[Postprandial glucose peaks in the pathogenesis of cardiovascular disease in diabetes mellitus; implications for metabolic control].
Explore the source record for details and available documents.
Blood Glucose↗
Biomedical subjects
R J Heine
Publications and source records attributed to R J Heine.
[Initiating insulin therapy in patients with diabetes mellitus type 2: in a transmural setting is at least as effective as in an outpatient setting; a retrospective study with a 4-year follow-up].
OBJECTIVE: Assessing whether the initiation of insulin therapy in patients with diabetes mellitus type 2 can be delivered as effectively in a structured transmural care model as in the more usual outpatients structure. DESIGN: Retrospective comparative cohort study. METHOD: In 1997 data were collected from 52 patients with diabetes mellitus type 2 all of whom were above 40 years of age and transferred to insulin therapy in 1993: 25 in a transmural care setting and 27 in an outpatients setting, both in Amsterdam, the Netherlands. Both groups were treated according to one protocol concerning the initiation and monitoring of insulin therapy, treatment goals and follow-up. Outcome measures were: percentage of glycated haemoglobin (HbA1c), health status, self-care behaviour and patient satisfaction. In 1993 the mean age was (transmural/outpatients setting): 67.5/65.3 years; percentage of men: 32%/48%; mean duration of diabetes: 7.3/10.6 years; HbA1c: 9.1%/9.3%; mean body mass index: 27.4/29.1 kg/m2. RESULTS: In the period 1993-1997 the mean HbA1c decreased from 9.1% to 7.2% in the transmural care group and from 9.3% to 7.6% in the outpatients care group (both: p = 0.000). The percentage of patients with poor glycaemic control (HbA1c > 8%) decreased from 60 to 8 in the transmural care group and from 59 to 15 in the outpatients care group. The percentage of patients with good glycaemic control (HbA1c < 7%) increased from 4 to 52 in the transmural care group and from 11 to 30 in the outpatients care group. No statistically significant differences were found between the patient groups with respect to health status, self-care behaviour and patient satisfaction. CONCLUSION: The transfer of patients with diabetes mellitus type 2 insulin therapy in a shared care setting was at least as effective as in an outpatients setting.
Aged↗
Beyond postprandial hyperglycaemia: metabolic factors associated with cardiovascular disease.
Type II (non-insulin-dependent) diabetes mellitus is associated with a considerably enhanced risk of cardiovascular disease morbidity and mortality. Several epidemiological studies have shown an association between the 2-h glucose value after a 75 gm glucose load (2hPG) and mortality from all causes and from cardiovascular disease. The key question is whether postprandial glucose is related causally to the adverse outcomes (risk factors) or just a marker of risk. Since insulin resistance is one of the determinants of the 2hPG, factors associated with the insulin resistance syndrome, in particular postprandial hypertriglyceridaemia, also need to be considered. Glycaemic excursions could contribute to oxidative stress, endothelial dysfunction, formation of advanced glycation end-products and prolongation of the QTc interval. However, high postprandial concentrations of triglyceride rich lipoproteins, which can be partly attributed to obesity and insulin resistance, have now been recognised to affect endothelial function, to promote atherogenesis, and to be associated with coronary artery disease. On the basis of present evidence Type II diabetic patients require good overall glycaemic control, as reflected by target values of HbA(1 c). However, postprandial hyperglycaemia should be considered as a marker of underlying metabolic abnormalities. Therefore, at present there is no evidence to support the recommendation to consider postprandial hyperglycaemia as a treatment target in itself and would thus require intervention studies showing added benefit of selectively targeting at meal-related glucose excursions in patients with an adequate HbA(1 c). Drugs aiming at improving only postprandial glucose values are not likely to lower the excess mortality associated with Type II diabetes.
Blood Glucose↗
Components of the insulin resistance syndrome in seven-year-old children: relations with birth weight and the polyunsaturated fatty acid content of umbilical cord plasma phospholipids.
