J K Radder

Leiden University Medical Centre, Leiden, South Holland, Netherlands

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Publications (37)148.22 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.
    The Netherlands Journal of Medicine 01/2013; 71(1):22-5. · 2.38 Impact Factor
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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.
    The Netherlands Journal of Medicine 02/2011; 69(2):66-71. · 2.38 Impact Factor
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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.
    The Netherlands Journal of Medicine 06/2005; 63(5):164-9. · 2.38 Impact Factor
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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.
    Journal of Clinical Endocrinology &amp Metabolism 04/2005; 90(3):1495-501. · 6.43 Impact Factor
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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.
    Journal of the American College of Cardiology 07/2003; 42(2):328-35. · 14.09 Impact Factor
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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.
    Circulation 12/2002; 106(19):2442-7. · 15.20 Impact Factor
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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.
    Journal of Psychosomatic Research 03/2002; 52(2):97-106. · 3.27 Impact Factor
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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.
    Diabetic Medicine 03/2002; 19(2):157-61. · 3.24 Impact Factor
  • Diabetic Medicine - DIABETIC MED. 01/2002; 19(2):157-161.
  • Article: Letters
    Diabetic Medicine 12/2001; 18(5):423 - 424. · 3.24 Impact Factor
  • Diabetic Medicine 06/2001; 18(5):423-4. · 3.24 Impact Factor
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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.
    Diabetologia 05/2001; 44(4):437-43. · 6.49 Impact Factor
  • Patient Education and Counseling - PATIENT EDUC COUNS. 01/1998; 34.
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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.
    Diabetologia 04/1996; 39(4):391-400. · 6.49 Impact Factor
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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)
    Metabolism 04/1995; 44(3):291-7. · 3.10 Impact Factor
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    ABSTRACT: Obesity-associated hyperaminoacidemia is traditionally interpreted as a consequence of insulin resistance. We performed two different experiments to investigate the effects of both obesity-associated insulin resistance and the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) on amino acid metabolism. In the first experiment, we measured postabsorptive amino acid concentrations and their decline in response to an oral carbohydrate load in 19 obese nondiabetic women and 19 normal-weight nondiabetic controls. Obese subjects were more resistant to insulin with respect to its effects on glucose metabolism than normal-weight controls, as calculated by the method described by Matthews. However, postabsorptive plasma concentrations of the so-called large neutral amino acids (LNAA), namely phenylalanine, tyrosine, valine, leucine, and isoleucine, and their decrease in response to carbohydrate consumption were similar in both groups. In the second experiment, we compared the decrease of plasma concentrations of LNAA during a euglycemic, hyperinsulinemic clamp in obese subjects with and without NIDDM. Peripheral glucose uptake (PGU) was more impaired in NIDDM subjects compared with obese controls. Furthermore, hepatic glucose production (HGP) was less attenuated by insulin infusion in NIDDM than in control subjects. Postabsorptive plasma LNAA concentrations were not different in the two groups. Values obtained in either group were not different from the postabsorptive concentrations in the normal-weight control subjects of experiment 1. All amino acid levels decreased substantially in response to insulin infusion. The magnitude of the decrease was not significantly different in the two groups, except for a slightly greater decrease of the plasma isoleucine concentration in obese control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
    Metabolism 06/1994; 43(5):640-6. · 3.10 Impact Factor
