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Biomedical subjects

N J Wareham

Publications and source records attributed to N J Wareham.

107 records · Page 6Linked to original sources
PubMed1996

A confidential enquiry into deaths caused by asthma in an English health region: implications for general practice.

AIM: To determine the factors contributing to death from asthma in patients aged under 65 years in East Anglia in the early 1990s. METHOD: We have performed on ongoing confidential enquiry since January 1992. For the first time a general practitioner was included in the enquiry team. RESULTS: A review of the clinical and pathological data of the 50 patients reported in the first 3 years suggested that 36 of these deaths were attributable to asthma. Thirty-one patients died out of hospital (3 en route to the hospital), 2 in the Accident and Emergency department, and only 3 in hospital. Adverse social factors were found in 25 out of 34 patients, and adverse psychological characteristics in 23 of the 31 patients where these could be assessed. Only 7 appeared to have no adverse psychological or social factors. Routine medical care was considered appropriate in 20 patients, and inappropriate in 14. Twenty-four had received appropriate advice and education. Nine of the 21 patients, where this could be assessed, and half the relatives, failed to respond appropriately to worsening asthma symptoms during the fatal attack. No potentially preventable factors were identified in two women who died of end stage asthma. CONCLUSION: This enquiry has demonstrated that inadequacies in the medical care of asthma continue to occur, although less frequently than in previous asthma-death studies. In addition, 79% of the patients had experienced psychosocial factors which appeared important in contributing to their deaths. Recommendations for identifying and managing such "at risk' patients have been circulated to all general practitioners and chest physicians in the region.

Anti-Asthmatic Agents↗
PubMed1995

Decreased non-esterified fatty acid suppression and features of the insulin resistance syndrome occur in a sub-group of individuals with normal glucose tolerance.

To investigate causes of increased triglyceride concentrations in subjects with normal glucose tolerance (determined by oral glucose tolerance testing using World Health Organization criteria) 883 healthy subjects (389 men and 494 women) between 40 and 65 years of age were studied. Subjects were divided by gender into four groups according to 120-min glucose concentrations. Individuals in the highest quartile of glucose concentration had the highest mean triglyceride concentrations (p < 0.0001) and highest mean non-esterified fatty acid (NEFA) concentrations (p < 0.0001). There was also a clustering of cardiovacular risk factors normally associated with the insulin resistance syndrome in subjects in this group. Regression analysis showed that the most important determinants of triglyceride levels were smoking (men p = 0.001, women p = 0.005), waist:hip ratio (men p = 0.01, women p < 0.001) and NEFA suppression (men p = 0.02, women p = 0.005). NEFAs suppressed 16.7% in women compared to 2.4% in men during the first 30 min of the oral glucose tolerance test (p < 0.001). These results show that a clustering of cardiovascular risk factors associated with decreased NEFA suppression occurs in a sub-group of subjects with normal glucose tolerance and that the pattern of NEFA suppression differs between men and women.

Adult↗
PubMed1995

Role of insulin and proinsulin in diabetic vascular disease.

Associations between loss of glucose tolerance, insulin resistance, and ischemic heart disease (IHD) are of great current concern. Considerable controversy and uncertainty relates to the mechanism(s) that underlies these associations. Whilst there is some evidence in prospective studies of an association between hyperinsulinemia and future IHD, it is by no means strong or consistent between different studies. Hypertriglyceridemia is another possible factor involved in the linkage between glucose intolerance and IHD. There is good evidence for an affect of plasma nonesterified fatty acids (NEFA) to increase hepatic output of VLDL. Insulin, contrary to some suggestions, acts to lower plasma VLDL by actions directly on hepatic output and activation of adipose tissue lipoprotein lipase, and indirectly via the hormones affect of lowering plasma NEFA. Glycosylation and oxidation of lipoproteins may enhance their atherogenic potential. It is highly probable that procoagulant changes are also important processes predisposing to IHD. Associations between plasminogen activator inhibitor-1 and insulin, intact and 32,33 split proinsulin hypertriglyceridemia, and insulin resistance have been reported, but a unifying hypothesis explaining these links remains elusive. Epidemiological studies now repeated in a number of centers have shown links between infant mortality and birth weight and risk of IHD, and between birth weight and risk of impaired glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM). It has been proposed, therefore, that impairment of fetal and infant growth may underlie the associations between loss of glucose tolerance and risk of IHD. Animal models form the basis of much current research to test this concept.

