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Biomedical subjects

E S Kilpatrick

Publications and source records attributed to E S Kilpatrick.

36 records · Page 2Linked to original sources
PubMed1998

Biological variation of glycated hemoglobin. Implications for diabetes screening and monitoring.

OBJECTIVE: To assess the inherent potential of glycated hemoglobin as a screening test for type 2 diabetes by determining the biological variation in nondiabetic subjects. RESEARCH DESIGN AND METHODS: HbA1c values were measured by high-performance liquid chromatography (HPLC) in 12 nondiabetic subjects (7 men and 5 women; median age, 40 years [range, 21-55 years]) on 10 fortnightly occasions. The nondiabetic index of individuality (IOI) for HbA1c (i.e., the square root of the ratio of intra- to interindividual variance) was determined. Any test with an IOI of 1.4 has the most potential in disease screening, while one of 0.6 will be of little value. RESULTS: The analytical variance contributed to 9% of the total test variance, intraindividual variance, 6%; and interindividual variance, 85%. The IOI was, therefore, only 0.27. Thus, nondiabetic HbA1c values vary markedly between subjects, while values in the same individual change little with time. As such, to lie outside the assay reference range, the HbA1c values of some nondiabetic subjects must exceed 12 SD from their usual mean value, while in others a change of only 2 SD would be sufficient. CONCLUSIONS: This fundamental characteristic of HbA1c means that even if analytical methods improve, glycated hemoglobin measurements will always be of limited value when screening for type 2 diabetes. If similar interindividual differences also exist in diabetic subjects, then patients with the same glycemic control may vary by at least 1-2%, which has implications in setting glycated hemoglobin targets.

Adult↗
PubMed1998

Biological variation of cystatin C: implications for the assessment of glomerular filtration rate.

To assess the inherent potential for detecting mild to moderate reductions in glomerular filtration rate, this study determined the biological variability of serum cystatin C and creatinine in 12 healthy subjects. After accounting for analytical variation, interindividual variance accounted for 93% and intraindividual variance accounted for 7% of serum creatinine biological variation. As such, to lie outside the assay reference interval, some subjects must exceed 13 SD from their usual mean value, whereas in others, a change of only 2 SD would be sufficient. For cystatin C, interindividual variation explained 25% and intraindividual variance explained 75% of biological variability. Therefore, the upper limit of the population reference interval for cystatin C is seldom more than 3-4 SD from the mean value of any healthy individual. The critical difference for sequential values significant at P < or = 0.05 was calculated as 37% for serum cystatin C and 14% for serum creatinine. We conclude that cystatin C is potentially a better marker for detecting impaired renal function than serum creatinine, but serum creatinine is probably still the better marker for detecting temporal changes of renal function in individuals with established renal disease.

Adult↗
PubMed1997

Problems in the assessment of glycaemic control in diabetes mellitus.

The measurement of glycated haemoglobin and serum fructosamine to assess the recent glycaemic control of diabetic patients has become well established. Likewise, the monitoring of blood glucose using glucose test strips and meters has become popular in both the community and in the hospital inpatient environment. However, despite improvements in the methods of analysis, clinically inaccurate assessments of glycaemia can still occur. Specific problems such as the lack of standardization in assays are in the process of being resolved, but inherent difficulties associated with these measures remain. Clinicians should be aware that these tests still need to be interpreted in conjunction with clinical prudence.

Aging↗
PubMed1996

The effects of ageing on glycation and the interpretation of glycaemic control in Type 2 diabetes.

To investigate the discrepancy in the assessment of glycaemic control using glycated haemoglobin (HbA1C) and glycated proteins (fructosamine), the effect of age on these variables was measured in non-diabetic individuals. In 232 non-diabetics, there was a linear relationship between HbA1C and age (r = 0.49, p < 0.0001). Mean HbA1C rose from 3.82% to 4.44% between the ages of 20 and 70. Consequently, when Type 2 diabetic patient samples (n = 128, median age 63 years) were classified according to European guidelines into good or poor glycaemic control using both an age-matched (n = 101) and a younger (n = 108, median age 37 years) non-diabetic reference population, fewer patients were in good control (14% vs. 25%) and more in poor control (73% vs. 53%) when the younger reference population was used (both p < 0.05). In a subgroup of 126 non-diabetic subjects, HbA1C rose with age (r = 0.48), but serum fructosamine and fasting glucose did not (r = 0.07, r = 0.009, respectively, p = NS). Age-associated differences in non-diabetic HbA1C values may affect the assessment of glycaemic control in diabetic patients. It may also partly explain discrepancies found when comparing fructosamine with HbA1C as a measure of glucose control. Age-related HbA1C reference intervals may therefore be required for the treatment of patients and the accurate auditing of clinic performance.

