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Biomedical subjects

T A Chowdhury

Publications and source records attributed to T A Chowdhury.

At least 19 recordsLinked to original sources
PubMed1999

Human leucocyte antigen and insulin gene regions and nephropathy in type I diabetes.

AIMS/HYPOTHESIS: Diabetic nephropathy seems to have a strong genetic component. Genes involved in the genetic susceptibility to Type I (insulin-dependent) diabetes have been suggested to have a role in the development of diabetic nephropathy. This study aimed to examine the role of human leucocyte antigen and insulin genes in susceptibility to nephropathy in patients with Type I diabetes. METHODS: We carried out a genetic association study examining insulin gene polymorphisms using three large cohorts of patients with Type I diabetes: nephropathy (n = 258), long duration non-nephropathy (n = 153) and a recently diagnosed (sporadic) diabetic cohort (n = 264). Human leucocyte antigen typing results were obtained in a smaller number due to assay failures (n = 182, 126 and 200 respectively). RESULTS: No significant difference was seen in the distribution of human leucocyte antigen A, B, C, DR, DQA1 and DQB1 haplotypes and alleles between the three diabetic cohorts. No significant difference was seen in insulin '+' and '-' genotypes and alleles between the three diabetic cohorts. CONCLUSIONS/INTERPRETATION: Human leucocyte antigen and insulin gene loci are unlikely to have a major role in the susceptibility to nephropathy in Caucasian patients with Type I diabetes in the United Kingdom.

Adult↗
PubMed1999

Comparison of secondary prevention measures after myocardial infarction in subjects with and without diabetes mellitus.

OBJECTIVES: To survey and compare secondary prevention measures in diabetic and non-diabetic patients following myocardial infarction (MI). DESIGN: Follow-up of a cohort of patients who suffered their first MI 1 year previously. SETTING: Three district general hospitals. MAIN OUTCOME MEASURES: Review 1 year post-MI for signs of left ventricular failure (LVF), serum cholesterol, smoking status, weight, blood pressure and glycaemic control. Assessment of appropriate treatment with aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering therapy before discharge and at least 1 year post-MI. RESULTS: A total of 189 non-diabetic and 86 diabetic patients were studied. Most patients received beta-blockers and aspirin appropriately, and most gave up smoking. In non-diabetic subjects, cholesterol fell significantly (P < 0.05), as did the proportion of patients with cholesterol > 5.5 mmol L(-1) (P < 0.05), whereas cholesterol did not fall significantly in diabetic subjects, due to a lower proportion of patients being on lipid-lowering therapy (27.5 vs. 37.9%). A higher proportion of non-diabetic patients with LVF were treated with ACE inhibitors compared with diabetic subjects (73.6 vs. 61.%). Glycaemic control did not improve in the diabetic subjects. CONCLUSIONS: Patients with diabetes do not receive optimal secondary prevention measures compared with their non-diabetic counterparts. This issue needs to be addressed by all units dealing with patients with diabetes in order to reduce the mortality and morbidity of MI in such patients.

Adrenergic beta-Antagonists↗
PubMed1999

The aetiology of Type I diabetes.

The aetiology of Type I diabetes involves both genetic and environmental factors. The genes implicated are 'susceptibility genes', which modify risk. Individual susceptibility genes may not be required and are not sufficient for disease development. The strongest genetic risk component is encoded within the major histocompatibility complex (MHC) and is designated IDDM I. The HLA-DQ genes contribute to the risk, but so may other MHC-encoded genes. The susceptibility encoded by IDDM2 refers to a variable number of tandem repeats in the insulin gene region. Many other genomic regions have been designated as susceptibility intervals potentially containing candidate genes. Environmental factors appear to be important in disease expression in either a causative or a protective role. Epidemiological data indicate that such factors operate from early in life. Viral infection(s) may have a disease-initiating and/ or accelerating effect. A potential diabetogenic role for cows' milk protein remains unconfirmed. Further research is necessary to elucidate fully the aetiological factors involved and how they interact.

Animals↗
PubMed1999

Pregnancy outcome in women with insulin-dependent diabetes mellitus complicated by nephropathy.

We retrospectively analysed pregnancy complicated by diabetic nephropathy in patients attending a University teaching hospital (1990-97), to examine fetal/maternal outcomes. Fetal outcomes included early intrauterine deaths, stillbirths, neonatal/perinatal mortality, size for gestational age, malformations, and need for neonatal unit care. Maternal outcomes included change in frequency of hypertension or severe proteinuria, serum creatinine data, and caesarean section rate. There were 21 pregnancies in 18 women, resulting in 21 live infants. Neonatal mortality (RR 10, 95% CI 0-3.9), perinatal mortality (RR 5, 95% CI 0-3.3) and congenital malformations (RR 5.0, 95% CI 0.3-26.3) were greater than in the background population. At delivery, 76% of babies were appropriate in size for gestational age; 57% were preterm, all of whom required neonatal unit care. The caesarean section rate was 90.5% vs. 20% in the background population (RR 4.5, 95% CI 3.4-5.0) (p < 0.05). Hypertension frequency (p < 0.001) and high-grade proteinuria (p < 0.05) increased from booking to delivery. Although the take-home baby rate was 90%, perinatal/neonatal mortality, congenital malformations and caesarean sections, in addition to maternal morbidity, were significantly higher in women with diabetic nephropathy than in the background population.

Adult↗
PubMed1999

Genetic determinants of diabetic nephropathy.

