal transplant patients and graft survival of clinical, laboratory, and echocardiographic parameters commonly measured prior to surgery. PATIENTS: Forty-seven consecutive diabetics with preoperative echocardiograms at the time of transplantation. METHODS: Clinical history, standard chest roentgenogram, electrocardiogram, blood tests, echocardiograms, and HLA testing at baseline; follow-up from 2 to 7 years with periodic reassessment of graft function. RESULTS: Patient survival did not appear to be influenced by age, sex, or type of allograft. A history of either myocardial infarction, congestive heart failure, or angina was present in 15 patients with 3-year survival of 50% (72% if not present, p less than 0.05). Histocompatibility testing did not impact on survival. Serum sodium, potassium, calcium, phosphate, and calcium-phosphate product did not discern different survival groups. A hematocrit greater than 30% was present in 15 patients with 3-year survival of 43% (73% if not present, p less than 0.05). Greater than 10% antibody sensitization of the recipient resulted in a 3-year survival of 38% in eight patients (68% if not present, p less than 0.05). Radiologic evidence of cardiomegaly or congestive heart failure and standard electrocardiographic evidence for left ventricular hypertrophy or strain did not impact on survival. Echocardiographic measurements of left ventricular end-diastolic diameter, posterior wall thickness, or ejection fraction were also not predictive. Increased end-systolic diameter (10 patients, 30% 3-year survival versus 69%, p less than 0.05) and decreased velocity of circumferential fiber shortening (11 patients, 45% 3-year survival versus 71%, p less than 0.05) both appeared to be related to survival. Increased accuracy of prediction could be obtained by adding risk factors so that a history of coronary artery disease and increased end-systolic diameter predicted 3-year survival of 42% versus 82% if neither was present. In terms of graft survival, no clinical, radiographic, or electrocardiographic result yielded predictive information. Among the laboratory tests, only highly antibody-sensitized patients (eight patients, 0% 3-year survival versus 66% 3-year survival, p less than 0.001) showed different survival patterns. Echocardiographic elevated end-systolic diameter predicted a significantly (p less than 0.001) decreased graft survival (3-year survival 33% versus 63%). CONCLUSION: Preoperative prediction of patient and graft survival in diabetic renal transplantation may be enhanced by echocardiographic assessment of systolic load and function. For patients with normal systolic function, whose hematocrit is below 30%, with preformed antibodies less than 10%, renal transplantation has an excellent prognosis; invasive cardiac procedures are not likely required. Since these risk factors are likely additive, a high-risk group may be identified. These latter patients should undergo coronary angiography.