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Biomedical subjects

C D Stehouwer

Publications and source records attributed to C D Stehouwer.

At least 127 records · Page 7Linked to original sources
PubMed1998

Carotid artery stiffness is increased in microalbuminuric IDDM patients.

OBJECTIVE: In IDDM, the development of microalbuminuria, which is associated with an elevation in blood pressure within the normal range, is a risk factor for future cardiovascular disease. Vascular stiffness might be one of the factors involved because it increases systolic blood pressure and the workload of the heart. RESEARCH DESIGN AND METHODS: We investigated carotid artery stiffness with a noninvasive ultrasound method in 24 microalbuminuric and 53 normoalbuminuric IDDM patients and in 54 healthy control subjects. RESULTS: The distensibility coefficient, a measure of intrinsic vascular wall elasticity, was decreased in microalbuminuric IDDM (21.6 x 10(-3)/kPa) as compared with normoalbuminuric IDDM (24.8 x 10(-3)/kPa) and control subjects (25.9 x 10(-3)/kPa; P = 0.02). This result was based on a higher blood pressure in microalbuminuric patients. After correction for the difference in blood pressure, the distensibility coefficients were similar in the three groups. In the two diabetic patient groups taken together, age, blood pressure, female sex, diabetes duration, and cigarette smoking were determinants of a decreased distensibility. CONCLUSIONS: Blood pressure is a major determinant of increased arterial stiffness in microalbuminuric IDDM patients. Increased arterial stiffness may contribute to the accelerated progression of complications if concomitant hypertension exists.

Adolescent↗
PubMed1998

The 1997 American Diabetes Association criteria versus the 1985 World Health Organization criteria for the diagnosis of abnormal glucose tolerance: poor agreement in the Hoorn Study.

OBJECTIVE: Recently, the American Diabetes Association (ADA) introduced new diagnostic criteria. These new criteria are based on fasting plasma glucose levels, avoiding the burdensome oral glucose tolerance test (OGTT). We compared the 1997 ADA criteria with the 1985 World Health Organization (WHO) criteria with respect to the prevalence of diabetes and the cardiovascular risk profile in the population of the Hoorn Study RESEARCH DESIGN AND METHODS: The Hoorn Study is a population-based survey of 2,484 men and women, aged 50-75 years. An OGTT was performed and cardiovascular risk factors were determined in 2,378 subjects without known diabetes. Subjects were categorized according to both sets of diagnostic criteria. RESULTS: Although the prevalence of diabetes was similar for both sets of criteria, 47 of 120 (39.2%) subjects who were diagnosed with diabetes according to the 1997 ADA criteria were not classified as having diabetes when using the 1985 WHO criteria. Similarly, of 285 subjects diagnosed with impaired fasting glucose by the 1997 ADA criteria, 195 (68.4%) were classified as having normal glucose tolerance by the 1985 WHO criteria. The overall agreement was poor (kappa 0.33; 95% CI 0.28-0.38). Subjects who were diagnosed as having diabetes by either set of criteria had an adverse cardiovascular risk profile, which was between the cardiovascular risk profiles of concordant normal and concordant diabetic subjects. CONCLUSIONS: In this study both sets of criteria diagnosed a similar number of diabetic subjects, but many of the subjects shifted between glucose intolerance categories. With either set of criteria, a considerable number of subjects at risk of developing diabetes and subjects carrying an increased risk of cardiovascular disease, as reflected by an adverse cardiovascular risk profile, will be missed.

Blood Glucose↗
PubMed1998

Ambulatory blood pressures and autonomic nervous function in normoalbuminuric type I diabetic patients.

