R C Turner's research while affiliated with University of Oxford and other places
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Publications (317)
To determine risk factors related to the incidence and progression of diabetic retinopathy over 6 years from diagnosis of Type II (non-insulin-dependent) diabetes mellitus.
This report describes 1919 patients from within the United Kingdom Prospective Diabetes Study (UKPDS), with retinal photographs taken at diagnosis and 6 years later and with com...
Elevated proinsulin secretion and islet amyloid deposition are both features of Type 2 diabetes but their relationship to beta-cell dysfunction is unknown. To determine if islet amyloid polypeptide (IAPP) secretion is disproportionate with other beta-cell products at any stage of glucose intolerance, 116 subjects were studied. Non-diabetic subjects...
To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.
Prospective observational study. Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland. Participants: 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, wh...
To assess the effect of diet on fasting plasma lipids and lipoproteins in patients with newly diagnosed Type 2 diabetes.
A total of 2,906 patients each underwent 3 months' diet therapy before allocation to therapy in a randomized controlled clinical trial. Lipids and lipoproteins were measured at diagnosis and after 3 months' diet.
The mean body we...
To determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.
Prospective observational study. Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland.
4801 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether random...
SUMMARY Aims To assess the effect of diet on fasting plasma lipids and lipoproteins in patients with newly diagnosed Type 2 diabetes. Methods A total of 2906 patients each underwent 3 months' diet therapy before allocation to therapy in a randomized controlled clinical trial. Lipids and lipoproteins were measured at diagnosis and after 3 months' di...
To estimate the cost effectiveness of conventional versus intensive blood glucose control in patients with type 2 diabetes.
Incremental cost effectiveness analysis alongside randomised controlled trial.
23 UK hospital clinic based study centres.
3867 patients with newly diagnosed type 2 diabetes (mean age 53 years).
Conventional (primarily diet) gl...
Objective: To estimate the cost effectiveness of conventional versus intensive blood glucose control in patients with type 2 diabetes.
Design: Incremental cost effectiveness analysis alongside randomised controlled trial.
Setting: 23 UK hospital clinic based study centres.
Participants: 3867 patients with newly diagnosed type 2 diabetes (mean age 5...
The hormone leptin is considered to contribute to body weight regulation through modulation of feeding behavior and energy expenditure. The aim of the present study was 1) to assess the day-to-day within-subject variation (biovariability) of serum leptin concentrations in healthy subjects and 2) to investigate whether this variation is associated w...
The transmission disequilibrium test with use of trios (an affected proband with both parents) is a robust method for assessing the role of gene variants in disease that avoids the problem of population stratification that may confound conventional case/control studies and allows the detection of parent-of-origin effects. Trios have played a major...
Adequate comparisons of the relative performance of different tests of beta-cell function are not available. We compared discrimination of commonly used in vivo tests of beta-cell function across a range of glucose tolerance in seven subjects with normal glucose tolerance (NGT), eight subjects with impaired glucose tolerance (IGT), and nine subject...
To determine whether microaneurysms, in the absence of other lesions, have a predictive role in the progression of diabetic retinopathy in Type II (non-insulin-dependent) diabetes mellitus.
Retinal photographs taken at diagnosis in patients participating in the United Kingdom Prospective Diabetes Study, and thereafter at 3 yearly intervals, were as...
Aims/hypothesis. To determine whether microaneurysms, in the absence of other lesions, have a predictive role in the progression of diabetic retinopathy in Type II (non-insulin-dependent) diabetes mellitus. Methods. Retinal photographs taken at diagnosis in patients participating in the United Kingdom Prospective Diabetes Study, and thereafter at 3...
Adequate comparison of the relative performance of insulin sensitivity tests is not yet available. We compared the discrimination of four insulin sensitivity tests, commonly used in vivo, across a range of glucose tolerance.
Normal (n = 7), impaired glucose tolerant (n = 8) and Type II (non-insulin-dependent) diabetic subjects (n = 9) had in random...
