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R Rottiers

Publications and source records attributed to R Rottiers.

At least 19 recordsLinked to original sources
PubMed2005

Combined positivity for HLA DQ2/DQ8 and IA-2 antibodies defines population at high risk of developing type 1 diabetes.

AIMS/HYPOTHESIS: Prevention trials in first-degree relatives of type 1 diabetic patients are hampered by large interindividual differences in progression rate to diabetes. We investigated whether specific combinations of immune and genetic markers can identify subgroups with more homogeneous progression to clinical onset. METHODS: Antibodies against islet cell cytoplasm (ICA), insulin (IAA), glutamate decarboxylase (GADA) and IA-2 protein (IA-2A) were measured in 790 non-diabetic control subjects and 4,589 first-degree relatives under age 40. RESULTS: On first sampling, 11.1% of the siblings presented at least one antibody type (p<0.001 vs other relatives). During follow-up (median 52 months) 43 subjects developed type 1 diabetes (31 siblings, ten offspring of a diabetic father, two offspring of a diabetic mother). Using Kaplan-Meier survival analysis and Cox regression, IA-2A conferred the highest 5-year diabetes risk (>50%) irrespective of the number of antibodies present. In initially IA-2A-positive relatives (n=58) progression to hyperglycaemia depended more on HLA DQ status than on type of kinship (84% progression in the presence of DQ2/DQ8 vs 32% in its absence; p<0.003). In IA-2A-negative relatives (n=4,531) 5-year progression to diabetes increased with the number of other antibodies (ICA, GADA and/or IAA) (p<0.001) but overall did not exceed 10% even for two or more antibodies. Among relatives initially positive for one or more antibody type other than IA-2A (n=315), there was significantly more progression to diabetes (overall still <10%) in carriers of DQ2 (p<0.001 vs no DQ2), regardless of DQ8 status. CONCLUSIONS/INTERPRETATION: These observations suggest that the HLA-DQ-inferred risk of diabetes can proceed through two distinct pathways distinguished by IA-2A status. Combined positivity for DQ2/DQ8 and IA-2A defines a more homogeneous high-risk population for prevention trials than those used so far.

Adolescent↗
PubMed2004

Obese type 2 diabetics and obese patients have comparable plasma phospholipid fatty acid compositions deviating from that of healthy individuals.

There exist controversial reports regarding the differences in phospholipid fatty acids in type 2 diabetic and obese patients as compared to controls. The study was aimed at assessing the combined effect of type 2 diabetes and obesity on the fatty acid composition of plasma phospholipids. The experimental group consisted of 23 Belgian obese type 2 diabetics on Metformin. Two control groups were used: healthy lean and obese individuals in the same BMI range as the diabetics. Plasma phospholipids were isolated and their fatty acids and vinyl ether moieties were determined. Significance was set at P < 0.01. Plasma phospholipid fatty acids and plasmalogen-derived dimethyl acetals in diabetics deviated in many respects from these of lean controls but were not significantly different from those of obese non-diabetic patients. Therefore, the deviations of the fatty acid pattern of plasma phospholipids in type 2 diabetes may be attributed to obesity rather than to diabetes itself.

Adult↗
PubMed2004

GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients.

BACKGROUND: Progressive beta-cell failure is a characteristic feature of type 2 diabetes; consequently, beta-cell secretagogues are useful for achieving sufficient glycaemic control. The European GUIDE study is the first large-scale head-to-head comparison of two sulphonylureas designed for once-daily administration used under conditions of everyday clinical practice. DESIGN: Eight hundred and forty-five type 2 diabetic patients were randomized to either gliclazide modified release (MR) 30-120 mg daily or glimepiride 1-6 mg daily as monotherapy or in combination with their current treatment (metformin or an alpha-glucosidase inhibitor) according to a double-blind, 27-week, parallel-group design. Efficacy was evaluated by HbA1c and safety by hypoglycaemic episodes using the European Agency definition. RESULTS: HbA1c decreased similarly in both groups from 8.4% to 7.2% on gliclazide MR and from 8.2% to 7.2% on glimepiride. Approximately 50% of the patients achieved HbA1c levels less than 7%, and 25% less than 6.5%. The mean difference between groups of the final HbA1c was -0.06% (noninferiority test P < 0.0001). No hypoglycaemia requiring external assistance occurred. Hypoglycaemia with blood glucose level < 3 mmol L(-1) occurred significantly less frequently (P = 0.003) with gliclazide MR (3.7% of patients) compared with glimepiride (8.9% of patients). The distribution of the sulphonylurea doses was similar in both groups. CONCLUSIONS: This study provides new insights into therapeutic strategies using sulphonylureas. It shows that gliclazide MR is at least as effective as glimepiride, either as monotherapy or in combination. The safety of gliclazide MR was significantly better, demonstrating approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.

