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Biomedical subjects

D R McCance

Publications and source records attributed to D R McCance.

At least 37 records · Page 2Linked to original sources
PubMed1999

A comparison of the naloxone test with the insulin stress test in patients following transsphenoidal surgery.

OBJECTIVE: To study the reliability of the naloxone test in assessing the hypothalamic-pituitary-adrenal (HPA) axis in patients following transsphenoidal pituitary surgery, by comparison with the insulin stress test (IST). Also, to establish a normal range for the response to naloxone in healthy controls. DESIGN: All patients had the IST performed, soluble insulin 0.1-0.3 U/kg (usually 0.15 U/kg) being administered intravenously, followed by venous sampling for plasma glucose and serum cortisol at 0, 15, 30, 45, 60, 75 and 90 minutes. Naloxone (125 micrograms/kg body weight) was similarly administered to all patients 6 days later, with sampling at -15, 0, 15, 30, 45, 60, 90 and 120 minutes for plasma glucose, serum cortisol and plasma ACTH. The naloxone test was also performed on control subjects using an identical protocol. SUBJECTS: Twenty patients (11F/9M) aged 48.8 +/- 2.8 years (mean +/- SE) 4-6 weeks following transsphenoidal pituitary surgery. Twelve normal healthy control subjects (6F/6M) aged 31.5 +/- 3.0 years. MEASUREMENTS: Serum cortisol was measured by radioimmunoassay and plasma ACTH by immunoradiometric assay. RESULTS: Adequate hypoglycaemia (< or = 2.0 mmol/l) was achieved in all patients. Peak cortisol was > 550 nmol/l in 17 subjects (range: 572-867 nmol/l) and a subnormal response observed in 3 (peak cortisol 163-498 nmol/l). In the 17 patients with a normal cortisol response to hypoglycaemia the response to naloxone was extremely variable, with serum cortisol falling in 4 and an increment of < or = 100 nmol/l in 6 others. In the 3 patients who failed the IST, two responded to naloxone and one did not. In normal controls, 3 of the 12 had little or no response to naloxone. CONCLUSIONS: As the naloxone test fails to produce a response in all normal subjects it is impossible to define a 'normal' response. The numerous discrepancies with the IST in patients are further evidence of the test's lack of reliability in assessing the HPA-axis and it is consequently not a viable alternative to traditional dynamic methods such as the IST.

Adrenocorticotropic Hormone↗
PubMed1999

Endothelial function in offspring of Type 1 diabetic patients with and without diabetic nephropathy.

AIMS: Familial aggregation of diabetes and nephropathy has been observed in several populations. Various interpretations have included underlying genetic mechanisms possibly mediated by a predisposition to hypertension. Endothelial dysfunction is now recognized as central to these conditions and offers a unifying mechanism to explain the disease aggregation. To test this hypothesis, we have examined endothelial function in healthy subjects at differing risks for diabetic nephropathy. METHODS: Endothelial function was assessed in 12 healthy offspring (nine male (M)/three female (F); age 25.8+/-1.2 years, mean +/- SEM) of parents with Type 1 diabetes mellitus (DM) and end-stage renal disease compared with 12 control offspring (9 M/3 F; age 26.3+/-1.3 years) of parents with long duration (>20 years) Type 1 DM but without evidence of nephropathy. Forearm blood flow responses to brachial artery infusion of acetylcholine (endothelium-dependent), sodium nitroprusside (endothelium-independent), noradrenaline and the competitive inhibitor of basal nitric oxide release N(G)-monomethyl-L-arginine were assessed using venous occlusion plethysmography. RESULTS: There were no significant differences between the groups in von Willebrand factor, fasting plasma glucose (4.2+/-0.1 vs. 4.0+/-0.2 mmol/l) or in 24-h ambulatory blood pressure. Similarly, the groups did not differ in vasodilation to acetylcholine (P = 0.75) and sodium nitroprusside (P = 0.79) or in vasoconstriction to noradrenaline (P = 0.45) and N(G)-monomethyl-L-arginine (P = 0.30). CONCLUSION: These data do not support a role for endothelial dysfunction in the familial aggregation of diabetic nephropathy.

