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Biomedical subjects

M Buysschaert

Publications and source records attributed to M Buysschaert.

At least 19 recordsLinked to original sources

Variability in erythrocyte fructosamine 3-kinase activity in humans correlates with polymorphisms in the FN3K gene and impacts on haemoglobin glycation at specific sites.

BACKGROUND: Part of the fructosamines that are bound to intracellular proteins are repaired by fructosamine 3-kinase (FN3K). Because subject-to-subject variations in erythrocyte FN3K activity could affect the level of glycated haemoglobin independently of differences in blood glucose level, we explored if such variability existed, if it was genetically determined by the FN3K locus on 17q25 and if the FN3K activity correlated inversely with the level of glycated haemoglobin. RESULTS: The mean erythrocyte FN3K activity did not differ between normoglycaemic subjects (n = 26) and type 1 diabetic patients (n = 31), but there was a wide interindividual variability in both groups (from about 1 to 4 mU/g haemoglobin). This variability was stable with time and associated (P < 0.0001) with two single nucleotide polymorphisms in the promoter region and exon 6 of the FN3K gene. There was no significant correlation between FN3K activity and the levels of HbA1c, total glycated haemoglobin (GHb) and haemoglobin fructoselysine residues, either in the normoglycaemic or diabetic group. However, detailed analysis of the glycation level at various sites in haemoglobin indicated that the glycation level of Lys-B-144 was about twice as high in normoglycaemic subjects with the lowest FN3K activities as compared to those with the highest FN3K activities. CONCLUSION: Interindividual variability of FN3K activity is substantial and impacts on the glycation level at specific sites of haemoglobin, but does not detectably affect the level of HbA1c or GHb. As FN3K opposes one of the chemical effects of hyperglycaemia, it would be of interest to test whether hypoactivity of this enzyme favours the development of diabetic complications.

Adult↗

The role of alexithymia factors in glucose control of persons with type 1 diabetes: a pilot study.

OBJECTIVE: To clarify the respective contribution of demographic characteristics, health conditions and three psychological variables (depression, anxiety, alexithymia) for glycaemic control measured by glycated hemoglobin (HbA1c). MATERIALS AND METHODS: Sixty-four persons diagnosed with type 1 diabetes completed psychological measures and demographic information at admission (T1) to the hospital and in a follow-up (+8 weeks) (T2). Additional information about their health conditions was also considered. RESULTS: At T1, the alexithymia factor "difficulties describing feelings" (DDF) predicted HbA1c over and above the predictive power of demographic information, health conditions, anxiety, and depression. Additionally, higher decrease in HbA1c from T1 to T2 was predicted by higher scores on the alexithymia factor DDF at admission over and above the other predictors. CONCLUSION: DDF is an important predictor of glucose control. Scoring higher on this factor is related to poorer glycaemic control at admission. Additionally, people with higher scores on this factor seem to benefit highly from the treatment administered at the hospital.

Adolescent↗

Bone density and markers of bone remodeling in type 1 male diabetic patients.

AIMS: To assess the prevalence and severity of bone disease in type 1 diabetic patients and to determine serum markers of bone remodeling as well as their relationship with bone mineral density (BMD). METHODS: BMD [by dual energy x-ray absorptiometry (DXA)] and serum markers of bone remodeling [osteocalcin, c-terminal telopeptide of type I collagen (CTX)], leptin and osteoprotegerin (OPG) were measured in 42 adult males with type 1 diabetes. Twenty-four non-diabetic subjects served as controls. RESULTS: In 40% of the patients, osteopenia at the lumbar spine (L1-L4) and/or at the left hip was found, and 7% met criteria for osteoporosis. L1-L4 BMD z-score was correlated with age (r=0.365, P=0.018) and a similar trend was observed at left hip. L1-L4 BMD z-score was negatively correlated with CTX and osteocalcin (r=-0.343, P=0.028; r=-0.376, P=0.024, respectively). A significant correlation was evidenced between BMD z-score at both lumbar spine and left hip and leptin values (r=0.343, P=0.03; r=0.395, P=0.012, respectively) but after adjustment for weight this correlation was no longer significant. Osteocalcin, CTX and leptin concentrations were comparable between patients and controls, while OPG concentrations tend to be higher in diabetic subjects (P=0.08). CTX was negatively correlated with age (r=-0.390, P=0.012) and positively correlated with osteocalcin (r=0.696, P<0.001). OPG was positively correlated with age (r=0.507, P=0.001). CONCLUSION: Our results suggest that in diabetic subjects osteopenia is a relatively frequent complication but bone loss is attenuated with age progression. Whether this is also mediated by OPG and/or leptin remains to be confirmed.