Diabetic Angiopathies↗
PubMed1995

Undiagnosed glucose intolerance in the community: the Isle of Ely Diabetes Project.

The Isle of Ely Diabetes Project is a prospective population-based study of the aetiology and pathogenesis of Type 2 diabetes mellitus. Between 1990 and 1992, 1156 subjects aged between 40 and 65 years underwent a standard 75 g oral glucose tolerance test (OGTT). A total of 1122 individuals who were not known to have diabetes completed the test and were classified according to WHO criteria; 51 subjects (4.5%) had previously undiagnosed diabetes and 188 (16.7%) had impaired glucose tolerance. The subjects with newly diagnosed glucose intolerance were significantly older, more obese, and shorter than those with normal glucose tolerance. Blood pressure, cholesterol, triglyceride, and LDL-cholesterol concentrations were elevated and HDL-cholesterol levels were lower among those with abnormal rather than normal glucose tolerance. In multiple regression analyses stratified by gender and including age, body mass index, and the waist-hip ratio as covariates, there were significant differences between those with normal and abnormal glucose intolerance in blood pressure, triglyceride, and HDL-cholesterol, but not total or LDL-cholesterol. In both male and female subjects, height had a significant independent negative association with the plasma glucose at 120 min after administration of oral glucose (standardized beta coefficient = -0.12, p < 0.01).

Adult↗
PubMed1995

Excessive secretion of insulin precursors characterizes and predicts gestational diabetes.

Using assays that specifically measure insulin, intact proinsulin, and 32,33 split proinsulin, we examined the beta-cell secretory response to an oral glucose tolerance test (OGTT) in 64 women with gestational diabetes mellitus (GDM) and 154 pregnant normoglycemic control subjects of comparable age and body mass index. Women with GDM were characterized by a lower 30-min insulin increment (40.8 [34.9-47.6] vs. 58.6 [53.6-64] pmol insulin/mmol glucose, P < 0.001; geometric mean [95% confidence interval]) and a higher plasma insulin level at 120 min (702 [610-808] vs. 444 [400-492] pmol/l, P < 0.001). 32,33 split proinsulin levels were elevated in GDM patients in both fasting (9.1 [7.3-11.4] vs. 6.7 [6.0-7.5] pmol/l, P < 0.02) and 120-min (75.2 [62.9-90.0] vs. 52.2 [46.7-58.3] pmol/l, P < 0.001) samples, respectively. Intact proinsulin levels were significantly elevated at 120 min in the women with GDM (21.3 [18.1-25.1] vs. 14.8 [13.4-16.3] pmol/l, P < 0.001). Thus, the qualitative abnormalities of insulin secretion in GDM patients (low 30-min insulin increment, high 120-min plasma insulin, and elevated 32,33 split proinsulin) are similar to those seen in nonpregnant subjects with impaired glucose tolerance. To determine whether measures of proinsulin-like molecules (PLMs) might assist in the prediction of GDM, women who had a 1-h glucose level of > 7.7 mmol/l after a 50-g glucose challenge at 28-32 weeks' gestation had insulin and PLMs measured in the 1-h sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Hypertriglyceridaemia in subjects with normal and abnormal glucose tolerance: relative contributions of insulin secretion, insulin resistance and suppression of plasma non-esterified fatty acids.

