J K Radder

Leiden University, Leyden, South Holland, Netherlands

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Publications (38)155.45 Total impact

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    ABSTRACT: Background: Despite good glycaemic control (according to the internationally accepted level of HbA1c < 7% (53.0 mmol/mol)) the incidence of macrosomia in pregnant women with diabetes is still very high. We measured HbA1c levels in each of the three trimesters of pregnancy in a cohort of healthy women to determine whether the upper reference level for good glycaemic control in diabetic pregnant females should be lower than the internationally accepted level. Secondly we investigated whether changes in HbA1c values in the course of pregnancy are associated with birth weight. Methods: We determined HbA1c by high-performance liquid chromatography in 103 healthy pregnant women. The results were corrected with a method which was certified by the National Glycohaemoglobin Standardisation Program (NGSP) and standardised to the Diabetes Control and Complication trial reference assay. All women had a body mass index (BMI) < 30, none of the women had diabetes in the family in the first and/or second degree. The multiparous women had no history of macrosomia or small for gestational age infants. Results: In the first trimester mean ± SD (range) HbA1c (n=93) was 4.7 ± 1.25% (27.9 ± 13.7 mmol/mol) (3.9-5.4% (19.1-35.5 mmol/mol)), in the second trimester (n=86) 4.6 ± 1.33% (26.8 ± 14.6 mmol/mol) (3.7-5.7% (16.9-38.8 mmol/mol)) and in the third trimester (n=71) 4.9 ± 1.39% (30.1 ± 15.2 mmol/mol) (4.0-6.0% (20.2-42.1 mmol/mol)). The calculated upper reference HbA1c values for the three trimesters were 5.4, 5.5 and 5.8% (35.5, 36.6 and 39.9 mmol/mol), respectively, compared with 6.5% (47.5 mmol/mol) in non-pregnant women in our hospital. We found a significant correlation between the differences of the first and second trimester HbA1c values and the birth weight percentiles (r=-0.251; p=0.032). All 44 women with a decrease in the HbA1c value from the first to the second trimester had a birth weight percentile ≤ 90. In the 30 women with no change or an increase in the HbA1c value from the first to the second trimester there was no relation between HbA1c values and birth weight percentiles, but seven of the 30 (23.3%) had a birth weight percentile of > 90. Conclusions: HbA1c is lower in all three trimesters of normal pregnancy compared with the level in non-pregnant women, and the change in HbA1c from the first to the second trimester predicts (the percentile of) birth weight. This could implicate that in order to prevent macrosomia in pregnant women with diabetes one should aim at lower HbA1c levels than the internationally accepted level, and at a decrease in HbA1c from the first to the second trimester.
    No preview · Article · Feb 2013 · The Netherlands Journal of Medicine
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    ABSTRACT: Diabetes mellitus type 1 (DM1) is associated with other autoimmune disorders. To our knowledge, there are no longitudinal data considering the long-term clinical relevance of organ-specific antibodies (OS-Ab) in DM1 patients. We performed a long-term retrospective longitudinal study in order to investigate the presence and diagnostic accuracy (positive predictive value: PPV and negative predictive value: NPV) of OS-Ab in DM1 patients. In a retrospective longitudinal study, the presence of OS-Ab and related organ function were analysed in 396 DM1 patients (184 F/212 M, age 44 ± 13 years, age at onset of DM1 21 ± 13 years), with a median follow-up time of 23 ± 10 years. OS-Ab frequencies at baseline were: antibodies against thyroglobulin (Tg-Ab) 4.3%, antibodies against thyroid peroxidase (TPO-Ab) 8.1%, Tg- and/or TPO-Ab 10.4%, antibodies against parietal cells (PCA) 5.8% and antibodies against adrenal cortex (ACA) 0.5%. The occurrence of (sub)clinical hypothyroidism was higher in patients with Tg-Ab (47%) or TPO-Ab (42%) than in those without these antibodies (6.2 and 5.1%, respectively, p<0.001). PPV and NPV for Tg-Ab were 0.60 and 0.88, respectively, for TPO -Ab 0.54 and 0.91. Also in patients with PCA, organ dysfunction occurred more often (61%) than in patients without PCA (9.7%, p<0.001). PPV for PCA was 0.61 and NPV 0.90. NPV and PPV for ACA could not be calculated because of the low prevalence. Conclusion: Long-term follow-up of 396 DM1 patients shows that the presence of thyroid antibodies and/ or parietal cell antibodies is clearly associated with dysfunction of the corresponding organ.
