A comparison of the monofilament with other testing modalities for foot ulcer susceptibility.

We studied the number of testing sites and the proportion needed to be insensate for the optimal assessment of foot ulcer risk with the 10 g monofilament. Also, we compared the sensitivity and specificity of the 10 g monofilament with other methodologies. Fifty-two individuals with either a current foot ulcer, a history of a foot ulcer or the presence of Charcot neuroarthopathy and 51 individuals with no history of any of these conditions were assessed with the 10 g monofilament at four sites on each foot, the 128 Hz tuning fork at the halluces, the Biothesiometer at the halluces and the modified neuropathy disability score. Sensitivities and specificities were calculated for the various modalities. The Biothesiometer and the neuropathy disability score had the highest sensitivities (0.92 for both). The 128 Hz tuning fork tested only at the halluces (criterion: >or=1 insensate site) had the same sensitivity (0.86) as the 10 g monofilament tested at eight sites (criterion: >or=1 insensate site) with similar specificities (0.56 and 0.58, respectively). The Biothesiometer and the modified neuropathy disability score tend to be more sensitive than the 10 g monofilament for the assessment of individuals at risk for foot ulcers. The 128 Hz tuning fork tested at only two sites is as sensitive as the 10 g monofilament tested at eight sites. These data suggest that the 10 g monofilament may not be the optimum methodology for identifying individuals at risk of foot ulcers.

Use of the Semmes-Weinstein monofilament in the strong heart study. Risk factors for clinical neuropathy.

OBJECTIVE: We used the Semmes-Weinstein 5.07 monofilament to assess the prevalence of foot insensitivity and its relationship to potential risk factors. RESEARCH DESIGN AND METHODS: There were 3,638 American Indian participants from Arizona, North and South Dakota, and Oklahoma who attended a study clinic on two occasions: baseline and follow-up, 4 years later. Oral glucose tolerance tests were performed at the visits for those who had not previously been diagnosed as having diabetes. A total of 2,051 participants were diagnosed with diabetes before the study or at the subsequent study visits. At the follow-up visit, participants were tested for their ability to sense the 5.07 (10 g) monofilament at 10 sites of the foot. The prevalence of foot insensitivity was ascertained, and its relation to characteristics of participants was assessed in both univariate and logistic regression analyses. RESULTS: Diabetic participants had a much higher prevalence of foot insensitivity (defined as greater than or equal to five incorrect responses) than nondiabetic participants (14 vs. 5%, respectively). However, marked foot insensitivity was uncommon within the first few years of diagnosis of diabetes. Among the diabetic participants, those diagnosed before study entry had the highest prevalence of foot insensitivity. The prevalence of foot insensitivity was highest in the Arizona Indians (22 vs. 9% in the Dakotas and 8% in Oklahoma). In a logistic regression analysis, foot insensitivity was significantly and independently related to center (Arizona versus others), age, duration of diabetes, and height. CONCLUSIONS: Marked foot insensitivity is prevalent in the diabetic American Indian population, especially in Indians in Arizona; however, this insensitivity is apparently uncommon for several years after the diagnosis of diabetes. The data show that Indians with diabetes are particularly vulnerable to the risk of foot ulceration and that the diagnostic screening of diabetes may lead to better prevention of sensory neuropathy and subsequent foot ulceration.

The degree of blood pressure evaluation and end organ damage with severe hypertension: a case-control study.

To investigate the association of blood pressure and end-organ damage in patients with severe hypertension in a case-controlled manner, 26 patients with syndromes of acute end-organ damage and severe hypertension were compared with 25 patients with severe but asymptomatic hypertension for a variety of demographic, clinical, and basic laboratory values. Differences were assessed with the Chi-square test and multiple logistic regression analysis. End-organ damage was significantly associated with a degree of systolic and diastolic blood pressure elevation, a history of hypertensive crisis, serum creatinine, and a history of alcohol use, in multivariate analysis. The relationship to creatinine and a history of hypertensive crisis were not present in univariate analysis. The possible relationships of these factors to the pathophysiology of hypertensive crisis are discussed.

Plasma lipid levels at diagnosis in type 2 diabetic patients.