BACKGROUND: In insulin-dependent diabetes mellitus (IDDM) patients with normal urinary albumin excretion (UAE) controversy exists about the presence of blood pressure (BP) elevation and an attenuation of BP decline during sleep. SUBJECTS AND METHODS: These issues were studied in 60 IDDM patients and 55 healthy control subjects with 24 h ambulatory blood pressure monitoring. In addition, in the IDDM patients two cardiovascular reflex tests were performed to study autonomic nervous function. RESULTS: 55 IDDM patients had 4.4/3.1 mm Hg higher 24 h systolic/diastolic pressures when compared with 55 healthy matched controls (P = 0.005/0.009). The diastolic BP decline during sleep was significantly attenuated in IDDM patients compared to healthy volunteers (18.9 vs 22.2%, P = 0.01). The maximum/minimum (max/min) ratio of the RR' interval of the lying to standing test (lower values indicating (incipient) parasympathetic dysfunction) was positively related to the decline of the diastolic BP during sleep in the diabetic patients. This relationship did not persist after adjusting for decline of heart rate during sleep. CONCLUSIONS: IDDM patients with normal UAE, compared with healthy control subjects, have higher BPs during both the waking and sleeping periods and a decreased diastolic BP decline during sleep. In these patients both the diastolic BP decline and the heart rate decline during sleep were related to the max/min ratio. These findings are consistent with the hypothesis that attenuation of diastolic BP decline during sleep is at least partly due to (incipient) damage to the parasympathetic nervous system, which, through a blunted heart rate decline, leads to a decreased decline of cardiac output during sleep.

Adult↗
PubMed1998

The effects of sex steroids on plasma levels of marker proteins of endothelial cell functioning.

We studied thirteen male-to-female (M-->F) and ten female-to-male (F-->M) transsexuals who, for four months, received cross-sex treatment with, respectively, ethinylestradiol and cyproterone acetate, and with testosterone esters. We assessed the effects of treatment on plasma levels of tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), vWF-propeptide (vWF:AgII) and big-endothelin-1 (big-ET-1), four proteins that are markers of endothelial cell functioning. We also measured urokinase-type PA (uPA) and plasminogen activator inhibitor-type 1 (PAI-1), which may not be endothelium-derived but share major clearance pathways with tPA. In M-->F transsexuals, mean plasma levels of tPA (minus 4.4 ng/ml), big-ET-1 (minus 0.8 pg/ml), uPA (minus 0.5 ng/ml) and PAI-1 (minus 26 ng/ml) decreased (all Ps < or =0.02). The level of vWF increased (plus 24%; P = 0.005), while vWF: AgII did not change (P = 0.49). In F-->M transsexuals, levels of big-ET-1 increased (plus 0.4 pg/ml; P = 0.02), while tPA, uPA and PAI-1 did not change (all Ps >0.25). In this group vWF decreased (minus 14%; P = 0.06), but vWF:AgII did not change (P = 0.38). Estrogens and androgens have clear effects on plasma levels of endothelial marker proteins. The mechanisms behind these effects are complex and appear to involve both altered secretion (big-ET-1) and processing and/or clearance (vWF and possibly tPA). Therefore, effects of hormones on the levels of endothelial marker proteins do not necessarily reflect changes in endothelial cell functioning, at least with regard to changes in vWF level associated with the oral administration of high doses of ethinylestradiol and cyproterone acetate to healthy men and the parenteral administration of testosterone to healthy women.

Biomarkers↗
PubMed1998

Distinct associations of HbA1c and the urinary excretion of pentosidine, an advanced glycosylation end-product, with markers of endothelial function in insulin-dependent diabetes mellitus.