    Full-text · Article · Feb 2011 · The Netherlands Journal of Medicine
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    L.C.G. De Graaff · J.W.A. Smit · J.K. Radder
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    ABSTRACT: As diabetes mellitus type 1 (DM1) is associated with other autoimmune diseases, clinical tools are needed to diagnose and predict the occurrence of other autoimmune diseases in DM1. We performed a systematic search of the literature on the prevalence, and the diagnostic and prognostic significance of organ-specific autoantibodies in DM1, focusing on the most prevalent autoimmune diseases in DM1: Hashimoto's disease, autoimmune gastric disease, Addison's disease and coeliac disease. We found 163 articles that fulfilled our selection criteria. We analysed and compared the prevalence of autoantibodies in DM1 and control populations, studied the relation between antibody prevalence and age, gender, race and DM1 duration and studied the relation between the presence of autoantibodies and organ dysfunction. Because of the large variation in population characteristics and study design, a uniform conclusion on the relation of these autoantibody prevalences with age, gender, race, DM1 duration and target organ failure cannot be drawn easily. In addition, most studies reviewed used a cross-sectional design. Therefore, few data on the predictive value of the organ-specific antibodies in DM1 populations are present in these studies. Obviously, prospective studies are needed to fill this gap in knowledge. Despite these restrictions, the general picture from the present review is that the prevalence of the organ-specific autoantibodies is significantly higher in DM1 than in control populations. Given the relevant risk for organ failure in DM1 patients with autoantibodies against thyroid, gastric, adrenal and intestinal antigens, we recommend checking these autoantibodies in these patients at least once, for instance at the diagnosis of DM1. For detailed advice on assessing the different organ autoantibodies and function we refer to the summaries in the results section.
    Preview · Article · Jul 2007 · The Netherlands Journal of Medicine
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    ABSTRACT: American studies have shown positive effects of Blood Glucose Awareness Training (BGAT) on the recognition of hypoglycaemia. We evaluated the effects of BGAT among Dutch patients, and compared individual training with training in the original group format. Fifty-nine type 1 diabetes patients participated in BGAT in either a group (n = 37) or an individual (n = 22) setting. Before and one year after training they performed up to 70 measurements, two to four a day, at home on a handheld computer. During each measurement they estimated their blood glucose (BG), indicated whether they would be participating in traffic and raised their BG on the basis of their estimation, and then measured their BG. The incidence of severe hypoglycaemia and traffic accidents was also assessed. BGAT had positive effects on hypoglycaemic awareness, decisions not to drive and to raise the blood glucose during hypoglycaemia, severe hypoglycaemic episodes and traffic accidents. The accuracy of BG estimations only improved after group training, while after individual training patients tended to measure more or more extremely high BG values. The training improved awareness of hypoglycaemia, and seems worthy of implementation in The Netherlands.
    No preview · Article · Jun 2005 · The Netherlands Journal of Medicine
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    ABSTRACT: Central obesity, insulin resistance, inflammation, as well as vascular changes are common in patients with type 2 diabetes. In this study we assessed the relationship among stiffness of the carotid artery, visceral fat, and circulating inflammatory markers in type 2 diabetic subjects. Carotid stiffness, quantified as the distensibility coefficient (DC), was measured by ultrasound in asymptomatic, normotensive patients with uncomplicated, well-controlled type 2 diabetes and in controls. Body fat distribution was quantified by magnetic resonance imaging. In patients, the carotid DC was inversely associated with visceral fat area (r = -0.660; P = 0.005) and plasma levels of C-reactive protein (CRP; r = -0.687; P = 0.002), but most strongly with plasma IL-6 (r = -0.766; P < 0.001). In multivariate analysis, the association between DC and visceral fat disappeared after adjustment for CRP and IL-6. Correction for age, body mass index, blood pressure, glycosylated hemoglobin, or fasting plasma glucose did not affect the association between carotid DC and inflammatory markers. Thus, carotid stiffness is associated with visceral obesity in patients with uncomplicated type 2 diabetes, but this association seems to be mediated by circulating IL-6 and CRP, of which IL-6, at least in part, originates from adipose tissue and stimulates hepatic CRP production.