Diabetes Mellitus, Type 2↗
PubMed2002

IA-2 autoantibodies predict impending type I diabetes in siblings of patients.

AIMS/HYPOTHESIS: Multiple islet autoantibody positivity is currently believed to best predict progression to Type I (insulin-dependent) diabetes mellitus. We compared its predictive value with that of positivity for a particular type of islet autoantibody, directed against the IA-2 antigen. METHODS: Autoantibodies against islet cell cytoplasm (ICA), insulin (IAA), GAD (GADA) and IA-2 (IA-2A) were measured at initial sampling in 1724 non-diabetic siblings (median age [range]:16 [0-39] years) of Type I diabetic patients with a median follow-up of 50 months. RESULTS: On initial sampling 11% of siblings were positive for one antibody type or more and 2.1% for three of more types. During follow-up, 27 antibody-positive siblings developed diabetes. Using survival analysis, the risk for clinical onset within 5 years was 34% in subjects positive for three or more types compared with 13% in those with one type or more. Progression to diabetes amounted to 12% within 5 years among siblings positive for IAA, 20% for ICA, 19% for GADA but 59% for IA-2A (p<0.001 vs absence of the respective antibody). IA-2A were detected in 1.7% of all siblings and in 56% of the prediabetic subjects on first sampling. Initial positivity for two or three antibody markers was associated with a higher progression rate in IA-2A positive as compared to IA-2A negative siblings (p=0.001). In absence of IA-2A initial positivity for another antibody (IAA, ICA or GADA) conferred a low (<10% within 5 years) risk of diabetes compared to subjects lacking this antibody. CONCLUSIONS/INTERPRETATION: In siblings of Type I diabetic patients, IA-2A positivity is a more direct predictor of impending clinical onset than multiple antibody positivity per se. Assessment of IA-2A status allows us to select subjects with homogeneously high risk of diabetes for participation in prevention trials.

Adolescent↗
PubMed2001

Male-to-female excess in diabetes diagnosed in early adulthood is not specific for the immune-mediated form nor is it HLA-DQ restricted: possible relation to increased body mass index.

UNLABELLED: AIMS/HYPOTHESIS. We investigated whether the reported HLA-DQ/DR restricted male-to-female (M:F) excess in Type I (insulin-dependent) diabetes mellitus also exists in Belgian patients, is specific for immune-mediated diabetes, remains genotype-restricted after adjustment for age at diagnosis, and is associated with sex-dependent environmental factors. METHODS: Autoantibodies, HLA-DQ and 5'INS (5'insulin gene) polymorphisms were assessed in 2,532 diabetic patients (all phenotypes) diagnosed under 40 years of age. Autoantibodies and body mass index (expressed as a standard deviation score by comparison to age-matched and sex-matched control subjects; SDS-BMI) were measured in 1986 siblings or offspring of Type I diabetes patients (0-39 years). RESULTS: In patients aged 15-39 years at diagnosis, the male-to-female ratio was 1.5 or more regardless of their antibody status and significantly higher (p < 0.001) than that in the age-matched Belgian general population. There was no sex bias in patients under 15 years of age. Overall, the male-to-female ratio was significantly higher in patients without HLADQA1*0301-DQB1*0302 (p < or = 0.003) but stratification in age groups and multivariate analysis identified age as the major determinant of male-to-female ratio. The SDS-BMI increased (p < 0.01) in male antibodypositive relatives (n = 103) but not in female antibody-positive (n = 92) or in antibody-negative relatives (n = 1,791). This phenomenon tended to be restricted to male relatives who were positive only for glutamate decarboxylase antibodies (n = 44). CONCLUSIONS/INTERPRETATION: The male-to-female excess in Belgian diabetic patients diagnosed in early adulthood is not specific for immune-mediated Type I diabetes and not HLA-DQ or 5'INS restricted. Our data suggest that, similar to Type II (non-insulin-dependent) diabetes mellitus, the metabolic burden of obesity and insulin resistance could preferentially precipitate postpubertal clinical onset in male subjects with slowly progressive subclinical (immune-mediated) diabetes.

Adolescent↗
PubMed2001

Risk factors for progression to proliferative diabetic retinopathy in the EURODIAB Prospective Complications Study.