Although plasma insulin and triglyceride concentrations are positively correlated in many studies, the relationships between insulin resistance, insulin secretion and hypertriglyceridaemia remain unclear. To study these associations, subjects between the ages of 40 and 64 were randomly selected from a general practice register and invited to attend for a standard oral glucose tolerance test for measurement of insulin, triglyceride and non-esterified fatty acid concentrations. The study comprised 1122 subjects who were not previously known to have diabetes and who completed the test. Using the World Health Organisation criteria, 51 subjects were classified to have non-insulin-dependent diabetes mellitus, 188 had impaired glucose tolerance and 883 subjects had normal glucose tolerance. Triglyceride concentrations in subjects with glucose intolerance were elevated compared to those in control subjects, even after adjustment for age, obesity and gender (p < 0.001 for subjects with diabetes and p < 0.01 for those with impaired glucose tolerance compared to normal subjects). In separate multiple regression analyses for males and females, the most important determinants of the plasma triglyceride concentration were the area under the non-esterified fatty acid suppression curve (p < 0.001 in both genders) and the waist-hip ratio (p < 0.001 for men and < 0.01 for women). The fasting insulin concentration was independently associated with triglyceride concentration in women only (p < 0.01). The most important determinant of the area under the non-esterified fatty acid suppression curve in men was the 30-min insulin increment, a measure of insulin secretion, (p < 0.001) whereas for women age (p < 0.001) and the body mass index (p < 0.01) were the most important.

Adult↗
PubMed1993

A district confidential enquiry into deaths due to asthma.

BACKGROUND: The aim was to establish a continuing district based confidential enquiry into deaths from asthma. METHODS: A confidential enquiry was conducted in an English health district. Subjects comprised 24 residents of the Norwich health district aged between 16 and 65 years who had died between 1988 and 1991 with asthma as the principal cause of death. RESULTS: Twenty one of the patients (88%) died away from hospital. Overall the routine asthma management was appropriate in all respects in only four patients. In five cases the drug treatment was considered inappropriate, in 10 cases (42%) there was no written evidence that the patient had received advice and education, and only six cases had a written management plan. In 17 patients (71%) the fatal attack of asthma developed rapidly (in under three hours). The medical care during the final attack was found to have been inappropriate in six cases. Seventeen cases (71%) had psychological or social factors that were considered to have been of potential importance. CONCLUSIONS: This study has shown the feasibility of organising a confidential enquiry into asthma deaths within a health district. The distinguishing features of such an enquiry are that it is continuing, that the quality of care given to those patients who died is compared against a recognised standard, and that there is a structured system for feeding back the conclusions of the enquiry to the local medical community.

Asthma↗
PubMed1984

Chemotherapy and autografting for chronic granulocytic leukaemia in transformation: probable prolongation of survival for some patients.

Between June 1977 and July 1983 51 patients with Ph1-positive chronic granulocytic leukaemia (CGL) in transformation were treated either by chemotherapy or by chemoradiotherapy followed by autografting with haemopoietic stem cells collected from their peripheral blood at the time of diagnosis. Forty-eight patients were restored to a second chronic phase. The median duration of survival after autografting was 26 weeks (range 2-152 weeks). Twenty-one patients with relatively long durations of second chronic phase were treated again by autografting as consolidation or when transformation recurred; this selected group of patients survived longer than the 30 patients treated by autografting only once (medians 52 v. 13 weeks respectively, P less than 0.01). There was no significant influence of the patients' age, splenectomy status, type of transformation, treatment pre-autograft or number of nucleated cells autografted on the duration of survival. Three patients treated in myeloid blastic transformation were restored to partially Ph1-negative haemopoiesis. We conclude that this approach to the management of CGL in transformation can offer benefit for a minority of patients and that further chemotherapy and autografting for patients still in second chronic phase may be valuable.

Adolescent↗
PubMed1982

Relationship of the duration of the chronic phase in chronic granulocytic leukaemia to the need for treatment during the first year after diagnosis.