Adult↗
PubMed1999

Advances in management of Type 1 diabetes and pregnancy.

Obstetricians will need to update themselves on the recent changes in terminology and in diagnostic criteria for Type 1 diabetes mellitus. This still remains a high-risk obstetric situation, in spite of optimistic reports from centres of excellence. Pregnancy-associated hypertension may be closely related to insulin resistance. A number of concepts and hypotheses are based on the central role of insulin in fetal development.

Diabetes Mellitus, Type 1↗
PubMed1999

Relationship of endothelial function to birth weight in humans.

OBJECTIVE: Low birth weight has been associated with hyperlipidemia, hypertension, diabetes, and coronary heart disease in adult life, but the precise mechanism is debated. The endothelium is thought to play a pivotal role in each of the above conditions with abnormalities being detectable before the development of overt disease. To investigate the possibility that endothelium has a role in mediating the excessive risk of adult vascular disease associated with low birth weight, endothelial function was assessed in young healthy adults who were either of low or normal birth weight at term. RESEARCH DESIGN AND METHODS: Twelve low birth weight (2.2 +/- 0.05 kg, mean +/- SEM) subjects (six men/six women; age 28 +/- 0.2 years) and twelve age- and sex-matched normal birth weight (3.3 +/- 0.07 kg) control subjects were studied. The L-arginine-nitric oxide pathway was assessed in the forearm vascular bed by using venous occlusion plethysmography during intra-arterial brachial infusion of acetylcholine, sodium nitroprusside, norepinephrine, and NG-monomethyl-L-arginine (L-NMMA). Von Willebrand factor, a noninvasive marker of endothelial dysfunction, was also measured. Comparisons were made using Student's t test. RESULTS: Von Willebrand factor was significantly elevated in low birth weight compared with normal birth weight subjects (136.9 +/- 12.7 vs. 95.6 +/- 9.5%; P = 0.016). The groups did not differ in the responses to acetylcholine (P = 0.76), sodium nitroprusside (P = 0.84), norepinephrine (P = 0.21), or L-NMMA (P = 0.35). CONCLUSIONS: The finding of elevated von Willebrand factor in low birth weight subjects is suggestive of endothelial cell injury but does not appear to be associated with dysfunction of the L-arginine-nitric oxide pathway.

Acetylcholine↗
PubMed1999

Basal nitric oxide production is impaired in offspring of patients with essential hypertension.

There is considerable evidence that endothelium-dependent nitric oxide (NO)-mediated vasodilatation in response to acetylcholine is impaired in essential hypertension, whereas the endothelium-independent response to sodium nitroprusside is normal. More limited data have suggested that there is also reduced vasoconstriction in response to N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of basal NO release. As it is not known whether endothelial dysfunction in hypertension, if indeed present, is a cause or consequence of the condition, we have studied the normotensive offspring of parents with essential hypertension. Both basal and stimulated vascular responses were examined in 12 normotensive offspring [mean age (+/-S.E.M.) 26.1+/-1.4 years] of parents with essential hypertension and compared with those in 12 age-matched offspring (mean age 25.6+/-1.1 years) of normotensive subjects. Forearm blood flow was measured simultaneously in both arms by venous occlusion plethysmography, both at baseline and during intra-arterial brachial infusion of increasing doses of acetylcholine, sodium nitroprusside, noradrenaline and L-NMMA. There were no significant differences between the groups in the responses to acetylcholine, sodium nitroprusside or noradrenaline. In contrast, the vasoconstrictor response to L-NMMA was significantly blunted in the offspring of hypertensive parents compared with that in the offspring of normotensive parents (P=0.005). Thus endothelial dysfunction, as demonstrated by impaired basal production of NO, is present in subjects at high risk of essential hypertension, and does not occur simply as a consequence of the condition.

Acetylcholine↗
PubMed1998

Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study.