AIMS/HYPOTHESIS: Proliferative diabetic retinopathy (PDR), a leading cause of blindness, cannot be totally prevented by optimizing metabolic and blood pressure control and responds to no specific treatment other than partially destructive retinal photocoagulation. Recognizing risk factors using large-scale epidemiological studies could help identify targets for treatment. The EURODIAB Prospective Complications Study (PCS) includes the largest cohort so far of patients with Type I (insulin-dependent) diabetes mellitus. METHODS: Baseline data were collected between 1989 and 1991 on 3250 patients who were recalled for follow-up. Physical examination, biochemical tests and assessment of complications were done on both occasions. In particular, 1249 patients had retinal photographs taken both basally and after an average of 7.3 years. RESULTS: Proliferative retinopathy had developed in 157 patients (cumulative incidence 17.3/1000 patient-years; 95%-CI: 13.6-21.1). HbA(1c) (standardized regression estimate--SRE = 3.03, CI 2.49-3.69), diabetes duration (1.71, 1.42-2.06), age at diagnosis < 12 (1.66, 1.11-2.50), diastolic blood pressure less than or equal to 83 (1.50, 1.03-2.20) and waist-to-hip ratio (1.50, 1.03-2.20) were all independent predictors for progression to PDR when entered simultaneously into a logistic regression model. Including retinopathy at baseline maintained the effects of metabolic control and pre-pubertal onset only. Including the albumin excretion rate maintained the effect of control but reduced SRE for pre-pubertal onset to 1.49 (0.94-2.33). There was no evidence for a threshold effect for HbA(1c)concentrations at baseline and progression to proliferative retinopathy. CONCLUSION/HYPOTHESIS: Metabolic control and duration of diabetes are strong indicators of progression to proliferative retinopathy. Onset of diabetes before puberty could be an additional independent risk factor.

Adolescent↗
PubMed2001

Circulating plasma vascular endothelial growth factor and microvascular complications of type 1 diabetes mellitus: the influence of ACE inhibition.

AIMS: To determine whether circulating plasma vascular endothelial growth factor (VEGF) is elevated in the presence of diabetic microvascular complications, and whether the impact of angiotensin-converting enzyme (ACE) inhibitors on these complications can be accounted for by changes in circulating VEGF. METHODS: Samples (299/354 of those with retinal photographs) from the EUCLID placebo-controlled clinical trial of the ACE inhibitor lisinopril in mainly normoalbuminuric non-hypertensive Type 1 diabetic patients were used. Albumin excretion rate (AER) was measured 6 monthly. Geometric mean VEGF levels by baseline retinopathy status, change in retinopathy over 2 years, and by treatment with lisinopril were calculated. RESULTS: No significant correlation was observed between VEGF at baseline and age, diabetes duration, glycaemic control, blood pressure, smoking, fibrinogen and von Willebrand factor. Mean VEGF concentration at baseline was 11.5 (95% confidence interval 6.0--27.9) pg/ml in those without retinopathy, 12.9 (6.0--38.9) pg/ml in those with non-proliferative retinopathy, and 16.1 (8.1--33.5) pg/ml in those with proliferative retinopathy (P = 0.06 for trend). Baseline VEGF was 15.2 pg/ml in those who progressed by at least one level of retinopathy by 2 years compared to 11.8 pg/ml in those who did not (P = 0.3). VEGF levels were not altered by lisinopril treatment. Results were similar for AER. CONCLUSIONS: Circulating plasma VEGF concentration is not strongly correlated with risk factor status or microvascular disease in Type 1 diabetes, nor is it affected by ACE inhibition. Changes in circulating VEGF cannot account for the beneficial effect of ACE inhibition on retinopathy.

Adult↗
PubMed2001

Glycemic index in the diet of European outpatients with type 1 diabetes: relations to glycated hemoglobin and serum lipids.

BACKGROUND: Little is known about the variation of the glycemic index (GI) in the diet of European outpatients with type 1 diabetes and how the GI of a commonly consumed diet is associated with metabolic control. OBJECTIVE: The present study examined the calculated dietary GI of European outpatients with type 1 diabetes for possible relations to glycated hemoglobin (Hb A(1c)) and serum lipid concentrations. DESIGN: The relation of the GI (calculated from a 3-d dietary record) to Hb A(1c), serum cholesterol (total, LDL, and HDL), and fasting triacylglycerol was analyzed in 2810 people with type 1 diabetes from the EURODIAB Complications Study. RESULTS: The GI was independently related to Hb A(1c) (P = 0.0001). Compared with the highest GI quartile (median GI: 89), adjusted Hb A(1c) in the lowest GI quartile (median GI: 75) was 11% lower in patients from southern European centers and 6% lower in patients from northern, western, and eastern European centers. Of the serum lipids, only the HDL cholesterol in patients from these European centers was independently related to the GI (P = 0.002). In southern European centers, the consumption of pasta, temperate-climate fruit, white bread, and potatoes largely determined the patients' dietary GI, whereas in the northern, western, and eastern European centers, consumption of bread, potatoes, and temperate-climate fruit was most relevant. CONCLUSIONS: This study in European patients with type 1 diabetes showed that a lower dietary GI is related to lower Hb A(1c) concentrations, independently of fiber intake. The consumption of bread and pasta had the biggest effect on the overall dietary GI of European outpatients.