    Full-text · Article · Apr 2005 · Journal of Clinical Endocrinology & Metabolism
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    J K Radder · J van Roosmalen
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    ABSTRACT: Congenital malformations and macrosomia in infants of women with type 1 diabetes mellitus (DM1) still occur, even if diabetic control is considered 'good' (i.e. HbA1c below the nonpregnant upper reference value of 6.3%). We, therefore, measured HbA1c in healthy, pregnant women to determine whether the upper reference value for pregnant women should be lower than the nonpregnant value. We investigated HbA1c, measured by high-performance liquid chromatography (HPLC), in two groups of healthy primigravid women. Group 1 (n=30; 30.0 +/- 5.3 (mean +/- sd) years; body mass index (BMI) before pregnancy 21.7 +/- 5.3 kg/m2) had a gestational age of 30 weeks (34.6 +/- 2.5) pregnant. None of the women had diabetes in the family in the first and/or second degree. Group 1 had an HbA1c of 4.3 +/- 0.3% (range 3.9-5.0) and in group 2 the HbA1c was 4.7 +/- 0.4% (range 3.6-5.9) (p < 0.001). No relation was found between HbA1C and BMI vs birth weight, corrected for gestational age, within the groups. Healthy, pregnant women had a low HbA1C, particularly in the first trimester of pregnancy. This might implicate that for prevention of congenital malformations and macrosomia in pregnant DM1 women and HbA1C should be below 5% in the first trimester of pregnancy and below 6% in the third trimester.
    Full-text · Article · Jan 2005 · The Netherlands Journal of Medicine
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    ABSTRACT: This study evaluated myocardial function in relation to high-energy phosphate (HEP) metabolism in asymptomatic patients with uncomplicated type 2 diabetes mellitus using magnetic resonance (MR) techniques. Myocardial dysfunction may occur in patients with type 2 diabetes mellitus in the absence of coronary artery disease or left ventricular (LV) hypertrophy. The mechanisms underlying this diabetic cardiomyopathy are largely unknown, but may involve altered myocardial energy metabolism. We assessed myocardial systolic and diastolic function and HEP metabolism in 12 asymptomatic normotensive male patients with recently diagnosed, well-controlled type 2 diabetes and 12 controls, using MR imaging and phosphorus-31-nuclear MR spectroscopy (31P-MRS) on a 1.5 T clinical scanner; 31P-MR spectra were quantified, and myocardial HEP metabolism was expressed as phosphocreatine to adenosine-triphosphate (PCr/ATP) ratio. No differences were found in LV mass and systolic function between patients and controls. However, early (E) acceleration peak, deceleration peak, peak filling rate, and transmitral early-to-late diastolic peak flow (E/A) ratio, all indexes of diastolic function, were significantly decreased in patients compared with controls (p < 0.02). In addition, myocardial PCr/ATP in patients was significantly lower than in controls (1.47 vs. 1.88, p < 0.01). Inverse associations were found between myocardial PCr/ATP and E acceleration peak, E deceleration peak, and E peak filling rate (all, p < 0.05). These results indicate that altered myocardial energy metabolism may contribute to LV diastolic functional changes in patients with recently diagnosed, well-controlled and uncomplicated type 2 diabetes.
    Preview · Article · Jul 2003 · Journal of the American College of Cardiology
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    ABSTRACT: Type 2 diabetes is associated with accelerated atherosclerosis. Because cell-derived microparticles support coagulation and inflammation, they may be involved in atherogenesis. We characterized circulating microparticles both in patients with uncomplicated, well-regulated type 2 diabetes and in healthy subjects, as well as their relationship with coagulation and metabolic control. Microparticles were isolated from plasma, stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. Microparticle numbers and origin were comparable in the two groups, but the median number of TF-positive microparticles was twice as high in patients than in controls (P=0.018). Patients had higher percentages of TF-positive microparticles from T-helper cells (P=0.045), granulocytes (P=0.004), and platelets (P=0.002). Subpopulations of TF-positive microparticles from platelets and T-helper cells exposed granulocytic markers. Correlations were found between the numbers of various TF-positive microparticle subpopulations and body mass index, fasting plasma glucose and insulin, or tumor necrosis factor-alpha and serum HDL cholesterol. Microparticles from patients generated less thrombin in vitro (P=0.007). Microparticle numbers did not correlate with in vivo coagulation markers prothrombin fragment F(1+2) and thrombin-antithrombin complexes. TF, possibly of granulocytic origin, is exposed on microparticle subpopulations in asymptomatic patients with well-regulated type 2 diabetes. TF-positive microparticles are associated with components of the metabolic syndrome but not with coagulation. Thus, TF on microparticles may be involved in processes other than coagulation, including transcellular signaling or angiogenesis.
