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Background: Asymptomatic peripheral arterial disease (PAD) is common amongst the elderly and is a risk factor for cardiovascular morbidity and mortality. PAD can be assessed by non-invasive tests such as the ankle/brachial pressure index (ABPI) at rest and Doppler flow velocity (DFV) scanning, but these tests may underestimate the prevalence of PAD. The aim of this study was to estimate the added value, for the detection of PAD, of the one-minute exercise test, defined as positive if the drop of the ankle systolic pressure was more than 30 mmHg. We also investigated whether the combination of the ABPI at rest and the one-minute exercise test could replace DFV scanning., Materials and Methods: We studied this in a random sample (n = 631) of a 50- to 75-year-old population., Results: Of these subjects 11% (66/631) had an abnormal ABPI (< 0.9) and 16% (102/631) had an abnormal DFV curve. Of this sample 72% of the subjects performed a one-minute exercise test. Of all subjects 6% (27/451) had an abnormal ABPI (< 0.9) and 12% (54/451) had an abnormal DFV curve. The one-minute exercise test revealed seven cases of PAD (beyond the 67 already identified) which were not detected by an abnormal ABPI at rest and/or DFV scanning. As a result the prevalence of PAD increased by 2%. All patients with an aortoiliac or femoropopliteal obstruction had an ABPI at rest < 0.9. The sensitivity of the combination of the ABPI at rest and the one-minute exercise test to detect abnormal DFV curves was low for crural obstructions., Conclusion: The one-minute exercise test slightly improves the detection of peripheral arterial disease in the general population.

Background: Retinopathy is the leading cause of blindness among patients with type 2 diabetes mellitus (DM). Hyperhomocysteinemia is a recently recognized risk factor for cardiovascular disease, independent of established risk factors., Objective: To study the association between the homocysteine level and retinopathy among subjects with and without DM., Methods: We studied an age-, sex-, and glucose tolerance-stratified random sample of a 50- to 75-year-old general white population in the Hoorn Study (N = 625). Retinal vascular changes (retinopathy) were assessed using ophthalmoscopy and/or fundus photography. Hyperhomocysteinemia was defined as a serum total homocysteine level greater than 16 micromol/L., Results: The prevalence of retinopathy was 9.8% (28/285) in subjects with normal glucose tolerance, 11.8% (20/169) in those with impaired glucose tolerance, 9.4% (10/106) in those with newly diagnosed type 2 DM, and 32.3% (21/65) in those with known type 2 DM. The prevalence of retinopathy was 10.3% (39/380) in subjects without hypertension and 16.3% (40/245) in subjects with hypertension; it was 12.0% (64/534) in subjects with a serum total homocysteine level of 16 micromol/L or less and 16.5% (15/91) in those with a serum total homocysteine level of more than 16 micromol/L. After stratification for DM and adjustment for age, sex, glycosylated hemoglobin, and hypertension, the odds ratio (95% confidence interval) for the relation between retinopathy and hyperhomocysteinemia was 0.97 (95% confidence interval, 0.42-2.82) in patients without DM and 3.44 (95% confidence interval, 1.13-10.42) in patients with DM (P =.08 for interaction)., Conclusion: The findings suggest that hyperhomocysteinemia may be a risk factor for retinopathy in patients with type 2 DM, but probably not in patients without DM. Arch Intern Med. 2000;160:2984-2990

A high serum total homocysteine (tHcy) level is an independent risk factor for cardiovascular disease. Because it is not known whether the strength of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease, we compared the three separate risk estimates in an age-, sex-, and glucose tolerance-stratified random sample (n=631) from a 50- to 75-year-old general white population. Furthermore, we investigated the combined effect of hyperhomocysteinemia and diabetes mellitus with regard to cardiovascular disease. The prevalence of fasting hyperhomocysteinemia (>14.0 micromol/L) was 25.8%. After adjustment for age, sex, hypertension, hypercholesterolemia, diabetes, and smoking, the odds ratios (ORs; 95% confidence intervals) per 5-micromol/L increment in tHcy were 1.44 (1.10 to 1.87) for peripheral arterial, 1.25 (1.03 to 1.51) for coronary artery, 1.24 (0.97 to 1.58) for cerebrovascular, and 1.39 (1.15 to 1.68) for any cardiovascular disease. After stratification by glucose tolerance category and adjustment for the classic risk factors and serum creatinine, the ORs per 5-micromol/L increment in tHcy for any cardiovascular disease were 1.38 (1.03 to 1.85) in normal glucose tolerance, 1.55 (1.01 to 2.38) in impaired glucose tolerance, and 2.33 (1.11 to 4.90) in non-insulin-dependent diabetes mellitus (P=.07 for interaction). We conclude that the magnitude of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease in a 50- to 75-year-old general population. High serum tHcy may be a stronger (1.6-fold) risk factor for cardiovascular disease in subjects with non-insulin-dependent diabetes mellitus than in nondiabetic subjects.

Only sparse and contradictory data are available on peripheral somatic nerve function in relation to the total range of glucose tolerance. A random sample (n = 708) of people, stratified by age, sex, and glucose tolerance, from a Caucasian population aged 50 to 74 years was invited to undergo an examination including measures of large-fibre nerve function (ankle and knee reflexes, vibration sense, vibratory perception threshold (VPT) at the foot) and one measure of small-fibre function (thermal discrimination threshold (TDT) at the foot). A total of 267 subjects with a normal glucose tolerance (NGT), 167 with impaired glucose tolerance (IGT), 90 with newly diagnosed diabetes mellitus (NDM), and 73 with previously known diabetes (KDM) were included. KDM was associated with the highest prevalence of large-fibre nerve dysfunction. Within the range from NGT to NDM, most large-fibre function measures showed a decline with decreasing glucose tolerance. The TDT showed a decrease with an increase in fasting and post-load insulin levels (p < 0.05). We conclude that glucose intolerance is associated with impaired peripheral large-fibre nerve function, an association which seems to apply even in the non-diabetic range. Higher insulin levels were associated with a better small-fibre nerve function.

