Influence of cardiovascular diseases upon the results of the cardiovascular reflex tests in diabetic and nondiabetic subjects

Summary Cardiovascular reflex tests are used to assess cardiac autonomic neuropathy in diabetes mellitus. Cardiovascular diseases (CVD) are known to alter baroreflex mechanisms. Diabetic patients are at a high risk for cardiovascular complications. In order to prove whether cardiovascular diseases reduce the diagnostic value of the cardiovascular reflex tests in diabetic autonomic neuropathy unselected groups of 274 nondiabetic and 103 diabetic patients were studied: E/I, 30/15, and Valsalva ratios, sustained handgrip test and blood pressure response to standing. Both groups were subdivided into young (≤45 years) and older (>45 years) patients and into subjects with and without CVD. In young nondiabetic patients with CVD, E/I and Valsalva ratios were significantly lower than in those without CVD. In young diabetic patients with CVD, only E/I ratios were significantly reduced compared to those without CVD. The tests reflecting sympathetic nerve function did not differ between patients with and without CVD, neither in the nondiabetic nor in the diabetic subjects. In the older nondiabetic and diabetic patients, cardiovascular reflexes were generally impaired, but did not show any difference between subjects with and without CVD. In young diabetic patients suffering from CVD, the diagnostic value of cardiovascular reflex tests is reduced as far as cardiac autonomic neuropathy is concerned. In older patients, the tests are not suitable for the diagnosis of diabetic autonomic neuropathy. More specific methods are required.     

Changes in autonomic nervous function during the 4-year follow-up in middle-aged diabetic and nondiabetic subjects initially free of coronary heart disease

Objectives. To study the changes in autonomic nervous function during the 4-year follow-up period in diabetic patients and to investigate factors predicting autonomic nervous dysfunction Design. A 4-year follow-up study. Setting. At baseline the study subjects without known cardiovascular disease were recruited from a large group of diabetic and nondiabetic subjects selected randomly from a baseline population. Subjects. Middle-aged control subjects (n=44), patients with insulin-dependent diabetes mellitus (n=32) and patients with non-insulin-dependent diabetes mellitus (n=32) were studied at baseline and after the 4-year follow-up. Interventions. Autonomic nervous function tests and exercise test at baseline and after the 4-year follow-up. Results. At the baseline, heart rate variation during deep breathing was significantly lower in patients with insulin-dependent diabetes (13.0±1.2 beats min^?1; P<0.05) and in patients with non-insulin-dependent diabetes (12.9±1.5 beats min^?1; P<0.05) than in control subjects (16.6±1.1 beats min^?1). At baseline, autonomic nervous function score was significantly higher indicating disturbed autonomic nervous function in patients with insulin-dependent diabetes (1.74±0.19; P<0.01) than in control subjects (1.24±0.14), but the difference was not significant between control subjects and patients with non-insulin-dependent diabetes (1.47±0.12). During the follow-up, autonomic nervous function score increased in patients with noninsulin-dependent diabetes to 2.00±0.21 (P<0.001, as compared to baseline), but did not change in patients with insulin-dependent diabetes (1.77±0.18) or control subjects (1.22±0.12). In both diabetic groups, the deterioration of autonomic nervous function score during the 4-year follow-up was associated with poor glycaemic control at baseline. Clinical manifestation of coronary heart disease was found in three (7%) control subjects, 12 (37%; P<0.001) patients with insulin-dependent diabetes and 11 (34%; P<0.01) patients with non-insulin-dependent diabetes mellitus at follow-up examination. Autonomic nervous function was more abnormal in those insulin-dependent diabetic patients with coronary heart disease than those without. Conclusions. During the 4-year follow-up the impairment in autonomic nervous function occurred mainly in patients with noninsulin-dependent diabetes. Poor glycaemic control appears to be an important determinant of the progression of autonomic nervous dysfunction in diabetes.     