Dysfunction of the vascular endothelium is considered an early step in the development of diabetic angiopathy. Hyperglycaemia results in endothelial dysfunction, both through direct effects of glucose and through formation of advanced glycosylation end-products (AGEs). We hypothesized that the effects of glucose and AGEs on endothelial function in insulin-dependent diabetes mellitus (IDDM) are distinct and are reflected by distinct plasma markers of endothelial function. We therefore measured plasma levels of von Willebrand factor (vWF), soluble (s) E-selectin and vascular cell adhesion molecule-1 (sVCAM-1), and evaluated the relationship with HbA1c and urinary excretion of pentosidine, an AGE product, in 56 patients with IDDM. Urinary pentosidine excretion was higher in the diabetic than in a control group (n = 60) of similar age (P < 0.0001) and showed a steeper increase with age (P < 0.02 vs controls). In the diabetic group, sE-selectin was correlated to HbA1c (r = 0.52, P < 0.0001), whereas sVCAM-1 was not (r = 0.11, P = 0.47). In contrast, sVCAM-1 showed a trend towards a correlation with log (pentosidine excretion) (r = 0.27, P = 0.06), whereas sE-selectin did not (r = -0.16, P = 0.27). Log(vWF) was correlated to HbA1c (r = 0.50, P < 0.0001) and tended to correlate with log (pentosidine excretion) (r = 0.25, P = 0.07). Multivariate analyses with both pentosidine and HbA1c as independent variables showed significant associations of sE-selectin with HbA1c, of sVCAM-1 with pentosidine, and of log(vWF) with both HbA1c and pentosidine (all P-values < 0.02). Our results imply that the effects of glucose and AGEs on the endothelium can be reflected by distinct endothelial markers. Plasma sE-selectin may reflect short-term effects of glucose on the endothelium, sVCAM-1 the effects of AGEs, and vWF the combined effect of glucose and AGEs.

Adult↗
PubMed1998

von Willebrand factor (vWf) as a plasma marker of endothelial activation in diabetes: improved reliability with parallel determination of the vWf propeptide (vWf:AgII).

Elevated plasma von Willebrand factor (vWf) levels are found in diabetes and other vasculopathies, and predict cardiovascular mortality. vWf is stored and released from endothelial cell secretory granules, along with equimolar amounts of its propeptide (vWf:AgII). In the present study, we examined plasma propeptide levels as a marker of endothelial secretion in vivo, using an ELISA based on monoclonal antibodies. vWf but not propeptide levels are influenced by blood groups, explaining in part the smaller variation in plasma propeptide levels among normal individuals. In both controls and insulin-dependent diabetic patients, we found a close correlation between propeptide and immunoreactive vWf levels (r2=0.54, p <0.0001). vWf and propeptide were elevated in patient subgroups with microalbuminuria or overt diabetic nephropathy, whereas only the propeptide was significantly elevated in the normoalbuminuric subgroup. This observation suggests that in conjunction with vWf, propeptide measurements may improve the identification of endothelial activation, which occurs frequently even without increased urinary albumin excretion. In 12 NIDDM patients, a 3-week diet enriched in monounsaturated fat (MUFA) resulted in parallel decreases in vWf (-22%, p <0.05) and propeptide (-17%, p <0.05) levels, indicating that the experimental diet affected endothelial secretion rather than vWf catabolism. A carbohydrate-enriched control diet did not significantly influence either marker. Our results suggest that concomitant determinations of plasma vWf and propeptide are useful tools to assess endothelial activation in vivo, and reinforce our previous conclusion that a diet rich in MUFA can improve endothelial function in NIDDM.

Adult↗
PubMed1997

[Microalbuminuria in essential hypertension: of limited value as an indicator of patients with a high risk for complications].

Microalbuminuria is usually defined as a urinary albumin excretion of 30-300 mg/24 h (i.e. 20-200 micrograms/min) measured, in view of the short-term variation of 15-30%, in at least 2 out of 3 urine samples. An alternative definition is: an albumin-creatinine ratio of 2-20 mg/mmol creatinine. Microalbuminuria is an indicator of an enhanced risk of chronic kidney failure and cardiovascular disease in diabetic patients and of cardiovascular disease in the elderly general population. It is not known whether these relationships exist in essential hypertension as well. In essential hypertension there is, however, a relationship between microalbuminuria and endothelial dysfunction, impaired regulation of renal haemodynamics and an increased risk of left ventricular hypertrophy and hypertensive retinopathy. By screening for microalbuminuria a group of patients can be distinguished who have a relatively high risk for the presence of complications of hypertension. It is not certain, however, that more intensive treatment of such patients (e.g. with ACE inhibitors) is useful. Consequently, for the time being, screening of patients with essential hypertension for microalbuminuria is of little practical importance.

