Which test for diagnosing diabetes?
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Biomedical subjects
Publications and source records attributed to D R McCance.
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The role of alcohol in causing acute medical admissions is recognised but not well quantified. Using a questionnaire we have studied prospectively alcohol intake in patients aged 18-60 years admitted to a medical unit and have analysed the contribution of alcohol to their admission. One hundred and six patients (61 male: 45 female) who fulfilled our preset age criteria were studied. Alcohol intake (mean +/- SEM) was 9 +/- 1 and 12 +/- 1 units on average and heavy drinking days respectively, and 38 +/- 6 units during their last drinking week. Gamma glutamyl transferase (GGT) was > 60 U/l (upper limit of normal) in 29 (n = 92). Eighteen (30%) men had drunk > 50 units and seven (16%) women had taken > 35 units in their last drinking week. In 25 (41%) men and 11 (24%) women alcohol intake was felt to contribute to their admission. In this subgroup, intake was 15 +/- 2 and 20 +/- 1 units on average and heavy drinking days respectively, and 87 +/- 13 units in the last drinking week. GGT was available in 29 and was abnormal in 18. Admission diagnoses were drug overdose (n = 16), alcohol withdrawal symptoms (n = 7), liver disease (n = 6), haematemesis (n = 14) and others (n = 3). Fifteen (42%) felt they had a definite alcohol problem. The use and abuse of alcohol contributes significantly to the general medical workload in the age group studied.
OBJECTIVE: To compare the ability of tests measuring two hour plasma glucose, fasting plasma glucose, and glycated haemoglobin concentrations in predicting the specific microvascular complications of non-insulin dependent diabetes mellitus. DESIGN: Cross sectional and longitudinal analysis of the relation between complications and concomitant results of the three tests. SETTING: Gila River Indian Community, Arizona. SUBJECTS: Pima Indians (cross sectional, n = 960), aged 25 years or above who were not receiving insulin or oral hypoglycaemic treatment at the baseline examination. MAIN OUTCOME MEASURES: Development of retinopathy and nephropathy. RESULTS: Cross sectionally, frequency distributions of logarithms of the three sets of results were bimodal, with the prevalence of retinopathy and nephropathy being, respectively, 12.0-26.7 and 3.9-4.2 times as high above as below cut off points which minimised overlap (two hour plasma glucose concentration 12.6 mmol/l; fasting plasma glucose concentration 9.3 mmol/l; glycated haemoglobin (HbA1c) concentration 7.8%). Longitudinally, each of the three measures of glycaemia significantly predicted the development of retinopathy (P < 0.0001) and nephropathy (P < 0.05). Receiver operating characteristic curves showed that two hour plasma glucose concentration was superior to fasting plasma glucose concentration (P < 0.05) for prevalent cases of retinopathy, but otherwise no variable had a significant advantage for detecting incident or prevalent cases of either complication. CONCLUSIONS: These findings suggest that determination of glycated haemoglobin or fasting plasma glucose concentrations alone may be acceptable alternatives to measuring glucose concentration two hours after challenge with 75 g glucose for the diagnosis of diabetes.
OBJECTIVE: To determine the prevalence of diabetes in relation to birth weight in Pima Indians. DESIGN: Follow up study of infants born during 1940-72 who had undergone a glucose tolerance test at ages 20-39 years. SETTING: Gila River Indian community, Arizona. SUBJECTS: 1179 American Indians. MAIN OUTCOME MEASURE: Prevalence of non-insulin dependent diabetes mellitus (plasma glucose concentration > or = 11.1 mmol/l two hours after ingestion of carbohydrate). RESULTS: The prevalence was greatest in those with the lowest and highest birth weights. The age adjusted prevalences for birth weights < 2500 g, 2500-4499 g, and > or = 4500 g were 30%, 17%, and 32%, respectively. When age, sex, body mass index, maternal diabetes during pregnancy, and birth year were controlled for, subjects with birth weights < 2500 g had a higher rate than those with weights 2500-4499 g (odds ratio 3.81; 95% confidence interval 1.70 to 8.52). The risk for subsequent diabetes among higher birthweight infants (> or = 4500 g) was associated with maternal diabetes during pregnancy. Most diabetes, however, occurred in subjects with intermediate birth weights (2500-4500 g). CONCLUSIONS: The relation of the prevalence of diabetes to birth weight in the Pima Indians is U shaped and is related to parental diabetes. Low birth weight is associated with non-insulin dependent diabetes. Given the high mortality of low birthweight infants selective survival in infancy of those genetically predisposed to insulin resistance and diabetes provides an explanation for the observed relation between low birth weight and diabetes and the high prevalence of diabetes in many populations.
