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R C Turner

Publications and source records attributed to R C Turner.

At least 145 records · Page 8Linked to original sources
PubMed1989

Analysis of the pro-opiomelanocortin gene in non-insulin dependent diabetic families.

Products of the pro-opiomelanocortin gene have been shown to have marked effects on insulin secretion. Selective antagonists of beta-endorphin have been reported to correct the impaired insulin secretory response to glucose seen in non-insulin dependent diabetes. Families with an autosomal dominant pattern of inheritance of diabetes were studied for possible linkage between diabetes and the pro-opiomelanocortin locus by examining the inheritance of a Rsa 1 restriction fragment length polymorphism. In two families with classical Type 2 diabetes there were recombinants between the disease and the pro-opiomelanocortin locus. In a family with maturity-onset diabetes of the young there were only two informative meoises, but there was a crossover between the disease and the pro-opiomelanocortin gene locus. Inherited defects in or near the pro-opiomelanocortin gene locus are unlikely to be directly involved in the aetiology of non-insulin dependent diabetes.

Alleles↗
PubMed1988

Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes.

In fasting nondiabetic subjects, insulin is secreted in regular pulses every 12 to 15 minutes, but patients with non-insulin-dependent diabetes lack regular oscillatory insulin secretion. To investigate whether abnormal insulin oscillations are an early feature of diabetes, we studied 10 minimally glucose-intolerant first-degree relatives of patients with non-insulin-dependent diabetes and 10 controls matched for age and obesity. We performed a time-series analysis of fasting plasma insulin levels in blood samples obtained at 1-minute intervals for 150 minutes. Fasting plasma glucose levels were higher in the relatives than in the controls (mean +/- SD, 5.4 +/- 0.7 vs. 4.4 +/- 0.3 mmol per liter). Autocorrelation of pooled data showed no regular oscillatory activity in the relatives but a 13-minute cycle in the controls (r = 0.23, P less than 0.001). Similarly, Fourier transform analysis showed no significant peak in the relatives but the expected significant peak at 13 to 14 minutes in the controls (P less than 0.05). First-phase (0 to 10 minutes) insulin secretory responses to glucose administered intravenously were not significantly impaired in the relatives (geometric mean, 188 pmol per liter [26.2 mU per liter]; range of SD, +103 to -67 pmol per liter [+14.4 to -9.3 mU per liter]), as compared with the controls (geometric mean, 231 pmol per liter [32.2 mU per liter]; range of SD, +131 to -83 pmol per liter [+18.2 to -11.6 mU per liter]). We conclude that abnormal oscillatory insulin secretion may be an early phenomenon in the development of non-insulin-dependent diabetes.

Adult↗
PubMed1988

Type 2 (non-insulin-dependent) diabetes mellitus. New genetics for old nightmares.

In the last five years, genetic markers for a large number of diseases have been localised using linkage analysis of DNA polymorphisms in affected families. The site of the genetic defect or defects leading to Type 2 (non-insulin-dependent) diabetes mellitus, a common illness with a major genetic component, remains unknown. This is due, at least in part, to the lack of large well-defined Type 2 diabetic pedigrees suitable for linkage analysis. There are several features of the disease which make large pedigrees difficult to find. The late age of onset of most probands means that informative older generations are often dead, while there is difficulty in detecting disease in younger generations. The diagnostic criteria for diabetes are, as yet, dependent on an arbitrary cut-off along a continuum of plasma glucose. The high prevalence of the disease may also produce problems as, in any given family, diabetogenic genes may be contributed by more than one parent. Varieties of the disease with a well-defined inheritance, such as maturity onset diabetes of youth, are more suitable for linkage analysis but might be due to defects at a different gene locus. Despite these difficulties, once large well-defined pedigrees have been found, linkage analysis using both candidate genes and random highly polymorphic markers is the strategy most likely to find genetic markers for the disease.

Diabetes Mellitus, Type 2↗
PubMed1988

Linkage analysis of the human insulin receptor gene in type 2 (non-insulin-dependent) diabetic families and a family with maturity onset diabetes of the young.