Adolescent↗
PubMed2000

Different risk factors of microangiopathy in patients with type I diabetes mellitus of short versus long duration. The EURODIAB IDDM Complications Study.

AIMS/HYPOTHESIS: To identify factors associated with early development of and late protection from microvascular complications in subjects with Type I (insulin-dependent) diabetes mellitus. METHODS: The frequency of microvascular complications and their relation to risk factors were studied in 300 Type I diabetic subjects with short duration of disease (< or = 5 years) compared with 1062 subjects with long duration (> or = 14 years). Microvascular disease was defined as the presence of either retinopathy (assessed from centrally-graded retinal photographs) or urinary albumin excretion rate of more than 20 micrograms/min. RESULTS: The prevalence of microvascular disease was 25% in the short duration group. In the long duration group 18% had no evidence of microvascular complications. In the short duration group factors associated with early development of complications were cigarette smoking and a family history of hypertension. Subjects free of microvascular complications in spite of long duration of diabetes had better glycaemic control, lower blood pressure, better lipid profile and lower von Willebrand factor levels. CONCLUSION/INTERPRETATION: At the early stages of Type I diabetes, cigarette smoking and genetic susceptibility to hypertension are important risk factors for microvascular complications. At a later stage, additional risk factors are poorer glycaemic control, higher blood pressure, and an unfavourable lipid profile possibly associated with endothelial dysfunction. Many of these factors are amenable to long-term intervention which should be started as soon as possible in the course of the disease.

Cohort Studies↗
PubMed2000

Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry.

OBJECTIVE: To investigate whether the presence of antibody markers at diagnosis could help predict the rapid decrease in residual beta-cell function noted in some, but not all, patients with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: We measured random C-peptide levels (radioimmunoassay); islet cell cytoplasmic antibodies (ICA) (indirect immunofluorescence); and antibodies against IA-2 protein, 65-kDa glutamate decarboxylase, and insulin (liquid-phase radiobinding assays) in 172 patients <40 years of age with type 1 diabetes. The patients had been consecutively recruited at diagnosis by the Belgian Diabetes Registry and were followed for 2 years. RESULTS: Two years after diagnosis, random C-peptide levels had decreased significantly (P < 0.001) in ICA+ patients but not in ICA- patients. C-peptide values <50 pmol/ were noted in 88% of patients diagnosed before 7 years of age, in 45% of patients diagnosed between ages 7 and 15 years, and in 29% of patients diagnosed after 15 years of age (P < 0.001). In cases of clinical onset before age 15 years, a rapid decline in random C-peptide values was observed almost exclusively in patients with high-titer ICA (> or =50 Juvenile Diabetes Foundation [JDF] units) at diagnosis (69 vs. 17% in patients with lower ICA titers, P < 0.001). In patients diagnosed after 15 years of age, 36% of patients with ICA titers > or =12JDF units developed low C-peptide levels compared with 14% of patients with ICA titers < 12 JDF units (P < 0.03). Multivariate analysis confirmed that C-peptide levels after 2 years were inversely correlated with ICA levels (P < 0.001) and to a lesser degree positively correlated with age at diagnosis (P < 0.02), regardless of the levels or number of molecular autoantibodies. CONCLUSIONS: Young age at diagnosis and high-titer ICA identify a group of type 1 diabetic patients at high risk of rapidly losing residual beta-cell function. Using these selection criteria, it is possible to better target beta-cell-preserving interventions to patients with or without such rapid progression, depending on the nature of the tested substance. The ICA assay measures clinically relevant antibodies not detected in antibody assays that use recombinant human autoantigens for substrate.

Adolescent↗
PubMed1997

Reduced frequency of severe hypoglycemia and coma in well-controlled IDDM patients treated with insulin lispro. The Benelux-UK Insulin Lispro Study Group.