Partitioning the symptoms of hypoglycaemia using multi-sample confirmatory factor analysis

Summary The allocation of hypoglycaemic symptoms to autonomie or neuroglycopenic groups tends to occur on an a priori basis. In view of the practical need for clear symptom markers of hypoglycaemia more scientific approaches must be pursued. Substantial evidence is presented from two large scale studies we performed which support a three factor model of hypoglycaemic symptomatology, based on the statistical associations discovered among symptoms reported by diabetic patients. Study 1 involved 295 insulin-treated outpatients and found that 11 key hypoglycaemic symptoms segregated into three clear factors: autonomie (sweating, palpitation, shaking and hunger) neuroglycopenic (confusion, drowsiness, odd behaviour, speech difficulty and incoordination), and malaise (nausea and headache). The three factors were validated on a separate group of 303 insulin-treated diabetic out-patients. Confirmatory factor analyses showed that the three factor model was the optimal model for explaining symptom covariance in each group. A multi-sample confirmatory factor analysis tested the rigorous assumptions that the relative loadings of symptoms on factors across groups were equal, and that the residual variance for each symptom was identical across groups. These assumptions were successful, indicating that the three factor model was replicated in detail across these two large samples. It is suggested that the results indicate valid groupings of symptoms that may be used in future research and in clinical practice.     

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index

Summary Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. ’Up BRS' sequences–increases in systolic blood pressure associated with lengthening of R-R interval, and ’down BRS' sequences–decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. ’Up BRS' when supine was 11.2 ± 1.5 ms/mmHg (mean ± SEM) compared with 20.4 ± 1.95 in control subjects (p < 0.003) and when standing was 4.1 ± 1.9 vs 7.6 ± 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 ± 1.2 vs 22 ± 2.6 (p < 0.001) and standing was 4.4 ± 1.9 vs 7.3 ± 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05–0.15 Hz as low-frequency and 0.2–0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 ± 62.8 vs 746.6 ± 77.6 ms² p = 0.002) and high frequency bands 125.2 ± 12.9 vs 459.3 ± 89.8 ms² p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 ± 0.53 vs 4.6 ± 0.55, p < 0.002 supine: 3.8 ± 0.49 vs 6.6 ± 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients. [Diabetologia (1996) 39: 1385–1391] Received: 9 April 1996 and in revised form: 19 July 1996     

Combination of cardiorespiratory reflex parameters and heart rate variability power spectrum analysis for early diagnosis of diabetic cardiac autonomic neuropathy

AimThe study objective was to compare cardiorespiratory reflex (CR-R) parameters and heart rate variability power spectrum (HRV-PS) analysis in the diagnosis of cardiac autonomic neuropathy (CAN) in diabetic patients.MethodsFour CR-R tests (Valsalva manoeuvre, deep breathing, and two successive 5-minute periods with the subject supine and standing, respectively) were performed in 399 diabetic patients (58.6% male, median age: 51 years) and 105 healthy controls (40% male, median age: 34 years). Patients with two or more abnormal CR-R parameters were classified as CAN+, while those with only one abnormal CR-R parameter were considered CAN ‘borderline’. HRV-PS was performed in all study participants.ResultsThe low-frequency (LF) area with the patient standing was reduced in CAN+ diabetics (median 35.6 normalized units [nu], n = 31), in CAN ‘borderline’ diabetics (median 64.3 nu, n = 70) and even in diabetics without CAN (median 89.4 nu, n = 298) versus control subjects (median 93.7 nu; P < 0.001, P < 0.001 and P < 0.05, respectively). Adding the abnormal (< 2.5 nu) LF area to the diagnostic criteria in CAN ‘borderline’ patients caused 11 (15.7%) patients to be considered CAN+.ConclusionCombining abnormal CR-R parameters (I – E and I/E the most specific) with HRV-PS (particularly the LF area with the subject standing) allowed diagnosis of diabetic CAN at an earlier stage.     