OBJECTIVE: To evaluate temporal trends in the incidence of rheumatoid arthritis (RA). METHODS: Incident cases of RA were identified among a population-based cohort of Pima Indians in Arizona over the period 1965-1990. RESULTS: Among 2,894 subjects, 78 incident cases of RA were identified. The age-adjusted incidence declined by 55% in men (Ptrend = 0.225), and by 57% in women (Ptrend = 0.017) after controlling for oral contraceptive or estrogen use and for pregnancy experience. During the same period, age-adjusted prevalence rates of active RA decreased by 29% in men (Ptrend = 0.63) and by 40% in women (Ptrend = 0.02). Fewer than 17% of subjects with known RA were taking slow-acting antirheumatic drugs (SAARDs) in 1990. CONCLUSION: The decrease in incidence and prevalence of RA in this population over such a short period implicates the involvement of an environmental factor(s), other than exogenous estrogens, in the pathogenesis of the disease. However, the possibility that the observed decrease might be explained by an increased use of SAARDs in subjects with RA cannot be excluded.
OBJECTIVE: To compare the diagnostic properties of the Rome 1961 criteria for active rheumatoid arthritis (RA) and the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 criteria for RA with regard to their ability to classify, diagnose, and predict outcome in RA. METHODS: Analysis of cross-sectional and longitudinal data from repeated health examinations and review of clinical records of 3,509 Pima Indians followed up from January 1966 to December 1990. RESULTS: The ACR 1987 criteria identified approximately 50% of the cases identified by the Rome 1961 criteria, in both cross-sectional and longitudinal analyses. The ACR 1987 criteria were better predictors of subsequent development of a clinically supported diagnosis and treatment with slow-acting antirheumatic drugs (both P < 0.001), but were less sensitive than the Rome 1961 criteria for detecting cases for which there already was a clinically supported diagnosis (P < 0.001). CONCLUSION: In a population-based analysis, the ACR 1987 criteria are less sensitive for detecting clinical disease, but predict a clinically more severe prognosis, compared with the Rome 1961 criteria. The sensitivity of both sets of criteria to identify clinical disease is improved if multiple examinations or inactive disease are taken into account.
Metabolic abnormalities antedate the development of non-insulin-dependent diabetes mellitus (NIDDM) by some years. How these metabolic abnormalities relate to the genetic component of the disease and to the subsequent prediction of diabetes is unknown. The present study was designed to examine the association of parental diabetes with relative weight, fasting and 2-h plasma glucose and fasting and 2-h serum insulin in childhood, and to identify which of these variables were most predictive of subsequent NIDDM. Subjects comprised 1258 Pima Indians aged 5-19 years with normal glucose tolerance participating in a longitudinal population-based study. Age-sex-adjusted values of relative weight, fasting and 2-h glucose and fasting and 2-h insulin were positively associated with parental diabetes. Only one of 138 subjects with two non-diabetic parents developed diabetes. Among 1120 subjects with at least one diabetic parent, 101 (9.0%) developed diabetes during a mean follow up of 8.4 years. Fasting insulin was a significant predictor of diabetes, but did not add to the predictive value of relative weight. Relative weight and 2-h and fasting plasma glucose were the variables most predictive of NIDDM in childhood and adolescence. Against a background of parental diabetes, high fasting insulin concentrations predict diabetes, compatible with the hypothesis that insulin resistance is an early metabolic abnormality leading to NIDDM. In this study, however, its predictive power did not add significantly to that of relative weight, with which it was correlated.(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: To evaluate the relationships among gravidity, obesity, and non-insulin-dependent diabetes mellitus in Pima Indian women. SUBJECTS AND METHODS: Pima Indian women (n = 2,779) participating in a longitudinal epidemiologic study of diabetes were evaluated in both cross-sectional and longitudinal analyses. RESULTS: The prevalence of non-insulin-dependent diabetes was higher among women who had never been pregnant than among those who had been pregnant (age- and obesity-adjusted odds ratio = 2.0; 95% confidence interval = 1.5 to 2.7). Controlled for age and obesity, nondiabetic women who had never been pregnant had significantly higher fasting plasma glucose concentrations by 2% (P = 0.004), higher fasting serum insulin concentrations by 8% (P = 0.09), and higher 2-hour serum insulin concentrations by 10% (P = 0.07) than nondiabetic women who had been pregnant. Among 1,025 women observed for an average of 8 years, those who had not been pregnant by the baseline examination were at significantly higher risk for developing non-insulin-dependent diabetes before the age of 40 years (incidence rate ratio = 1.5; 95% confidence interval = 1.2 to 2.1), but that difference could be accounted for by a higher degree of obesity. CONCLUSIONS: We hypothesize that Pima Indian women who have a high risk for non-insulin-dependent diabetes develop obesity and hyperinsulinemia at an early age, and that may be responsible for decreased fertility because of associated changes in sex hormones.