Adult↗

The MTHFR CT polymorphism confers a high risk for stroke in both homozygous and heterozygous T allele carriers with Type 2 diabetes.

OBJECTIVE: Individuals with Type 2 diabetes are at increased risk of stroke. Plasma homocysteine (tHcy) is an independent risk factor for cardiovascular (CV) disease. The methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism (thermolabile variant C(677)T) is associated with CV risk, partly as a result of increased Hcy, especially in homozygous subjects. AIM: To relate the occurrence of the MTHFR polymorphism with stroke prevalence by examining allelic frequency and genotype distribution in 165 subjects with Type 2 diabetes studied for the presence of thermolabile C(677)T MTHFR mutation. RESULTS: Mean age was 67.7 years, and tHcy 18.2 micromol/l. T allele frequency was 38.5%. MTHFR genotypes were: normal (CC) 40%; heterozygous (CT) 43%; homozygous (TT) 17%. Serum levels of folic acid and B12 vitamin were within normal limits. Stroke prevalence was 14%. Sixty-four per cent of stroke-free subjects had the normal C allele vs. 46% in stroke subjects. The frequencies of genotypes (CC-CT-TT) were (%): 44-41-15 in stroke-free vs. 17-57-26 in stroke patients. Coronary (CAD) and peripheral artery disease (PAD) were common in all groups, with no differences according to genotypes. Stroke prevalence was markedly higher in genotypes CT and TT (18 and 21%) compared with CC (6%). Mean tHcy levels were higher in TT subjects. CONCLUSION: The allelic frequency of C(677)T MTHFR mutation in Type 2 diabetes subjects with stroke is markedly different from that of subjects without stroke. Genotypic characteristics suggest that C(677)T MTHFR mutation confers a higher risk for stroke to both homozygous and heterozygous T allele carriers that cannot be ascribed solely to raised tHcy and/or lower folate status in CT subjects, nor to phenotypic expression of conventional risk factors for stroke. The impact of the MTHFR polymorphism on stroke may result from T allele-linked deleterious effects, or C allele-linked protection. Confirmatory studies are warranted, as this cohort was not randomly selected, and a type 1 error cannot be ruled out.

Aged↗

Prospective screening for biopsy proven coeliac disease, autoimmunity and malabsorption markers in Belgian subjects with Type 1 diabetes.

AIMS: To determine prospectively the prevalence of biopsy proven coeliac disease (CD) in an adult Type 1 diabetic population from Belgium with regards to associated auto-immunity and malabsorption. METHODS AND RESULTS: Determination in 400 Type 1 diabetic patients of serum anti-endomysial and/or anti-transglutaminase auto-antibodies. All subjects with abnormal serology underwent an intestinal biopsy. Ten patients (2.5%) had positive antibodies. Diagnosis of CD was confirmed by an intestinal biopsy. Eight patients were symptom-free, although laboratory findings suggesting malabsorption were prominent in the presence of CD [microcytic anaemia, iron and folate deficiencies, low levels of 25(OH)vitamin D3, calcium and cholesterol]. Other auto-immune conditions, especially vitiligo, were found in patients with CD. CONCLUSIONS: Asymptomatic coeliac disease occurs frequently in adult Type 1 diabetic patients, and is often associated with subclinical malabsorption. Screening should be part of routine evaluation, to implement life-long dietary gluten avoidance.

Adolescent↗

C677T methylene-tetrahydrofolate reductase mutation in type 2 diabetic patients with and without hyperhomocysteinaemia.

OBJECTIVE: The aim of the study was to determine the prevalence of the C677T mutation in a cohort of type 2 diabetic patients with and without elevated total plasma homocysteine (tHcy). METHODS: 80 type 2 diabetic patients with hyperhomocysteinaemia (group 1, tHcy: 21.3 +/- 6.7 micromol/L) and 50 subjects with normal levels (group 2, tHcy 11.2 +/- 2.3 micromol/L) were studied. C677T mutation was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Homozygosity was present in 23% of patients in group 1 and 8% in group 2 (P<0.02). No significant difference in heterozygosity frequency was observed between patients with and without hyperhomocysteinaemia. T allele frequency was 0.43 in group 1 and 0.35 in group 2. CONCLUSION: C677T mutation is frequent in diabetic patients with hyperhomocysteinaemia and could contribute, besides non genetic factors, to increased levels of tHcy.