AIMS/HYPOTHESIS: According to the foetal origins hypothesis, there is a relation between foetal nutrition and adult glucose intolerance. In adults, insulin resistance has been associated with dietary polyunsaturated fatty acids. We examined whether the availability of polyunsaturated fatty acids during foetal life, as indicated by the fatty acid composition of cord blood samples, relates to childhood body composition and glycaemic control. METHODS: Fatty acid concentrations in umbilical cord blood were determined by gas-liquid chromatography in a birth-cohort of infants. When the children were seven years old, fasting glucose, insulin, proinsulin, and leptin levels were measured in 259 of these children, and relations with cord plasma fatty acid concentrations were studied. RESULTS: Cord plasma phospholipid gamma-linolenic acid and dihomo- gamma-linolenic acid concentrations were negatively related to insulin concentrations and calculated insulin resistance (homeostasis model assessment) at seven years of age. The gamma-linolenic acid concentrations were also negatively related to body fatness and proinsulin and leptin concentrations at seven years of age. No association was found for other polyunsaturated fatty acid concentrations at birth. Adjusted for age, sex, current weight, and gestational age, a lower birth weight related to higher values of insulin resistance variables. The highest insulin concentrations were found in children with a low birth weight and a low gamma-linolenic acid concentration at birth. The relations between gamma-linolenic acid concentration at birth and fasting insulin and calculated insulin resistance remained statistically significant when adjusted for birth weight. CONCLUSION/INTERPRETATION: These findings indicate that foetal availability or metabolism of gamma-linolenic acid could be involved in the early origins of insulin resistance.
Adult↗
Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality?
Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule-1 (sICAM-1) concentration and risk of cardiovascular and all-cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM-1 may promote mortality. Six hundred and thirty-one subjects taken from a general population of the middle-aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000. Subjects who died had higher levels of sICAM-1 than those who survived (506(164) vs. 477(162) ng mL(-1), respectively). After adjustment for age, gender and glucose tolerance status, subjects with sICAM-1 levels in the upper quartile (> or =550 ng mL(-1)) had a relative risk of cardiovascular mortality of 2.05 (95% confidence interval, 1.10-3.81) compared to subjects with sICAM-1 levels in the other quartiles. Further adjustment for classical cardiovascular risk factors or indicators of (sub)clinical atherosclerosis, endothelial dysfunction, inflammation and renal function did not materially alter this relative risk. A high sICAM-1 level was more frequent in subjects with type 2 diabetes than in subjects with a normal glucose tolerance (33.3 vs. 17.8%). Individuals with a plasma concentration of sICAM-1 higher than 550 ng mL(-1) had a cardiovascular mortality risk that was twice that of individuals with a lower concentration. Classical cardiovascular risk factors (sub)clinical atherosclerosis, endothelial dysfunction and inflammation do not explain this excess risk.
Aged↗
Impact of diabetes duration and cardiovascular risk factors on mortality in type 2 diabetes: the Hoorn Study.
BACKGROUND: Several studies have reported differences in the mortality risk between diabetic subjects detected by screening and known diabetic patients. We studied mortality in relation to diabetes duration, and the contribution of other cardiovascular risk factors to the elevated risk. MATERIALS AND METHODS: Participants were type 2 diabetic subjects (n = 174) of a population-based cohort study. Of these, 95 were diagnosed by screening. Known diabetic subjects were grouped into two categories of diabetes duration, with a median duration of 2.4 and 11.2 years, respectively. We assessed the contribution of classical cardiovascular risk factors (dyslipidaemia, hypertension, and prior myocardial infarction), and of new cardiovascular risk factors (microalbuminuria, von Willebrand factor, sVCAM-1 and C-reactive protein) to the mortality risk during nearly 10 years of follow up. Cox's proportional hazards model was used to study the association of diabetes duration and mortality. RESULTS: The age- and sex-adjusted relative risks of mortality were 2.06 (95% C.I. 1.04-4.10) and 3.19 (1.64-6.20) for the patients with short- and long-term diabetes compared with the screening-detected diabetic subjects, respectively. Adjustment for cardiovascular risk factors resulted in a reduction of mortality risk in both groups: 1.13 (0.51-2.50) and 2.39 (1.18-4.83), respectively. Mortality risk significantly increased with increasing diabetes duration, even after multiple adjustment (P-value for trend ranged from < 0.001-0.018). CONCLUSIONS: Mortality risk increased with increasing diabetes duration. In subjects with short diabetes duration the mortality risk could largely be attributed to other risk factors. In subjects with a longer diabetes duration, however, the elevated mortality risk was independent of these cardiovascular risk factors.