3-Deoxyglucosone (3-DG) is a reactive dicarbonyl sugar thought to be a key intermediate in the nonenzymatic polymerization and browning of proteins by glucose. 3-DG may be formed in vivo from fructose, fructose 3-phosphate, or Amadori adducts to protein, such as N epsilon-fructoselysine (FL), all of which are known to be elevated in body fluids or tissues in diabetes. Modification of proteins by 3-DG formed in vivo is thought to be limited by enzymatic reduction of 3-DG to less reactive species, such as 3-deoxyfructose (3-DF). In this study, we have measured 3-DF, as a metabolic fingerprint of 3-DG, in plasma and urine from a group of diabetic patients and control subjects. Plasma and urinary 3-DF concentrations were significantly increased in the diabetic compared with the control population (0.853 +/- 0.189 vs. 0.494 +/- 0.072 microM, P < 0.001, and 69.9 +/- 44.2 vs. 38.7 +/- 16.1 nmol/mg creatinine, P < 0.001, respectively). Plasma and urinary 3-DF concentrations correlated strongly with one another, with HbA1c (P < 0.005 in all cases), and with urinary FL (P < 0.02 and P = 0.005, respectively). The overall increase in 3-DF concentrations in plasma and urine in diabetes and their correlation with other indexes of glycemic control suggest that increased amounts of 3-DG are formed in the body during hyperglycemia in diabetes and then metabolized to 3-DF. These observations are consistent with a role for increased formation of the dicarbonyl sugar 3-DG in the accelerated browning of tissue proteins in diabetes.
BACKGROUND: Screening for non-insulin-dependent diabetes mellitus (NIDDM) can be useful in clinical practice and in epidemiologic and genetic studies, but the available information for choosing between screening methods is limited. In this study, characteristics of several screening tests for NIDDM were compared. METHODS: Among Pima Indians participating in an epidemiologic study, the sensitivity and specificity for detecting NIDDM of fasting plasma glucose (FPG) levels and two measures of glycated hemoglobin (HbA1 or HbA1c) were compared in 2092 fasting subjects. Glycated hemoglobin, quantitative glycosuria, and dipstick glycosuria were compared in 237 nonfasting subjects. Diabetes was diagnosed using an oral glucose tolerance test if the 2-hour postload venous plasma glucose concentration was 11.1 mmol/L (200 mg/dL) or greater. The area under the relative operating characteristic curve was used to compare tests. RESULTS: In fasting subjects, the sensitivity for detecting diabetes with 98% specificity was 78.8% for HbA1 level of 7.5% or greater, 80.3% for HbA1c level of 6.3% or greater, and 88.0% for FPG level of 6.83 mmol/L (123 mg/dL) or greater. By relative operating characteristic analysis, there were no significant differences between FPG and HbA1c, but FPG was significantly more sensitive than HbA1. In nonfasting subjects the sensitivity at 98% specificity was 92.9% for HbA1 level of 7.3% or greater, 80.6% for quantitative urine glucose level of 1.94 mmol/L (35 mg/dL) or greater, and 64.3% for trace or greater of dipstick glycosuria. The area under the relative operating characteristic curve was significantly greater for glycated hemoglobin than for either measure of glycosuria. CONCLUSIONS: Although FPG has the best screening properties, HbA1c, HbA1, and quantitative urine glucose also provide high specificity and approximately 80% sensitivity in detecting NIDDM. The choice of a particular method could depend on cost, convenience, and availability.