    Preview · Article · Dec 2002 · Circulation
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    ABSTRACT: Aims The aims of the present study were: (i) to evaluate the effects of a Dutch translation and adaptation of Blood Glucose Awareness Training (BGAT-III) on blood glucose (bg) perception, glycaemic control, and decisions not to drive or to raise the bg during hypoglycaemia; (ii) to compare the effects of individual and group BGAT. Methods Fifty-nine patients with Type 1 diabetes participated in BGAT in either a group or an individual setting. Before and after BGAT, 39 (66%) of them completed 30–70 measurements on a hand-held computer (hhc). During every measurement, they estimated their bg, indicated whether they would drive or raise their bg on the basis of their estimation, and then measured their bg. Results Individual and group BGAT did not have significantly different effects (P = 0.35–0.98). Overall, BGAT did not significantly affect bg perception (P = 0.11–0.65). Before BGAT patients recognized a mean of 32% of their hypoglycaemic episodes, after BGAT a mean of 39% (P = 0.12). After BGAT, patients more often decided not to drive when their bg was low (P = 0.03). They tended to decide more often to raise their bg during hypoglycaemia (P = 0.09). Conclusions The effects of BGAT were smaller than expected. Possible reasons for this negative outcome may be the adapted version of BGAT (shorter in duration), a lack of statistical power, or a difference between American and European samples in their reaction to BGAT.
    No preview · Article · Mar 2002 · Diabetic Medicine
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    ABSTRACT: To assess relationships between hypoglycaemic awareness and diabetes-related, psychosocial and demographic characteristics. Ninety-eight type 1 diabetic patients completed questionnaires on somatic awareness (Somatic Awareness Questionnaire, SAQ), negative affectivity (Positive And Negative Affectivity Schedule, PANAS), symptom beliefs, bustle and variety of daily life. They then performed up to 70 measurements on a hand-held computer, during 4 to 6 weeks, at home. During every measurement, they rated the presence of 20 symptoms on a 0-6 scale, and estimated and measured their blood glucose level. The percentage of recognised hypoglycaemic episodes was calculated from these data, and used as a measure of hypoglycaemic awareness. Hypoglycaemic awareness was negatively associated with disease duration and antecedent hypoglycaemia, and positively associated with the use of an insulin pump instead of injections, variety in the daily life, somatic awareness, sensitivity of the symptom beliefs and female gender. However, only 17% of the variance in hypoglycaemic awareness was explained. Psychosocial variables contribute to hypoglycaemic awareness, to a moderate but statistically significant extent.
    No preview · Article · Mar 2002 · Journal of Psychosomatic Research
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    ABSTRACT: The aims of the present study were: (i) to evaluate the effects of a Dutch translation and adaptation of Blood Glucose Awareness Training (BGAT-III) on blood glucose (bg) perception, glycaemic control, and decisions not to drive or to raise the bg during hypoglycaemia; (ii) to compare the effects of individual and group BGAT. Fifty-nine patients with Type 1 diabetes participated in BGAT in either a group or an individual setting. Before and after BGAT, 39 (66%) of them completed 30-70 measurements on a hand-held computer (hhc). During every measurement, they estimated their bg, indicated whether they would drive or raise their bg on the basis of their estimation, and then measured their bg. Individual and group BGAT did not have significantly different effects (P = 0.35-0.98). Overall, BGAT did not significantly affect bg perception (P = 0.11-0.65). Before BGAT patients recognized a mean of 32% of their hypoglycaemic episodes, after BGAT a mean of 39% (P = 0.12). After BGAT, patients more often decided not to drive when their bg was low (P = 0.03). They tended to decide more often to raise their bg during hypoglycaemia (P = 0.09). The effects of BGAT were smaller than expected. Possible reasons for this negative outcome may be the adapted version of BGAT (shorter in duration), a lack of statistical power, or a difference between American and European samples in their reaction to BGAT.