Aged↗
Screening for Type 2 diabetes: an exploration of subjects' perceptions regarding diagnosis and procedure.
AIM: To explore the psychological impact of a stepwise population-screening project for Type 2 diabetes. METHODS: As part of a stepwise population screening project for Type 2 diabetes in the Hoorn region, The Netherlands, an explorative interview study was conducted. The psychological impact of screening was studied using semistructured interviews in 40 subjects: 20 who were diagnosed with Type 2 diabetes, and 20 subjects who were at increased risk of having diabetes but who did not meet criteria for diabetes. Transcripts were analysed using techniques of content analysis. RESULTS: Newly diagnosed subjects reported limited understanding of their elevated blood glucose levels. None, with the exception of one, was alarmed by the diagnosis. Having Type 2 diabetes was not experienced as severe and no concerns were expressed. Adjusting diet was perceived as a major change by some. All newly diagnosed subjects had informed close relatives and friends of the diabetes, who were in general not alarmed by the news. Both groups positively judged the screening procedure. In general the screening procedure was considered as useful and not experienced as burdensome. CONCLUSIONS: This explorative study suggests that the psychological impact of screening in newly diagnosed subjects is limited. Both those who were and those who were not diagnosed with Type 2 diabetes judged the screening procedure positively.
Attitude to Health↗
Continuous intraperitoneal insulin infusion in patients with 'brittle' diabetes: favourable effects on glycaemic control and hospital stay.
AIMS: To evaluate the effects of continuous intraperitoneal insulin infusion (CIPII) using implantable pumps on glycaemic control and duration of hospital stay in poorly controlled 'brittle' Dutch diabetes patients, and to assess their current quality of life. METHODS: Thirty-three patients were included. Glycaemic control was retrospectively assessed with HbA(1c) levels acquired before implantation, 1 year later and at long-term follow up of 58 months. Duration of hospital stay the year before and the year following first implantation was extracted from hospital records. Determinants of long-term glycaemic response were sought. Self-report questionnaires were administered at 58 months follow-up only, to assess current psychopathology and quality of life. RESULTS: Mean HbA(1c) decreased from 10.0 +/- 2.3% to 9.0 +/- 1.8% (P = 0.039) 1 year after implantation and stabilized at 9.0 +/- 1.6% (P = 0.023) during long-term follow-up. Median number of hospital days in the 20 patients suffering from hospital admission before implantation decreased from 45 the year before implantation to 13 the year after (P = 0.005). Patients with a higher baseline HbA(1c) showed a larger long-term response (P < 0.001). Relatively low levels for quality of life were found, as well as a higher than expected number of patients with psychiatric symptoms. CONCLUSIONS: CIPII proved effective in complex patients with a history of poor control and hospital admission. Despite a substantial long-term improvement in glycaemic control and diminished hospital stay, normal levels of glycaemic control and quality of life were not attained.
Adult↗
Longitudinal assessment of the development of diabetic polyneuropathy and associated risk factors.