OBJECTIVE: Several studies have suggested that use of the short-acting insulin analog, insulin lispro, in multiple injection therapy may reduce the risk of hypoglycemia in comparison with regular insulin. This effect might be more pronounced in well-controlled patients, since intensive treatment of IDDM increases the rate of severe hypoglycemic events. This study evaluated the effects of insulin lispro on glycemic control and hypoglycemia rates in well-controlled IDDM patients. RESEARCH DESIGN AND METHODS: This was an open, randomized, 6-month crossover study of 199 IDDM patients. Glycemic control was evaluated by HbA1c, home blood glucose measurements, and rate and timing of hypoglycemic events. At the end of the study, patients completed an evaluation form regarding therapy-related quality of life. RESULTS: HbA1c remained constant at approximately 7.3% throughout the study. Meal-related glucose excursions were significantly lower with insulin lispro compared with regular insulin (mean -0.8 +/- 1.7 vs. 1.1 +/- 1.6 mmol/l, P < 0.001), as was the within-day variability (M value 27.7 +/- 19.7 vs. 30.2 +/- 23.1, P = 0.007). The incidence of severe hypoglycemic events (58 vs. 36, P = 0.037) including coma (16 vs. 3, P = 0.004) was significantly lower with insulin lispro than with regular insulin. Patients felt that insulin lispro increased flexibility and freedom of lifestyle. CONCLUSIONS: In well-controlled IDDM patients, insulin lispro is associated with a lower risk of severe hypoglycemia and coma.

Adult↗
PubMed1985

Self blood glucose monitoring: evaluation of Haemo-Glukotest 20-800R, Visidex I and Reflolux.

Trained staff-members evaluated the accuracy of Haemo-Glukotest 20-800R (= HG 20-800R), Visidex I and Reflolux in 135 blood glucose measurements. A glucose-oxidase method was used as reference method. Although the correlation between the 3 methods tested was excellent, more detailed analysis revealed for all methods a clear deviation from the real blood glucose, especially in the low blood glucose range. This might result in an inappropriate adaptation of the insulin dose, when the estimated blood glucose is used in connection with a classic algorithm. Apart from this limitation, Reflolux had the best accuracy, followed by HG 20-800R. If stored in a desiccated tube, the HG 20-800R strip can be reliably re-read (visually or with Reflolux) even after 7 days. Visidex I is unsuitable for storage and re-reading.

Blood Glucose↗
PubMed1984

Androgen plasma levels in male diabetics.

Plasma level of androgens were studied in 47 normal male controls (20-50 yr-old; mean age 38 yr) and in a group of forty-one male diabetics (23-55 yr-old; mean age: 37.5 yr). Of these 36 showed type II and 5 type I diabetes. The results showed that while the mean basal plasma LH was unchanged, there was a decrease in testosterone levels in the diabetics. Moreover, testosterone binding globulin (TeBG) capacity appeared to be augmented and, as a consequence, the apparent free testosterone concentration (AFTC) was markedly decreased. It is interesting to note that the anomalies in androgen secretion observed are rather similar to those found in elderly man and could play some role (with other factors) in the onset of the frequent sexual disturbances in male diabetics.

Adult↗
PubMed1984

Diabetes mellitus in dogs: relationship of obesity to glucose tolerance and insulin response.

The IV glucose-tolerance test was performed in 71 diabetic dogs (fasting glycemia greater than 6.70 mmol/L) and in 20 healthy dogs. All diabetic dogs were characterized by various degrees of glucose intolerance as expressed by an abnormal glucose disappearance coefficient. On the basis of the fasting plasma insulin concentration (Io), insulin peak response (IPR), the insulinogenic index (delta I/delta G), and the total insulin secretion (TIS), the diabetic dogs were classified, as follows: Type I dogs (n = 32) which had the severe clinical signs of diabetes and an absence of certain diagnostic responses: Io, IPR, delta I/delta G, and TIS. Type II dogs (n = 15) which also had marked diabetic signs and an absence of IPR, delta I/delta G, and TIS responses. The dogs were further subdivided into obese and nonobese groups; the Io was within acceptable limits in the nonobese group (n = 8), but was markedly increased in the obese group (n = 7). Type III dogs (n = 24) had no diabetic signs and a fasting plasma glucose less than 12 mmol/L. They were also subdivided into obese and nonobese groups. The nonobese dogs (n = 13) had Io values within acceptable limits and decreased IPR, delta I/delta G, and TIS. In contrast, the obese dogs had increased Io, IPR, delta I/delta G, and TIS. Statistical analyses indicated that the TIS and IO were highly significant linear functions of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