Search PubMed⌕ Search

Biomedical subjects

R C Turner

Publications and source records attributed to R C Turner.

At least 73 records · Page 4Linked to original sources
PubMed1995

U.K. Prospective Diabetes Study. XV: Relationship of renin-angiotensin system gene polymorphisms with microalbuminuria in NIDDM.

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/liter)] were matched with two control groups of diabetic patients without microalbuminuria [median urinary albumin 7 (5 to 10) mg/liter] for variables known to be associated with raised urinary albumin concentration including hemoglobin A1c and triglyceride. One control group was also matched for blood pressure and the other group was not, to allow assessment of interactions with hypertension. Association with the I/D polymorphism of the ACE gene and M235T variant of the angiotensinogen gene (AGT) with microalbuminuria and retinopathy was examined. There were no significant differences in genotype frequency between cases and controls for ACE or AGT irrespective of blood pressure matching. However, among subjects with microalbuminuria, those with the ACE DD genotype had a significantly greater urinary albumin excretion than individuals with a non-DD genotype [median 88 (68 to 170) mg/liter vs. 67 (53 to 113) mg/liter, P < 0.001]. More subjects with the DD than non-DD genotype had persistent albuminuria > 100 mg/liter, twice the upper normal range (60% vs. 38%, P = 0.006). When increased albumin excretion occurs, the presence of the ACE DD genotype appears to be associated with higher urinary albumin levels. No association with retinopathy was observed.

Albuminuria↗
PubMed1995

Mutation of the glucagon receptor gene and diabetes mellitus in the UK: association or founder effect?

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 dependent) diabetes and 1/425 (0.2%) of geographically matched controls and have therefore replicated association of the GCG-R mutation with classical type 2 diabetes (Fisher's exact test p = 0.008). An increased frequency of the mutation of the GCG-R gene was also found in probands of type 1 (insulin dependent) diabetic multiplex (affected sib pair) families, (10/404, 2.5%). However, a lack of preferential transmission from parents heterozygous for the mutation, to affected type 1 diabetic sibs may suggest population stratification. This in turn cannot be excluded as an alternative explanation for the difference in frequency of the GCG-R gene mutation between subjects with type 2 diabetes and normal controls.

Diabetes Mellitus, Type 1↗
PubMed1995

Clinical characteristics of subjects with a missense mutation in glucokinase.

The clinical characteristics of subjects with a missense glucokinase mutation, gly299-->arg, were studied in a large pedigree, BX, initially characterized by some members having Maturity Onset Diabetes of the Young (MODY). Glucose tolerance, beta cell function and insulin sensitivity were measured with Homeostasis Model Assessment (HOMA) and with a 'Continuous Infusion of Glucose with Model Assessment' (CIGMA) test. Diabetic complications were clinically assessed. Subjects with glucokinase gly299-->arg were the same age, height, and obesity as the subjects without the mutation. Diabetes was usually asymptomatic at diagnosis and was treated with diet alone in 15 of the 18 subjects. Five of the 11 adult females had been diagnosed when they developed gestational diabetes. The fasting plasma glucose concentrations at the time of study were 4.3-12.6 mmol l-1, with the higher levels being in the more obese (p < 0.05) and in the older subjects (p < 0.05). In subjects with the mutation, beta cell function was impaired, being geometric mean 63% (normal-100%) compared with 126% in the subjects without the mutation (p < 0.001) measured by HOMA and in a subset assessed by CIGMA 59% and 127% (p < 0.01), respectively. There was no difference in fasting insulin concentrations, insulin sensitivity, lipid concentrations or blood pressure between the groups. The haemoglobin A1c was raised (mean 6.5% compared with 5.5% in the subjects without the mutation), but microvascular and macrovascular complications were uncommon. The subjects with the mutation did not have microalbuminuria but had an impaired vibration perception threshold compared with subjects without the mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

High prevalence of hepatitis C infection in Afro-Caribbean patients with type 2 diabetes and abnormal liver function tests.