Adult↗
PubMed1996

Concentration--effect and concentration--toxicity relations with lamotrigine: a prospective study.

This prospective study was designed to ascertain whether measurement of lamotrigine (LTG) concentrations in the epilepsy clinic could be used to predict the onset of complete seizure control or the emergence of adverse effects. LTG was initiated in doses of 25 or 50 mg daily in 69 patients with newly diagnosed or poorly controlled epilepsy and was increased monthly in 50-mg increments until the patient became seizure-free for at least 6 months or developed adverse effects that abated after a reduction in dosage. LTG and other antiepileptic drug (AED) concentrations were measured at each clinic visit but were not supplied to the investigator examining the patients. Overall, 19 patients either withdrew due to lack of efficacy or defaulted from the clinic. Of the remaining 50 patients, 32 (19 monotherapy, 13 polytherapy) became seizure-free at widely varying daily LTG doses (median 200 mg, range 25-850 mg) and concentrations (median 3.8 mg/L, range 1.4-18.7 mg/L). Likewise, the 18 patients (5 monotherapy, 13 polytherapy) who experienced intolerable side effects showed substantial variations in daily LTG doses (median 300 mg, range 100-900 mg) and concentrations (median 4.0 mg/L, range 0.4-18.5 mg/L). No useful concentration-effect or concentration-toxicity relation with LTG could be demonstrated in this study; therefore, we believe that routine therapeutic drug monitoring with this new AED is not currently indicated.

Adolescent↗
PubMed1995

The effect of haemolysis on blood glucose meter measurement.

A study was performed to assess the effect of varying degrees of sample haemolysis on the measurement of blood glucose by the Accutrend, Companion 2, ExacTech, Glucometer II, Glucometer 4, One Touch II, and Reflolux II blood glucose meters. Fresh venous blood was sonicated to induce complete haemolysis and then added in increasing proportions to homologous untreated blood to obtain nine samples with free haemoglobin concentrations up to 50 g l-1. The Accutrend meter showed the only significant (p < 0.05) linear relationship to degree of haemolysis (r = 0.988, p < 0.0001). For every 7% of red cells lysed, the Accutrend value increased by 15%. All other meters gave results which were within 15% of the non-haemolysed value. However, extreme (100%) haemolysis not only affected the Accutrend (glucose value 108% greater than reference) but also the ExacTech (+98%), the Glucometer II (-32%), and the Companion 2 (-41%). Thus, unwitting use of a haemolysed sample to measure whole blood glucose may, with the Accutrend in particular, lead to erroneous results.

Blood Glucose↗
PubMed1994

Glycated haemoglobin values: problems in assessing blood glucose control in diabetes mellitus.

OBJECTIVE: To see whether two measures of glycated haemoglobin concentration--the haemoglobin A1 (HbA1) value and the haemoglobin A1c (HbA1c) value--assess blood glucose control differently in diabetes. DESIGN: Diabetic patients had glycaemic control assessed on the basis of HbA1 and HbA1c values measured by the same high performance liquid chromatography instrument and on the basis of HbA1 measured by electrophoresis. SETTING: A diabetic outpatient clinic. SUBJECTS: 208 diabetic patients and 106 non-diabetic controls. MAIN OUTCOME MEASURES: Glycated haemoglobin concentrations classified according to European guidelines as representing good, borderline, or poor glycaemic control by using standard deviations from a reference mean. RESULTS: Fewer patients were in good control (25;12%) and more poorly controlled (157;75%) as assessed by the HbA1c value compared with both HbA1 assays (39 (19%) and 130 (63%) respectively when using high performance liquid chromatography; 63 (30%) and 74 (36%) when using electrophoresis). The median patient value was 8.0 SD from the reference mean when using HbA1c, 5.9 when using HbA1 measured by the same high performance liquid chromatography method, and 4.1 when using HbA1 measured by electrophoresis. CONCLUSIONS: Large differences exist between HbA1 and HbA1c in the classification of glycaemic control in diabetic patients. The HbA1c value may suggest a patient is at a high risk of long term diabetic complications when the HbA1 value may not. Better standardisation of glycated haemoglobin measurements is advisable.