AIMS: To longitudinally assess risk factors for diabetic polyneuropathy (DPN) severity, and to longitudinally assess risk factors for the change of DPN severity during 2-4 years of follow-up. METHODS: From 1995 to 1999, 486 Type 2 diabetes patients in general practice were examined annually with regard to DPN severity and its possible risk factors. DPN severity was assessed with a clinical neurological examination (CNE) which included pinprick sense, light touch sense, vibration sense and ankle jerk. Longitudinal (multivariate) linear associations of (change of) CNE score and predicting variables were analysed using multilevel analyses. RESULTS: In this population, 50% of participants were men and had a mean age of 65.4 years, almost one-third (31.7%) of the participants had a CNE score > 4 at baseline and were classified with DPN. CNE score significantly increased during follow-up. Among participants not graded with DPN at baseline, 21.3% progressed towards a CNE score > 4 after 3 years of follow-up. Longitudinal multivariate analyses showed that age, diabetes duration, HbA1c, height, body mass index and ankle-arm index together best predicted CNE score during follow-up. Change of CNE score during follow-up was best predicted by age, diabetes duration and HbA1c, with the latter being the strongest predictor. CONCLUSIONS: Although several factors are longitudinally associated with DPN, HbA1c, age and diabetes duration were the best predictors of CNE change during follow-up. Therefore, improving glycaemia remains an important amenable factor in preventing worsening of diabetic polyneuropathy.
Age of Onset↗
Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population: The Hoorn Study.
CONTEXT: Persons with impaired glucose tolerance (IGT) are known to have an elevated risk of developing diabetes mellitus. Less is known about diabetes risk among persons with impaired fasting glucose (IFG) or with normal glucose levels. OBJECTIVE: To determine the incidence of diabetes in relation to baseline fasting and postload glucose levels and other risk factors. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study conducted from October 1989 to February 1992 among 1342 nondiabetic white residents of Hoorn, the Netherlands, aged 50 to 75 years at baseline, in whom fasting plasma glucose (FPG) levels and glucose levels 2 hours after a 75-g oral glucose tolerance test were measured at baseline and at follow-up in 1996-1998. MAIN OUTCOME MEASURES: Cumulative incidence of diabetes, defined according to the diagnostic criteria of the World Health Organization (WHO-1985 and WHO-1999) and the American Diabetes Association (ADA-1997), during a mean follow-up of 6.4 years, compared among participants with IFG, IGT, and normal glucose levels at baseline. RESULTS: The cumulative incidence of diabetes was 6.1%, 8.3%, and 9.9% according to the WHO-1985, ADA, and WHO-1999 criteria, respectively. The cumulative incidence of diabetes (WHO-1999 criteria) for participants with both IFG and IGT was 64.5% compared with 4.5% for those with normal glucose levels at baseline. The odds ratios for diabetes (WHO-1999 criteria), adjusted for age, sex, and follow-up duration, were 10.0 (95% confidence interval [CI], 6.1-16.5), 10.9 (95% CI, 6.0-19.9), and 39.5 (95% CI, 17.0-92.1), respectively, for those having isolated IFG, isolated IGT, and both IFG and IGT. In addition to FPG and 2-hour postload glucose levels (P<.001 for both), the waist-hip ratio also was an important risk factor for developing diabetes (P =.002). CONCLUSION: In this study, the cumulative incidence of diabetes was strongly related to both IFG and IGT at baseline and, in particular, to the combined presence of IFG and IGT.
Aged↗
Drug therapy for management of obesity.
Explore the source record for details and available documents.
Appetite Depressants↗
The potential role of adenosine in the pathophysiology of the insulin resistance syndrome.
An increased intracellular availability of the co-enzyme A esters of long-chain fatty acids is thought to underlie many aspects of the insulin resistance syndrome. However, the cause of clustering of a hyperdynamic circulation, sympathetic activation, hypertension, hyperuricaemia, and a raised haematocrit in the insulin resistance syndrome remains to be elucidated. We propose a mechanism that expands the etiological role of long-chain fatty acids. By inhibiting adenine nucleotide translocators, elevated intracellular concentrations of the co-enzyme A esters of long-chain fatty acids impair mitochondrial oxidative phosphorylation. This is expected to result in a chronic systemic increase in extracellular adenosine concentrations. As adenosine stimulates the sympathetic nervous system, induces systemic vasodilatation, stimulates erythropoiesis, and induces renal vasoconstriction with renal sodium retention, increased extracellular ADO concentrations may be the common denominator explaining the above-mentioned and still unexplained phenomena associated with the insulin resistance syndrome. Along the same lines, hyperuricaemia can be explained by the fact that adenosine is broken down to urate and because of increased renal urate retention.