Objectives: To study the distribution of peripheral vascular disease and the relationship to diabetes., Design: Prospective population based study of Dutch caucasian inhabitants., Methods: From a total of 10,500 subjects aged between 50 and 75 years, 2484 Caucasian inhabitants were screened with respect to their glucose tolerance. Subjects using oral antidiabetic agents or insulin were classified directly as having diabetes mellitus. The other participants were screened using two oral glucose tolerance tests and classified using WHO criteria. A group of 173 people with diabetes and a representative age/sex stratified sample of 288 non-diabetic subjects were seen in the vascular laboratory. Carotid artery disease was investigated with Duplex scanning, arm and leg artery obstructions with real time frequency analysis of continuous wave Doppler signals and indirect blood pressure measurements., Results: Comparing diabetic with non-diabetic subjects, we found significantly more obstructions of the carotid arteries (8.7 vs 2.8%), arm arteries (2.3 vs 0%), as well as leg arteries (31.8 vs. 18.4%). The same holds if only the crural artery obstructions were compared (23.7 vs 16.0%). Two of the four diabetic subjects with arm artery obstructions had retrograde vertebral flow, three of them had carotid artery obstructions as well, and three also had leg artery obstructions. More than half of the subjects with a carotid artery obstruction, also had leg artery obstructions., Conclusions: Peripheral vascular disease is common in diabetes, but most are asymptomatic.

We investigated the cross-sectional association between peripheral arterial disease and glycaemic level in an age, sex, and glucose tolerance stratified random sample from a 50-74-year-old Caucasian population. Subjects treated with oral hypoglycaemic agents or insulin were classified as having known diabetes mellitus (KDM) (n = 67). Using two oral glucose tolerance tests, and based on World Health Organisation criteria, all other participants were categorized as having a normal (NGT) (n = 288), an impaired (IGT) (n = 170), or a diabetic (NDM) (n = 106) glucose tolerance. Prevalence rates of ankle-brachial pressure index less than 0.90 were 7.0%, 9.5%, 15.1% and 20.9% in NGT, IGT, NDM and KDM subjects, respectively (chi-square test for linear trend: p < 0.01). Prevalence rates of any peripheral arterial disease (ankle-brachial pressure index < 0.90, at least one monophasic or absent Doppler flow curve or vascular surgery) were 18.1%, 22.4%, 29.2% and 41.8% in these categories (chi-square test for linear trend: p < 0.0001). The prevalence of any peripheral arterial disease was higher in KDM and NDM than in NGT (p < 0.03, p < 0.0001, respectively), whereas no statistically significant difference was demonstrated between IGT and NGT. The same applied when using the ankle-brachial pressure index criterion. Logistic regression analyses showed that any arterial disease was significantly associated with HbA1c, fasting and 2-h post-load plasma glucose after correction for cardiovascular risk factors (odds ratios and 95% confidence intervals 1.35; 1.10-1.65 per %, 1.20; 1.06-1.36 and 1.06; 1.01-1.12 per mmol/l, respectively), whereas it was not associated with fasting and 2-h post-load specific insulin. Ankle-brachial pressure indices were not associated with either plasma glucose parameters or insulin in univariate or multivariate analyses. In conclusion, parameters of glucose tolerance are independently associated with any peripheral arterial disease, whereas insulin is not.

To evaluate the test-retest reproducibility of vibratory perception (VPT) and thermal discrimination (TDT) thresholds on the foot in older adults, we examined 20 50-76-year-old subjects with, and 19 without non-insulin-dependent diabetes mellitus. Adjusted reference values for both thresholds were obtained by assessing the relations with age, body height, and sex among 216 subjects with normal glucose tolerance, of the same age, sampled randomly from a geographically defined general population. The VPT appeared to be more reproducible than the TDT (reliability coefficient 0.89 vs. 0.54). The reproducibility of the VPT was inversely related to age and better for men than for women. Diabetes and glycemic level did not affect the reproducibility of either threshold. Both thresholds were related to age and height. Women had a higher VPT than men. The relations between sex and sensory thresholds at the lower limb, reported in previous studies, were probably confounded by height.

The isozyme distribution, kinetic properties and intracellular localization of hexokinase (ADP:D-hexose-6-phosphotransferase, EC 2.7.1.1) were studied in erythrocytes, blood platelets, lymphocytes and granulocytes. Soluble and particulate fractions were separated by a rapid density centrifugation method after controlled digitonin-induced cell lysis. In lymphocytes and platelets the major part of total activity was particle-bound (78 and 88%, respectively). In granulocytes and erythrocytes most of the hexokinase activity was found in the cytosol. All cell types, except granulocytes, contain mainly the type I isozyme. Platelets contain only type I hexokinase, while in lymphocytes a minor amount of type III is present in the soluble fraction (less than 10% of total activity). The major constituent of granulocytes is type III hexokinase (70-80% of total activity), the remaining 20-30% is type I hexokinase. Erythrocytes contain a multibanded type I hexokinase. The substrate affinities of the type I hexokinase do not differ significantly between the different cell types or between soluble, bound and solubilized fractions. Only soluble hexokinase from lymphocytes shows a slightly decreased Km apparent for glucose (P less than 0.05).