Treatment with diet alone, insulin, sulfonylurea, or metformin is known to improve glycemia in patients with type 2 diabetes mellitus, but which treatment most frequently attains target fasting plasma glucose (FPG) concentration of less than 7.8 mmol/L (140 mg/dL) or glycosylated hemoglobin A1c (HbA1c) below 7% is unknown.
To assess how often each...
To determine the degree to which alpha-glucosidase inhibitors, with their unique mode of action primarily reducing postprandial hyperglycemia, offer an additional therapeutic approach in the long-term treatment of type 2 diabetes.
We studied 1,946 patients (63% men) who were previously enrolled in the U.K. Prospective Diabetes Study (UKPDS). The pa...
To investigate modifiable and nonmodifiable risk factors for stroke in type 2 diabetes mellitus.
A total of 3776 patients aged 25 to 65 years newly diagnosed as having type 2 diabetes mellitus without known cardiovascular or other serious disease were studied for a median of 7.9 years. An initial stepwise evaluation of risk factors was done in 2704...
The biological variation of some commonly assessed metabolic variables in healthy subjects has not been studied extensively. The aim of the study was to assess, in 12 healthy subjects (6 male and 6 female; mean (SD) age; 22.7 (1.5) years) following an overnight fast, the day-to-day variation of body fat (impedance method), triglycerides, nonesterif...
We set out to investigate the extent to which siblings of diabetic subjects perceived themselves likely to develop Type 2 diabetes mellitus (DM) when offered screening tests.
Nondiabetic siblings, aged 35-74 years, of Type 2 diabetic patients who were more than 35 years old at diagnosis had fasting plasma glucose measured in a study to determine he...
Comparison studies between physiological tests are often unsatisfactory for assessing their ability to distinguish between subjects. We recommend a simple but comprehensive protocol, using duplicate testing, that compares tests using 1) the discriminant ratio (DR) between the underlying between- and within-subject SDs, 2) correlation coefficients a...
Type II (non-insulin-dependent) diabetes mellitus has a substantial genetic component; however, its molecular basis remains largely unknown. The mode of inheritance is likely to be polygenic, with penetrance influenced by environmental factors. Although the familial aggregation of Type II diabetes is acknowledged, there is little data concerning th...
Type II (non-insulin-dependent) diabetes mellitus has a substantial genetic component; however, its molecular basis remains
largely unknown. The mode of inheritance is likely to be polygenic, with penetrance influenced by environmental factors. Although
the familial aggregation of Type II diabetes is acknowledged, there is little data concerning th...
The objective of the U.K. Prospective Diabetes Study (UKPDS), initiated in 1977, was set up to determine whether improved blood glucose control in people with type 2 diabetes will prevent the complications of diabetes. The UKPDS was also designed to determine whether there are differences between conventional policy (diet therapy) and three differe...
Non-insulin dependent diabetes mellitus (NIDDM) has a substantial genetic component. Impaired insulin secretion, insulin insensitivity in muscle and adipose tissue, and elevated hepatic glucose production are the major pathophysiological features of NIDDM. Insulin insensitivity is also a feature of the insulin resistance syndrome, which describes t...
Objectives: To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or beta blockers, compared with less tight control in hypertensive patients with type 2 diabetes.
Design: Cost effectiveness analysis incorporating within trial analysis and estimation of impact on life expectancy through u...
Background In patients with type 2 diabetes, intensive blood-glucose control with insulin or sulphonylurea therapy decreases progression of microvascular disease and may also reduce the risk of heart attacks. This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage. Methods Of 4075 patients...
Background Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared...
Objective:
To estimate the incidence of myocardial infarction (MI) by ethnicity in subjects with diabetes and to examine the effect of ethnicity, adjusting for differences in cardiovascular risk factors.
Research design and methods:
For a prospective study, 4,974 patients with newly diagnosed type 2 diabetes, aged 25-65 years, were recruited fro...
