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Biomedical subjects

M Hill

Publications and source records attributed to M Hill.

At least 37 records · Page 2Linked to original sources

Significant reduction of endemic MRSA acquisition and infection in cardiothoracic patients by means of an enhanced targeted infection control programme.

Due to increasing methicillin-resistant Staphylococcus aureus (MRSA) infection in cardiothoracic patients at St Thomas' Hospital, an enhanced infection control programme was introduced in September 2000. It was based on UK national guidelines on the control of MRSA and targeted additional identified risk factors for surgical site infection (SSI). It included recognition of the problem by senior staff and their taking responsibility for it; intensive support, education and advice from the infection control team; improved ward and theatre hygiene; pre-admission, admission and weekly MRSA screening; isolation and clearance treatment; nursing care pathways for MRSA colonized patients; and teicoplanin plus gentamicin surgical prophylaxis. The effectiveness of the programme was assessed by retrospective analysis of computerized patient data for the 16 months before and after the introduction of the programme. There was no significant change in the number of operations or the proportion of patients admitted with MRSA, although nine patients were cleared of carriage before admission. However, there were significant falls in the proportion of patients acquiring MRSA on the ward [38/1036 to 14/921, P=0.003, RR 2.4 (95%CI 1.32-4.42)] and in the rate of bloodstream MRSA infections [12/1075 to 2/956, P=0.014, RR 5.34 (95%CI 1.20-23.78)]. Sternal and leg wound infections both halved (from 28/1075 to 13/956 and 16/1075 to 7/956, respectively) but this did not reach statistical significance. These results demonstrate that an enhanced, targeted infection control programme based on the UK national guidelines, SSI prevention guidelines and local risk assessment can reduce the incidence of nosocomial MRSA acquisition and invasive infection in cardiothoracic patients in the face of continuing endemic risk.

Antibiotic Prophylaxis↗

Psychobehavioral and nutritional predictors of weight loss in obese women treated with sibutramine.

OBJECTIVE: To reveal whether baseline body mass index (BMI), and psychobehavioral and nutritional markers were significant predictors of the change in BMI observed after 4 and 12 months in obese women enrolled in a weight reduction program, including low-energy diet, increased physical activity, cognitive behavior therapy and sibutramine. The impact of changes in psychobehavioral and nutritional markers observed after 4 and 12 months of treatment on BMI changes was also investigated. DESIGN: During a double-blind placebo-controlled 4-month period, subjects received either sibutramine (10 mg/day) or placebo. Then, an open phase with sibutramine administered to all patients continued until month 12. SUBJECTS: In total, 80 obese women (age: 43.9+/-10.6 y, BMI: 36.7+/-4.8 kg/m(2)). MEASUREMENTS: The dependent variable was change in BMI while baseline BMI, mode of treatment, the Beck depression score, the three items (dietary restraint, disinhibition and perceived hunger) of the Eating Inventory (EI), energy and macronutrient intakes were independent variables. At 1-week dietary records were analyzed using a computer software for assessing energy and macronutrient intake. RESULTS: Multiple regression analysis revealed that the BMI loss at month 4 was significantly influenced by mode of treatment and initial BMI, whereas a borderline negative relationship was observed with the baseline restraint score. Baseline BMI, depression score, restraint score and total energy intake predicted weight loss at month 12. These predictive variables accounted for 43.8% of the variance in BMI loss at 12 months. When relationships between the BMI loss and changes in all included psychobehavioral and nutritional parameters were considered after 12 months of treatment, a drop in the disinhibition score of the EI appeared the only significant factor affecting the BMI decrease. CONCLUSIONS: Our results suggest that psychobehavioral and nutritional characteristics can be used as predictors of weight loss in response to a comprehensive weight management program including pharmacological treatment with sibutramine.

Adolescent↗

Mutation analysis in 51 patients with haemophilia A: report of 10 novel mutations and correlations between genotype and clinical phenotype.