OBJECTIVE: To determine the effect of rheumatoid arthritis (RA) on mortality rates. METHODS: Longitudinal analyses of data from a cohort of Pima Indians from the Gila River Indian Community in Arizona, who were followed up during the period February 1965 through December 1989. RESULTS: Among 2,979 study subjects aged > or = 25 years, there were 858 deaths, 79 of which occurred in subjects with RA (36 men, 43 women). Age- and sex-adjusted mortality rates were slightly higher in subjects with RA than in those without (mortality rate ratio 1.28, 95% confidence interval [95% CI] 1.01-1.62). Among those with RA, mortality rates were higher in older subjects (mortality rate ratio 1.51 per 10-year increase in age, 95% CI 1.22-1.88), in male subjects (mortality rate ratio 2.23, 95% CI 1.44-3.45, adjusted for age), and in subjects with proteinuria (mortality rate ratio 1.88, 95% CI 1.02-3.46, adjusted for age and sex). Mortality rate ratios for these risk factors were similar in subjects without RA. In addition, among subjects with RA, rheumatoid factor (RF) positivity was predictive of death (mortality rate ratio 1.94, 95% CI 1.10-3.43), and the excess mortality was found primarily among subjects who were seropositive. The death rate from cardiovascular disease (mortality rate ratio 1.77, 95% CI 1.10-2.84) and from liver cirrhosis or other alcohol-related disease (mortality rate ratio 2.52, 95% CI 1.06-6.01) was increased in persons with RA. CONCLUSION: The results of this population-based study suggest that although the risk of mortality in subjects with RA is significantly higher than in those without RA, the risk ratio is in the lower range of that described previously in studies of clinic-based cohorts. RF positivity as a predictor of early death among subjects with RA indicates that the immunologic processes in seropositive RA may contribute to the events that eventually lead to early death.
To identify factors related to the development of end-stage renal disease after the onset of proteinuria, its incidence was determined in 364 Pima Indians aged 35 years or older with Type 2 (non-insulin-dependent) diabetes mellitus and proteinuria (protein-to-creatinine ratio > or = 0.5 g/g). Of these 364 subjects, 95 (36 men, 59 women) developed end-stage renal disease. The cumulative incidence was 40% 10 years after and 61% 15 years after the onset of proteinuria. The incidence of end-stage renal disease was significantly related to the duration of diabetes, the duration of proteinuria, higher 2-h plasma glucose concentration, type of diabetes treatment, and the presence of retinopathy at the time of recognition of the proteinuria, but not to age, sex, or blood pressure. Duration of proteinuria influenced the risk of end-stage renal disease, contingent, however, upon the duration of diabetes at the onset of proteinuria. The higher cumulative incidence of end-stage renal disease 15 years after the onset of proteinuria in Pima Indians (61%) than in Caucasians from Rochester, Minnesota (17%) may be attributable, in part, to the younger age of onset of Type 2 diabetes in Pima Indians than in Caucasians, to ethnic differences in susceptibility to renal disease, or to lower death rates among the Pima Indians from competing causes of death, such as coronary heart disease.
OBJECTIVE: We assessed the endocrine outcome after transsphenoidal surgery for Cushing's disease. DESIGN: Five-year (mean) follow-up (range 1 month-12 years) of patients undergoing transsphenoidal surgery for Cushing's disease between 1977 and 1990; review of case notes, current clinical and biochemical assessment including 24-hour urinary free cortisol. SETTING: Northern Ireland. SUBJECTS: Forty-one patients (33F: 8M); mean age at diagnosis 39.1 years (9-72 years). MAIN OUTCOME MEASURES: Measurements of early post-operative 0800 h serum cortisol and 24-hour urinary free cortisol at least 24 hours after withdrawal of oral hydrocortisone therapy. This was followed by low dose dexamethasone testing. Current 24-hour urinary free cortisol measurements. Retrospective definition of cure. RESULTS: Twenty-seven patients were either cured or improved by surgery, 14 were considered definite failures. Of 19 patients cured, eight had unmeasurable early post-operative 0800 h serum cortisol levels while of 15 tested, 13 had complete suppression with dexamethasone and two suppressed normally but to still measurable levels (39 and 60 nmol/l respectively). Seventeen patients in total have subsequently had bilateral adrenalectomy of whom two have developed Nelson's syndrome. Seven of the 41 patients were shown to have definite cyclical cortisol secretion first diagnosed post-operatively in three patients. Hormone deficiency included TSH (5), LH/FSH (1), cortisol (1) and ADH (temporary in 7, permanent in 1). In all, seven patients had some type of permanent hormonal deficiency post-operatively. CONCLUSIONS: Transsphenoidal surgery offers a worthwhile cure rate without the necessity of life-long endocrine therapy. Post-operative endocrine assessment must be rigorous so that early further management can be planned in the significant percentage of patients in whom cure is not achieved. Early complete suppression on low dose dexamethasone testing is very suggestive of cure but repeated and long-term monitoring of 24-hour urinary free cortisol is advisable.