Aged↗

Prevalence of thyroid cancer in Graves' disease: a retrospective study of a cohort of 103 patients treated surgically.

BACKGROUND: Thyroid nodules in patients with Graves' disease (GD) are common, and the incidence of coexisting thyroid carcinoma is a much debated subject, which is addressed in this study. METHODS: In order to determine the incidence rate of coexisting malignancy, a retrospective study was conducted on 103 patients who underwent surgery for GD between 1990 and 2000 at the Cliniques Universitaires Saint-Luc in Brussels, Belgium. The patients were classified into groups. Those in group I had a solitary palpable nodule (4.9%), those in group II multiple palpable nodules (12.6%), group IIIa had nodule(s) revealed by imaging techniques (incidentalomas: 17.5%), and group IIIb had diffuse non-nodular goiter (65%). RESULTS: Patients with nodules (groups I, II, and IIIa) were found to have significantly more thyroid carcinomas than those with diffuse non-nodular goiters (P=0.02), and the rate of malignancy was significantly increased when the nodules were palpable (groups I and II; P=0.03). Eight patients (7.8%) were diagnosed as having coexisting carcinomas, all but one being microcarcinomas. CONCLUSIONS: Well-differentiated papillary carcinomas are found to coexist with GD surgically treated (7.8%) and occur most frequently in GD with palpable nodular lesions (35%). Even though the majority (88%) of coexisting carcinomas are microcarcinomas, the presence of palpable nodules justifies further evaluation and follow-up.

Journal Article↗

Comparative performance of serum cystatin-c versus serum creatinine in diabetic subjects.

OBJECTIVE: Serum cystatin-C, a protein with constant production rate, undergoes glomerular filtration. Cystatin-C is a candidate surrogate marker, allegedly superior to serum creatinine, for estimating glomerular filtration rate, due to its high correlation with absolute measurement of the latter. The aim of this study was to assess from intra- and inter-subject variability the performance of cystatin-C in a cohort of diabetic patients spanning a wide range of kidney function and to compare it to that of serum creatinine. RESEARCH DESIGN AND METHODS: 98 consecutive diabetic in-patients (45 type 1 and 53 type 2) were included. Mean age was 53 +/- 15 years (1SD). Creatinine clearance was 98 ml/min (median; range: 16-244). We used the discriminant ratio (DR) methodology to compare the performance of serum cystatin-C vs. that of creatinine to segregate subjects according to their glomerular filtration rate. RESULTS: Serum creatinine values on day 1 and 2 were 1.10 +/- 0.76 and 1.07 +/- 0.89 mg/dl and concentrations of cystatin-C were 1.10 +/- 0.60 and 1.06 +/- 0.63 mg/L. A close linear relationship was observed between means of duplicates for creatinine and cystatin-C (Pearson product-moment correlation 0.92). DR was obtained from the ratio of the underlying between-subject to the within-subject standard deviations. DR values were 5.23 for creatinine and 8.82 for cystatin-C (P<0.0001), implying superior discriminating ability for cystatin-C. Once adjusted for attenuation, measured Pearson product-moment correlation rose from 0.92 to 0.97. The DR methodology allowed for deriving an unbiased linear regression equation between methods, with slope and intercept at 0.79 and 0.23, respectively. CONCLUSIONS: Serum cystatin-C better discriminates among a population of type 1 and 2 diabetic patients with regard to their estimated glomerular filtration rate when compared with conventional serum creatinine measurement.

Blood Pressure↗

Clinical expression and insulin sensitivity in type 2 diabetic patients with heterozygous mutations for haemochromatosis.