We report the results of genetic analysis on a series of 51 patients attending this Haemophilia Comprehensive Care Centre. The most common cause of severe haemophilia A--the factor VIII intron 22 inversion was detected in eight families and the factor VIII intron 1 inversion in three families. Mutation analysis was carried out on the remaining patients by nucleotide sequencing of genomic DNA after screening with conformation-sensitive gel electrophoresis (CSGE) or denaturing high-performance liquid chromatography (dHPLC). A total of 27 different FVIII non-inversion mutations were detected. Severe haemophilia was associated with 12 null mutations (six nonsense, six frameshift) and four missense mutations. A further 11 different missense mutations were associated with moderate or mild disease. To our knowledge, six null mutations [1950del 4(tttg), 3270-75insA, 4416del 10, 6735-38delA, W1029X, Y1792X] and four missense mutations (E1682K, M1947V, P2048L, P2143L) have not been previously published. Each novel missense mutation occurred at a highly conserved residue, no other candidate mutation was detected on screening the entire coding region of the FVIII gene and they were not detected in a screen of individuals without haemophilia A. The genotype-phenotype correlations of the FVIII mutations detected will be discussed.

Base Sequence↗

Decrease in serum dehydroepiandrosterone level after fenofibrate treatment in males with hyperlipidemia.

The influence of steroid hormones on plasma lipids and lipoproteins was confirmed by many studies. On the other hand, the effect of plasma lipids on metabolism of steroid hormones has so far not been examined. The objective of this research project was to determine (1) the levels of cortisol, testosterone, estradiol, dehydroepiandrosterone (DHEA), its sulfate (DHEAS), 7-hydroxylated DHEA, and SHBG in men suffering from mixed hyperlipidemia (HPL) (n=23, age 46.1+/-7.9 years) in comparison with healthy male volunteers (n=17, age 45.1+/-15.6 years); (2) whether therapy with fenofibrate influences the levels of the above mentioned steroids and SHBG; (3) what are the correlations between lipids and steroids in healthy males and HPL patients before and after therapy. Compared to controls, untreated patients had significantly higher estradiol and free testosterone index (IFT) levels (p<0.0003 and p<0.02, respectively) and significantly lower SHBG (p<0.02). Due to fenofibrate therapy, a significant decrease of TC, TG, and DHEA levels occurred (mean decrease: 14 %, 52 % and 21 %, respectively). Triglycerides correlated negatively with testosterone and SHBG in healthy subjects. HDL-C correlated positively and consequently, atherogenic index correlated negatively with 7-hydroxylated epimers of DHEA in treated patients. This is the first study dealing with the influence of fenofibrate administration on the steroid levels. Taking together, the most important is the finding of decrease DHEA levels after fenofibrate therapy. It could be explained, at least in part, by the effect of the fenofibrateon on the biosynthesis of DHEA and its regulation.

Adult↗

Premature androgenic alopecia and insulin resistance. Male equivalent of polycystic ovary syndrome?

BACKGROUND: Polycystic ovary syndrome (PCOS), the most frequent endocrinopathy in women with estimated prevalence of 5-10 %, is characterised by a hormonal and metabolic imbalance of polygene autosomal trait. The complexity of symptoms and genetic base started up the hypothesis on the existence of male equivalent of PCOS. Precocious loss of hair before 30 years of age was suggested as one of the male symptoms of this syndrome. OBJECTIVES: The aim was to confirm the association of lower levels of follicle stimulating hormone (FSH) and sexual hormone binding globulin (SHBG) or higher free androgen index (FAI) in premature balding men with a reduced insulin sensitivity. PATIENTS/METHODS: The study included 30 men with premature hair loss (defined as grade 3 vertex or more on the alopecia classification scale by Hamilton with Norwood modification) starting before 30 years of age. The hormonal values of the investigated group were compared with those regarded as normal reference values obtained in a group of 256 males in the age of 20-40 years during the Czech population study of iodine deficiency. In all men with premature baldness besides hormonal level determinations insulin tolerance test was carried out. RESULTS: The observed group was divided into two subgroups. The first one showed similar hormonal changes as women with PCOS, namely subnormal SHBG, FSH or increased FAI. The other had either no anomalies in steroid spectrum or only lower SHBG. The groups did not differ either in BMI or in age. The group with hormonal profile resembling that of women with PCOS, showed significantly higher insulin resistance than the group without these changes. CONCLUSIONS: The findings are consistent with the hypothesis that at least a part of the men with premature androgenic alopecia could be considered as a male equivalent of the polycystic ovary syndrome of the women. These premature balding men represent a risk group for the development of impaired glucose tolerance or diabetes mellitus type 2.