Secondary failure of plasma glucose control following initial successful response to diet therapy may be due to dietary indiscretion, or to progression of the intrinsic diabetic condition. We report a 10-year prospective natural history study of 432 newly diagnosed diabetic patients aged 40-69 years undertaken to assess the effect of intensive dietary management, where patients were transferred to insulin, or oral hypoglycaemic therapy (tolbutamide, metformin) by predetermined criteria of weight and plasma glucose. Secondary failure to diet therapy occurred in 41 patients in years 2-4, 67 patients in years 5-7, and 51 patients in years 8-10; 173 patients remained on diet alone until death or the end of the study. Continuation on diet alone was associated with a lower ongoing fasting plasma glucose, greater beta-cell function assessed by an oral glucose tolerance test at 6 months, and increasing age. The rate of rise of fasting plasma glucose was inversely related to the duration of successful dietary therapy, but mean weight remained constant in all groups while on diet alone. The ongoing fall in beta-cell function assessed by HOMA modelling closely mirrored the progressive rise in fasting plasma glucose: there was no change in mean insulin sensitivity in any of the groups.

Adult↗
PubMed1997

Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes.

The glycoxidation products Nepsilon-(carboxymethyl)lysine and pentosidine increase in skin collagen with age and at an accelerated rate in diabetes. Their age-adjusted concentrations in skin collagen are correlated with the severity of diabetic complications. To determine the relative roles of increased glycation and/or oxidation in the accelerated formation of glycoxidation products in diabetes, we measured levels of amino acid oxidation products, distinct from glycoxidative modifications of amino acids, as independent indicators of oxidative stress and damage to collagen in aging and diabetes. We show that ortho-tyrosine and methionine sulfoxide are formed in concert with Nepsilon-(carboxymethyl)lysine and pentosidine during glycoxidation of collagen in vitro, and that they also increase with age in human skin collagen. The age-adjusted levels of these oxidized amino acids in collagen was the same in diabetic and nondiabetic subjects, arguing that diabetes per se does not cause an increase in oxidative stress or damage to extracellular matrix proteins. These results provide evidence for an age-dependent increase in oxidative damage to collagen and support previous conclusions that the increase in glycoxidation products in skin collagen in diabetes can be explained by the increase in glycemia alone, without invoking a generalized, diabetes-dependent increase in oxidative stress.

Adolescent↗
PubMed1997

Macrovascular disease and hyperglycaemia: 10-year survival analysis in Type 2 diabetes mellitus: the Belfast Diet Study.

The relationship between macrovascular disease and blood glucose control in long-term follow-up of Type 2 (non-insulin-dependent) diabetes mellitus is difficult to study because of the gradual rise in fasting plasma glucose due to ongoing beta-cell failure. We used time-dependent covariates in Cox's proportional hazards model to allow variables measured annually during a 10-year prospective follow-up to be related to risk of myocardial infarction or cerebrovascular accident. Data for 432 newly diagnosed diabetic patients were available, 112 of whom suffered myocardial infarction (fatal or non-fatal). Analysis of baseline measurements only gave relative hazards (95% CL) of 1.04 (0.99, 1.09) per mmol l(-1) increase in fasting plasma glucose, 1.43 (1.12, 1.83) per decade increase in age and 1.07 (0.98, 1.17) per 10 % increase in percentage of ideal weight. Analysis incorporating ongoing measurements gave corresponding figures of 1.07 (1.02, 1.12) for fasting plasma glucose, 1.64 (1.23, 2.20) for age and 1.06 (0.95, 1.18) for percentage of ideal weight. The risk of myocardial infarction while on insulin treatment 1.09 (0.58, 2.06) or oral agents 1.41 (0.86, 2.31) was not significantly elevated relative to dietary treatment. Baseline smoking status, systolic blood pressure, and previous myocardial infarction were also significant predictors of myocardial infarction. Similar relationships were found for cerebrovascular accident and total mortality. Increasing fasting plasma glucose is a significant independent predictor of macrovascular disease in diabetes.

Adult↗
PubMed1997

Diagnosing diabetes mellitus--do we need new criteria?