Moderate elevations of serum transaminases are frequently found in patients with diabetes mellitus and are often attributed to fatty infiltration of the liver without further investigation. Recent studies of patients with end-stage liver disease have suggested a possible association between Hepatitis C virus (HCV) antibody positivity and the development of diabetes (mostly Type 2). As a first step in the examination of any potential association between HCV and Type 2 diabetes in subjects without overt liver disease, we examined 200 British patients with Type 2 diabetes (100 White Caucasians, 50 Asians, and 50 Afro-Caribbeans), recruited from the United Kingdom Prospective Study of Diabetes, half of whom had a significant elevation of alanine aminotransferase (ALT) on at least two occasions and half of whom had consistently normal ALT levels. In Afro-Caribbean Type 2 diabetic subjects 7/25 (28%) patients with abnormal ALT and 1/25 (4%) with normal ALT were HCV antibody positive. Among White Caucasian subjects 6/50 (12%) patients with abnormal LFTs and 0/50 with normal LFTs were HCV antibody positive and in Asians the prevalence was 2/25 (8%) and 0/25, respectively. This study suggests that persistent mild to moderate elevation of serum transaminases in a patient with Type 2 diabetes should not automatically be attributed to the metabolic disturbances of diabetes. Particularly in Afro-Caribbean subjects, HCV infection is a major diagnostic consideration. The question of whether HCV infection itself may have a diabetogenic action is worthy of further investigation.

Adult↗
PubMed1995

Drugs on the horizon for treatment of type 2 diabetes.

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 active drugs that lack toxicity. Agents that reduce insulin resistance include the thiazolidinediones, which are very effective in animals. Of these, the only one that has been maintained in clinical evaluation appears from preliminary data to have an effect that although still useful, is not greater than that reported for current oral agents. Agents that reduce non-esterified fatty acid levels by inhibiting lipolysis, thereby allowing increased peripheral uptake of glucose, have so far given minimal reduction in glycaemia. The development of fatty acid oxidation inhibitors to reduce gluconeogenesis in the liver has been hampered by toxicity, but additional new agents are being studied. The most promising new approach for enhancing insulin secretion has been suggested by the demonstration that pharmacological doses of GLP-1 (7-36 amide), a natural enteric incretin hormone, improves pancreatic beta-cell and alpha-cell sensitivity to glucose and can induce normal basal glucose levels in diabetic man. The future development of GLP-1 agonists will be of great interest. This is timely as other insulin secretogogues, such as alpha 2 adrenergic blockers have proved relatively ineffective. Anti-obesity agents would in theory be beneficial, but have either had limited efficacy or have been avoided because of concern about long-term safety. Until new pharmaceutical agents become available, if near-normal glycaemia is to be achieved, many more Type 2 diabetic patients will need insulin therapy. When full insulin replacement therapy is not feasible, reducing the fasting blood glucose level towards normal with a single daily basal insulin supplement, either alone or in combination with oral agents, could become a more widely used therapy.

Blood Glucose↗
PubMed1995

HLA typing for DR3 and DR4 using artificial restriction fragment length polymorphism PCR from archival DNA.

AIM: To develop polymerase chain reaction based artificial restriction fragment length polymorphism (artificial RFLP PCR) assays for DR3 and DR4 alleles of the multiallelic DRB1 locus and to apply them to paraffin wax embedded archival material. METHODS: Sixty five samples from DRB1 typed cell lines were analysed using the artificial RFLP PCR method to determine the specificity and sensitivity of the system. RESULTS: The artificial RFLP PCR method for typing the DRB1 locus showed 100% accuracy in the 65 samples previously typed using allele specific PCR and serology. The samples included 18 combinations of alleles that included DR3, 18 that included DR4, four that were DR3/DR4 heterozygotes, and 10 samples that were neither DR3 nor DR4. Typing of 10 paraffin wax embedded samples using artificial RFLP PCR was in complete agreement with previous typing at the DRB1 locus. CONCLUSION: The application of artificial RFLP PCR for the analysis of multiallelic loci, such as those of the HLA system, in archival DNA samples has been achieved. Artificial RFLP PCR is a robust, easily implemented, non-isotopic system and may be useful for large retrospective studies.

Alleles↗
PubMed1995

Type II diabetes: clinical aspects of molecular biological studies.