    No preview · Article · Mar 2002 · Diabetic Medicine
  • Article: Letters

    No preview · Article · Dec 2001 · Diabetic Medicine

  • No preview · Article · Jun 2001 · Diabetic Medicine
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    ABSTRACT: Insulin resistance for glucose metabolism is associated with hyperlipidaemia and high blood pressure. In this study we investigated the effect of primary hyperlipidaemia on basal and insulin-mediated glucose and on non-esterified fatty acid (NEFA) metabolism and mean arterial pressure in hyperlipidaemic transgenic mice overexpressing apolipoprotein C1 (APOC1). Previous studies have shown that APOC1 transgenic mice develop hyperlipidaemia primarily because of an impaired hepatic uptake of very low density lipoprotein (VLDL). Basal and hyperinsulinaemic (6 mU.kg-1.min-1), euglycaemic (7 mmol/l) clamps with 3(-)3H-glucose or 9,10(-)3H-palmitic acid infusions and in situ freeze clamped tissue collection were carried out. The APOC1 mice showed increased basal plasma cholesterol, triglyceride, NEFA and decreased glucose concentrations compared with wild-type mice (7.0 +/- 1.2 vs 1.6 +/- 0.1, 9.1 +/- 2.3 vs 0.6 +/- 0.1, 1.9 +/- 0.2 vs 0.9 +/- 0.1 and 7.0 +/- 1.0 vs 10.0 +/- 1.1 mmol/l, respectively, p < 0.05). Basal whole body glucose clearance was increased twofold in APOC1 mice compared with wild-type mice (18 +/- 2 vs 10 +/- 1 ml.kg-1.min-1, p < 0.05). Insulin-mediated whole body glucose uptake, glycolysis (generation of 3H2O) and glucose storage increased in APOC1 mice compared with wild-type mice (339 +/- 28 vs 200 +/- 11; 183 +/- 39 vs 128 +/- 17 and 156 +/- 44 vs 72 +/- 17 mumol.kg-1.min-1, p < 0.05, respectively), corresponding with a twofold to threefold increase in skeletal muscle glycogenesis and de novo lipogenesis from 3-(3)H-glucose in skeletal muscle and adipose tissue (p < 0.05). Basal whole body NEFA clearance was decreased threefold in APOC1 mice compared with wild-type mice (98 +/- 21 vs 314 +/- 88 ml.kg-1.min-1, p < 0.05). Insulin-mediated whole body NEFA uptake, NEFA oxidation (generation of 3H2O) and NEFA storage were lower in APOC1 mice than in wild-type mice (15 +/- 3 vs 33 +/- 6; 3 +/- 2 vs 11 +/- 4 and 12 +/- 2 vs 22 +/- 4 mumol.kg-1.min-1, p < 0.05) in the face of higher plasma NEFA concentrations (1.3 +/- 0.3 vs 0.5 +/- 0.1 mmol/l, p < 0.05), respectively. Mean arterial pressure and heart rate were similar in APOC1 vs wild-type mice (82 +/- 4 vs 85 +/- 3 mm Hg and 459 +/- 14 vs 484 +/- 11 beats.min-1). 1) Hyperlipidaemic APOC1 mice show reduced NEFA and increased glucose metabolism under both basal and insulin-mediated conditions, suggesting an intrinsic defect in NEFA metabolism. Primary hyperlipidaemia alone in APOC1 mice does not lead to insulin resistance for glucose metabolism and high blood pressure.
    Full-text · Article · May 2001 · Diabetologia

  • No preview · Article · May 1998 · Patient Education and Counseling
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    ABSTRACT: Using reverse transcription-competitive polymerase chain reaction, we measured the abundance of the mRNAs encoding the two spliced isoforms of insulin receptor in aged and mildly insulin-deficient rats. Twelve-month-old rats were characterized by peripheral insulin resistance and decreased glucose tolerance. Mild insulin deficiency, obtained by neonatal streptozotocin treatment, was associated with glucose intolerance due to reduced glucose-stimulated insulin response. Both models were associated with a decrease in the relative abundance of the mRNA with exon 11 in liver, heart, adipose tissue, and tibialis muscle, whereas a slight increase was seen in the extensor digitorum longus and no change in the soleus muscle. In the three muscles, the expression of the form without exon 11 largely predominated (>90%). In heart and adipose tissue, the two isoforms were expressed at a similar level in control rats. In both tissues, the form without exon 11 increased in streptozotocin-treated rats, whereas the absolute level of the form with exon 11 decreased in old rats. Although a decreased level of the variant with exon 11 correlated with insulin resistance of whole body glucose uptake, our results indicated that changes in the expression of the insulin receptor variants were secondary events and thus not the cause of the insulin resistance in old and mildly insulin-deficient rats.