BACKGROUND: Elevated iron metabolism indices as well as liver enzymes abnormalities have been reported in type 2 diabetic patients. The aim of this study was to determine the clinical and biological characteristics of overweight or obese type 2 diabetic subjects, with and without heterozygosity for HFE gene mutation (C282Y or H63D). We also assessed their insulin sensitivity and B cell function. METHODS: 90 patients (age and diabetes duration: 61 +/- 11 and 12 +/- 8 years [mean +/- 1 SD]) were included. BMI was 32 +/- 6 kg/m(2). HbA(1c) was 8.9 +/- 1.8%. HFE genotyping was performed by PCR and restriction enzyme cleavage. Insulin sensitivity and B cell function were measured by the Homeostasis Model Assessment (HOMA). RESULTS: Heterozygosity for C282Y (wt/C282Y) or H63D (wt/H63D) allele was found in 11 and 12 subjects respectively. There were no major differences in clinical status and iron parameters according to the single allelic presence of C282Y or H63D. However, systolic blood pressure [BP] was lower when such mutation was present. Insulin sensitivity and B cell function (HOMA) were comparable. When the cohort was divided according to gender, we found higher serum iron in females with than in those without HFE mutation (91 +/- 27 vs 73 +/- 25 microgram/dl;P=0.049), while a transferrin saturation index above 45% was observed in 36% of females with a mutation (vs 7% in wt/wt;P=0.06). When analysis was performed according to the presence of each particular mutation, we observed a transferrin saturation index higher than 45% in 60% of wt/C282Y patients vs 21% in the wt/wt group (P=0.008). A significantly lower BP was also identified in wt/C282Y patients. Cholesterol-HDL was 38 +/- 11 vs 46 +/- 12 mg/dl in wt/C282Y and wt/wt subjects, respectively (P=0.045). There were no differences in iron status, BP or lipids between wt/wt and wt/H63D subjects. CONCLUSION: Type 2 diabetic patients, in particular females, with mono-allelic C282Y mutation, had slightly increased iron parameters. Systolic BP and cholesterol-HDL were also lower in wt/C282Y subjects. No difference in insulin sensitivity or B cell function was observed in the presence of mono-allelic HFE mutations.

Adult↗

A type 2 diabetes screening program by general practioners in a Belgian at risk population.

OBJECTIVE: This study was designed to set up in Belgium a national screening program in order to evaluate the prevalence of undiagnosed impaired glucose tolerance and type 2 diabetes in a general population with at least one risk factor. MATERIAL AND METHODS: 10.201 individuals were screened by 1.466 general practioners between 1995 and 1998 (age: 57 +/- 16 years; BMI: 28 +/- 5 kg/m2; mean +/- 1SD). A three step diagnosis protocol was followed (blood glucose at random; fasting plasma glucose and, if needed, a 75 g oral glucose tolerance test). WHO criteria were used for diagnosis. RESULTS: Impaired glucose tolerance was found in 3% of individuals, while 11% had diabetes. Patients with abnormal glucose metabolism were older (P<0.001) and had an higher BMI (P<0.001) than non-diabetic subjects. The prevalence of undiagnosed diabetes was slightly higher (14 vs. 11%) when using a fasting plasma glucose threshold of 126 mg/dl (instead of 140 mg/dl) as recommended by the ADA experts. CONCLUSION: Undiagnosed abnormal glucose metabolism, in particular diabetes, is particularly frequent in a Belgian at risk population.

Adult↗

An unusual neuropathy in a diabetic patient: evidence for intravenous immunoglobin-induced effective therapy.

We report the case of a 68-year old type-2 diabetic male patient who was admitted to hospital for progressive weakness in the right lower limb. Although his metabolic control was good, he lost more than 20 kg of weight. Despite intensive physio- and vitaminotherapy, his neurological condition kept on degrading with a severe amyotrophy and pain of the right thigh. He was unable to walk and to stand alone. Besides a yet known sensitive polyneuropathy, the electrophysiological study revealed an obvious motor involvement with signs of demyelination and axonal degeneration. Combined with the albuminocytologic dissociation observed in the cerebrospinal fluid, these specific clinical and electrophysiological features led us to postulate a diagnosis of inflammatory neuropathy. The patient underwent a treatment by methylprednisolone and immunoglobins that rapidly induced a striking improvement of his neurological condition. This case report illustrates that rare forms of neuropathy such as inflammatory neuropathies close to chronic inflammatory demyelinating polyneuropathy (CIDP) can occur in diabetic patients and superimpose on the more commonly described forms of neuropathies. It recalls the importance of recognizing CIDP-like neuropathies because unlike other forms of neuropathy, inflammatory neuropathies are perfectly curable.

Aged↗

Erectile dysfunction and lower androgenicity in type 1 diabetic patients.