Adolescent↗
PubMed1994

Intra-operative blood glucose measurements. The effect of haematocrit on glucose test strips.

Variations in haematocrit are known to affect the accuracy of reagent strip tests for glucose. We have investigated 10 patients during cardiopulmonary bypass, where intra-operative decreases in haematocrit occur. Whole blood glucose concentrations were measured on five occasions at 30 min intervals during the procedure using the Glucometer II, One Touch II and Reflolux II meters as well as a reference instrument (YSI Model 23 AM). Haematocrits were recorded simultaneously. Overall, for every 10% fall in haematocrit, Glucometer II measurements rose by 22% (r = 0.74, p < 0.00001), One Touch II measurements fell by 3% (r = 0.44, p < 0.002) and the Reflolux II measurements showed no significant variation. The One Touch II showed closer agreement to the reference (mean bias 0.3 mmol.l-1 (95% between +0.86 and -0.26)) than the Reflolux II (bias 1.58 (+3.40 to -0.24)) or the Glucometer II (bias 3.25 (+6.18 to 0.32)). Thus, depending on the meter used, spuriously large intraoperative changes in blood glucose may seem to arise where patient haematocrit varies.

Adult↗
PubMed1994

Variations in sample pH and pO2 affect ExacTech meter glucose measurements.

A study was conducted to assess the effect of changes in sample pH and pO2 on the Accutrend, ExacTech Companion, Glucometer II, One Touch II, and Refloflux II blood glucose meters. Venous blood was tonometered after the addition of strong acid or alkali to produce 10 samples with a pH range of 6.54 to 7.73 but with a similar mean pO2 (9.09 +/- 0.096 (SEM) kPa) and pCO2 (5.52 +/- 0.024 kPa). The ExacTech showed a > 15% deviation from the value obtained at pH 7.40 below pH 6.95 and above pH 7.85 (r = 0.69, p = 0.026). Ten further samples were made with a pO2 range of 2.0 to 33.6 kPa but mean pH (7.28 +/- 0.012) and pCO2 (7.98 +/- 0.25 kPa) kept alike. The ExacTech was accurate at pO2 = 11.5 kPa but deviated by > 15% below pO2 = 5.8 kPa and above 22.9 kPa (r = -0.95, p = 0.00002). The Accutrend and One Touch II required a pO2 change of 42 and 45 kPa to achieve the same error (r = -0.82 and r = -0.67 respectively). Thus caution is required in the interpretation of ExacTech glucose measurements in severely acidotic or hypoxic patients.

Blood Glucose↗
PubMed1994

A ward comparison between the One Touch II and Glucometer II blood glucose meters.

A 6-week clinical evaluation of the One Touch II blood glucose meter was performed in a medical ward specializing in diabetic patients and compared to the existing Glucometer II system. Nursing staff trained in both methods performed 267 capillary blood glucose measurements using the two meters. A reference capillary blood glucose was performed simultaneously on 129 of these occasions using a Yellow Springs Instrument analyser. The One Touch II correlated better with the reference (r = 0.97) than the Glucometer II (r = 0.86) and was equally close or closer to the Yellow Springs Instrument on 82% of occasions. A greater proportion of samples measured by the One Touch II were within 15% of the reference value (83% vs 66%). There were also 17 cases where the One Touch II was able to give a measurement which was outwith the analytical range of the Glucometer II. A questionnaire revealed the nursing staff unanimously preferred using the One Touch II to their present meter. It is concluded that in a ward setting the One Touch II meter showed improved accuracy, usefulness in its wider analytical range, and a greater user preference in comparison to the Glucometer II.

Blood Glucose↗
PubMed1994

Low-density lipoprotein particle size in type 2 diabetic patients and age matched controls.