Amylin, a secretory peptide of beta-cells, is the constituent peptide of islet amyloid, which is characteristic of NIDDM, and changes in amylin secretion in response to therapies may influence the rate of production of islet amyloid. The primary objective of this study was to determine whether therapy with sulfonylurea or basal insulin in NIDDM wou...
Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on sulphonylurea therapy convert to insulin progressively as the sulphonylureas ‘fail’. The rate of failure and the features of those who fail have been poorly described. To assess secondary failure rates of sulphonylureas, we report on the responses in 1305 patients with newly dia...
Patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) on sulphonylurea therapy convert to insulin progressively as the sulphonylureas 'fail'. The rate of failure and the features of those who fail have been poorly described. To assess secondary failure rates of sulphonylureas, we report on the responses in 1305 patients with newly dia...
To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes mellitus.
A stepwise selection procedure, adjusting for age and sex, was used in 2693 subjects with complete data to determine which risk factors for coronary artery disease should be included in a Cox proportional hazards model.
3055 white patients (mean...
To report on the prevalence of retinopathy in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) and to evaluate the relationship of retinopathy to clinical and biochemical variables.
A multicenter, randomized, controlled clinical study of therapy in patients with NIDDM.
Patients were part of the United Kingdom Prospectiv...
Self-referred subjects (N = 227) thought to be at risk of developing non-insulin-dependent diabetes mellitus (NIDDM) and with fasting plasma glucose (FPG) in the range of 5.5 to 7.7 mmol.L-1 on two consecutive tests 2 weeks apart were randomized to reinforced or basic healthy-living advice. They were simultaneously allocated either to a sulfonylure...
Objective:
To assess the efficacy over 3 years of the addition of metformin to maximum sulfonylurea therapy in type 2 diabetes.
Research design and methods:
This multicenter randomized open-controlled trial was conducted in outpatient diabetes clinics in 15 U.K. hospitals. A total of 591 subjects who had already been randomly allocated to sulfon...
Self-referred subjects (N = 227) thought to be at increased risk of developing diabetes who had fasting plasma glucose (FPG) values in the range of 5.5 to 7.7 mmol.L-1 on two consecutive occasions 2 weeks apart were randomized to sulfonylurea therapy (gliclazide, < or = 160 mg.d-1) or to a control group allocated either to double-blind placebo or t...
Autoantibodies to islet-cell cytoplasm (ICA) and glutamic acid decarboxylase (GADA) can occur in apparently typical, non-insulin dependent diabetes mellitus (type 2). We investigated whether the presence of either or both antibodies characterises a subtype of diabetes and provides better prediction of requirement for insulin therapy by 6 years' fol...
Subjects at increased risk for developing non-insulin-dependent diabetes mellitus (NIDDM) were encouraged via a public awareness campaign, general practitioners, or a direct approach (in the case of women with previous gestational diabetes) to attend one of three English and two French centers for fasting plasma glucose (FPG) measurement. Of 1,580...
Our objective was to design a structured approach to maintaining comparability of biochemical data during a long clinical trial. Maintaining the comparability of clinical and biochemical data obtained in long-term studies is essential, even though analytical methods in the laboratory may be changed, conventions on specimen handling and storage revi...
To assess the effect of age at diagnosis on the initial prevalence and subsequent risk of the progression of diabetic tissue damage in patients with NIDDM.
The prevalence of Q-wave myocardial infarction, absent dorsalis pedis pulses, retinopathy, absent ankle jerks, hypertension, and microalbuminuria were determined at baseline and at 3 and 6 years...
Subjects with NIDDM have increased plasma proinsulin concentrations, compared with nondiabetic subjects, both in absolute terms and as a proportion of circulating insulin-like molecules. It remains uncertain whether this reflects a primary beta-cell defect in proinsulin processing or is secondary to hyperglycemia. We addressed this question by asse...