Adult↗

The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients.

BACKGROUND: Neither oral contraceptives (COC) nor metformin are an optimal modality for the long-term treatment of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate whether a combination of both is beneficial over COC monotherapy. METHODS: Altogether, 30 women were included in the study and 28 finished the protocol. The patients were randomly assigned to two groups treated with either COC (COC group) or COC and metformin (1500 mg/day) (METOC group) for 6 months. Anthropometric parameters, androgens, lipids, fasting insulin, glucose and sex hormone binding globulin (SHBG) concentrations were measured before and at the end of the sixth cycle of treatment. The insulin sensitivity index was evaluated using the euglycaemic clamp. RESULTS: There were no significant changes in anthropometric parameters, fasting glucose or insulin sensitivity in either group. Total testosterone, free androgen index, androstenedione and dehydroepiandrosterone decreased and SHBG increased significantly in both groups. When comparing the effect of both treatments, only a more pronounced decrease in free androgen index was found in the METOC group. CONCLUSIONS: Adding metformin slightly modified the treatment effect of COC, causing a more significant decrease in the free androgen index but having no additional positive impact on lipids, insulin sensitivity, SHBG or testosterone. The available data do not offer enough evidence to advocate the standard use of combined treatment in PCOS. Whether the combination might be beneficial for specific subgroups of patients is of further interest.

Adult↗

Elderly patients with fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer derive similar benefit without excessive toxicity when treated with irinotecan monotherapy.

Elderly patients are recommended to have a reduced starting dose (300 mg m(-2) once every 3 weeks) of irinotecan monotherapy. The aims of this analysis are to compare toxicity and survival according to age, performance status (PS), gender and prior radical pelvic radiotherapy (RT). The primary end points were overall survival and an irinotecan-specific toxicity composite end point (TCE) defined as the occurrence of grade 3 or 4 diarrhoea, neutropenia, febrile neutropenia, fever, infection or nausea and vomiting. Between 1997 and 2003, 339 eligible patients with advanced colorectal cancer (CRC) progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered in a multicentre randomised trial. All patients commenced irinotecan at 350 mg m(-2) once every 3 weeks. There were no differences in proportions of patients developing TCE by age (<70 vs > or =70 : 37.8 vs 45.8%; P=0.218), PS (0-1 vs 2 : 39.3 vs 41.5%; P=0.793) or prior RT (RT vs no RT : 45.1 vs 38.5%; P=0.377). Males experienced more toxicity than females (44.3 vs 32.6%; P=0.031), but this was not significant after controlling for other co-variates (P=0.06). Patients aged > or =70 had similar objective responses (11.1 vs 9%; P=0.585) and survival (median 9.4 vs 9 months; log rank P=0.74) compared to younger patients. Elderly patients derive the same benefit without experiencing more toxicity with second-line irinotecan treatment for advanced CRC. Our data do not support the recommendation to reduce the starting dose for the elderly patients.

Adult↗

Flutamide suppresses adrenal steroidogenesis but has no effect on insulin resistance and secretion and lipid levels in overweight women with polycystic ovary syndrome.

The authors evaluate the effects of 2 months of treatment with 250 mg flutamide daily on adrenal steroidogenesis (ACTH test) and metabolic parameters (lipids, insulin resistance) in 12 PCOS women aged 33.8 +/- 7.5 years and with a BMI of 33.6 +/- 4.2 kg/m2. Significant decreases in basal DHEA-S (p < 0.0001), DHEA (p < 0.01) and androstenedione (p < 0.05), in the ACTH-stimulated levels of DHEA-S (p < 0.0001), testosterone (p < 0.05) and in ACTH-stimulated 17beta-hydroxysteroid dehydrogenase activity (p < 0.01) were observed. No significant change in basal blood glucose, insulin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or in insulin resistance, as estimated by the insulin tolerance test, was found. Flutamide is effective in reducing adrenal androgen production in overweight women, but has no effect on lipid spectrum or on insulin resistance.

17-Hydroxysteroid Dehydrogenases↗

Treatment for swallowing difficulties (dysphagia) in chronic muscle disease.