Postprandial hypotension in elderly subjects: spectral analysis of heart rate variability and electrogastrograms

Background. In order to clarify the mechanism of postprandial hypotension in the elderly, the influence of gastric motility and autonomic nervous activity on hypotensive reactions after meals was investigated, using electrogastrograms (EGGs) and spectral analysis of heart rate variability. Methods. EGGs, heart rate variability, blood pressure, and blood catecholamine levels before and after a meal were measured in 20 healthy young subjects (mean age, 25.6 ± 5.6 years; young group) and in 20 healthy elderly subjects (mean age, 78.3 ± 5.6 years; elderly group). Results. In the analy-sis of heart rate variability, no significant changes were observed in the low-frequency component (LF power), high-frequency component (HF power), or LF/HF ratio after the meal in the young group. In the other hand, the LF/HF ratio was significantly increased after the meal in the elderly group. In the EGG analysis, the peak power amplitudes after the meal were significantly increased compared with those before the meal in both groups. After the meal, the peak power amplitudes in the young group were significantly greater than those in the elderly group. The baseline blood noradrenaline level (before the meal) was higher in the elderly group than in the younger group, but the level of this catecholamine in the elderly group did not increase significantly after the meal. Conclusions. It is suggested that the down-regulation of catecholamine may be one of the causes of postprandial hypotension in the elderly. The response to secreted catecholamine and the compensatory response to decreased blood flow in the systemic circulation were impaired in the elderly group, which finding may explain the high incidence of postprandial hypotension in the elderly subjects. Received: January 9, 2001 / Accepted: August 10, 2001     

Comparison of BT-PABA test and fecal chymotrypsin measurements in normal subjects and diabetic patients

Summary A N-benzoil-L-tyrosil-PABA test on 6h urine collection, a plasma PABA assay 2h after administration and a fecal chymotrypsin assay were performed on 66 patients (36 controls and 30 type 2 diabetic patients on insulin therapy). All patients were hospitalized and without gastrointestinal and renal disease. The mean values of plasmatic PABA and fecal chymotrypsin were significantly lower in the diabetic group than in the controls (p<0.025 and p<0.01, respectively), although they remained within normal range. But this was not the case for PABA urinary excretion values. This may indicate a slower but more protracted PABA absorption during the third or fourth hour with the result that urinary excretion over 6h is not greatly affected. There was good correlation between fecal chymotrypsin values and both PABA urinary excretion values and serum PABA values, a trend observed both in diabetics (p<0.005 and p<0.001, respectively) and in controls (p<0.001 and p<0.005, respectively). This could indicate that even at lower mean levels, the diabetic patients show the same behavior pattern and therefore maintain the same indexes of correlation as the control population. Our results suggest that these indirect, but simple, economical and well-tolerated tests could be considered a valid alternative for investigating pancreatic function especially in those patients that cannot be tested by a Secretin-Cerulein test.     

Tissue factor activities of streptozotocin induced diabetic rat tissues and the effect of peanut consumption

BACKGROUND: Tissue factor (TF) is considered to be a major regulator of normal haemostasis and thrombosis. Circulating TF activity is suggested to be associated with diabetes mellitus. Various tissues and body fluids have TF activity. The aim of the present study was to investigate the TF activity of streptozotocin (STZ) induced diabetic rat tissues. Peanut consumption is reported to be associated with decreased risk of type 2 diabetes. Therefore, the effect of peanut consumption on the TF activity of STZ induced diabetic rat tissues, and haemostatic parameters such as protrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen levels were determined. METHODS: Twenty-four Wistar rats were divided into 3 groups of 8 rats each as control, STZ-induced diabetic and diabetic + peanut group. Twelve weeks later, TF activity of liver, kidney, spleen, heart, kidney, lung, pancreas and aorta and haemostatic parameters were determined. RESULTS: In the diabetic group, TF activities of liver, kidney and spleen increased (p < 0.01) whereas the TF activity of brain decreased (p < 0.01) compared to the control group. Peanut consumption in the diabetic group decreased the TF activity of spleen and aorta (p < 0.01; p < 0.05). Haemostatic parameters did not change significantly in the groups. CONCLUSION: Elevated TF activity in diabetic rat tissues, may contribute to the increased risk of atherothrombotic disease that accompanies the diabetic complications whereas the decreased brain TF activity may be due to a different haemostatic mechanism to protect this vital organ from the diabetic status. The decreased TF activity of peanut given diabetic rat tissues might protect these tissues from the risk of thrombosis.     

