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Biomedical subjects

V J McCann

Publications and source records attributed to V J McCann.

At least 19 recordsLinked to original sources
PubMed1996

Microalbuminuria in type 2 diabetes: an independent predictor of cardiovascular mortality.

BACKGROUND: Microalbuminuria has been shown to be associated with cardiovascular mortality in type 2 diabetic subjects. It is unclear to what extent this is due to the increased prevalence of other cardiac risk factors. AIMS: To examine the relationship of urine albumin excretion to cardiovascular mortality and to determine its status as an independent risk factor. METHODS: In a prospective longitudinal study from 1986-1993 we followed 666 type 2 diabetic subjects from a diabetes outpatient service. Cardiovascular risk factors including urine albumin concentration were measured at study entry. Cox proportional hazards regression was used to determine risk factors for mortality. The hazard ratios of microalbuminuria and macroalbuminuria for all cause, cardiovascular and coronary heart disease mortality were determined after accounting for other cardiac risk factors including blood pressure, glycated haemoglobin, total cholesterol, HDL cholesterol, triglycerides, urea, smoking, body mass index, patient age and disease duration. RESULTS: The prevalence of urine albumin of 30-300 mg/L at study entry was 31.7%. A total of 167 deaths occurred (80 from cardiovascular disease). Mortality hazard ratios in subjects with urine albumin of 30-300 mg/L as compared to < 30 mg/L, adjusted for age, sex and other cardiovascular risk factors were 1.77 (95% CI 1.22-2.57, p = 0.002) for all causes, 2.34 (95% CI 1.38-3.99, p = 0.002) for cardiovascular and 1.78 (95% CI 0.97-3.26, p = 0.061) for coronary heart disease (CHD) mortality. Other factors significantly associated with cardiovascular mortality included diastolic blood pressure, HDL cholesterol and glycated haemoglobin. Total cholesterol and log triglyceride were significantly associated with CHD mortality. Disease duration, age at diagnosis, smoking and body mass index were not related to cardiovascular or CHD mortality. CONCLUSIONS: We confirm microalbuminuria as an independent predictor of mortality in type 2 diabetes despite its association with a number of conventional cardiovascular risk factors.

Albuminuria↗
PubMed1994

Mortality and coronary heart disease in diabetes mellitus.

A clinic-based study of 1,063 patients with Type 2 diabetes recruited from 1973 to 1982 identified 533 deaths (attributed to coronary heart disease in 268 cases) by 31 December 1989. When compared to the general population of Australia the overall standardised mortality ratio was 1.42 (95 per cent confidence interval (CI) 1.26 to 1.58) for females and 1.19 (CI 1.03 to 1.35) for males. Cox regression analysis showed that having coronary heart disease or absence of foot pulses at the time of entrance to the study were the major independent risk factors for overall mortality after adjustment for initial age. Elevated cholesterol and blood pressure were found to be major independent risk factors for death from coronary heart disease.

Adult↗
PubMed1992

Type 1 diabetes and latent pernicious anaemia.

OBJECTIVE: To determine the prevalence of latent pernicious anaemia (PA) in Type 1 diabetics. DESIGN: Patients with Type 1 diabetes were screened at two yearly intervals on a continuing basis. SETTING: Diabetic Unit, Royal Perth Hospital, Western Australia. PATIENTS: Three hundred and seventy-one patients, 156 females and 215 males, attending a diabetic clinic. They were classified as having Type 1 diabetes on the basis of age of onset less than 40 years and requiring insulin from the start. MAIN OUTCOME MEASURES: Serum cobalamin levels were measured and studies of thyroid function and a blood count were done. Patients with a reduced serum level of cobalamin had tests for cobalamin absorption. RESULTS: Six patients had a low serum cobalamin level; five showed malabsorption of the vitamin which could be corrected by the addition of intrinsic factor. Four of these patients had no clinical signs of PA. The fifth was mildly anaemic (haemoglobin level 111 g/L) and had megaloblastic bone marrow. He was classified as having frank PA. The sixth patient was not available for further testing. These results give a prevalence of latent PA of 11 per 1000 in Type 1 diabetics, compared with 3.9 per 1000 in diabetics with clinically manifest disease and 1.27 per 1000 in the general population. All four patients with latent PA had hypothyroidism, based on low thyroxine levels, increased levels of thyroid stimulating hormone and the presence of thyroid antibodies. CONCLUSION: Latent PA is not uncommon in Type 1 diabetics. It has a long preclinical course and occurs in those patients with thyroid disease. The screening of Type 1 diabetics for latent PA has worthwhile benefits as a "preventive" health measure.