OBJECTIVE: We assessed the current role of bilateral adrenalectomy in the overall management strategy of hypercortisolism. DESIGN: Retrospective review of case notes. PATIENTS: Twenty-six patients (20F/6M); mean age 46 years (range 15-70 years), median duration of follow-up 5.25 years (0.6-19.1 years) who had undergone bilateral adrenalectomy at the Royal Victoria Hospital since 1972. Eighteen had had prior transsphenoidal surgery which did not control the hypercortisolism. MEASUREMENTS: Morbidity, mortality, incidence of Nelson's syndrome. RESULTS: Surgery was performed through bilateral postero-lateral incisions (20 patients) or a long epigastric incision (six patients). The mean combined weight of the adrenals at surgery was 11.2 g. Twenty patients received subcutaneous heparin and 18 antibiotic prophylaxis peri and post-operatively. There was no operative mortality. Minor complications included one post-operative wound infection and a small pneumothorax requiring drainage. Major complications occurred in two other patients, both with pre-existing invasive pituitary tumours and considered at high risk because of age and general debility. One patient had a massive pulmonary embolus and the other a subphrenic abscess post-operatively. This latter patient, the only mortality, died from an unrelated cause three years post-operatively. Six patients have subsequently undergone pituitary surgery and three have received external pituitary irradiation therapy for expanding tumours. CONCLUSIONS: Bilateral adrenalectomy, in experienced hands, is a relatively safe and useful management option in patients with hypercortisolism. Growth of a pituitary adenoma post-operatively is now the most worrying complication.
Previous cross-sectional studies have shown a significant correlation between limited joint mobility (LJM) and the microvascular complications of Type 1 diabetes, but whether LJM precedes and, therefore, may be regarded as an early marker for complications is unknown. Twenty-two Type 1 diabetic patients (10 male/12 female; diabetes duration at follow-up 20.1 +/- 1.3 (SEM) years) with LJM, and 22 subjects matched for age, sex, and duration of diabetes, without LJM were observed over a 10-year period. Both groups were free of retinopathy and negative for 'dipstick' proteinuria at baseline. After 10 years, of 22 patients with LJM, 10 had developed background and 3 proliferative retinopathy compared with 9 and 1 control subjects, respectively. Microalbuminuria (20 < or = albumin excretion rate < 200 micrograms min-1) was present in 3 and macroalbuminuria (albumin excretion rate > or = 200 micrograms min-1) in 2 of LJM patients compared with 6 and 1 control subjects, respectively. Ankle and toe vibration perception thresholds, HbA1, mean HbA1 (a mean of serial HbA1 measurements obtained during the 10-year follow-up period), and arterial blood pressure did not differ between the two groups (p > 0.05). At 10-year review, 9 of the control subjects had developed LJM of whom 4 had retinopathy and 4 microalbuminuria. Thus, while LJM may be another 'chronic complication' of diabetes, its presence does not appear to predict those at increased risk of developing microvascular complications.
