P.J. Beks

Hyperhomocysteinemia Is Associated With an Increased Risk of Cardiovascular Disease, Especially in Non–Insulin-Dependent Diabetes Mellitus A Population-Based Study

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.

Peripheral arterial disease in relation to glycaemic level in an elderly Caucasian population: the Hoorn study.

SummaryWe 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 ofany 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 ofany 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 anklebrachial pressure index criterion. Logistic regression analyses showed thatany arterial disease was significantly associated with HbA1c, fasting and 2-h postload 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 withany peripheral arterial disease, whereas insulin is not. [Diabetologia (1995) 38: 86–96]

Carotid artery stenosis is related to blood glucose level in an elderly Caucasian population: the Hoorn Study

Summary Cross-sectional associations between carotid artery stenosis (CAS) on the one hand, and parameters of glycaemia and specific insulin levels on the other, were investigated in an age, sex, and glucose tolerance stratified random sample from a 50–74-year-old Caucasian population. Subjects treated with insulin or oral hypoglycaemic agents were classified as having known diabetes mellitus (KDM) (n = 66). Using two oral glucose tolerance tests, and based on the World Health Organisation criteria, all other participants were classified as having a normal (NGT) (n = 287), an impaired (IGT) (n = 169) or a diabetic (NDM) (n = 106) glucose tolerance. CAS was defined haemodynamically using duplex scanning. The crude prevalences of only moderate (16–49 %) CAS were 6.6 %, 7.1 %, 5.7 % and 12.1 % in NGT, IGT, NDM and KDM subjects, respectively. For any severe ( ≥ 50 %) CAS, crude prevalences were 2.8 %, 4.7 %, 9.4 % and 7.6 %. The prevalence of any severe CAS was higher in NDM (p < 0.01) and KDM subjects (p = 0.07) than in NGT subjects. The prevalence of a history of stroke or transient ischaemic attack was 1.7 %, 1.8 %, 2.8 % and 1.5 % in NGT, IGT, NDM and KDM, respectively. In univariate logistic regression analysis, HbA1 c, serum fructosamine, fasting and 2-h post-load glucose were significantly associated with any severe CAS. In multivariate analyses controlling for other risk factors, only HbA1 c and 2-h post-load plasma glucose remained significantly associated (odds ratios: 1.29 per % and 1.09 per mmol/l, respectively) in separate models. No association could be shown between either fasting or 2-h post-load specific insulin and any severe CAS in either univariate or multivariate analyses. In conclusion, HbA1 c and 2-h post-load plasma glucose are independently associated with any severe CAS, whereas specific insulin is not. [Diabetologia (1997) 40: 290–298]

Peripheral somatic nerve function in relation to glucose tolerance in an elderly caucasian population: The Hoorn study

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.

Evaluation of the one-minute exercise test to detect peripheral arterial disease

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.