Combination of stem cell factor and granulocyte colony-stimulating factor mobilizes the highest number of primitive haemopoietic progenitors as shown by pre-colony-forming unit (pre-CFU) assay

Fifty-two patients with poor prognosis carcinoma of the breast underwent peripheral blood stem cell (PBSC) mobilization using five different regimens. The yields of primitive haemopoietic progenitors were quantified by a recently described pre-colony-forming unit (pre-CFU) assay using limiting dilution analysis (LDA). Results of days 14 and 35 pre-CFU were also correlated with conventional CD34+ cell enumeration, CFU-GM (granulocyte-macrophage) and long-term culture-initiating cell (LTCIC) assays. The yield of pre-CFUs with the combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) was significantly higher than with G-CSF alone, cyclophosphamide (Cyclo) and granulocyte-monocyte colony-stimulating factor (GM-CSF), interleukin (IL)-3 and GM-CSF, or Cyclo alone. No significant correlation between neutrophil engraftment and pre-CFU could be demonstrated. Furthermore, CFU-GM was shown to bear a stronger correlation with pre-CFU and LTCIC than CD34+ cell measurement; thus, CFU-GM remains a useful biological tool for haemopoietic stem cell assay. We conclude that the combination of G-CSF and SCF mobilizes the highest number of pre-CFUs as measured by functional pre-CFU assay, which provides an alternative measurement of primitive haemopoietic progenitors to the LTCIC assay.     

因子分析在代谢综合征研究中的应用

关于代谢综合征(MS)是否存在、构成组分、病理生理学机制及其临床意义等方面存在较多争议.因子分析(FA)是一种寻找潜在因子的模型分析方法,主要包括探索性因子分析(EFA)和验证性因子分析(CFA).至今已有很多关于MS的研究采用FA方法,为MS作为一种综合征的存在及其生物学机制提供了证据.     

糖尿病肾病并发下肢动脉病变的相关因素分析

目的探讨糖尿病肾病（DN）和糖尿病并发下肢动脉病变（PAD）的相关影响因素。方法选取,DN患者235例（DN组）,单纯糖尿病患者102例（DM组）,测定两组踝肱指数（ABI）及其他相关指标,研究下肢动脉病变发生情况及其影响因素。结果DN组下肢动脉病变发生率（63．0％）高于DM组（11．8％）,差别有统计学意义;DNPAD＋组、DNPAD-组、DMPAD＋组、DMPAD-组的年龄、SBP、DBP、LDL-C、FPG、肾小球滤过率（GFR）、纤维蛋白原（FBG）、UAlb／Cr、24h尿蛋白定量差别均具有统计学意义;DN组发生下肢动脉病变的可能影响因素是SBP、UAlb／Cr、GFR、24h尿蛋白定量;DM组发生下肢动脉病变的可能影响因素是SBP、DBP、24h尿蛋白定量。结论收缩压、纤维蛋白原和尿蛋白可能是DN患者并发下肢动脉病变的预警因子,应对其进行筛查,并给予积极的治疗,从而减少或延缓下肢血管病变的发生及发展。     

Power spectral analysis of the electrocardiogram in diabetic children

Summary In recent years it has been shown that alteration in heart rate variability can be used for the objective assessment of autonomic function in adult diabetic patients. Using a microcomputer based system for on-line monitoring and analysis of heart rate variability by power spectral analysis, 100 children with Type 1 (insulin-dependent) diabetes mellitus were studied. A highly significant negative correlation was identified between heart rate variability and duration of diabetes (r = −0.88,p < 0.0001). The mean heart rate variability in patients with diabetes of duration 3 years or more was significantly lower in comparison to age-matched control subjects. A highly significant negative correlation was evident between heart rate variability and mean HbA₁ in patients with duration of diabetes of 5 years or more. A mean HbA, over 10% during this period was associated with the greatest reduction in heart rate variability. Serial measurements of heart rate variability in diabetic children may be of predictive value prior to the onset of symptomatic neuropathy.     