To investigate the contribution of glycation and oxidation reactions to the modification of insoluble collagen in aging and diabetes, Maillard reaction products were measured in skin collagen from 39 type 1 diabetic patients and 52 nondiabetic control subjects. Compounds studied included fructoselysine (FL), the initial glycation product, and the glycoxidation products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine, formed during later Maillard reactions. Collagen-linked fluorescence was also studied. In nondiabetic subjects, glycation of collagen (FL content) increased only 33% between 20 and 85 yr of age. In contrast, CML, pentosidine and fluorescence increased five-fold, correlating strongly with age. In diabetic patients, collagen FL was increased threefold compared with nondiabetic subjects, correlating strongly with glycated hemoglobin but not with age. Collagen CML, pentosidine and fluorescence were increased up to twofold in diabetic compared with control patients: this could be explained by the increase in glycation alone, without invoking increased oxidative stress. There were strong correlations among CML, pentosidine and fluorescence in both groups, providing evidence for age-dependent chemical modification of collagen via the Maillard reaction, and acceleration of this process in diabetes. These results support the description of diabetes as a disease characterized by accelerated chemical aging of long-lived tissue proteins.
Glycation, oxidation, and browning of proteins have all been implicated in the development of diabetic complications. We measured the initial Amadori adduct, fructoselysine (FL); two Maillard products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine; and fluorescence (excitation = 328 nm, emission = 378 nm) in skin collagen from 39 type 1 diabetic patients (aged 41.5 +/- 15.3 [17-73] yr; duration of diabetes 17.9 +/- 11.5 [0-46] yr, [mean +/- SD, range]). The measurements were related to the presence of background (n = 9) or proliferative (n = 16) retinopathy; early nephropathy (24-h albumin excretion rate [AER24] > or = 20 micrograms/min; n = 9); and limited joint mobility (LJM; n = 20). FL, CML, pentosidine, and fluorescence increased progressively across diabetic retinopathy (P < 0.05, P < 0.001, P < 0.05, P < 0.01, respectively). FL, CML, pentosidine, and fluorescence were also elevated in patients with early nephropathy (P < 0.05, P < 0.001, P < 0.01, P < 0.01, respectively). There was no association with LJM. Controlling for age, sex, and duration of diabetes using logistic regression, FL and CML were independently associated with retinopathy (FL odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01-1.12, P < 0.05; CML OR = 6.77, 95% CI = 1.33-34.56, P < 0.05) and with early nephropathy (FL OR = 1.05, 95% CI = 1.01-1.10, P < 0.05; CML OR = 13.44, 95% CI = 2.00-93.30, P < 0.01). The associations between fluorescence and retinopathy and between pentosidine and nephropathy approached significance (P = 0.05). These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and suggest that protein glycation and oxidation (glycoxidation) may be implicated in the development of diabetic retinopathy and early nephropathy.
OBJECTIVE: To examine the relationship between sensory modalities of neurological function and antecedent glycemic control in IDDM patients. RESEARCH DESIGN AND METHODS: Examinations were conducted on 220 IDDM patients (age at onset < 25 yr, duration < 18 yr) for the presence or absence of the right or left ankle reflex and determination of vibration perception threshold at each medial malleolus and great toe using biothesiometry. These parameters were related to the concurrent HbA1 and to a mean of serial measurements (mean HbA1) over the previous 6 yr. RESULTS: Ankle reflexes were absent in 39 (right ankle) and 41 (left ankle) patients, respectively. Mean (right + left) ankle and toe VPTs were 8.7 +/- 3.6 and 6.3 +/- 4.2 (mean +/- SD) (arbitrary units), respectively. Both the mean and concurrent HbA1 were significantly different in patients with absent ankle reflexes (11.6 +/- 1.9 and 12.2 +/- 2.8%, respectively) compared with present ankle reflexes (10.3 +/- 1.7, 10.3 +/- 2.1%) (P < 0.0001). Similarly, a present ankle reflex was related to mean HbA1 arbitrarily divided into groups < 10, 10-12, > 12% (P = 0.0009). In contrast, mean ankle VPT (8.0 +/- 2.2, 8.8 +/- 3.1, and 10.3 +/- 6.2) and toe VPT (5.5 +/- 2.2, 6.1 +/- 2.9, and 8.5 +/- 8.2) did not increase significantly with poor glycemic control (P > 0.05). Age, right ankle reflex, retinopathy, 24-h urinary albumin excretion rate, and erect systolic blood pressure were the only independent variables predicting the toe VPT using linear regression analysis. CONCLUSIONS: These findings support a role for glycemic control in neurological dysfunction in IDDM patients, but also suggest that other unknown factors may be involved.