BACKGROUND: The management of dysphagia (difficulty in swallowing), a common complication of long-term progressive muscle disease in children and adults, is currently unclear. OBJECTIVES: Our objective was to determine the most appropriate intervention for dysphagia in people with chronic, untreatable, non-inflammatory muscle disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register, Cochrane Central Register of Controlled Trials (Cochrane Library Issue 2, 2003), MEDLINE (from January 1966 to Week 2 June 2003), EMBASE (from January 1980 to Week 2 June 2003), AMED (from January 1985 to Week 2 June 2003), LILACS (from January 1982 to June 21 2003) and CINAHL (from January 1982 to Week 2 June 2003) and contacted authors of published studies and other experts. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials of adults and children with chronic untreatable non-inflammatory muscle disease. The interventions under review included dietary modification, swallowing manoeuvres, a range of surgical interventions and enteral feeding. Our primary outcome was stabilisation of previously documented progressive weight loss not attributable to any other cause or weight gain of at least 5 kg in adults or increase in weight to at least the 10th centile in children, maintained for at least six months following the intervention. Secondary outcomes were: reduction in laryngeal penetration of bolus and/or aspiration observed on videofluoroscopy (modified barium swallow), reduction in chest infections attributable to aspiration over a six-month period, improvement in quality of life using a validated rating scale, the proportion of subjects who refused the intervention, the proportion of carers who refused the intervention, and serious adverse events related to the intervention within the first twelve months after intervention. DATA COLLECTION AND ANALYSIS: We identified no randomised controlled trials. We identified seven case series reporting the results of surgical intervention for moderate to severe dysphagia, and one reporting on the outcome of feeding advice and enteral feeding in children with a congenital myopathy. MAIN RESULTS: No studies were found that fulfilled the inclusion criteria. Therefore it was not possible to determine the benefit or otherwise of surgical intervention (cricopharyngeal myotomy or upper oesophageal dilatation) for oculopharyngeal muscular dystrophy or other chronic progressive muscle diseases, and dietary advice or enteral feeding for children with congenital myopathy, compared with no intervention or an alternative intervention. REVIEWERS' CONCLUSIONS: There are no trials that have adequately evaluated treatments in the management of dysphagia for chronic muscle disease. It is therefore not possible to decide on the most appropriate treatment for a given individual based on current evidence.

Adult↗

Postmenopausal serum androstenedione levels are associated with the calcitonin receptor gene polymorphism T1377c. A pilot study.

We tested the hypothesis that homeostasis of sex-steroids is related to the calcitonin receptor (CALCR) genotype. To determine the CALCR genotype PCR amplification followed by digestion with Alul restriction enzyme were carried out according to Nakamura et al. Indeed, a single nucleotide difference at position 1377 of cDNA generates two alleles (CC genotype or TT genotype). Serum estradiol, testosterone and their precursors androstendione (AD) and DHEA levels were estimated in a cohort of 113 postmenopausal women. While serum DHEA levels did not differ between the individual allele combinations, AD levels as well as AD/DHEA ratio were higher in carriers of TC and CC genotypes than those with TT genotype (p<0.05 and p<0.02, respectively, ANCOVA). We postulate that the 3beta-hydroxysteroid dehydrogenase activity is associated with C allele at least in C19 steroids. The data correspond with the functionality of CALCR.

Alleles↗

An ultrasonic transducer array for velocity measurement in underwater vehicles.

A correlation velocity log (CVL) is an ultrasonic navigation aid for marine applications, in which velocity is estimated using an acoustic transmitter and a receiver array. CVLs offer advantages over Doppler velocity logs (DVLs) in many autonomous underwater vehicle (AUV) applications, since they can achieve high accuracy at low velocities even during hover manoeuvres. DVLs require narrow beam widths, whilst ideal CVL transmitters have wide beam widths. This gives CVLs the potential to use lower frequencies thus permitting operation in deeper water, reducing power requirements for the same depth, or allowing the use of smaller transducers. Moving patterns in the wavefronts across a 2D receiver array are detected by calculating correlation coefficients between bottom reflections from consecutive transmitted pulses, across all combinations of receiver pairings. The position of the peak correlation value, on a surface representing receiver-pairing separations, is proportional to the vessel's displacement between pulses. A CVL aimed primarily for AUVs has been developed. Its acoustical and signal processing design has been optimised through sea trials and computer modelling of the sound field. This computer model is also used to predict how the distribution of the correlation coefficients varies with distance from the peak position. Current work seeks to increase the resolution of the peak estimate using surface fitting methods. Numerical simulations suggest that peak estimation methods significantly improve system precision when compared with simply identifying the position of the maximum correlation coefficient in the dataset. The peak position may be estimated by fitting a quadratic model to the measured data using least squares or maximum likelihood estimation. Alternatively, radial basis functions and Gaussian processes successfully predict the peak position despite variation between individual correlation datasets. This paper summarises the CVL's main acoustical features and signal processing techniques and includes results of sea trials using the device.