Plasma lipid measurements were obtained at the time that 545 subjects were screened for diabetes mellitus. Both the women and men diagnosed with diabetes had significantly higher triglyceride levels (p < 0.05) and lower high-density-lipoprotein cholesterol (HDL-cholesterol) levels (p < 0.05) than those with normal glucose tolerance. Low-density-lipoprotein cholesterol (LDL-cholesterol) levels were only higher in the diabetic women (p < 0.001). Differences in lipid values were diminished somewhat with allowances for the waist-hip ratio. HDL-cholesterol values were inversely related to fasting insulin levels in the normoglycaemic men and women (p < 0.01), but not in the diabetic individuals. Triglyceride levels were strongly positively related to insulin values in the normoglycaemic men and women (p < 0.001 for both), while associations tended to be smaller in the diabetic subjects. In 13 of the diabetic individuals who were not medicated for diabetes over a period of 17.5 +/- 4.6 months, changes in HDL-cholesterol levels were positively related (p = 0.80, < 0.001) and changes in triglyceride levels inversely related (r = -0.70, p < 0.01) to changes in insulin values. These data indicate that at diagnosis Type 2 diabetic patients have an atherogenic lipid pattern that may be related in part to differences in adipose distribution. In addition, the data suggest that HDL-cholesterol is positively related and triglyceride inversely related to insulin action.

A comparison of adiposity measures for screening non-insulin dependent diabetes mellitus.

We compared the accuracies of adiposity distribution measures (waist and hip circumferences, subscapular and triceps skinfold thicknesses, waist-hip and subscapular-triceps ratios) with a measure of adiposity extent (body mass index) for screening non-insulin dependent diabetes mellitus (NIDDM). Of 521 subjects (218 men and 303 women) who had 2 h oral glucose tolerance tests, 43 men and 28 women were found to have NIDDM. Allowing for age, ethnicity, and family history in analyses of covariance, the subscapular skinfold thickness and the ratio of the subscapular to triceps skinfold thicknesses were significantly higher (P < 0.05) in both the men and women found to have diabetes than in their non-diabetic counterparts. The waist-hip ratio was also significantly higher in diabetic women; however, the elevation was not as marked in diabetic men (P = 0.06). The body mass index did not differ between diabetic and non-diabetic men and was only moderately elevated in diabetic women (P = 0.04). Receiver-operator curves were employed to examine the relative accuracies of the body mass index, waist-hip ratio, and subscapular skinfold thickness for screening NIDDM. In both men and women, the waist-hip ratio and subscapular thickness were superior to the body mass index. These data suggest that certain measures of adiposity distribution are more accurate than measures of overall adiposity extent for screening NIDDM and that they may be useful in screening programmes.

A prospective study of sensory function in patients with type 2 diabetes.

Sensory function was prospectively examined in 201 Type 2 diabetic patients over a 2-year period. Quantitative sensory testing for vibration, cool, warm, and pressure perception at the hallux was performed at baseline, 1-month, 1-year, and 2-year visits. There were statistically significant increments of thresholds for all sensory modalities from the baseline visit to the 1-year visit (p < 0.001) and from the 1-year visit to the 2-year visit (p < 0.001). Thirty percent of 77 subjects considered to be at low risk for foot ulceration at baseline progressed to a higher risk category at the 2-year visit. There were no significant differences in mean glycosylated haemoglobin, height, sex distribution, age, or diabetes duration when patients who had a faster progression of insensitivity were compared with patients who had a slower progression. There was a high degree of autocorrelation between baseline and 2-year visits for all sensory modalities (r = 0.83 to r = 0.88, p < 0.001 for all). Also, changes in sensory thresholds from the baseline to 2-year visits for one modality tended to correlate with other modalities (r = 0.36 to r = 0.70, p < 0.001 for all). These data indicate that an appreciable proportion of Type 2 diabetic patients are at risk for a marked rate of decline of sensory function, and suggest a need for at least yearly quantitative sensory testing.

The relationship of total lymphocyte count to CD4 lymphocyte counts in patients infected with human immunodeficiency virus.

A simple, inexpensive alternative to CD4 counts would facilitate the management of asymptomatic and early symptomatic patients with HIV infection. In this report, a high correlation was found between CD4 counts and total lymphocyte counts calculated from complete blood counts in a cohort of ambulatory HIV-infected patients. Using these data, patients with CD4 counts above and below 500 cells/mm3, 200 cells/mm3, and those with and without symptoms can be identified with a high degree of predictive value. The availability and lower cost of lymphocyte counts make them an attractive alternative to CD4 counts in managing asymptomatic and early symptomatic patients with HIV infection.

Sensory function at diagnosis and in early stages of NIDDM in patients detected through screening.