The current classification and diagnostic criteria for diabetes mellitus were introduced by the United States National Data Group in 1979 and endorsed by the World Health Organization in 1980, with modifications in 1985 and 1994. The criteria, chosen to reflect the risk of complications, were the synthesis of considerable thought and expertise and represented a consensus which, it was hoped, would prove helpful to all those involved with diabetes-practising clinician, research scientist and epidemiologist alike. The inconvenience, variability and non-physiological nature of the oral glucose tolerance test (OGTT) are well-recognised. In spite of these limitations the 2-h post-load plasma glucose has remained the standard against which all other tests have been evaluated. This article reviews the original justification for the OGTT, and in the light of more recent epidemiological research seeks to place the current diagnostic criteria for diabetes into a pathophysiological, diagnostic and prognostic perspective.

Blood Glucose↗
PubMed1996

Assessment of cure after transsphenoidal surgery for Cushing's disease.

The best long-term results of transsphenoidal surgery appear to be in those patients who have unmeasurable serum cortisol levels in the immediate post-operative period. This appears to be due to isolated ACTH deficiency in the remaining normal pituitary gland. In our experience, however, long-term clinical remission may be possible with measurable serum cortisol levels post-operatively. The cortisol response to ACTH or CRF appears to provide no greater discrimination than basal measurements and is possibly less helpful than dexamethasone suppression. The prolonged clinical remission that we have seen in some patients with early measurable but low cortisol levels, together with the possible operative morbidity and partial success of repeat surgery, suggests careful assessment before a recommendation is made of an immediate second operation in these patients. The possibility of cyclical secretion of cortisol must be considered both pre and post-operatively. Finally, as experience with transsphenoidal surgery is still relatively short, all these patients need continuing endocrine follow-up in centres with adequate experience of the condition. For the individual patient we recommend that decisions regarding further therapy are based on 0800-0900 h serum cortisol levels, an index of cortisol production (serum cortisol day profiles or 24 hour urinary free cortisol), and the response to low dose dexamethasone suppression in the early post-operative period.

Cushing Syndrome↗
PubMed1996

Weight fluctuation, mortality and vascular disease in Pima Indians.

OBJECTIVE: To examine the relationship of weight fluctuation to mortality rates and incidence of vascular disease. SUBJECTS: A cohort of Pima Indians, 572 of whom had non-insulin-dependent diabetes mellitus and 766 without diabetes. DESIGN: Individuals were invited biennially to research examinations. The root mean square error (RMSE) of the linear trend of weight with time for the first four examinations after age 20 years was used as an index of weight fluctuation. Subjects were followed from the fourth examination until death or until 31 December 1991. The mortality rate ratio (MRR) and its 95% confidence interval (CI) for those with a high weight fluctuation index relative to those with a lower value were determined. The median duration of follow up was 9.3 (range 0.1-22.6) years. MEASUREMENTS: All cause mortality (n = 356); incidence of diabetic retinopathy (n = 145), diabetic nephropathy (n = 132) and electrocardiographic abnormalities (n = 82). RESULTS: There was no significant relationship between weight fluctuation and mortality for diabetic subjects (MRR = 1.0, 95% CI 0.8-1.3, p = 0.91). Nondiabetic subjects with a high weight fluctuation index had a higher mortality rate than those with a lower index (MRR = 1.5, 95% CI 1.0-2.1, p = 0.03); the association was stronger among men than among women. The excess mortality in the high weight fluctuation group was not due to cardiovascular diseases, but to noncardiovascular causes and the risk for alcohol-related death was particularly increased. Weight fluctuation was not associated with the incidence of diabetic retinopathy, nephropathy or electrocardiographic abnormalities. CONCLUSIONS: A high weight fluctuation index was associated with higher mortality rates in nondiabetic, but not in diabetic, Pima Indians. The excess mortality is largely due to noncardiovascular causes of death and may reflect lifestyle factors associated with weight fluctuation, rather than its metabolic effects.

Adult↗
PubMed1995

Early and late insulin response as predictors of NIDDM in Pima Indians with impaired glucose tolerance.