A 58-yr-old obese white Caucasian male type 2 diabetic, entered into the UK Prospective Diabetes Study, was found to have raised fasting total proinsulin levels 708 pmol/L(-1) (normal range, 3-16 pmol/L(-1)) and normal specific plasma insulin level 29 pmol/L(-1) (normal range, 21-75 pmol/L(-1)). Immunoreactive plasma insulin, measured by RIA, was 5...
A 58-yr-old obese white Caucasian male type 2 diabetic, entered into the UK Prospective Diabetes Study, was found to have raised fasting total proinsulin levels 708 pmol/L21 (normal range, 3-16 pmol/L21) and normal specific plasma insulin level 29 pmol/L21 (nor- mal range, 21-75 pmol/L21). Immunoreactive plasma insulin, mea- sured by RIA, was 503 p...
Signals derived from the metabolism of glucose in pancreatic beta-cells lead to insulin secretion via the closure of ATP-sensitive K+ channels (KATP). The cloning of the gene encoding the beta-cell inward rectifier Kir6.2 (Bir), a subunit of the beta-cell KATP channel, provided the opportunity to look for mutations in this gene that might contribut...
We measured plasma leptin and insulin concentrations across a spectrum of obesity in 829 white Caucasian, 154 Afro-Caribbean, and 204 Asian type 2 diabetic subjects. Although the leptin concentrations covered a large range, there were no subgroups of diabetic subjects with very high or low leptin levels that would suggest mutations in the leptin ge...
Maturity-onset diabetes of the young (MODY) type 3 is a dominantly inherited form of diabetes, which is often misdiagnosed as non-insulin-dependent diabetes mellitus (NIDDM) or insulin-dependent diabetes mellitus (IDDM). Phenotypic analysis of members from four large Finnish MODY3 kindreds (linked to chromosome 12q with a maximum lod score of 15) r...
We have recently shown that mutations in the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the cause of one form of maturity-onset diabetes of the young (MODY3). Here, we report the exon-intron organization and partial sequence of the human HNF-1alpha gene. In addition, we have screened the ten exons and flanking...
The gut hormone, glucagon-like peptide-1 (GLP-1) is a potent insulin secretogogue with potential as a therapy for non-insulin-dependent diabetes mellitus (NIDDM). GLP-1 has been shown to reduce glucose concentrations, both basally, and, independently, in response to a single meal. For it to be an effective treatment, it would need to be administere...
Some patients with Type 2 (non-insulin-dependent) diabetes mellitus possess a mitochondrial mutation in the tRNA(Leu(UUR)) gene at position 3243 bp. These subjects show a maternal mode of inheritance and often have hearing defects. In French and Japanese populations, this mutation may be present in 1-3% of subjects with a family history of diabetes...
Insulin receptor substrate-1 (IRS-1), beta 3-adrenergic-receptor (beta 3-AR) and glycogen synthase (GS) genes are candidate genes for non-insulin-dependent diabetes mellitus (NIDDM), insulin resistance, dyslipidaemia and obesity. We studied white Caucasian subjects with NIDDM, 227 being randomly selected, 49 NIDDM within the top two percentiles of...
Glucagon-like peptide 1 (GLP-1) is a natural enteric incretin hormone, which is a potent insulin secretogogue in vitro and in vivo in humans. Its effects on overnight glucose concentrations and the specific phases of insulin response to glucose and nonglucose secretogogues in subjects with NIDDM are not known. We compared the effects of overnight i...
Insulin receptor substrate-1 (IRS-1), β3-adrenergic-receptor (β3-AR) and glycogen synthase (GS) genes are candidate genes for non-insulin-dependent diabetes mellitus (NIDDM), insulin resistance, dyslipidaemia and obesity. We studied white Caucasian subjects with NIDDM, 227 being randomly selected, 49 NIDDM within the top two percentiles of insulin...
The Diabetes Control and Complications Study has shown that improved blood glucose control would delay the progress of microvascular complications of diabetes. However, in patients with non-insulin-dependent diabetes mellitus, the major morbidity and mortality arises from premature cardiovascular disease. It is uncertain whether therapy aimed to im...