OBJECTIVE: We studied whether sensory function abnormalities are present at diagnosis and whether they develop in the early stages of non-insulin-dependent diabetes (NIDDM). RESEARCH DESIGN AND METHODS: Quantitative assessments of vibration sensitivity at the hallux and index fingers, and thermal sensitivity at the hallux were performed at screening (2-h oral glucose tolerance tests) for diabetes in 364 individuals. Twenty-five subjects diagnosed with NIDDM and 25 matched nondiabetic subjects were restudied after an interval of 12-41 mo. RESULTS: When those with NIDDM (n = 41) or impaired glucose tolerance (IGT) (n = 38) were compared with nondiabetic subjects, there were no significant differences in sensory function indices. However, the vibration threshold and HbA1c were related among those found to be hyperglycemic (IGT and NIDDM combined P less than 0.05; NIDDM alone P less than 0.05). Among diabetic subjects, the vibration threshold and interaction term of height and Hba1c were positively related in a multiple regression analysis (P less than 0.01). There were increments in all sensory thresholds in diabetic patients at follow-up (P less than 0.05 for all). Increments were smaller in control subjects. CONCLUSIONS: These data suggest that although sensory function tends to be normal at diagnosis in NIDDM patients, there appears to be a diminution in sensory function as the disease progresses. An interaction between metabolic factors and height may influence sensory function early in the course of NIDDM.

Comparison of the lipid profiles of Cubans and other Hispanics with non-Hispanics.

We compared the plasma lipid profiles of Cuban Americans and other Hispanic-American subgroups with those of non-Hispanics. High-density lipoprotein cholesterol levels were lower and triglyceride levels were higher when Hispanic women were compared with non-Hispanic women, and this pattern was also apparent for men. The lower high-density lipoprotein cholesterol and higher triglyceride levels were consistent for both Cuban and non-Cuban Hispanics. There were higher waist-hip ratios and insulin levels in both Hispanic men and women. When allowances were made for these attributes in covariance analyses, the lipid differences were markedly diminished. These data suggest the lower high-density lipoprotein cholesterol and higher triglyceride levels are consistent across Hispanic subgroups and that this lipid pattern may be attributable at least in part to increased insulin resistance in Hispanics.

The prevalence and extent of vibration sensitivity impairment in men with chronic ethanol abuse.

We have studied vibration sensitivity impairment in 100 male alcoholic veterans and 52 control subjects who had no etiologic factors for peripheral neuropathy. Vibration sensitivity was quantitated at the hallux with the Vibration Sensitivity Tester. Alcoholic subjects had impairment of vibration sensitivity when compared with control subjects (p less than .001). This difference persisted when a covariance analysis was performed which included age (coefficient +/- SE: 1.40 +/- 0.35 units, p less than .001). Asymptomatic subjects also had vibration sensitivity impairment (p less than .01). In subjects whose ages were greater than or equal to 45 years, 47% of the alcoholics had poorer vibration sensitivity than did any of the controls. Among the alcoholic subjects there were significant correlations of the vibration perception threshold with both age (r = 0.39, p less than .001) and drinking duration (r = 0.35, p less than .001). In multiple regression analyses these associations remained significant (p less than .05). These data indicate that vibration sensitivity impairment is highly prevalent in alcoholic subjects and that impairment may even occur in those who are asymptomatic.

Comparison of quantitative sensory-threshold measures for their association with foot ulceration in diabetic patients.

We compared the accuracy of cutaneous pressure perception-threshold measurements with that of other sensory-threshold measurements for detecting diabetic foot ulcer patients. Three hundred fourteen non-insulin-dependent diabetic patients were studied, of whom 91 had either a current foot ulcer or a history of foot ulceration. Foot ulcer patients had much higher pressure perception thresholds at the hallux than those without foot ulcers (mean +/- SE 4.63 +/- 0.05 vs. 3.54 +/- 0.04 U, P less than 0.001). The magnitude of association was higher than that for vibration thresholds and markedly greater than those for cool and warm thresholds. Pressure thresholds were highly accurate for identifying foot ulcer patients. At a threshold level of 4.21 U, the sensitivity was 0.84, with a specificity of 0.96. At similar sensitivities for vibration and thermal thresholds, specificities were lower. Foot ulceration and cutaneous pressure perception threshold are strongly associated. Pressure-threshold measurements are extremely accurate and perform at least as well as other quantitative sensory tests in identifying foot ulcer patients. Assessment of the foot pressure threshold may have promise as a simple and inexpensive method for detecting diabetic patients at risk for foot ulcers.