Adenosine↗
Insulin-treated diabetes patients with fear of self-injecting or fear of self-testing: psychological comorbidity and general well-being.
OBJECTIVE: To examine psychological functioning and self-management behaviours of Dutch adult patients with insulin-requiring diabetes mellitus suffering from extreme fear of self-injecting (FSI) and/or fear of self-testing (FST). METHODS: A cross-sectional survey was performed in a sample of insulin-treated diabetes patients (n=1275; 51.1% male; age 49.7+/-15.8 years; 58.0% Type 1 diabetes), assessing FSI and FST. Patients completed the questionnaires concerning trait/state anxiety, depression, fear of hypoglycemia, diabetes-related distress, diabetes self-care activities, and general well-being. Comparisons were made on these measures between patients with extremely high scores on FSI and/or FST (> or = 95th percentile) and the other patients. Patients with extreme scores on FSI and/or FST were invited to take part in a second survey to assess the prevalence of major depression, common fears/phobias, and psychoneuroticism. RESULTS: People with extreme FSI/ FST scores, as compared to the other patients, reported higher levels of trait/state anxiety and depression. This group also reported more fear of hypoglycaemia and diabetes-related distress, had lower levels of general well-being, and reported less frequent self-monitoring of blood glucose. The second survey showed 11.1% of patients with extreme FSI/FST reporting scores indicating major depression. Prevalence of scores greater than or equal to the high scores on phobias (38.0-63.3%) and psychoneuroticism (27.8%) were consistently higher than norm group prevalences. DISCUSSION: Extreme levels of FSI and/or FST are associated with high diabetes-related distress, poor general well-being, and psychological comorbidity, as well as poorer adherence to the diabetes treatment regimen. It is concluded that patients with extreme FSI/FST are often burdened with more than this specific phobia.
Adult↗
Characteristics of pancreatic beta-cell secretion in Type 2 diabetic patients treated with gliclazide and glibenclamide.
The aim of the present cross-over study was to compare the beta-cell response to gliclazide and glibenclamide administered orally during and following a hyperglycaemic clamp in sulphonylurea treated Type 2 diabetes. Nine patients (6 males), aged 61.4 (S.D. 6.9) years with a body mass index of 27.5 (3.1) kg m(-2) and HbA(1c) at baseline of 7.2 (0.9)% were included. Eight healthy control subjects underwent the same tests. Patients received 80-240 mg gliclazide or 5-15 mg glibenclamide for 6 weeks. Thirty minutes after administration of 160 mg of gliclazide or 10 mg of glibenclamide a 1-h hyperglycaemic clamp (11.0 mmol l(-1)) was begun, and followed by a 3.5-h observation period. Nadir blood glucose levels were 4.2 (1.0), 4.3 (1.2) and 3.4 (1.0) mmol l(-1) for glibenclamide gliclazide and controls, respectively (both P=0.07 vs. controls). Glucose levels decreased slowly and linearly in people with diabetes and reached nadirs after 204 (8) and 198 (18) min, respectively, after cessation of glucose infusion, while in controls, glucose levels declined steeply to a nadir at 98 (47) min (P<0.003 vs. both drugs). No first phase insulin secretion peak was observed in people with diabetes. Insulin levels remained elevated during the 3-h observation period in SU treated patients but, in control subjects decreased to baseline values within 2 h of the clamp. The proinsulin to C-peptide ratio increased during the observation period. In conclusion, the effects of glibenclamide and gliclazide on insulin secretion are very similar in patients with Type 2 diabetes who are in moderate glycaemic control, with a slow rise to lower amplitude, poor responsiveness to falling glucose levels, and raised proinsulin to C-peptide ratio.