    No preview · Article · Apr 1997 · The American journal of physiology
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    ABSTRACT: Short-term exposure of tissues to pulses of insulin generally leads to an enhancement of insulin action. We have investigated the possible beneficial effects of long-term near-physiological continuous vs pulsatile intravenous insulin treatment of insulin-deficient streptozotocin (70 mg/kg) diabetic rats on blood glucose control, in vivo insulin action and in vitro insulin action in isolated adipocytes. First, we determined the 24-h peripheral plasma insulin profiles in normal rats under precisely controlled mealfeeding conditions. Basal plasma insulin levels (40 +/- 9 microU/ml) oscillate with a periodicity of 11.9 +/- 0.9 min (p < 0.05), and an amplitude of 60 +/- 10%. Subsequently, the 24-h insulin profile was mimicked in diabetic (D) rats by a continuous (c) or pulsatile (p) (6-min double, 6-min off) insulin infusion rate for 2 weeks, using a programmable pumpswivel unit. Control (C) rats received vehicle treatment. In Cc, Dc, Cp and Dp daily urinary glucose loss and average plasma glucose levels were 0 +/- 0, 7.5 +/- 4.4, 0 +/- 0, 0.8 +/- 0.4 mmol and 6.7 +/- 0.2, 11.5 +/- 2.7, 6.6 +/- 0.1, 5.9 +/- 1.4 mmol/l, respectively. Hypoglycaemia (< 3 mmol/l) was observed in 10 and 20% of the blood samples collected from Dc and Dp rats, respectively. After 2 weeks of treatment, in vivo peripheral and hepatic insulin action was measured by the hyperinsulinaemic euglycaemic (6 mmol/l) clamp with [3-3H]-glucose infusion. Pre-clamp counter-regulatory hormone levels were similar among rats. Compared to Cc and Cp, Dc showed a reduction in insulin sensitivity and responsiveness for peripheral glucose uptake whereas Dp only showed a reduction in insulin sensitivity. Suppression of hepatic glucose production by insulin was similar among rats. After 2.5 weeks of treatment, epididymal adipocytes were isolated. Specific [125I]-insulin binding, basal and insulin-stimulated [U-14C]-glucose uptake and isoproterenol-stimulated glycerol output were comparable among rat adipocytes. The inhibition of glycerol output by insulin was identical in Cp and Dp (V(max) = 48.6 +/- 6.1 and 42.3 +/- 4.6%) but blunted in Dc vs Cc (V(max) = 8.2 +/- 4.6 vs 44.0 +/- 7.2%, p < 0.01) adipocytes, suggesting a post-binding defect in the antilipolytic action of insulin in Dc rats. In conclusion, long-term near-physiological pulsatile intravenous insulin replacement in insulin-deficient diabetic rats is more efficient than continuous delivery in reducing blood glucose, lowering glucosuria, increasing insulin sensitivity and inhibiting lipolysis.