OBJECTIVE: To analyse the clinical characteristics and relevant hormonal profile in type 1 diabetic patients with and without ED. MATERIAL AND METHODS: Fifty one type 1 diabetic patients were studied. ED was assessed by direct interview. Chronic diabetic complications, smoking and alcohol status as well as current use of medications were recorded. Hormonal profile consisted of plasma LH, FSH, prolactin, androstenedione (Delta(4)), dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), free testosterone (FT), estradiol (E(2)), sex hormone binding globulin (SHBG), dihydrotestosterone (DHT), cortisol, TSH and free thyroxine (FT(4)). RESULTS: ED was present in 24 patients (47%) (group 1), who were older (P<0.001), had a longer diabetes duration (P<0.001) and a higher systolic blood pressure (P=0.017) when compared to the subjects who did not complain (group 2). ED was positively correlated to all diabetes-related complications (P<0.02). Antidepressive drug(s) were more frequent in group 1 (P=0.007), as well as prokinetics (P=0.043) and ACE-inhibitors (P=0.010). HbA(1)c was comparable. Patients with ED had lower levels of Delta(4) (P=0.003), DHEA (P<0.001), DHEA-S (P=0.002), FT (P=0.08) while SHBG (P=0.010) and LH (P=0.022) were higher compared to group 2. Multiple logistic regression analysis showed an independent association of ED with Delta(4) (P=0.016), DHEA-S (P=0.037), SHBG (P=0.001) and insulin dose (P=0.025). There was no significant difference for all other measured hormones. CONCLUSION: ED is impressively prevalent in type 1 diabetes and is associated with age, diabetes duration, chronic complications and decreased androgens.

Age Factors↗

Micro- and macrovascular complications and hyperhomocysteinaemia in type 1 diabetic patients.

OBJECTIVE: To determine the range of plasma homocysteine values in a cohort of type 1 diabetic subjects and to analyse the relationship between homocysteine levels and chronic degenerative complications. MATERIAL AND METHODS: 71 type 1 diabetic inpatients admitted for poor glycaemic control and/or treatment of complications, especially macroangiopathic, were included in this study. Chronic diabetic complications, smoking prevalence, as well as current use of drugs were recorded, alongside fasting plasma homocysteine. RESULTS: Age and diabetes duration were 51 (34-63) and 23 (13-32) years respectively (median [percentile 25-75]). HbA(1)c was 9.3% (8.2-10.5). Homocysteine was 9.2 (7.1-13.6) micromol/l, and 17% of patients had elevated homocysteinaemia on the basis of a laboratory cutoff value of 15 micromol/l. Folic acid and vitamin B(12) levels were within the normal range. Univariate statistical analysis showed a significant positive association between homocysteine and age (P<0.001), diabetes duration (P<0.001), systolic blood pressure (P<0.001), plasma creatinine (P<0.001), cholesterol/HDL-C (P=0.021) as well as with retinopathy (P=0.016) and all complications (P<0.001), and a negative correlation with folic acid (P=0.004) and creatinine clearance (P<0.001). Using a multiple regression analysis taking into account major variables, we confirmed an independent association of homocysteine with age (P=0.003), creatinine (P<0.001) and folic acid (P=0.014), but not with vascular complications. CONCLUSIONS: Increased homocysteine is present in 17% of a limited group of poorly controlled type 1 diabetic patients, and is associated with age, creatinine and folic acid levels. In this type 1 population, there was no independent correlation of homocysteine with vascular complications, in particular macroangiopathy.

Adult↗

Acute interstitial nephritis and fatal Stevens-Johnson syndrome after propylthiouracil therapy.

We report a case of acute interstitial nephritis and fatal Stevens-Johnson syndrome in a 90-year-old woman with amiodarone-induced hyperthyroidism, who had been treated for 5 weeks with propylthiouracil (PTU). On admission, the patient exhibited acute renal failure and generalized macular purpuric eruption. Acute interstitial nephritis and Stevens-Johnson syndrome were diagnosed and PTU withdrawn. Although renal function recovered after PTU withdrawal and corticosteroid therapy, the patient's condition worsened, and she died after developing multiple organ failure. Acute interstitial nephritis seems to be rarely associated with PTU therapy. Moreover, a literature review suggested that this could represent the first published report of a Stevens-Johnson syndrome developing during PTU therapy.

Acute Disease↗