Type II diabetes remains a genetic nightmare. The major problem is identifying suitable pedigrees, sib-pairs, and populations for study. Segregation analysis data suggest that type II diabetes is likely to be polygenic, although one or more major genes could also be involved. This and the high prevalence of diabetes affect the strategies for searching for genetic mutations. Linkage analysis in classical type II diabetes pedigrees is unlikely to be successful. In addition, affected sib-pair analysis is limited because both parents are often affected, leading to bilineal inheritance. Sib-pairs with both parents alive are unusual, so identity by descent analysis is rarely feasible. Strategies to reduce bilineal inheritance by identifying sib-pairs with one known nondiabetic parent or with the second sibling having mild subclinical diabetes may be worthwhile. Identification of individuals or pedigrees with an unusual phenotype that suggests a single gene disorder, such as maturity-onset diabetes of the young, will continue to be important, for this allows linkage analysis with markers near candidate genes and exclusion mapping of chromosomal regions using highly polymorphic markers. Population association studies with candidate genes can detect mutations that have a minor role in the majority proportion of diabetic subjects, but large numbers are required and great care must be taken to exclude ethnic group differences between the diabetic and normoglycemic populations. The study of small inbred communities might be helpful because they may have fewer diabetogenic genes than outbred populations, and this would increase the power of sib-pair and population association studies. Direct screening for mutations in candidate genes (with single-strand conformation polymorphism or heteroduplex screening or with direct sequencing) in patients with the appropriate pathophysiological abnormality can be a successful strategy. The identification of well-defined diabetic pedigrees, sib-pairs, and suitable matched diabetic and nondiabetic populations will be key to the discovery of the genes for diabetes.

Diabetes Mellitus, Type 2↗
PubMed1995

No evidence for mutations in a putative beta-cell ATP-sensitive K+ channel subunit in MODY, NIDDM, or GDM.

The beta-cell ATP-sensitive K+ (K-ATP) channel has a major role in glucose-induced insulin secretion. Screening the entire coding sequence of the gene for a putative beta-cell K-ATP channel subunit, K-ATP2, with single-strand conformation polymorphism did not show any mutations associated with diabetes in white Caucasian diabetic patients, including five pedigrees with maturity onset diabetes of the young (MODY), 25 patients with noninsulin-dependent diabetes mellitus (NIDDM) selected for marked beta-cell deficiency, 25 selected for mild diabetes presenting before age 50 years with fasting plasma glucose levels < 10 mmol/l, 25 unselected NIDDM patients, and 25 subjects with gestational diabetes mellitus (GDM) and subsequent raised fasting plasma glucose. In five large MODY pedigrees, linkage analysis with simple tandem-repeat polymorphisms (STRPs) near the K-ATP2 gene excluded linkage. In a population association study, no linkage disequilibrium for the STRP was found between 237 unselected white Caucasian NIDDM patients and 104 geographically matched and age-matched white Caucasian nondiabetic subjects. In addition, two silent polymorphisms were found with similar frequency in nondiabetic and diabetic subjects. Mutations in the gene for K-ATP2 are unlikely to be a major cause of MODY, NIDDM, or GDM.

Adenosine Triphosphate↗
PubMed1994

Patient-carried card prompts vs computer-generated prompts to remind private practice physicians to perform health maintenance measures.

BACKGROUND: We compared the efficacy of a computer-generated prompt sheet placed on the front of patients' charts with a patient-carried prompt card to remind physicians to perform selected health maintenance items. METHODS: A randomized prospective single-blind study was performed in private practice offices in rural eastern North Carolina, with 28 family practitioners and nine general internists participating. Twenty-two physicians were randomized to the computer prompt group and 22 to the card prompt group. Four physicians in the computer group did not complete the study because of computer software problems, and three physicians did not complete the study because their limited staff was unable to enter patient data into the computer. Before the intervention, 20 patient charts (10 males and 10 females) from each physician were audited for the performance of influenza vaccinations, stool for occult blood, pap smears, breast examinations performed by the physicians, and mammograms. One year after the intervention was instituted, chart audits for the above five items were done again on 20 different patient charts for each physician. RESULTS: There was a 7% increase in the performance of influenza vaccinations in the card group (17% vs 24%) compared with a 6% increase in the computer group (20% vs 26%). There was a 5% decrease in the performance of stool for occult blood in the card group (28% vs 23%) compared with a 1% increase in the computer group (30% vs 31%). There was an 11% decrease in the performance of pap smears in the card group (26% vs 15%) compared with a 3% increase in the computer group (23% vs 26%). There was a 2% decrease in the performance of breast examinations by the physician in the card group (35% vs 33%) compared with a 3% increase in the computer group (30% vs 33%). Finally, there was a 3% increase in the performance of mammograms in the card group (22% vs 25%) compared with an 11% increase in the computer group (15% vs 26%). CONCLUSIONS: Our data show a greater increase in performance of health maintenance items in the computer-prompted group. The performance of stool for occult blood, pap smears, breast examinations performed by the physician, and mammograms were increased more in the computer-prompted group than in the card group. However, there was not a statistically significant difference after intervention for any of the audited health maintenance items for either the computer group or the card group. Overall, health maintenance measures were performed in only a minority of appropriate patients.