From a data base of 203 patients with chronic granulocytic leukaemia (CGL) seen at our institution during the period 1972-1981, we identified 25 patients in whom duration of the chronic phase could be accurately determined and who had received only busulphan or no treatment at all during the first year after diagnosis. Twenty-one of the patients had Ph1 chromosome-positive disease but in four patients the Ph1 status was unknown. We found a significant correlation between the total dose of busulphan administered during the first year of disease (range 300-1,300 mg) and the duration of chronic phase disease (range 13-72 months). In confirmation of this relationship, we identified a further 11 patients in chronic phase continuing 47-136 months after diagnosis in whom the total dose of busulphan administered in the first year of disease ranged from 0 to 300 mg. We conclude that calculation of the total dose of busulphan administered in the first year after diagnosis of chronic phase disease might allow prediction of the duration of the chronic phase in other patients and could be of value in selecting candidates for experimental therapeutic approaches, such as bone marrow transplantation.

Adolescent↗
PubMedDate not supplied

Hormone replacement therapy and glucose tolerance in EPIC-Norfolk: a population-based study.

BACKGROUND: Hormone replacement therapy (HRT) can affect glucose homeostasis in postmenopausal women but it is unclear whether long-term use is associated with changes in glucose tolerance. The objective was to examine the relationship of glycated haemoglobin (HbA(1C)) concentration with HRT use in non-diabetic postmenopausal women. METHODS: A cross-sectional analysis of baseline data on 2753 postmenopausal women, aged 45-74 years who were recruited to the EPIC-Norfolk study between 1995 and 1998 was performed. Women completed a health and lifestyle questionnaire from which information on HRT use was obtained and gave blood for HbA(1C) assay. RESULTS: Of the women, 23% were current HRT users and 14% were former users. Mean HbA(1C) was significantly lower in current users compared to former and never users. This difference was independent of age, body mass index (BMI), waist-to-hip ratio (WHR), family history of diabetes, educational status, employment status, smoking history, history of alcohol consumption, parity, known illness and hysterectomy status. Compared to never users of HRT, the unadjusted odds ratio (OR) for being in the highest quintile of HbA(1C) distribution as opposed to the lowest was 0.28 (95% CI 0.20-0.39) for current users and 0.41 (0.32-0.53) for ever users. After adjustment for confounders, the OR were 0.52 (0.34-0.79) and 0.72 (0. 51-1.03) for current and ever users, respectively. CONCLUSION: Women currently using HRT have lower HbA(1C) levels not explained by known confounders though we cannot completely exclude a healthy user effect. Nevertheless, this population study suggest that current use of HRT was not associated with impairment of glucose tolerance in postmenopausal women.

Aged↗
PubMedDate not supplied

Diabetes risk score: towards earlier detection of type 2 diabetes in general practice.

BACKGROUND: Type 2 diabetes is common, costly and often goes unrecognised for many years. When patients are diagnosed, the majority exhibit associated tissue damage or established cardiovascular risk. Evidence is accumulating that earlier detection and management of diabetes and related metabolic abnormalities may be beneficial. We aimed to develop and evaluate a score based on routinely collected information to identify people at risk of having undetected diabetes. METHODS: A population-based sample of 1077 people, aged 40 to 64 years, without known diabetes, from a single Cambridgeshire general practice, underwent clinical assessment including an oral glucose tolerance test. In a separate 12-month study, 41 practices in southern England reported clinical details of patients aged 40 to 64 years with newly diagnosed Type 2 diabetes. A notional population was created by random selection and pooling of half of each dataset. Data were entered into a regression model to produce a formula predicting the risk of diabetes. The performance of this risk score in detecting diabetes was tested in an independent, randomly selected, population-based sample. RESULTS: Age, gender, body mass index, steroid and antihypertensive medication, family and smoking history contributed to the score. In the test population at 72% specificity, the sensitivity of the score was 77% and likelihood ratio 2.76. The area under the receiver-operating characteristic curve was 80%. CONCLUSIONS: A simple score, using only data that are routinely collected in general practice, can help identify those at risk of diabetes. This score could contribute to efficient earlier detection through case-finding or targeted screening.

Data Collection↗