Adult↗
PubMed1997

[Clinical thinking and decision making in practice. A patient with flank pain and anuria].

A 49-year-old man was admitted because of acute anuria. He had bilateral loin pain and was said to have been suffering from renal calculi seven years earlier. He used diclofenac as a pain killer. The renal pyela were mildly dilated. Eventually it became clear that the patient suffered from retroperitoneal fibrosis. This case illustrates (a) ureteral patency does not ensure actual urine flow; (b) non-steroidal anti-inflammatory drugs (NSAIDs) are a frequent cause of renal function loss, but only if there is an additional renal disease causing increased renal prostaglandin synthesis; (c) pattern recognition and verification are clinically relevant diagnostic tools.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

[Clinical judgement and decision making in practice. A patient with hemoptysis].

A 43-year-old man was admitted because of severe and recurring haemoptysis, which was eventually ascribed to Goodpasture's syndrome. In case of an aspecific sign such as haemoptysis experienced clinicians will try to restrict the differential diagnosis by concentrating on other signs that are relevant to the main problem. In haemoptysis these other signs are general illness, fever, shortness of breath, painful respiration, chronic productive cough, and signs or a history of cardiac or pulmonary disease. If the differential diagnosis consists mainly of rare disorders or rare manifestations of common disorders, all possibilities should be considered. If Goodpasture's syndrome is suspected, further specific diagnostic tests should be done without delay.

Adult↗
PubMed1997

Endothelial dysfunction and pathogenesis of diabetic angiopathy.

OBJECTIVE AND METHODS: To review, from the clinical perspective, the contribution of dysfunction of the vascular endothelium to the pathogenesis of diabetic micro- and macroangiopathy. RESULTS: Available data indicate that endothelial dysfunction in diabetes complicated by micro- or macroalbuminuria (renal microangiopathy) is generalised. The close linkage between microalbuminuria and endothelial dysfunction is an attractive explanation for the fact that microalbuminuria is a risk marker for atherosclerotic cardiovascular disease in diabetes. Endothelial dysfunction precedes the occurrence of even early diabetic microangiopathy. However, it is not clear whether endothelial dysfunction is a feature of the diabetic state per se or whether additional factors are required to induce endothelial dysfunction given the presence of diabetes. Convincing data from animal and in vitro models exist to indicate that endothelial dysfunction in diabetes may be related to hyperglycaemic pseudohypoxia, activation of protein kinase C, increased expression of transforming growth factor-beta and vascular endothelial growth factor, non-enzymatic glycation, oxidative stress, activation of the coagulation cascade, increased expression of tumour necrosis factor-alpha, and high levels of insulin and insulin precursor molecules. However, the importance of these proposed mechanisms have not yet been extensively assessed in diabetes in man. CONCLUSIONS: Endothelial dysfunction plays a key role in the pathogenesis of diabetic angiopathy in man. The biochemical basis of endothelial dysfunction in diabetic man, however, has yet to be fully elucidated.

Albuminuria↗
PubMed1997

Haemodynamic and biochemical responses to L-arginine and L-lysine infusions in normal subjects: L-arginine-induced vasodilatation cannot be explained by non-specific effects of cationic amino acids.