Adult↗
PubMed1994

Segregation analysis of NIDDM in Caucasian families.

Non-insulin-dependent diabetes mellitus (NIDDM) has a substantial genetic component, but the mode of inheritance and the molecular basis are unknown. We have undertaken segregation analysis of NIDDM after studying 247 subjects in 59 Caucasian nuclear pedigrees ascertained without regard to family history of the disorder. The analyses were performed using POINTER and COMDS, which are computer programs which apply statistical models to the data. POINTER analysis was performed defining the phenotype as a presence or absence of hyperglycaemia. Among single locus hypothesis, the analyses rejected a recessive model and favoured a dominant model, but could not statistically show that this fitted better than a mixed model (a single locus against a polygenic background) or a polygenic model. COMDS analysis assumed a continuum of hyperglycaemia from normality to NIDDM, classified family members into a series of diathesis classes with increasing plasma glucose levels and compared the distribution with that found by screening the normal population. This analysis improved the likelihood of a dominant single locus model and suggested a gene frequency of 7.4%. It raised the possibility of a second locus, but cannot identify or exclude a polygenic model. In conclusion, two types of segregation analyses rejected a recessive model and favoured a dominant model of inheritance, although they could not statistically show that this fitted better than the polygenic model. The results raised the possibility of a common dominant gene with incomplete penetrance, but genetic analysis of NIDDM needs to take into account the likelihood of polygenic inheritance with genetic heterogeneity.

Adult↗
PubMed1994

Non-linkage of the glucagon-like peptide 1 receptor gene with maturity onset diabetes of the young.

Glucagon-like peptide-1 (GLP-1) is a hormone derived from the preproglucagon molecule that is secreted by intestinal L cells and stimulates insulin secretion from beta cells. The GLP-1 receptor is a candidate gene for diabetes mellitus, as mutations may induce the impaired insulin response that is a characteristic feature of NIDDM. To study the relationship between the GLP-1 receptor gene and NIDDM, linkage of a microsatellite polymorphism flanking the GLP-1 receptor gene with diabetes was investigated in three Caucasian families with MODY and in the nuclear families of 12 NIDDM probands. A cumulative LOD score -8.50 excludes linkage in these MODY pedigrees. A LOD score of -1.24 in the NIDDM nuclear pedigrees makes linkage improbable. Mutations in or near the GLP-1 receptor gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees, but we cannot exclude a role for this locus in a polygenic model or a major role in some pedigrees.

Base Sequence↗
PubMed1994

Obesity associated insulin resistance occurs in hypopituitary subjects.

The study aimed to assess the role of pituitary hormones in the relationship between insulin resistance and obesity. Twelve male subjects with hypopituitarism secondary to surgery for a non-functioning pituitary adenoma were recruited. Subjects were receiving replacement hormones. Fasting plasma samples were taken for insulin, C-peptide, glucose, and lipids. Body mass index and blood pressure were measured. In hypopituitary subjects on replacement therapy, a positive association between body mass index and fasting plasma insulin levels (r = 0.76, p < 0.004) was similar to that found in normal subjects. In conclusion pituitary function does not have a direct role in determining the relationship between fasting plasma insulin, an index of insulin resistance, and obesity.

Humans↗
PubMed1993

Association of low birth weight with beta cell function in the adult first degree relatives of non-insulin dependent diabetic subjects.