The possibility of linkage between the human insulin receptor gene locus and diabetes was examined in three Type 2 (non-insulin-dependent) diabetic families and one family with maturity onset diabetes of the young. Insulin receptor gene haplotypes were established using BglII, Rsal and Sstl restriction enzyme digests of genomic DNA from all available family members. The digested DNA was subjected to agarose gel electrophoresis, Southern blotted, and hybridised to 32P-labelled human insulin receptor gene cDNA. In the pedigree with maturity onset diabetes of the young, formal linkage analysis allowed exclusion of close linkage between the insulin receptor locus and diabetes (logarithm of the odds for linkage versus non-linkage was -5.35 at recombination fraction of 0.01). This confirms the absence of linkage between insulin receptor and diabetes which has been reported in two similar pedigrees. In the three Type 2 diabetic families there were a minimum of 4 recombinants between the insulin receptor locus and diabetes, which makes a direct role for insulin receptor defects unlikely. The importance of using realistic estimates of penetrance when performing linkage analysis in a disease with a late age of onset is emphasised. In contrast to the one previous linkage analysis study of the insulin receptor gene, no specific association of diabetes with the rare Sst1 S1(-) allele was observed in either the maturity onset diabetes of the young or the Type 2 diabetic families.

Adolescent↗
PubMed1988

The glucose stimulus-response curve of the beta-cell in physically trained humans, assessed by hyperglycemic clamps.

In order to examine the effect of habitual exercise on beta-cell responses over a wide range of plasma glucose levels, plasma insulin and C-peptide responses to 2 1/2-hour hyperglycemic clamps at 7.5, 10, and 15 mmol/L glucose were assessed in six trained athletes and six age- and weight-matched sedentary controls. Athletes were significantly fitter than controls (estimated maximal oxygen uptake [VO2 max] mean 44 v 30 mL.kg-1.min-1, P less than .05) and were more sensitive to insulin as assessed by dividing the mean glucose infusion rate over the last 20 minutes of the clamp by the steady-state plasma insulin (mean 0.44 v 0.19 mg.min-1.kg-1.nmol-1. L, respectively, P less than .01). Plasma C-peptide responses were lower in the athletes, both fasting (geometric mean 0.28 v 0.62 nmol/L, P less than .05), and at the end of all clamps (at 7.5, 10, and 15 mmol/L plasma glucose, respectively, 0.65 v 1.43, 1.25 v 2.85, and 2.40 v 4.46 nmol/L each, P less than .05). First-phase plasma C-peptide responses were lower in the athletes at the 10 and 15 mmol clamp levels. The slope of the glucose-C-peptide stimulus-response curve was approximately linear over the range examined, the slope being significantly shallower in athletes than controls for both first phase (P less than .01) and second phase (P less than .01). Plasma insulin responses were similar to C-peptide responses. The attenuation of beta-cell responsiveness over a wide glucose range may be an adaptation to the enhanced peripheral insulin sensitivity seen in athletes.

Adult↗
PubMed1988

The beta cell glucose stimulus-response curve in normal humans assessed by insulin and C-peptide secretion rates.

Insulin and C-peptide secretion rates have been measured and compared in 12 nondiabetic subjects to characterize the glucose stimulus-response of B cell secretion in man. On three different days, glucose concentrations were clamped for 150 minutes at 7.5, 10, and 15 mmol/L, respectively. Plasma samples taken during the clamps were assayed for C-peptide and insulin. C-peptide secretion rates were estimated by the technique of deconvolution. Model-based estimation of insulin secretion rates from insulin concentrations yielded concordant results. In response to glucose, C-peptide concentrations rose less quickly than did insulin concentrations, but the estimated first- and second-phase secretion rates were similar when assessed from either the C-peptide or insulin concentrations. First-phase secretion peaks were larger than inspection of the plasma concentration data might suggest, with median values of 1.3, 2.0, and 2.9 nmol/min for C-peptide in response to 7.5, 10, and 15 mmol/L glucose clamp levels, respectively. The second-phase reached steady state by 90 to 120 minutes, with median C-peptide secretion rates of 0.31, 0.56, and 0.85 nmol/min after 120 minutes at 7.5, 10, and 15 mmol/L, respectively. The slopes of the curves of steady-state insulin and C-peptide secretion rates v the four glucose levels (basal plus the three clamp levels) were maximally steep between 7.5 and 10 mmol/L in the majority of subjects, consistent with in vitro sigmoidal responses. A characterization of the secretory response of the B cell of normal humans at different glucose concentrations has been obtained. With appropriate models, insulin secretion rates may be estimated from either plasma insulin or C-peptide concentration data.

Adult↗
PubMed1988

Pathogenesis of NIDDM--a disease of deficient insulin secretion.