Aged↗
Effects of cognitive behavioural group training (CBGT) in adult patients with poorly controlled insulin-dependent (type 1) diabetes: a pilot study.
A substantial group of patients with type 1 diabetes has difficulty adhering to the treatment regimen, and as a consequence is at increased risk of developing microvascular complications. Cognitive behavioural interventions may help these patients to cope more effectively with their diabetes. We developed a 4 weeks cognitive behavioural group training (CBGT) for patients with type 1 (insulin-dependent) diabetes in persistent poor glycaemic control, to help them overcome negative beliefs and attitudes towards diabetes and improve their self-care behaviours. Feasibility and efficacy of CBGT were tested in a non-randomised prospective study in 24 poorly-controlled type 1 diabetes patients (mean age 35.2+/-11.1years; 15 female; mean HbA(1c) 9.3% (+/-1.2)), with assessments at 3 and 6 months follow-up. The programme was delivered in small groups (n=6-8), by a team of a diabetes nurse specialist and a psychologist. Primary outcome measures were glycosylated haemoglobin (HbA(1c)), diabetes-related emotional distress (PAID) and psychological well-being (WBQ-12). Changes in diabetes self-care activities (DSCI) were documented, along with perceived barriers in diabetes questionniare (BDQ) and fear of hypoglycaemia survey (HFS). Data were analysed using repeated measures analysis of variance. The CBGT proved to be feasible in this selected group of patients and was well appreciated. Following CBGT, mean HbA(1c) dropped by 0.8% at 6 months from baseline, while emotional well-being was preserved. It is concluded that CBGT is a promising intervention that deserves further evaluation in randomised controlled trials.
Adult↗
Brachial artery pulse pressure and common carotid artery diameter: mutually independent associations with mortality in subjects with a recent history of impaired glucose tolerance.
BACKGROUND: Decreased large artery function, as reflected by increased brachial artery pulse pressure and increased carotid artery diameter and stiffness, may contribute to the increased mortality risk that is observed in subjects with impaired glucose tolerance. We therefore investigated the association between brachial artery pulse pressure and carotid artery diameter and stiffness, which are estimates of central artery stiffness and arterial remodelling, respectively, and mortality in subjects with a recent history of impaired glucose tolerance. DESIGN: A prospective, population-based cohort study. We measured brachial artery pulse pressure by oscillometric blood pressure measurements, and common carotid artery diameter and distensibility and compliance coefficients by ultrasound in 140 subjects with a recent history of impaired glucose tolerance. During a median 6.6-year follow-up, 16 subjects died. RESULTS: Brachial artery pulse pressure and common carotid artery diameter were positively related to all-cause mortality [hazard ratios per standard deviation, 1.7 (1.2-2.5) and 2.1 (1.3-3.3), respectively]. Results were similar after adjustment for gender, age, waist-to-hip ratio, body mass index, total cholesterol concentration, pre-existent cardiovascular disease, and hypertension, and after additional mutual adjustment. Common carotid artery distensibility and compliance coefficients were not statistically significantly associated with mortality. CONCLUSIONS: Among subjects with a recent history of impaired glucose tolerance, brachial artery pulse pressure and common carotid artery diameter are independently associated with mortality risk. Stiffness of the central arteries may explain the association between pulse pressure and mortality risk. The association between carotid diameter and mortality risk is more likely to reflect arterial remodelling in response to atherosclerosis than that in response to increased local stiffness.
Aged↗
Phobia of self-injecting and self-testing in insulin-treated diabetes patients: opportunities for screening.