OBJECTIVE: To examine the relation between birth weight and beta cell function in the first degree relatives of non-insulin dependent diabetic subjects. DESIGN: Cross sectional study of 101 adults of known birth weight from 47 families which had at least one member with non-insulin dependent diabetes. SUBJECTS: 101 white adults aged mean 43 (SD 7) years. SETTING: Oxfordshire, England. MAIN OUTCOME MEASURES: Glucose tolerance was measured by continuous infusion glucose tolerance test. beta cell function and insulin sensitivity were calculated from the fasting plasma glucose and insulin concentrations with homeostasis model assessment. beta cell function was standardised to allow for the confounding effects of age and obesity. RESULTS: Twenty seven subjects had non-insulin dependent diabetes, 32 had impaired glucose tolerance, and 42 were normoglycaemic. Birth weight correlated with the beta cell function of the complete cohort (rs = 0.29, p = 0.005), the non-insulin dependent diabetic subjects (rs = 0.50, p = 0.023), and the non-diabetic subjects (rs = 0.29, p = 0.013). The non-insulin dependent diabetic (n = 27) and the non-diabetic (n = 74) subjects had similar mean (inter-quartile range) centile birth weight 50% (19%-91%), and 53% (30%-75%) respectively. Non-insulin dependent diabetic subjects had significantly lower beta function than the non-diabetic subjects: 69% (48%-83%) v 97% (86%-120%), p < 0.001. CONCLUSIONS: The cause of the association between low birth weight and reduced beta cell function in adult life is uncertain. Impaired beta cell function in non-insulin dependent diabetic subjects was not accounted for by low birth weight, and genetic or environmental factors are likely to be necessary for development of diabetes.

Adult↗
PubMed1993

Prevalence and pathophysiology of impaired glucose tolerance in three different high-risk white groups.

Insulin resistance and beta-cell function were assessed by a continuous infusion of glucose in the following three groups of white subjects at risk of developing impaired glucose tolerance and diabetes: 41 subjects who were the offspring of patients with type II diabetes, 26 general-population subjects with an increased fasting plasma glucose level of at least 5.6 mmol/L on screening, and 22 subjects who had had gestational diabetes but were now nondiabetic. Subjects had a mean (+/- 1 SD) age of 43 +/- 9 years and a body mass index (BMI) of 27 +/- 5 kg/m2. Subjects with previously increased fasting glucose levels were significantly more insulin resistant than a control group, taking into account BMI, age, and gender (% normal insulin sensitivity [%], 59 [50 to 79] v 87 [73 to 96]; P < .005), and previously gestationally diabetic subjects showed greater impairment of beta-cell function (% normal beta-cell function [% beta], 69 [60 to 87] v 97 [89 to 105]; P < .005). Diabetes (defined by World Health Organization criteria) or impaired glucose tolerance (defined as an achieved plasma glucose concentration [APG] > 95th percentile of an age- and weight-matched population) was identified in 22% of family members, 31% of fasting hyperglycemic subjects, and 41% of previously gestationally diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Prednisolone enhances beta-cell function independently of ambient glycemic levels in type II diabetes.

This study examined the changes in beta-cell response and insulin sensitivity induced by a single overnight dose of 15 mg prednisolone in eight type II diabetic subjects, seven nondiabetic normal controls, and eight subjects with a first-degree type II diabetic relative who were therefore at risk of developing diabetes. beta-Cell secretion was assessed by use of the hyperglycemic clamp technique, and insulin sensitivity was assessed with the clamp and the Continuous Infusion of Glucose with Model Assessment (CIGMA) technique. Subjects were studied in random order on two occasions, after placebo and after prednisolone administration. Normal subjects showed an increase of median fasting glucose level from 4.7 to 5.2 mmol.L-1 after prednisolone (P < .02) and at-risk subjects showed an increase from 4.8 to 5.5 mmol.L-1 (P < .005), whereas diabetic subjects showed no significant increase in median fasting plasma glucose level (7.0 mmol.L-1 after placebo and 6.3 mmol.L-1 after prednisolone). Six of these eight diabetic subjects showed a paradoxical decrease of fasting plasma glucose level after prednisolone therapy. All three groups showed a significant elevation of clamp steady-state plasma insulin levels following prednisolone, with a median percentage elevation of 46%, 66%, and 31% for normal, at-risk, and diabetic subjects, respectively. All three groups showed significant reduction in insulin sensitivity measured by CIGMA following prednisolone of 51%, 41%, and 25% of pre-prednisolone levels in normal, at-risk, and diabetic subjects, respectively, with a significantly greater reduction in normal subjects than in diabetics (P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