1. Pharmacological stimulation of the synthesis of nitric oxide (NO) may be important in the prevention or treatment of cardiovascular diseases. 2. There is much discussion as to whether the precursor of NO, L-arginine, is able to stimulate basal endothelial NO production. L-Arginine is known to have vasodilating effects. However, it is not clear whether L-arginine-induced vasodilatation is attributable to an increase in NO production or to other systemic effects of L-arginine. 3. To investigate further the mechanisms of the L-arginine-induced vasodilatation, we compared the responses to L-arginine with those to saline and L-lysine in healthy subjects. L-Lysine is not a substrate for NO synthesis, but shares many of L-arginine's other properties. 4. During L-arginine infusion, blood pressure decreased [systolic blood pressure from 120.2 (SD 8.8) to 117.3 (12.1) mmHg (P = 0.05); diastolic blood pressure from 65.3 (5.9) to 61.6 (7.9) mmHg (P < 0.01)], and heart rate and extracellular fluid volume increased. The total peripheral vascular resistance decreased during L-arginine infusion by 18.0 (11.4)% (P < or = 0.05 compared with baseline and compared with L-lysine infusion). These results indicate vasodilation. No changes were observed during L-lysine and saline infusion. 5. Plasma cyclic GMP (the second messenger for NO) increased during L-arginine but also during L-lysine infusion [from 5.7 (1.2) to 6.8 (1.7) nmol/l (P < 0.01), and from 5.8 (1.8) to 7.0 (2.9) nmol/l (P < 0.05) respectively]. Plasma L-citrulline (a by-product of NO synthesis from L-arginine) increased during L-arginine infusion from 30.6 (7.5) to 47.1 (9.9) mumol/l (P < 0.001), but also during L-lysine infusion from 32.7 (6.5) to 42.0 (8.3) mumol/l (P < 0.001). 6. Plasma electrolytes and atrial natriuretic peptide concentrations responded similarly to L-arginine and L-lysine infusion, indicating similar effects on osmolality, plasma volume expansion and potassium distribution. 7. In conclusion, although L-lysine infusion had effects that were similar to those of L-arginine infusion, no vasodilatation was observed. Therefore, these effects cannot account for the L-arginine-induced vasodilatation. This finding indirectly supports the hypothesis that the vasodilatation during L-arginine infusion might be mediated by an increase in NO synthesis. If so, our data suggest that the presumed markers for NO synthesis, plasma cyclic GMP and L-citrulline concentrations, do not accurately reflect this increase. Instead, the rise in plasma cyclic GMP may be related to the rise in ANP. The rise in L-citrulline may be related to competition with L-arginine for the same cell membrane transport mechanism and to stimulation of the urea cycle.

Adult↗
PubMed1997

Can reduction in hypertriglyceridaemia slow progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus?

The objective of this study was to investigate whether reduction in hypertriglyceridaemia is associated with a slower rate of progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus (NIDDM). Fifteen normotensive NIDDM patients with hypertriglyceridaemia (> 2.5 mmol L-1) and microalbuminuria were randomly selected to receive either placebo (eight patients) or gemfibrozil 600 mg b.i.d. (seven patients). Progression of microalbuminuria was assessed during a 12-month follow-up period with measurements, consisting of blood tests and triplicate 24-h urine collections, at 1, 3, 6, 9 and 12 months. All but one patient in the treatment group showed a favourable response (> or = 20% reduction) of hypertriglyceridaemia to gemfibrozil. One patient in the placebo group showed a spontaneous reduction in triglyceride levels. Progression of microalbuminuria was lower, although not statistically significantly so, in the treatment group (36%) than in the placebo group (65%). In the group with > or = 20% reduction in triglyceride levels, progression of MA was significantly lower than in the group with stable or increasing triglyceride levels (+1%, range -56% to +49% vs. +97%, range -35% to +202% respectively) (P = 0.03). Continued follow-up data of patients switching from placebo to gemfibrozil after the trial further support the role of serum triglyceride reduction in stabilizing albumin excretion. In conclusion, the results indicate that, in microalbuminuric NIDDM patients, effective treatment of dyslipidaemia could be associated with stabilization of urinary albumin excretion.

Adult↗
PubMed1997

Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus?