Type 2 diabetes is a familial disease and studies of both Caucasian and Japanese families have raised the possibility that a major susceptibility gene is involved. The majority of patients have both beta cell dysfunction and impaired insulin sensitivity but studies of relatives of Type 2 diabetic patients suggest that beta cell dysfunction is an early feature of the disease. Impaired insulin sensitivity, from acromegaly, Cushing's disease or steroid therapy, induces diabetes only in a small proportion of the population, and they may be those who have an inherited cell defect. We postulate that a single beta cell defect gene, on its own, may be insufficient to cause overt diabetes and would lead to life-long glucose intolerance unless associated with other defects such as impaired insulin sensitivity. The nature of such a postulated beta cell defect is uncertain. Whilst it has been reported to be specific to glucose, and not to non-glucose stimuli, this feature may be secondary to hyperglycaemia. The occurrence of islet amyloid in 70-90% of Type 2 diabetic patients, and rarely in the normal population, raises the possibility that amyloid deposition causing disruption of the islet is a factor which might affect beta cell function. Amyloid formation may be a primary abnormality or could be secondary to beta cell dysfunction induced by hyperglycaemia. A major susceptibility gene might predispose a proportion, perhaps 10-15%, of a Caucasian population towards diabetes. The subsequent development of diabetes in a particular patient is likely to depend on many factors including other genetic factors, a sedentary life style and obesity. In different populations different genetic influences may operate, including abnormalities of insulin receptor genes and glucose transporter genes, which may allow a beta cell abnormality to become expressed clinically.

Diabetes Mellitus, Type 2↗
PubMed1988

Diabetes mellitus and anaesthesia. A survey of the peri-operative management of the patient with diabetes mellitus.

A variety of methods are currently available for the management of the diabetic patient in the peri-operative period. A questionnaire about current clinical practice was sent to all anaesthetists in the Oxford region. The majority reported that minor surgery in both insulin treated and noninsulin treated diabetic patients warranted no intervention other than avoidance of meals and medication before surgery, and that, for major surgery, a glucose-insulin-potassium infusion should be used. Fifty one out of 71 respondents in the junior staff grades preferred this latter approach for intermediate surgical procedures in insulin treated patients compared with 27 out of 69 of the consultant staff. Most anaesthetists aimed for blood glucose levels of 7-13 mmol/litre in the peri-operative period. The literature is also reviewed.

Anesthesia↗
PubMed1988

Natural history of pancreatic islet B-cell function in type 2 diabetes mellitus studied over six years by homeostasis model assessment.

Islet B-cell function and insulin sensitivity were estimated with the aid of a mathematical model from repeated fasting plasma glucose and insulin measurements over a 6 year period in 131 patients with type 2 diabetes mellitus who could be managed satisfactorily on dietary therapy alone. They presented between the ages of 40 and 69 years, and were studied before and after one year of treatment, and then at regular intervals from 12 until 72 months later. A method of averaging the individual trends by means of a linear model regression technique was used to assess the progression of their diabetes. Dietary management over the first 12 months resulted in weight loss from 118% to 106% average body weight, and improved insulin sensitivity from 26% to 40% of normal (p less than 0.001). From 12 to 72 months, the fasting plasma glucose rose at a mean rate of 0.23 mmol/l per year (p less than 0.001) despite a rate of weight loss of 0.2% average body weight per year (p less than 0.01). The estimated islet B-cell function, expressed as a percentage of normal, decreased significantly (p less than 0.05) at a rate of 1.5% per year, with no statistically significant change in insulin sensitivity. Extrapolation suggests the reduction in B-cell function predated the departure of fasting plasma glucose from the normal range.

Adult↗
PubMed1988

Optimizing blood glucose control in type 2 diabetes: an approach based on fasting blood glucose measurements.

A structured approach to the management of Type 2 diabetes, aiming to reduce fasting blood glucose levels to near-normal, can provide effective blood glucose control with minimal risk of hypoglycaemia and in a manner acceptable to most patients. When the fasting blood glucose value is maintained in the region 4-6 mmol l-1, protein glycosylation and plasma triglyceride values usually become near-normal and this may help to prevent the development of long-term diabetic complications. We propose a simple management strategy, based on 3-monthly fasting blood glucose determination, which uses not more than two therapeutic agents at any one time. If diet and maximal oral therapy fail to keep fasting blood glucose levels below 6 mmol l-1 then the addition of a basal insulin supplement, e.g. from a once daily injection of ultralente insulin, can restore near-normal fasting blood glucose levels without the need for full insulin replacement therapy. In older patients, where long-term prevention of diabetic complications is not such an immediate priority, less strict blood glucose control may be reasonable, aiming to keep the fasting blood glucose values below 10 mmol l-1 in order to prevent symptoms secondary to glycosuria. Patients can be seen at a monthly general practice morning diabetic mini-clinic or with the aid of a nurse visiting elderly patients at home.