Journal Article↗

Modelling of particle paths passing through an ultrasonic standing wave.

Within an ultrasonic standing wave particles experience acoustic radiation forces causing agglomeration at the nodal planes of the wave. The technique can be used to agglomerate, suspend, or manipulate particles within a flow. To control agglomeration rate it is important to balance forces on the particles and, in the case where a fluid/particle mix flows across the applied acoustic field, it is also necessary to optimise fluid flow rate. To investigate the acoustic and fluid forces in such a system a particle model has been developed, extending an earlier model used to characterise the 1-dimensional field in a layered resonator. In order to simulate fluid drag forces, CFD software has been used to determine the velocity profile of the fluid/particle mix passing through the acoustic device. The profile is then incorporated into a MATLAB model. Based on particle force components, a numerical approach has been used to determine particle paths. Using particle coordinates, both particle concentration across the fluid channel and concentration through multiple outlets are calculated. Such an approach has been used to analyse the operation of a microfluidic flow-through separator, which uses a half wavelength standing wave across the main channel of the device. This causes particles to converge near the axial plane of the channel, delivering high and low particle concentrated flow through two outlets, respectively. By extending the model to analyse particle separation over a frequency range, it is possible to identify the resonant frequencies of the device and associated separation performance. This approach will also be used to improve the geometric design of the microengineered fluid channels, where the particle model can determine the limiting fluid flow rate for separation to occur, the value of which is then applied to a CFD model of the device geometry.

Journal Article↗

A dual frequency, ultrasonic, microengineered particle manipulator.

Ultrasonic standing waves can be used to generate forces on particles within a fluid. Recent work has concentrated on developing devices that manipulate the particles so that they are concentrated near the centre of the cavity. It is also possible to design a device that concentrates the particles at the wall of a cavity. This paper describes a device that has the capability of operating in several modes to allow concentration of particles at either the cavity wall or the centre of the cavity, depending on the driving frequency.

Journal Article↗

Hormonal profile of men with premature balding.

OBJECTIVE: Premature androgenic alopecia has been suggested as a feature of the male equivalent of the syndrome of polycystic ovary. However, the hormonal pattern of men with premature balding has been investigated in only a few studies with inconsistent results. MATERIAL AND METHODS: We examined 37 men with premature balding (defined as frontoparietal and vertex hair loss before the age of 30 years with alopecia defined as grade 3 vertex or more on the alopecia classification scale of Hamilton with Norwood modification). The plasma concentrations of total testosterone, dihydrotestosterone, epitestosterone, androstenedione, cortisol, 17-OH-progesterone (17OHP), estradiol, LH, FSH, prolactin, SHBG and TSH and free thyroxine were measured. RESULTS: The frequency of subnormal values in SHBG, FSH, testosterone and epitestosterone (but not in free androgen index) was significant in the balding men. A borderline significant trend was recorded with respect to increased levels in 17OH-P and prolactin. CONCLUSIONS: The hormonal pattern of a substantial number of men with premature balding resembles in some respects the hormonal pattern of women with polycystic ovary syndrome.

Adult↗

Female preclinical presenilin-1 mutation carriers unaware of their genetic status have higher levels of depression than their non-mutation carrying kin.