    No preview · Article · Apr 1996 · Diabetologia
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    ABSTRACT: Insulin action is subject to regulation at the level of the insulin receptor and at postreceptor levels. Starvation and diabetes are often associated with insulin resistance for glucose metabolism in various tissues. In muscle, fat, and liver, we examined whether changes in the functionality of the insulin receptor correlated with changes in insulin action in the starved and diabetic state. Insulin-stimulated receptor autophosphorylation reflects an early physiologic step in transmission of the insulin signal, and for that reason, changes in autophosphorylation activity of the insulin receptor were used as a marker to determine the functionality of the insulin receptor. Glycoprotein fractions prepared from skeletal muscle, diaphragm, epididymal fat, and liver of control, 3-day starved, short-term 3-day (S) diabetic (streptozotocin, 70 mg/kg intravenously), and long-term 6-month (L) diabetic (neonatal streptozotocin 100 micrograms/g intraperitoneally) rats were used in this study. Receptor activity was monitored by measuring insulin-stimulated [gamma-32P]adenosine triphosphate (ATP) receptor autophosphorylation. In addition, to obtain information about whether changes in receptor autophosphorylation are related to changes in receptor number, relative numbers of high-affinity insulin receptors were determined by affinity cross-linking of [125I]insulin to the receptor alpha-chain and quantitation of the yield of labeled receptor alpha-chain. Control, starved, S diabetic, and L diabetic rats had plasma insulin and glucose levels of 294 +/- 42, 90 +/- 24, 48 +/- 12, and 216 +/- 30 pmol/L and 6.7 +/- 0.2, 4.1 +/- 0.2, 23.3 +/- 0.7, and 21.6 +/- 2.9 mmol/L, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
    No preview · Article · Apr 1995 · Metabolism
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    ABSTRACT: The cardiovascular risk factor plasminogen activator inhibitor type 1 (PAI-1) has been associated with abdominal obesity, hypertension, hypertriglyceridemia, hyperinsulinemia, glucose intolerance, and type II diabetes, conditions known to be linked with insulin resistance. To determine whether PAI-1 is related to insulin resistance, we studied nine obese nondiabetics and 10 obese type II diabetics by means of a sequential hyperinsulinemic euglycemic clamp study. Plasma PAI-1 antigen (Ag) correlated significantly with peripheral insulin resistance, represented by the insulin level at which peripheral glucose uptake (PGU) is half-maximal ([ED50PGU] r = .87, P < .001). Multiple regression analysis including indices of hepatic and peripheral insulin action, fasting plasma insulin levels, triglyceride levels, blood pressure (BP), waist to hip ratio (WHR), and body mass index (BMI) disclosed ED50PGU to account for 76% of the variance of PAI-1 Ag. We suggest that PAI-1 contributes to the increased cardiovascular risk encountered with insulin resistance.
    No preview · Article · Aug 1993 · Metabolism
  • M. M. L. Wiersma · I M Bakker · J K Radder
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    ABSTRACT: In the rat, a high fat intake is believed to be associated with an increased risk for the development of glucose intolerance by inducing insulin resistance. The aim of this study was to investigate whether reduced insulin production may also play a role. Rats were treated with 0, 30, 60, and 90 mg of streptozotocin (STZ)/kg of body weight on the day of birth (0, 30, 60, and 90 nSTZ rats). At 3 or 6 months of age, glucose tolerance was assessed by the intravenous glucose tolerance test (IVGTT). STZ dose-dependently decreased first- and second-phase insulin responses and correspondingly impaired glucose tolerance. Following a 3-week high fat diet (HFD: 60% of calories as corn oil), insulin responses were higher in control as well as in STZ-treated rats both at 3 and 6 months of age. In 3-month-old rats this was accompanied by unchanged or increased glucose levels following the glucose load, whereas in 6-month-old 0 and 30 nSTZ rats glucose tolerance was slightly improved. After 6 weeks of HFD in 6-month-old rats, glucose tolerance was impaired compared to that after 3 weeks of HFD despite higher insulin responses. Continuing the HFD for up to 12 weeks further impaired glucose tolerance, but insulin responses were decreased compared to those after 6 weeks of HFD. These results indicate that very low dose neonatal STZ administration impairs glucose tolerance through decreased overall insulin responses. This may possibly be due to a reduction of B-cell number rather than an alteration of B-cell function. No clear evidence exists that a high fat intake per se negatively influences glucose-induced insulin responses, but this may become apparent after longer periods of high fat feeding.
    No preview · Article · Jul 1993 · Annals of the New York Academy of Sciences

Publication Stats

1k Citations
155.45 Total Impact Points

Institutions

  • 1989-2013
    • Leiden University
      • Leiden Amsterdam Center for Drug Research
      Leyden, South Holland, Netherlands
  • 1988-2007
    • Leiden University Medical Centre
      • Department of Psychiatry
      Leyden, South Holland, Netherlands
  • 1992
    • University of Texas Health Science Center at San Antonio
      • Division of Diabetes
      San Antonio, Texas, United States