The relation between the plasma lipoprotein pattern and the waist/hip ratio in non-diabetic individuals.

Relations between lipoprotein indices and the waist/hip ratio (WHR) were examined in normoglycemic subjects (124 women and 63 men). Among women, an atherogenic lipoprotein pattern was strongly associated with WHR. The relation was greater than that of the lipoprotein pattern with either the body mass index or the subscapular/triceps ratio, and was independent of these adiposity measures. The association between low-density-lipoprotein cholesterol (LDL-cholesterol) and WHR was much stronger in thinner women than in those more obese (r = 0.64 vs r = 0.22, p = 0.001 for difference). Men had a more atherogenic lipoprotein pattern than women; however, with allowances for WHR the lipoprotein patterns were similar. These findings suggest that: (1) WHR is more strongly related to plasma lipoproteins than other adiposity measures; (2) there is effect modification by the extent of adiposity for the relation between LDL-cholesterol and WHR; and (3) the adipose distribution may be important in explaining lipoprotein differences between men and women.

Determinants of quantitative sensory testing in non-neuropathic individuals.

We have studied characteristics of subjects that could potentially influence quantitative sensory measurements in 156 non-neuropathic individuals. All subjects had measurements of vibration perception at the hallux and index finger with the vibration sensitivity tester and measurements of cool and warm perception at the hallux with the thermal sensitivity tester. Age, height, and skin temperature were all inversely related (P less than 0.05) to vibration sensitivity at the hallux, while age was inversely related (P less than 0.01) to vibration sensitivity at the index finger. In multiple regression analyses the significant associations persisted (P less than 0.01). Neither cigarette smoking nor the occasional use of alcohol were related to the quantitative sensory indices. These data indicate that age, height, and skin temperature should be considered in the assessment of vibration perception and that thermal sensitivity is relatively resistant to these factors.

NPH human insulin: does it work in a once-a-day regimen?

A clinical transfer trial was conducted to ascertain whether semisynthetic human NPH insulin has a full 24-hour duration of therapeutic effect comparable to that of NPH insulin from animal sources. Diabetic patients requiring insulin and stabilized on a once-a-day (QD) regimen of animal NPH insulin were enrolled and entered a two-week run-in period during which the constancy of their insulin requirements and the stability of their glycemic control were assessed. At the end of the run-in phase, baseline measurements were made of fasting blood glucose (FBG), hemoglobin A1 C, C-peptide, and insulin antibodies. Patients then were transferred to a QD regimen of semisynthetic human NPH insulin (Novolin N) in the same dose as the animal insulin. Glycemic control was reassessed after 1, 4, and 8 weeks of therapy, and a global assessment of overall glycemic control was made at the conclusion of the study. Efficacy variables were analyzed for 39 patients. Most had non-insulin-dependent diabetes mellitus (NIDDM) and most were transferred from mixed beef/pork insulin. Six (15%) patients required significant adjustments in insulin dose or regimen; the remaining 85% completed the eight weeks of treatment with minimal changes in insulin dose. Mean values for FBG and hemoglobin A1 C did not change significantly between baseline and the end of the study. The only statistically significant change was an increase in mean body weight (P less than or equal to 0.01). Results of the investigators' global assessments showed that 74% of the patients had unchanged or improved control of glycemia after transferring to semisynthetic human NPH insulin. The average frequency of hypoglycemic events was not significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Specific assessments of warm and cool sensitivities in adult diabetic patients.

We have specifically examined warm and cool sensitivities in 60 diabetic and 43 nondiabetic individuals. Diabetic patients tended to have less warm and cool sensitivity than the control subjects (P less than .001 for age less than 50 yr and P less than .05 for age greater than or equal to 50 yr). Both patients asymptomatic for neuropathy and patients with symptoms had impairment of warm and cool sensitivity (P less than .05 for comparisons with control subjects). These differences persisted (P less than .05) in covariance analyses with age included as a covariate. There was a nonlinear association between warm sensitivity and hemoglobin A1c. Warm-sensitivity values in the lowest and middle tertiles of the hemoglobin A1c distribution were similar; however, warm-sensitivity values of patients in the highest tertile were markedly increased (P less than .05 for the comparison of the highest tertile with the lowest and middle tertiles combined). There tended to be more warm insensitivity than cool insensitivity among the diabetic patients, and this difference increased with worsening glycemia. These data indicate that both warm and cool sensations are markedly impaired in asymptomatic adult diabetic patients. They also suggest that warm sensitivity is more impaired than cool sensitivity, and that this is the result of a stronger association between warm sensitivity and metabolic factors.