OBJECTIVE: The aim of this study was to estimate the effect of metformin on the serum total homocysteine level in non-insulin-dependent diabetes mellitus (NIDDM) patients. An elevated serum total homocysteine level is a risk factor for atherosclerosis. Metformin decreases serum vitamin B12, and may thereby indirectly increase the serum total homocysteine level. DESIGN: A cross-sectional study in a primary care setting. SUBJECTS, MAIN OUTCOME MEASURES: Fasting serum total homocysteine level was measured in 40 NIDDM patients who had received treatment with metformin (500-2550 mg per day) for at least six months, and in 71 NIDDM patients not treated with metformin and matched for sex, age (+/- 5 years), serum creatinine (+/- 5 micromol L[-1]) and current smoking habits. 'Exposed' patients were matched with 'nonexposed' patients. A two-way analysis of variance was performed. RESULTS: The mean serum total homocysteine level was 11.5 micromol L(-1) in the metformin-exposed patients and 10.6 micromol L(-1) in the nonexposed patients. Thus, the metformin-exposed patients had slightly higher serum total homocysteine levels (difference 0.8 micromol L(-1), 95% confidence interval (-0.4-2.0 micromol L[-1]). Results were similar in men and women. Finally, no dose-response relationship between cumulative exposure to metformin (dose x duration of treatment) and the serum total homocysteine level could be demonstrated. CONCLUSION: We conclude that the effect of metformin on serum total homocysteine level in NIDDM patients, if any, is likely to be small.

Adult↗
PubMed1997

High prevalence of hyperhomocysteinemia and asymptomatic vascular disease in siblings of young patients with vascular disease and hyperhomocysteinemia.

Hyperhomocysteinemia (HHC) is associated with an increased risk of atherosclerotic vascular disease and may be inherited. Fasting and postmethionine HHC are independent risk factors that overlap to a limited extent. To study the familial occurrence of HHC, we investigated the prevalence of HHC (both fasting and after methionine) among 450 siblings of 167 consecutive young patients with vascular disease and postmethionine HHC. Furthermore, all subjects with postmethionine HHC (n = 125) were invited for noninvasive vascular testing; 101 (80.8%) agreed. Of those with a normal postmethionine plasma level (n = 325), we randomly selected 73 subjects for further studies; 53 agreed (72.6%). Thus, a total of 154 siblings underwent ultrasonography of the carotid arteries, measurement of ankle-brachial pressure indices at rest and after a treadmill exercise test, and exercise electrocardiographic stress testing. We observed HHC after methionine, fasting, or both, in 27.8% (95% CI, 23.7 to 31.9), 11.1% (CI, 8.2 to 14.0) and 8.7% (CI, 6.1 to 11.3) of the siblings. Abnormal peripheral, coronary, or carotid artery tests were observed in 35.7% (CI, 28.1 to 43.3), 7.1% (CI, 3.0 to 11.2), and 7.1% (CI, 3.0 to 11.2). Univariate and multivariate analyses revealed weak evidence of a relationship with homocysteine levels. In conclusion, we found a high prevalence of HHC and asymptomatic vascular disease in siblings of young patients with vascular (mainly peripheral arterial) disease and HHC. Our data raise the possibility that homocysteine does not play a major role in the early, asymptomatic phases of vascular disease, at least among siblings of young patients with vascular disease.

Adult↗
PubMed1997

Sodium, blood pressure, and arterial distensibility in insulin-dependent diabetes mellitus.

We investigated 24-hour ambulatory blood pressure and arterial distensibility, a marker of biophysical vessel wall properties, in 32 normoalbuminuric type I diabetic patients and 32 healthy control subjects on diets containing 50 mmol and 200 mmol sodium per day. The increase in daytime diastolic blood pressure from 50 to 200 mmol sodium was significantly higher in the diabetic patients than in the control subjects (2.3+/-4.9 versus 0.2+/-3.7 mm Hg, P<.05). On a high sodium regimen, femoral artery distensibility was decreased in the diabetic patients compared with the control subjects (19.2+/-7.6 versus 24.1+/-9.3 10[-3]/kPa, P<.05). Angiotensin-converting enzyme inhibition in the diabetic patients on a high sodium diet decreased daytime diastolic blood pressure and increased femoral artery distensibility. The blood pressure decrease in response to angiotensin-converting enzyme inhibition correlated significantly with the blood pressure increase to sodium (for 24-hour systolic and diastolic blood pressure, r=.72, P<.001 and r=.76, P<.001). In addition, we found that in the diabetic patients on a high sodium diet, the renal blood flow response to exogenous angiotensin II was not bimodally distributed, as is the case in essential hypertension, in which a subgroup of the patients are characterized by sodium sensitivity of the blood pressure and an abnormal renal blood flow response to exogenous angiotensin II ("nonmodulator phenotype"). These results show that blood pressure in insulindependent diabetes mellitus is sodium sensitive, but that this is not related to the nonmodulator phenotype, and suggest that in IDDM a relatively high sodium intake may be a factor that predisposes to the development of diabetic vascular disease.