Diabetic nephropathy is the most serious complication of diabetes mellitus. Progression of the condition leads to end-stage renal failure, and other complications of diabetes are also common in this group of patients. The onset of overt albuminuria in a patient with diabetes heralds an increased risk of death, particularly from cardiovascular disease. There is considerable evidence to show that nephropathy is influenced by genetic factors. Epidemiological studies show that only a minority of patients with diabetes develop nephropathy irrespective of glycaemic control, suggesting that a subgroup of patients are at higher risk of nephropathy. Marked ethnic variation is observed, with nephropathy being more common in certain ethnic groups. Familial clustering of nephropathy is also observed. Parental history of hypertension, diabetes or cardiovascular disease appears to predispose to nephropathy in patients with diabetes. A number of methods are available to dissect polygenic disease: animal models, genetic association studies (case-control studies), affected sib-pair studies, discordant sib-pair studies and transmission distortion analysis. Most published work has been based on association studies. Association studies have shown conflicting results often due to small numbers of cases and controls, and poor phenotypic characterization. The angiotensin-converting enzyme gene insertion (I)/deletion (D) polymorphism has been studied in detail, but does not appear to be a strong risk marker for nephropathy. It does, however, appear to have a role in response to angiotensin-converting enzyme inhibition, with II homozygotes being the most responsive and DD homozygotes the least. A number of other genetic loci have also shown positive associations with nephropathy, including apolipoprotein E, heparan sulphate and aldose reductase. More recently, affected sib-pair analysis and discordant sib-pair analysis have suggested possible genetic loci on chromosomes 3, 7, 9, 12 and 20. These have yet to be reproduced in larger numbers of families, and the specific gene regions on these chromosomes remain elusive. The evidence presented in this review strongly supports the role of genetic factors in nephropathy. Detection of strong genetic risk markers for nephropathy will allow further insights into the pathogenesis of nephropathy, and possibly the development of novel therapeutic agents for its treatment. It will also allow preventive therapy to be directed at those patients with the greatest risk for development of diabetic nephropathy.

Animals↗
PubMed1998

Glomerular filtration rate determination in diabetic patients using iohexol clearance--comparison of single and multiple plasma sampling methods.

Use of iohexol clearance has been described as the gold standard for the measurement of glomerular filtration rate (GFR). It is suggested that multiple plasma sampling following iohexol injection is required to accurately determine GFR by area under plasma clearance curve. The aim of this study was to determine whether single plasma sampling 4 h after injection of iohexol could accurately determine GFR in diabetic patients with mild to moderate renal failure, compared to multiple plasma sampling. A total of 120 GFR determinations in 36 patients with non-insulin dependent diabetic renal disease were done over 1 year. No acute deterioration was seen in renal function following injection of contrast in any patient. Strong correlation in GFR measurement was observed between the multiple plasma sampling method and the single plasma sampling method (r2 = 0.975). Single plasma sampling 4 h after bolus injection of iohexol is a safe and accurate method of determining GFR and change in GFR in diabetic subjects with mild to moderate renal impairment.

Diabetes Mellitus, Type 2↗
PubMed1998

Clinical, biochemical and immunological characteristics of relapsers and non-relapsers of thyrotoxicosis treated with anti-thyroid drugs.

OBJECTIVES: This study aims to correlate clinical, biochemical and immunological factors seen at diagnosis of thyrotoxicosis with subsequent relapse within 5 years. DESIGN: Retrospective review of case notes, and biochemical assessment at least 5 years after cessation of treatment. SETTING: A large general hospital endocrine clinic. SUBJECTS: Patients presenting with a first episode of thyrotoxicosis between 1988 and 1991 who were treated with antithyroid drugs for at least 18 months. Main outcome measures. Relapse was determined by examination of hospital records, general practice records, patient questionnaire and thyroid function tests. RESULTS: A total of 216 subjects presented for the first time with thyrotoxicosis, of whom 89 (41.2%) suffered a relapse of the disease. On univariate analysis, clinical factors associated with increased relapse include younger age at diagnosis, goitre, marked tachycardia, requirement for higher maintenance dose of carbimazole, higher FT4 levels at diagnosis and smoking. Factors not predictive of relapse include presence of thyroid eye signs, positive family history, atrial fibrillation or congestive cardiac failure, acropachy or pretibial myxoedema, and presence or absence of thyroid autoantibodies. Logistic regression analysis showed relapse was predominantly determined by an FT4 > 56.2 nmol L ', pulse rate > 110, presence of goitre and a positive smoking history (R2 = 0.36, P < 0.001). Presence of these four factors predicted relapse in 76 (85.4%) of the 89 patients who relapsed. CONCLUSIONS: Increased 'toxicity' of thyrotoxicosis, goitre and smoking are associated with relapse of thyrotoxicosis, and this may be helpful in determining which patients may be better managed with early ablative therapy.

Adult↗
PubMed1998

Elevated glycated haemoglobin in non-diabetic patients is associated with an increased mortality in myocardial infarction.

Diabetes is associated with increased mortality following acute myocardial infarction compared to the general population. Elevated glycated haemoglobin (HbA1c) in diabetic patients is also associated with increased mortality following acute myocardial infarction, while mild elevation in HbA1c are associated with impaired glucose tolerance. The aim of this study was to determine the influence of HbA1c on outcome of acute myocardial infarction in 253 non-diabetic patients, 46 of whom died in one year. In univariate analysis, risk factors for death included smoking, glucose, cholesterol and HbA1c. In logistic regression analysis HbA1c was an independent risk factor for death. Over one-third of the fatality group had an HbA1c in the highest quartile, compared to one-fifth of the surviving group (p = 0.02). Elevated HbA1c is a risk marker for short-term mortality following acute myocardial infarction in non-diabetic subjects.

Aged↗