Non-enzymatic glycation of low-density lipoprotein (LDL), and the predominance of small dense LDL particles may together contribute to the increased risk of atherosclerosis in diabetes. We aimed to establish whether the size of LDL particles is related to plasma triglyceride concentration, and to the extent of LDL glycation in type 2 diabetic patients. Sixteen men with type 2 diabetes and 16 age matched non-diabetic controls were studied. LDL size was measured by rapid density gradient ultracentrifugation, and LDL glycation by affinity chromatography. Modal LDL density correlated with plasma triglyceride concentrations in both diabetic and control groups (r = 0.86, P < 0.0001, and r = 0.76, P < 0.0008, respectively). There was no significant difference in these variables between the groups. LDL modal density showed no correlation with HbA1, serum fructosamine or plasma glucose in either group. In the diabetic group the degree of LDL glycation correlated with serum fructosamine (r = 0.74, P < 0.001), HbA1 (r = 0.65, P < 0.008), and with plasma glucose (r = 0.64, P < 0.008). Our results suggest that, in well controlled type 2 diabetic patients LDL size is independent of short-term glycaemic control but can be predicted by plasma triglyceride concentrations.

Adult↗
PubMed1993

Evaluation of glycaemic control limits using the Ames DCA 2000 HbA1c analyser.

The Ames DCA 2000 is a benchtop analyser that measures HbA1c by an agglutination inhibition immunoassay using a monoclonal antibody. Laboratory and nursing staff measured HbA1c on-site in 78 patients with Type 1 diabetes at the outpatient clinic. Significant correlations were noted with both the Corning Glytrac total HbA1 assay (r = 0.89) and the Novoclone assay for HbA1c (r = 0.95). Mean within-assay CV was 1.6% and 3.0% at HbA1c of 5.4% and 13.0%, respectively, while between-assay CVs were 4.2% and 3.8%. These results are as good as our routine laboratory method based on the Corning HbA1 assay. Locally derived reference population data for HbA1c were produced and patients were assigned to categories of good, acceptable, and poor glycaemic control using conventional recommendations for Type 2 diabetes. There was poor agreement between the methods, with only 22% of patients achieving good/acceptable control using the DCA 2000, while 46% of patients had an HbA1 in this range. It appears that the convention for derivation of control limits for HbA1 does not hold for this HbA1c assay.

Antibodies, Monoclonal↗
PubMed1993

Increased fetal hemoglobin in insulin-treated diabetes mellitus contributes to the imprecision of glycohemoglobin measurements.

An increased prevalence of fetal hemoglobin (HbF) has been described in pediatric insulin-dependent patients. The popular electroendosmotic method for glycohemoglobin includes HbF. In an adult population comprising 50 insulin-treated and 57 non-insulin-treated diabetic patients and 57 control subjects, we measured HbF by HPLC and measured glycohemoglobin by both HPLC and an electroendosmotic method. Of the insulin-treated patients, 46% had concentrations of HbF > or = 0.5%, compared with 25% of non-insulin-treated patients and 23% of controls (P < 0.02). In the insulin-treated patients, the two glycohemoglobin methods correlated best when the HPLC measurements included HbF (r = 0.92 vs r = 0.84). Fructosamine concentrations correlated best with glycohemoglobin concentrations determined by methods that accounted for HbF. The true between-batch CV of the electroendosmotic assay increased (from 4.33% to 8.33%) when variable interpatient HbF concentrations were included. Thus, HbF must be considered when interpreting glycohemoglobin measured by an electroendosmotic method and when comparing it with other measures of glycemic control.

Adolescent↗
PubMed1991

Serum fructosamine/haemoglobin A1 ratio predicts the future changes in haemoglobin A1 in type 2 (non-insulin dependent) diabetic patients.

The aim of the study was to define clinical interpretation of the parallel measurements of serum fructosamine and HbA1 in diabetic patients. We studied 14 type 2 diabetic patients over a 16-wk period. The cross-sectional analysis showed no correlation between serum fructosamine and HbA1 concentrations during the period of changing glycaemic control. The correlations, however, became significant (P less than 0.05) at 12 (r = 0.60) and 16 (r = 0.87) weeks, i.e. after glycaemia had stabilised. Longitudinal analysis of individual patients' data over the 16-wk period showed a significant correlation between serum fructosamine and HbA1 (r = 0.55 to r = 0.94) which was present in 8 out of 14 patients. The changes in fructosamine concentration preceded those observed in HbA1. The ratio of fructosamine/HbA1 predicted the changes in HbA1 over the following month (r = 0.54, P less than 0.001). Thus, we demonstrated that the parallel measurement of fructosamine and HbA1 provides information on future trends in HbA1 concentration in diabetic patients.

Adult↗