Effect of manufacturing process parameters on virus inactivation by dry heat treatment at 80 degrees C in factor VIII

BACKGROUND AND OBJECTIVES: Dry heat treatment at 80 degrees C for 72 h is used as a virus inactivation step for some coagulation factor concentrates such as Bio Products Laboratory's (BPL) factor VIII 8Y. In the current study, the effect of this process has been tested on a range of viruses. In addition the effect of various manufacturing process parameters on virus inactivation has been investigated. MATERIALS AND METHODS: Samples of product intermediate were obtained from manufacturing, spiked with virus and subjected to freeze drying and dry heat treatment. Virus inactivation was determined by infectivity assay. RESULTS: Freeze drying followed by dry heat treatment was effective for inactivating a wide range of enveloped and nonenveloped viruses. Sucrose or protein concentration had no effect on virus inactivation. Product presentation or the interruption of heat treatment also had no effect. The inactivation of some of the viruses was greater at higher residual water content but under such conditions the stability of the product was reduced. CONCLUSION: This virus inactivation step was effective for a wide range of viruses and over the range of process conditions encountered in manufacturing. This demonstrates the robustness of this process step.     

von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with Type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion

Summary High plasma levels of von Willebrand factor, an indicator of endothelial cell dysfunction, have been reported in both diabetic retinopathy and nephropathy. It is unclear, however, whether von Willebrand factor is related to diabetic retinopathy in the absence of diabetic nephropathy. The relationship between retinal status and plasma von Willebrand factor concentration was investigated in a cohort of 17 patients with Type 1 (insulin-dependent) diabetes mellitus who were followed-up for a median of 42 months. The patients were examined three times. They were selected for having had normal urinary albumin excretion and no evidence of retinopathy (on fundoscopy) at the first and second examination. They were then divided into two groups, according to absence (Group A;n=9) or presence (Group B;n=8) of retinopathy on fundoscopy or fluorescein angiography at the third examination. Urinary albumin excretion remained normal in all patients. Plasma von Willebrand factor levels were similar in both groups: (median) 128 vs 123 %, 164 vs 132% and 159 vs 130 % (first, second and third examination, respectively). Median changes in plasma von Willebrand factor were also similar: +7 vs +9 % and +5 vs +1 % (first-second and second-third examination). Patients in whom the plasma von Willebrand factor concentration increased had higher systolic blood pressure at the third examination (150±30 vs 130±12 mmHg,p=0.02) when compared to those in whom plasma von Willebrand factor did not increase, but were of similar age and had similar diabetes duration, retinal status, diastolic blood pressure, glycated haemoglobin and serum cholesterol concentration. These data do not support the hypothesis that increases in plasma von Willebrand factor concentration reflect retinal endothelial injury in Type 1 diabetic patients with normal urinary albumin excretion. In these patients, high or increasing plasma von Willebrand factor levels may be related to systolic blood pressure.     

Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects

Aims/hypothesis. We have previously shown that lactate protects brain function during insulin-induced hypoglycaemia. An adaptation process could, however, not be excluded because the blood lactate increase preceded hypoglycaemia.¶Methods. We studied seven healthy volunteers and seven patients with Type I (insulin-dependent) diabetes mellitus with a hyperinsulinaemic (1.5 mU · kg^–1· min^–1) stepwise hypoglycaemic clamp (4.8 to 3.6, 3.0 and 2.8 mmo/l) with and without Na-lactate infusion (30 μmol · kg^–1· min^–1) given after initiation of hypoglycaemic symptoms.¶Results. The glucose threshold for epinephrine response was similar (control subjects 3.2 ± 0.1 vs 3.2 ± 0.1, diabetic patients = 3.5 ± 0.1 vs 3.5 ± 0.1 mmol/l) in both studies. The magnitude of the response was, however, blunted by lactate infusion (AUC; control subjects 65 ± 28 vs 314 ± 55 nmol/l/180 min, zenith = 2.6 ± 0.5 vs 4.8 ± 0.7 nmol/l, p < 0.05; diabetic patients = 102 ± 14 vs 205 ± 40 nmol/l/180 min, zenith = 1.4 ± 0.4 vs 3.2 ± 0.3 nmol/l, p < 0.01). The glucose threshold for symptoms was also similar (C = autonomic 3.0 ± 0.1 vs 3.0 ± 0.1, neuroglycopenic = 2.8 ± 0.1 vs 2.9 ± 0.1 mmol/l, D = autonomic 3.2 ± 0.1 vs 3.2 ± 0.1, neuroglycopenic 3.1 ± 0.1 vs 3.2 ± 0.1 mmol/l) but peak responses were significantly attenuated by lactate (score at 160 min C = 2.6 ± 1 vs 8.8 ± 1, and 0.4 ± 0.4 vs 4.8 ± 1, respectively; p = 0.02–0.01, D = 1.3 ± 0.5 vs 6.3 ± 1.7, and 2.3 ± 0.6 vs 5.7 ± 1.1 p = 0.07–0.02). Cognitive function deteriorated in both studies at similar glucose thresholds (C = 3.1 ± 0.1 vs 3.0 ± 0.1, D = 3.2 ± 0.1 vs 3.3 ± 0.2 mmol/l). Although in normal subjects a much smaller impairment was observed with lactate infusion (Δ four-choice reaction time at 160 min = 22 ± 12 vs 77 ± 31 ms; p = 0.02), in Type I diabetic patients lactate infusion was associated with an improvement in cognitive dysfunction (0.2 ± 0.4 vs –38 ± 0.2 Δ ms, p = 0.0001).¶Conclusion/interpretation. A blood lactate increase after the development of hypoglycaemic symptoms reduces counterregulatory and symptomatic responses to insulin-induced hypoglycaemia and favours brain function rescue both in normal and diabetic subjects. These findings confirm that lactate is an alternative substrate to glucose for cerebral metabolism under hypoglycaemic conditions. [Diabetologia (2000) 43: 733–741]     