Adult↗
PubMed1997

Endothelial dysfunction: cause of the insulin resistance syndrome.

Insulin resistance has been proposed as the metabolic basis of atherogenesis. This hypothesis is based on the concept of the "insulin resistance syndrome," according to which insulin resistance is viewed as the primary abnormality that gives rise to dyslipidemia, essential hypertension, impaired glucose tolerance, and NIDDM. However, this hypothesis takes no account of the well-established and central role of vascular endothelium in the atherogenic process. Although endothelial injury is an early and prominent feature of atherogenesis, relatively little attention has been given to its metabolic consequences. In subjects with NIDDM, we have shown that endothelial dysfunction is associated with insulin resistance, raising the question of whether this relationship could be causal. In this article, we review the factors that are considered to be responsible for the development of endothelial dysfunction during atherogenesis, together with the metabolic consequences of endothelial dysfunction. While dysfunction of the endothelium in large and medium-sized arteries plays a central role in atherogenesis, we argue that dysfunction of peripheral vascular endothelium, at arteriolar and capillary level, plays the primary role in the pathogenesis of both insulin resistance and the associated features of the insulin resistance syndrome. We propose that the insulin resistance syndrome, together with many aspects of atherogenesis, can be viewed as the diverse consequences of endothelial dysfunction in different vascular beds. This new and testable hypothesis accounts for both the endothelial and metabolic abnormalities associated with atherogenesis.

Animals↗
PubMed1997

Determinants of progression of microalbuminuria in patients with NIDDM.A prospective study.

OBJECTIVE: To assess the degree of interindividual variation in the rate of progression of microalbuminuria and to identify determinants of progression of microalbuminuria in patients with NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 58 microalbuminuric NIDDM patients were followed for a period of at least 24 months. During this period, the level of microalbuminuria in these patients was assessed in triplicate 24-h urine samples on at least four separate visits. All patients had stable metabolic control and controlled blood pressure during follow-up. Microalbuminuria was defined as an albumin-to-creatinine ratio in 24-h urine of between 3 and 30 mg/mmol. The individual rates of progression of microalbuminuria were calculated from linear regression analysis. At baseline, the following data were collected for all patients: age, sex, ethnicity, time since diagnosis of NIDDM, smoking habits, drug use, blood pressure, BMI, HbA1c, serum creatinine, cholesterol, triglyceride, and HDL cholesterol concentrations. RESULTS: Microalbuminuria was found to progress linearly in time. Considerable differences in rates of progression of microalbuminuria were found, the absolute yearly change in albumin-to-creatinine ratio ranging from -5.2 to 12.9 mg/mmol. In bivariate analyses, serum triglyceride concentration, use of ACE inhibitors, mean arterial blood pressure, HDL cholesterol, and time since diagnosis of NIDDM correlated with progression of microalbuminuria (P < or = 0.05). In stepwise multiple regression analysis, a high triglyceride-to-HDL cholesterol ratio at baseline (P = 0.006) and the use of ACE inhibitors (P = 0.007) were identified as the only independent predictors of progression of microalbuminuria. CONCLUSIONS: The rate of progression of microalbuminuria in NIDDM differs considerably between subjects. Diabetic dyslipidemia (high serum triglyceride and low HDL cholesterol) is a predictor of more rapid progression of microalbuminuria in patients with well-controlled blood pressure.

Albuminuria↗