A high proportion of the female patients who are members of maturity onset diabetes of the young (MODY) pedigrees, and whose diabetes mellitus is due to a glucokinase mutation, originally presented with gestational diabetes. To establish whether glucokinase mutations could be a common cause of gestational diabetes, we studied 50 subjects who presen...
The ATP-sensitive K-channel plays a central role in insulin release from pancreatic beta cells. This channel consists of two subunits: a sulphonyl-urea receptor, SUR1, and an inwardly rectifying K-channel subunit, Kir6.2. We screened 135 white Caucasian patients with non-insulin-dependent diabetes mellitus (NIDDM) and 90 non-diabetic subjects for m...
NIDDM is a common heterogeneous disorder, the genetic basis of which has yet to be determined. The sulfonylurea receptor (SUR) gene, now known to encode an integral component of the pancreatic beta-cell ATP-sensitive potassium channel, IKATP, was investigated as a logical candidate for this disorder. The two nucleotide-binding fold (NBF) regions of...
Self-reported dietary intake was estimated from 3-day prospective food diaries completed by Type 2 diabetic patients in the UK Prospective Diabetes Study. All patients had received individual dietary advice and had been randomly allocated to diet, sulphonylurea or insulin therapy 3 months after diagnosis. A total of 132 patients (120 white Caucasia...
Two genes that have potentially important regulatory roles in insulin secretion are both located on chromosome 2q24.1. G-protein-coupled muscarinic potassium channel (GIRK1) is an inwardly rectifying K+ channel that helps to maintain the resting potential and excitability of cells. Mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH) cat...
To report the progress (after 9-year follow-up) of a study designed to determine whether improved glucose control in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) is effective in reducing the incidence of clinical complications.
A multicenter, randomized, controlled trial of different therapies for NIDDM. After initi...
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THE disease non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is characterized by abnormally high blood glucose resulting from a relative deficiency of insulin(1). It affects about 2% of the world's population and treatment of diabetes and its complications are an increasing health-care burden(2). Genetic factors are important in the aetiolo...
We performed a case-control study to determine whether molecular variants of genes of the renin-angiotensin system were associated with the presence of albuminuria in non-insulin dependent diabetes mellitus (NIDDM). A total of 180 diabetic patients with persistent microalbuminuria [median urinary albumin (interquartile range) of 74 (54 to 126 mg/li...
Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterised by an early age of onset and an autosomal dominant mode of inheritance. Only a proportion of cases are due to mutations in the glucokinase gene. We have studied five Caucasian MODY families, including the first MODY family to be described,...
Recent evidence suggests that a mutation of the glucagon receptor (GCG-R) gene is involved in the development of type 2 diabetes
in French patients. We have examined patients from three geographically distinct regions in the UK and found the GGT40 (Gly) to AGT40 (Ser) mutation to be present in 15/691 (2.2%) of patients with type 2 (non-insulin depe...
Type II diabetes is a major cause of morbidity and mortality, both from an increased risk of developing cardiovascular disease and from specific diabetic complications. At present, patients are often treated to prevent marked hyperglycaemia, that induces symptoms such as thirst. Moderately raised glucose levels are then accepted. At present, it is...
The deletion allele of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene has been suggested to be an independent risk factor for myocardial infarction, particularly in subjects judged to be "low-risk" by the criteria of lipid status and body mass index. In a prospective, matched case-control study, we have investigated t...
When diet therapy is no longer effective in keeping the fasting plasma glucose level < 6 mmol l-1, a basal insulin supplement from a long-acting insulin such as ultralente can be added instead of using a sulphonylurea or metformin. The dose of insulin required can be predicted from the level of the fasting plasma glucose and the degree of obesity,...
The only new pharmaceutical therapy for Type 2 (non-insulin-dependent) diabetes that has become available for clinical use in the last 40 years is the alpha-glucosidase inhibitor, acarbose, which reduces postprandial glucose levels by retarding digestion of complex carbohydrates in the gut. It has proved difficult to find other new metabolically ac...