Ultrasound organometry: the importance of body height adjusted normal ranges in assessing liver and spleen parameters among Chinese subjects with Schistosoma japonicum infection

Hepatosplenic measurements among 550 Chinese subjects, aged 3-59 years from Yueyang city--a nonendemic area for schistosomiasis in Hunan province, China--were performed to define normal ranges of ultrasound organometry for assessing hepatosplenic morbidity in Schistosoma japonicum infection. Measurements included the size of the liver (left lobe and right lobe), the main portal vein stem, the peripheral periportal vein branches, and spleen length and thickness. The results document the significant relationship between body height and organometric parameters. The reference values stratified by body height improve the accuracy of assessment. Thus, height-based normal ranges established in this study can be applied in hospital routine and in field studies of patients infected with S. japonicum in Hunan province and in other endemic areas of China.     

Insulin resistance is accompanied by increased von Willebrand factor levels in nondiabetic women: a study of offspring of type 2 diabetic subjects compared to offspring of nondiabetic subjects

OBJECTIVES: To examine whether levels of von Willebrand factor (vWF), fibrinogen and fibronectin are related to a parental history of type 2 diabetes and to determine possible explanatory factors for high versus low vWF and fibrinogen. DESIGN: Cross-sectional study. SUBJECTS, MAIN OUTCOME MEASURES: We compared vWF, fibrinogen and fibronectin in 88 nondiabetic offspring of type 2 diabetic subjects (relatives) and 103 offspring of nondiabetic subjects (controls). Other measurements included urinary albumin excretion rate, blood pressure, lipid profile and insulin resistance using homeostasis model assessment (HOMAIR). RESULTS: There were no significant differences in vWF (1.12 vs. 1.06 IU x mL(-1), P = 0.296), fibrinogen (3.2 vs. 3.1 g x L(-1); P = 0.263) or fibronectin (0.39 vs. 0.40 g x L(-1), P = 0.448) between relatives and controls. With multiple logistic regression we determined explanatory factors for high versus low vWF and fibrinogen. Age (P < 0.01), urinary albumin excretion rate (P < 0.05), ischaemic heart disease (IHD) (P < 0.05) were found to be significant explanatory factors for vWF above the median (1.10 IU x mL(-1)). Interaction between insulin resistance and sex was found. Odds ratio for high versus low insulin resistance was 18.39 (P < 0.001) for women and 1.92 (P = 0.32) for men. Body mass index (BMI) (P < 0.05), sex (P < 0.01), smoking status (P < 0.05) and IHD (P < 0.01) were significant explanatory factors for fibrinogen above the median (3.1 g x L(-1)). CONCLUSIONS: Levels of vWF, fibrinogen and fibronectin were not influenced by a parental history of type 2 diabetes. Insulin resistance was found to be a significant risk indicator for high vWF only in women. This may indicate that insulin resistance is a higher risk factor for women than for men, when the outcome is endothelial dysfunction possibly resulting in overt cardiovascular disease.