OBJECTIVES: To study depressive symptoms in preclinical presenilin-1 (PS1) related Alzheimer's disease. METHODS: Participants were 33 Mexican women at risk for inheriting PS1 mutations who were not demented. They were interviewed, underwent cognitive testing, and completed the Beck depression inventory (BDI). PS1 mutation status was determined. Mean BDI scores were compared between PS1 mutation carriers and non-carriers. The percentage of subjects who reported seeing a psychiatric professional, and the percentage complaining of memory loss were compared between groups. Regression analysis was used to determine whether mutation status predicted BDI scores after adjusting for age, education, mini-mental state examination, and subjective memory function. RESULTS: PS1 mutation carriers (n = 17) scored significantly higher than non-carriers (n = 16) on the BDI (mean score, 14.4 v 6.5, p = 0.017); 24% of mutation carriers and 12.5% of non-carriers admitted having sought help from a psychiatric professional (NS). Mutation status remained a significant predictor of BDI scores after adjusting for potential covariates. Though not demented, mutation carriers tended to score lower than non-carriers on several neuropsychological tests. CONCLUSIONS: Depressive symptoms can occur early in the course of PS1 related Alzheimer's disease, at least in women. This supports the hypothesis that depression may occur as a direct result of the neuropathology underlying Alzheimer's disease.

Adult↗

Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome.

OBJECTIVE: To compare the influence of transdermal and peroral oestrogen treatments in conjunction with cyproterone acetate (CPA) on metabolic and hormonal parameters in women with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: Twenty-four women with PCOS, aged 25.4+/-4.3 (mean+/-s.d.) years, body mass index 24.5+/-3.9 kg/m2 were randomly assigned to receive either transdermal oestradiol plus CPA (n=12) or a peroral oestradiol-CPA combination (n=12). Before and after 3 months of treatment, basal blood samples, euglycaemic hyperinsulinaemic clamp combined with indirect calorimetry and arginine tests were performed. ANOVA and Student's t-test or Wilcoxon's test were used for statistical analyses. RESULTS: After peroral oestradiol-CPA, insulin sensitivity (P<0.004) and the disposition index as the function of insulin sensitivity and secretion (P<0.0001) decreased significantly. Fasting insulin (P<0.05), cholesterol (P<0.05), high-density lipoprotein cholesterol (P<0.05) and sex-hormone binding globulin (P<0.0001) increased significantly. Dehydroepiandrosterone (P<0.05) and 17-OH progesterone (P<0.01) decreased significantly. After transdermal oestradiol+CPA, no significant changes were observed in sex-hormone binding globulin and androgen concentrations, insulin sensitivity or disposition index. CONCLUSIONS: In women with PCOS, peroral oestrogens (at doses common in combined oral contraceptives) led to a significant impairment in insulin secretion and action. In contrast, the transdermal application of oestrogens did not significantly influence insulin sensitivity.

Administration, Cutaneous↗

Polymorphism of INS VNTR is associated with glutamic acid decarboxylase antibodies and postprandial C-peptide in patients with onset of diabetes after 35 years of age.

Variability in the number of tandem repeats of the insulin gene (INS VNTR) is probably involved in the genetic regulation of insulin secretion. The aim of this study was to investigate the association of INS VNTR polymorphism with the presence of glutamic acid decarboxylase antibodies (GADA) and C-peptide levels in patients with the onset of diabetes after 35 years of age. We investigated 117 patients, median of age 63 (range 40-83) years, median of diabetes duration 8 (range 1-30) years; 31 GADA-positive and 86 GADA-negative subjects. INS VNTR polymorphism was typed indirectly using - 23HphI (T/A) polymorphism, which is in complete linkage disequilibrium with INS VNTR. The I/I, I/III and III/III genotypes were found in 22 (71 %), 8 (26 %), 1 (3 %) GADA-positive individuals and in 39 (45 %), 35 (41 %), 12 (14 %) GADA-negative individuals, respectively. The Class I allele and the genotype I/I were significantly associated with the presence of GADA (OR=2.72, CI 95 %=1.29-5.73 and OR=2.95, CI 95 %=1.22-7.13). The presence of Class III allele was significantly associated with a higher level of postprandial C-peptide in GADA-positive subjects, even when regarding the duration of diabetes. Our results of INS VNTR polymorphism in patients with the onset of diabetes after 35 years of age confirm the association of Class I INS VNTR with autoimmune diabetes and the protective effect of Class III INS VNTR on the insulin secretion in GADA-positive subjects.

Adult↗