AIMS: To define clinically relevant cut-off points for severe fear of self-injecting (FSI) and self-testing (FST) (phobia) in insulin-treated patients with diabetes, and to estimate the magnitude of these phobias in our research population. METHODS: FSI and FST were assessed in a cross-sectional survey using the Diabetes Fear of Injecting and Self-testing Questionnaire (D-FISQ). A sample of 24 insulin-treated adult diabetic patients was selected from the high-scorers on FSI and/or FST (> or = 95th percentile). FSI and FST were re-assessed, after which patients participated in a behavioural avoidance test (BAT), thereby determining the current level of avoidance of either self-injecting or self-testing. FSI and FST scores were linked to the outcome of the BATs. Cut-off scores for severe FSI/FST were determined and extrapolated to the total study population (n = 1275). RESULTS: Seven patients participated in the self-injecting BAT: two patients refused to perform an extra injection. In the self-testing BAT (n = 17) four patients declined to perform the extra blood glucose self-test. Extrapolation of FSI and FST cut-off scores to the total research population showed that 0.2-1.3% of the population scored in the severe FSI range. In FST, 0.6-0.8% of the total study population obtained scores in the cut-off range. CONCLUSIONS: Severe FSI and FST, characterized by emotional distress and avoidance behaviour, seems to occur in a small group of insulin-treated patients with diabetes. The D-FISQ can be of use to health care professionals (physicians, nurse specialists) in quickly providing valuable information on levels of FSI and FST in diabetes patients.
Adult↗
Prognostic implications of retinopathy and a high plasma von Willebrand factor concentration in type 2 diabetic subjects with microalbuminuria.
BACKGROUND: Microalbuminuria in subjects with type 2 diabetes may be heterogeneous with respect to clinical features, renal histology, and prognosis. There may be at least two types of microalbuminuria in diabetes, namely with and without generalized endothelial dysfunction. We investigated whether, among microalbuminuric subjects with type 2 diabetes, the presence of generalized endothelial dysfunction, as indicated by the presence of retinopathy or a high plasma von Willebrand factor (vWf) level, has prognostic implications. METHODS: In 173 type 2 diabetic subjects of a population-based cohort, we assessed the urinary albumin-to-creatinine ratio, the plasma vWf level, and the presence of retinopathy. The main outcome was cardiovascular mortality. RESULTS: The absolute difference in 7 years' cardiovascular mortality between microalbuminuric (albumin-to-creatinine ratio 2.0-30.0 mg/mmol) and normoalbuminuric subjects was higher in the presence as compared to the absence of retinopathy (55.6 vs 11.1%). The age- and sex-adjusted relative risk (95% confidence interval) of cardiovascular mortality, as compared to normoalbuminuric subjects without retinopathy, was 1.1 (0.1-9.2) for normoalbuminuric subjects with retinopathy, 1.8 (0.5-6.7) for microalbuminuric subjects without retinopathy, and 9.8 (3.1-30.9) for microalbuminuric subjects with retinopathy. The absolute difference in risk of 7 years' cardiovascular mortality between microalbuminuric and normoalbuminuric subjects was higher in the presence as compared to the absence of a high (>1.89 IU/ml) vWf level (49.8 vs 16.4%). The age- and sex-adjusted relative risk of cardiovascular mortality, as compared to normoalbuminuric subjects without a high vWf level, was 1.5 (0.4-5.5) for normoalbuminuric subjects with a high vWf level, 2.6 (0.7-9.6) for microalbuminuric subjects without a high vWf level, and 12.0 (2.9-49.5) for microalbuminuric subjects with a high vWf level. These differences in risk of cardiovascular mortality did not change materially after further adjustment for known duration of diabetes, hypertension, creatinine clearance, level of glycated haemoglobin and high-density lipoprotein cholesterol, and presence of cardiovascular disease. Analysis of all-cause instead of cardiovascular mortality showed a similar difference in risk of mortality between microalbuminuric subjects with or without retinopathy or a high vWf level. CONCLUSIONS: Among type 2 diabetic subjects with microalbuminuria, the presence of retinopathy or a high plasma vWf level affects the risk of cardiovascular death. Although larger studies are necessary, these findings support the concept that microalbuminuria in type 2 diabetes can occur in the absence or the presence of generalized endothelial dysfunction, and that the latter is a much more 'malignant' condition than the former.
Aged↗