Blood Glucose↗
PubMed1988

Suppression of insulin secretion by falling plasma glucose levels is impaired in type 2 diabetes.

The ability of Type 2 diabetic patients to suppress islet B-cell secretion in response to falling plasma glucose levels has been studied with two different protocols. (1) Five diet-treated diabetic patients and 6 normal subjects were studied after the termination of a hyperglycaemic clamp at 15 mmol l-1 for 150 min, with the plasma glucose levels then being allowed to fall and the glucose clamp re-established at 10 mmol l-1. The plasma insulin levels fell in normal subjects from 178 +/- 141 (+/- SD) mU l-1 at the end of the 15 mmol l-1 clamp to 147 +/- 97 mU l-1 (p less than 0.02) 20 min later, whereas in diabetic patients there was no significant change from 61 +/- 41 to 56 +/- 35 mU l-1, respectively (NS). (2) The second study was performed to assess the turn-off of islet B-cell secretion with diabetic patients and normal subjects starting at comparable plasma insulin levels. Twelve diet-treated diabetic patients and 11 normal subjects were given a continuous low-dose glucose infusion for 60 min at a rate of 5 mg kg-1 ideal body weight min-1, after which the infusion was turned off and the plasma glucose level allowed to fall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Retinal pigment epithelial change and partial lipodystrophy.

Cuticular drusen and retinal pigment epithelial changes were found incidentally in a 27 year old Lebanese woman during assessment of partial lipodystrophy. Her vision was normal despite involvement of both maculae. The patient had hypocomplementaemia, but serum C3 nephritic factor was absent and renal function was normal. She had impaired glucose tolerance and a continuous infusion of glucose with model assessment (CIGMA) test revealed low normal tissue insulin sensitivity and high normal pancreatic beta cell function. Mild fasting hypertriglyceridaemia (2.0 mmol/l) may have been secondary to impaired insulin sensitivity. Endocrine function was otherwise normal apart from a completely absent growth hormone response to adequate hypoglycaemia. The simultaneous occurrence of partial lipodystrophy and retinal pigmentary epithelial and basement membrane changes appears to be a newly recognized syndrome.

Adult↗
PubMed1988

Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes.

Morphometric analysis of the endocrine and exocrine pancreas was done on immunoperoxidase stained post-mortem tissue from 15 Type 2 diabetic and 10 age-matched control subjects. Thirteen of the 15 Type 2 diabetic patients had islet amyloid deposits (mean, 6.5% islet area) in the corpus (body, tail and anterior part of the head) but not in the caput (the "pancreatic polypeptide rich" part of the head) whereas none was seen in control subjects. In the corpus in diabetic subjects, the pancreatic area density of B-cells was decreased by 24% (p = 0.005) and A-cells increased by 58% (p less than 0.001) compared with control subjects. The mean A/B-cell ratio increased in the corpus from 0.27 in control subjects to 0.57 in Type 2 diabetic patients. Positive immunoreactivity for the amyloid constituent peptide, Diabetes Associated Peptide, was demonstrated in islet amyloid of diabetic subjects and in B-cells of control and diabetic subjects. The increase in A-cells may contribute to the hyperglucagonaemia and hyperglycaemia of Type 2 diabetes. The impaired insulin secretion in Type 2 diabetes may be due to a decrease in B-cells and to disruption of the islet structure by amyloid. Exocrine fat was similar in the control and diabetic subjects with both groups having more in the corpus than the caput. Diabetic subjects had increased exocrine fibrosis in the corpus region (p less than 0.001), but not in the caput. Exocrine fibrosis may be secondary to disordered islet cell function.

Aged↗
PubMed1988

Smoking cessation counseling by resident physicians in internal medicine, family practice, and pediatrics.

Residents in primary care specialties care for many patients who smoke cigarettes, but little is known about their smoking cessation counseling (SCC). We surveyed 309 residents (72 family practice, 171 internal medicine, and 66 pediatrics residents) in 13 programs to determine their practices, knowledge, attitudes, and training in SCC. More than 90% thought physicians are responsible for SCC, the majority routinely took smoking histories, and 80% attempted to motivate patients to quit smoking. However, 25% or fewer reported discussing obstacles to quitting, setting a quit date, prescribing nicotine gum, scheduling follow-up visits, or providing self-help materials. Family practice residents used more SCC techniques (1.8) than did internal medicine (0.8) and pediatrics (0.1) residents. Only 54% of residents reported recent SCC training and 13% reported formal SCC training. Recent training correlated with the number of counseling techniques used. Residents in primary care specialties report positive attitudes but inadequate practice and training in SCC.

Attitude of Health Personnel↗