Risk factors predicting deterioration to diabetes mellitus were examined in 181 subjects with impaired glucose tolerance. Fifty-seven subjects had impaired glucose tolerance on one occasion followed by normal glucose tolerance at a repeat oral glucose tolerance test, and 124 subjects had impaired glucose tolerance on two successive oral glucose tolerance tests. Subjects were followed for a median period of 5.0 years (range 1.0-17.2). The age- and sex-adjusted cumulative incidence of diabetes at 10 years of follow-up was higher in subjects who had impaired glucose tolerance on both tests (70%) than in those whose glucose tolerance was normal at the repeat test (53%), [rate ratio (RR) = 1.6, 95% confidence intervals (CI) = 1.0-2.5]. Proportional hazards analyses were used to identify baseline risk factors (measured at the repeat oral glucose tolerance test) for subsequent diabetes, and incidence rate ratios were calculated for the 90th percentile compared with the 10th percentile of each continuous variable for the whole group. In all subjects, in separate models, higher body mass index [RR = 2.0, 95% CI = 2.2-9.9], high fasting serum insulin concentrations [RR = 2.4, 95% CI = 1.4-4.2], and low early insulin response [RR = 0.5, 95% CI = 0.3-0.8] 30 min after a glucose load were significant predictors for deterioration to diabetes. In a multivariate analysis which controlled for age and sex, 120-min post-load glucose, fasting insulin and late insulin response predicted diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Diabetic nephropathy: a risk factor for diabetes mellitus in offspring.

Both non-insulin-dependent diabetes mellitus and diabetic nephropathy show familial aggregation. If diabetes and renal disease have independent determinants (genetic or otherwise), offspring of parents with diabetic renal disease should have a similar risk of diabetes to those offspring of parents with diabetes alone. To test this hypothesis, the prevalence of diabetes was examined in a population-based pedigree study in Pima Indian offspring of three mutually exclusive parental types: 1) diabetic with renal disease, 2) diabetic, but without renal disease and 3) non-diabetic. Among offspring of one diabetic parent and one non-diabetic parent (n = 320) the prevalence of diabetes at ages 15-24 years and 25-34 years was 0% and 11%, respectively if the diabetic parent did not have renal disease compared with 6% and 28% respectively if the diabetic parent did have renal disease. Corresponding rates for offspring of two diabetic parents (n = 121) were 10% and 17%, respectively if neither parent had renal disease compared with 30% and 50%, respectively if one parent did have renal disease. The presence of renal disease in a parent with diabetes relative to diabetes alone was associated with 2.5 times the odds of diabetes (95% confidence interval 1.4-4.3) in the offspring controlled for age, age at onset of parental diabetes and diabetes in the other parent using logistic regression. These findings provide support for parental diabetic renal disease, independent of age at onset of parental diabetes, conferring an increased risk for diabetes in the offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

The U-shaped association between body mass index and mortality: relationship with weight gain in a Native American population.

In order to determine whether weight loss explains high mortality rates in those with a low body mass index (BMI), the relationships between BMI, rate of weight gain and mortality were examined in Pima Indians. Subjects were 814 diabetic and 1814 nondiabetic participants in a longitudinal survey who had at least two examinations after age 20. Median duration of follow-up was 8.1 (range 0.03-25.1) years. BMI showed a U-shaped relationship with mortality rates in men with the lowest rates in the 30-35 kg/m2 category; an inverse relationship was seen in women. Subjects who were losing weight had higher mortality rates than those who were gaining. However, excess mortality among the lightest subjects was present among those who were gaining weight. Among nondiabetic subjects, the mortality ratio (MR) for BMI < 25 kg/m2 compared with 30-35 kg/m2 was 1.5 [95% confidence interval (CI) 1.0-2.2] unadjusted for weight gain, while the adjusted MR was 1.3 [95% CI 0.9-1.9]. Weight loss, which may reflect underlying illness, is associated with high mortality rates in Pima Indians but does not fully account for the high mortality in the lightest individuals.

Adult↗
PubMed1995

Four years' treatment of resistant acromegaly with octreotide.