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    ABSTRACT: It has been suggested that hyperinsulinemia per se may affect the levels of some counterregulatory hormones in the absence of hypoglycemia. We studied the effect of graded hyperinsulinemia and concomitant increased glucose metabolism on the levels of counterregulatory hormones by means of the 5-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-3H]-glucose infusion, in conscious rats. Insulin infusion rates (IIR) of 0, 0.5, 1, 3, and 16 mU/min, resulted in steady-state plasma insulin levels (mean +/- SEM) of 24 +/- 4, 44 +/- 3, 98 +/- 8, 418 +/- 48, and 6626 +/- 361 microU/ml, peripheral glucose uptake (PGU) of 3.1 +/- 0.2, 3.6 +/- 0.3, 5.4 +/- 0.3, 9.2 +/- 0.4, and 12.4 +/- 0.2 mg/min and hepatic glucose production (HGP) of 3.1 +/- 0.2, 2.4 +/- 0.4, 0.8 +/- 0.3, -0.1 +/- 0.2, and -0.5 +/- 0.3 mg/min, respectively. Plasma glucagon levels were half maximally suppressed between IIRs of 0.5 and 1 mU/min and maximally suppressed at 3 mU/min. The suppression exactly paralleled the inhibition of HGP (r = 0.87 +/- 0.04, p < 0.02) but not the stimulation of PGU (r = -0.66 +/- 0.12, p = NS). This suggests that the inhibition of HGP by insulin is at least partially mediated by a simultaneous suppression of plasma glucagon levels. The adrenal hormones corticosterone and epinephrine were not influenced during the clamp.(ABSTRACT TRUNCATED AT 250 WORDS)
    Physiology & Behavior 01/1994; 54(6):1141-8. · 3.16 Impact Factor
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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.
    Metabolism 08/1993; 42(8):945-9. · 3.10 Impact Factor
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    ABSTRACT: Insulin resistance contributes to the metabolic defects in non-insulin dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. In a double-blind placebo-controlled cross-over study, we examined hepatic and peripheral insulin action by the sequential hyperinsulinaemic-euglycaemic clamp technique with infusion of 3-[3H]-glucose in eight obese NIDDM patients and in eight obese non-diabetics, matched for age, sex and body mass index. Body weight was kept constant. After 14 days of fluoxetine, 60 mg daily, in NIDDM half-maximal peripheral glucose uptake was achieved at a lower insulin level than after placebo (ED50pgu: 180.5 +/- 25.8 vs. 225.3 +/- 39.9 mU/l, P < 0.05), but not in non-diabetics (140 +/- 15.3 vs. 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral glucose uptake (Vmaxpgu) did not change significantly. Multivariate analysis disclosed no differences in the effect of fluoxetine between NIDDM and non-diabetics. When non-diabetics and NIDDM were considered together, only the most insulin-resistant individuals demonstrated a decrease in ED50pgu (P < 0.001). Likewise, only the individuals with the most outspoken hepatic insulin resistance demonstrated a decrease in insulin level, at which hepatic glucose production (HGP) is completely suppressed (HGP0) (P < 0.01). In conclusion, fluoxetine improves peripheral and hepatic insulin action in obese insulin-resistant subjects irrespective of its weight lowering effect.
    International Journal of Obesity 01/1993; 16 Suppl 4:S55-61. · 5.22 Impact Factor
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    ABSTRACT: Amylin, also called islet amyloid polypeptide (IAPP), or diabetes-associated peptide (DAP) is a recently discovered 37 amino acid polypeptide which has been shown to be co-secreted with insulin from the pancreatic beta-cell. The peptide turned out to be the major constituent of pancreatic amyloid deposits which are frequently found in the pancreas of type II diabetic patients. Therefore, a role for amylin in the aetiology of type II diabetes was hypothesized. To investigate this possibility, several studies have been performed to elucidate whether amylin is able to impair insulin secretion and action, two characteristic features of type II diabetes mellitus. These studies suggest that it is unlikely that amylin has a direct inhibitory effect on insulin secretion. Amyloid deposits, however, which are derived from the in situ polymerization and precipitation of amylin, may impair beta-cell function during type II diabetes by damaging and covering beta-cells. Furthermore, it has been shown that amylin has the potential to antagonize the action of insulin on glucose metabolism by increasing hepatic glucose production and by decreasing muscle, but not adipocyte glucose uptake. For these reasons, it has been suggested that amylin might be involved in the pathophysiology of type II diabetes and obesity, disease states which are characterized by abnormal beta-cell function and insulin resistance. In addition, amylin was shown to induce hypocalcaemia by inhibiting osteoclast-mediated bone resorption in a calcitonin-like manner. Therefore, amylin is likely to be involved in both the modulation of glucose and calcium metabolism.
    The Netherlands Journal of Medicine 09/1992; 41(1-2):82-90. · 2.38 Impact Factor

Publication Stats

808 Citations
148.22 Total Impact Points

Institutions

  • 1989–2013
    • Leiden University Medical Centre
      • • Department of Obstetrics
      • • Department of Endocrinology and General Internal Medicine
      Leiden, South Holland, Netherlands
  • 2005
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Medical Psychology
      Amsterdam, North Holland, Netherlands
  • 2002–2005
    • VU University Medical Center
      Amsterdamo, North Holland, Netherlands