The association between heart rate and glycemia in adult diabetic subjects.

We have studied the association between heart rate and glycemia in 221 diabetic and 109 non-diabetic adult subjects. Supine and standing heart rates were both statistically significantly higher (P less than 0.001) in the diabetic patients than in the control subjects. Among the diabetics, both the supine and standing heart rates were positively associated with hemoglobin A1c (r = 0.26, P less than 0.001 and r = 0.27, P less than 0.001 respectively). Patients with hemoglobin A1c values greater than 10.00% had a mean heart rate of 84.2 +/- 2.4, while those with hemoglobin A1c values less than 6.00% had a mean of 74.0 +/- 1.5 (P less than 0.001). The associations between heart rate and hemoglobin A1c persisted (P less than 0.001) with allowances for potential confounding variables in multiple regression analyses. The 15:30 difference, an indicator of parasympathetic function, was not associated with either heart rate or glycemia. These data suggest that the heart rate elevation in adult diabetic patients is the result of metabolic abnormalities.

The association between symptomatic sensory neuropathy and body stature in diabetic patients.

In the diabetic patient the clinical manifestations of peripheral neuropathy occur more commonly in the distributions of longer neurons. Utilizing height as a proxy variable, we have examined whether neuron length is also a determinant for the occurrence of peripheral neuropathy among diabetic patients. In studies performed at two sites (Sheffield and Miami) the heights of diabetic patients with symptomatic peripheral neuropathy were compared with those of non-neuropathic diabetic patients. At each site the neuropathic patients were significantly taller (P = 0.02 for Sheffield and P = 0.01 for Miami). These data were not biased by age or race. Body stature (as a proxy for neuron length) appears to be a constitutional risk factor for diabetic peripheral neuropathy.

Neurofunctional testing for the detection of diabetic peripheral neuropathy.

We have studied associations of neurofunctional testing with other indexes of diabetic peripheral neuropathy in patients unselected for neuropathy. The tests included vibratory sensitivity (assessed with the Vibration Sensitivity Tester and the Biothesiometer) and thermal sensitivity (assessed with the Thermal Sensitivity Tester). Values for diabetic patients were markedly higher than those of control subjects. The neurofunctional tests were strongly correlated with each other. There were also significant associations between the neurofunctional and nerve conduction indexes. Asymptomatic patients had higher values than those of the control subjects for each test. When clinical and nerve-conduction criteria were a better indicator than thermal sensitivity. Neurofunctional testing appears to be useful for both the clinical and research assessments of diabetic peripheral neuropathy.

Influence of height on quantitative sensory, nerve-conduction, and clinical indices of diabetic peripheral neuropathy.

We have examined associations between height and quantitative sensory, nerve-conduction, and clinical indices of diabetic peripheral neuropathy in adult diabetic patients. Vibratory sensitivity was strongly related to height when measurements were made with either the vibration sensitivity tester (P = .02) or the biothesiometer (P less than .01); however, there was no relation between thermal sensitivity (as measured with the thermal sensitivity tester) and height. The peroneal and posterior tibial motor nerve-conduction velocities were inversely related to height (P less than .05 for both). When age and diabetes duration were included as variables in multiple regression analyses, the associations with height became stronger. Clinical indices of peripheral neuropathy were also related to height in these analyses. Glycosylated hemoglobin was significantly related to thermal sensitivity and the peroneal and posterior tibial motor nerve-conduction velocities but not to vibratory sensitivity. These data indicate that height has a marked influence on quantitative sensory, nerve-conduction, and clinical indices of diabetic peripheral neuropathy.

Attribute frequency and misclassification bias.

Allowances for potential misclassification bias were performed for three epidemiologic studies. Although the error rates were assumed to be identical for the three studies, there were differences in the degree and even in the direction of the bias. It is shown that they are the result of differences in the true frequencies of the misclassified attributes in these studies. In this regard, the relation of misclassification bias to predictive value is described. Misclassification bias is highly dependent upon the interactions between error rates and the true frequencies of attributes. In general, relative risk estimates are more subject to substantial bias from disease misclassification when cohort studies have very low disease frequencies. Odds ratio estimates are more likely to be substantially biased from exposure misclassification when case-control studies have either very high or very low exposure frequencies. Attribute frequency is an important determinant of bias from misclassification.