This study was designed to ascertain the long-term safety and efficacy profile of the somatostatin analogue octreotide as treatment of refractory acromegaly. Eight patients (aged 21-62 years) with persistent growth hormone (GH) elevation (duration 1-15 years) despite previous therapy were studied. Octreotide was given subcutaneously in increasing doses for the first year to a maximum of 500 micrograms three times daily. The dose then was reduced to 200 micrograms three times daily for the next 3 years. At annual assessments, 24-h GH profiles, insulin-like growth factor I (IGF-I) and a side-effect profile including gall-bladder ultrasound were studied. Oral glucose tolerance tests (75 g) were performed basally and after 6 months and 3 years of therapy. Haemoglobin A1 (HbA1) was also assessed. Side effects were recorded. Mean GH (+/- SEM) was 36.0 +/- 9 mU/l basally and was reduced significantly at all subsequent assessments on therapy (4-year mean, 9.4 +/- 2.1 mU/l). The IGF-I level also remained suppressed and was normalized in four of eight patients who remained on octreotide. Fasting plasma glucose and HbA1 were not changed by therapy but 2-h glucose was elevated after 6 months and 3 years (basal mean, 7.6 mmol/l (5.3-9.0 mmol/l); 3-year mean, 10.7 mmol/l (8.4-15.7 mmol/l); p < 0.05). Five patients developed gallstones and in three these had disappeared following 1 year of bile salt dissolution therapy. Octreotide continues to suppress serum GH and IGF-I long term without attenuation of effect. Gallstone formation is a major side effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1995

Rate of weight gain, weight fluctuation, and incidence of NIDDM.

The relationships of rate of weight gain and weight fluctuation to incidence of non-insulin-dependent diabetes mellitus (NIDDM) were examined in Pima Indians. The 1,458 subjects were participants in a prospective study with examinations approximately every 2 years. Rate of weight gain was defined as the slope of the regression line of weight with time for two or more consecutive examinations > or = 2 years apart and weight fluctuation as the root-mean-square departure from this line for four examinations. Among men, incidence of NIDDM was strongly and significantly related to rate of weight gain (e.g., age-adjusted incidence = 56.7/1,000 person-years in those with weight gain > or = 3 kg/year and 16.9/1,000 person-years for those losing weight [Ptrend < 0.01]). In women, weight gain was significantly related to diabetes incidence only in those who were not initially overweight (body mass index < 27.3 kg/m2). In contrast to the relationship with weight gain, weight fluctuation was not associated with incidence of diabetes in either sex. These findings suggest that weight control in overweight individuals may be a more effective strategy for prevention of NIDDM in men than in women, whereas prevention of obesity may prevent diabetes in both sexes. Concern about a diabetogenic effect of weight fluctuation should not deter weight-control efforts.

Adult↗
PubMed1995

Comparison of body size measurements as predictors of NIDDM in Pima Indians.

OBJECTIVE--To determine and compare the abilities of various anthropometric measurements to predict the development of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indian men and women. RESEARCH DESIGN AND METHODS--A total of 290 male and 443 female Pima Indians were followed for up to 6 years for the development of NIDDM. A proportional hazards analysis was used to assess the ability of anthropometric measurements evaluated at baseline to predict NIDDM. Receiver operating characteristic (ROC) curves were used to compare individual variables in predicting NIDDM. RESULTS--In separate models controlled for age and sex, body mass index (BMI), waist circumference, thigh circumference, waist-to-thigh ratio (WTR), weight, and percentage body fat (PBF) estimated by bioelectric resistance each predicted NIDDM, which developed in 30 men and 52 women. The highest incidence rate ratios (IRRs; for 1 SD of a variable) were for WTR in men and for PBF in women, although the confidence interval (CI) for PBF was wide. In stepwise analyses, WTR was the most significant predictor in men (IRR for 1 SD = 1.58, 95% CI = 1.20-2.07), and BMI was the most significant predictor in women (IRR for 1 SD = 1.65, 95% CI = 1.29-2.11). However, by ROC analyses, thigh circumference was the only variable significantly worse than WTR in men or BMI in women at predicting NIDDM. CONCLUSIONS-- Measurements such as waist circumference, WTR, weight, and BMI may be useful as more complicated measurements, such as PBF by bioelectrical resistance, for identifying groups of individuals whose body habitus places them at high risk of developing NIDDM.

Adolescent↗