Anemia, Pernicious↗
PubMed1986

Reference ranges for serum C4 concentrations in subjects with and without C4 null alleles.

Serum C4 concentrations were measured in 102 healthy subjects and 90 subjects with type I diabetes mellitus. A wide range was observed in the group as a whole (0.08-0.67 g/l; mean = 0.26 g/l; SEM = 0.01 g/l). After C4 allotyping it was possible to subgroup 134 of these subjects according to the number of C4 null alleles present. C4 concentrations in the group with two null alleles were lower than in the group without null alleles (mean 0.2 v 0.37 g/l; p less than 0.001). C4 concentrations in the group with one C4 null allele were intermediate and significantly different from those of the group without null alleles (mean 0.24 v 0.37 g/l; p less than 0.001). Appropriate analysis has defined reference ranges for serum C4 concentrations in subjects with two, one, or zero C4 null alleles. Interpretation of low serum C4 concentrations should take account of the number of C4 null alleles present.

Adult↗
PubMed1986

Prevalence of diabetic complications in relation to risk factors.

The prevalence of diabetic complications is reported from a cross-sectional study of rural diabetic subjects in Western Australia. Logistic-regression analysis has been used to discover potential risk factors associated with each complication. A distinction has been made between time-related variables (age, age at diagnosis, duration of diabetes) and other risk variables. We have attempted to identify the major time-related risk variables for each complication and then examined the effect of other risk variables after accounting for the major time-related variables. The important time-related variables were found to be duration of diabetes for retinopathy, age for macrovascular disease, duration and age at diagnosis of diabetes for sensory neuropathy, and age for renal impairment. When matched on these important time-related variables, the overall prevalences of complications for insulin-dependent (IDDM) compared with non-insulin-dependent (NIDDM) diabetic patients were essentially the same. An exception is renal impairment, for which IDDM patients had a higher prevalence than did NIDDM patients of the same age. After allowing for time-related variables, the analysis also demonstrates positive independent associations between diabetic control (glycosylated hemoglobin) and retinopathy and between diabetic control and macrovascular disease. Plasma cholesterol (positively) and high-density lipoprotein cholesterol (negatively) were related independently to both macrovascular disease and renal impairment. Very few differences in the risk-factor profiles for complications were found for IDDM compared with NIDDM patients after allowing for time-related variables.

Age Factors↗
PubMed1985

Susceptibility to IDDM is marked by MHC supratypes rather than individual alleles.

107 patients with insulin-dependent diabetes mellitus (IDDM) were typed for HLA A, B, C-, and DR antigens, and for complement C4A, C4B, and Bf alleles, and the results were compared with those of a combined reference group of 332 appropriately matched healthy subjects. Supratypes (allelic combinations) were identified from the phenotype of each group, and it was shown that the frequency of several supratypes is increased in patients with IDDM, in particular supratypes (A1 Cw7) B8 C4AQ0 C4B1 BfS DR3 (P = 0.0001), (A30 Cw-) B18 C4A3 C4BQ0 BfF1 DR3 (P = 0.0003), (A2 Cw3) B62 C4AR C4B2.9 BfS DR4 (P = 0.0002), and three other supratypes including DR4. It was also shown that increases in the frequency of individual alleles are secondary to increases in supratype frequency. Moreover, supratypes appeared to interact; the presence of two relevant supratypes being particularly important. The absolute risk of IDDM was approximately 0.5 in subjects who were homozygous for B18 C4A3 C4BQ0 BfF1 DR3. We concluded that genetic susceptibility is best recognized by MHC supratypes rather than isolated alleles, and that supratype combinations make the identification of even greater disease risk possible.

Alleles↗
PubMed1984

Thyrogastric autoimmunity and MHC associated alleles at the C4 locus in patients with type 1 (insulin-dependent) diabetes.

HLA antigens, complement allotypes, insulin antibodies and thyrogastric autoantibodies were determined in 69 patients with Type 1 (insulin-dependent) diabetes defined by a tendency to ketosis, non-obesity and insulin requirement within 2 years of diagnosis. Analysis of HLA and C4 allotypes suggested that Type 1 diabetes was associated with only certain DR3- and DR4-containing supratypes. Low antibody response to insulin was associated with all HLA-DR3, being present in 89% of those with DR3 compared with 48% of those without. Thyrogastric autoantibodies were associated with a null allele at the C4A locus, usually with HLA-B8-C4AQO-C4B1-BfS-DR3. These results indicate that, unlike Type 1 diabetes, low insulin antibody response was associated with all HLA-DR3. Thyrogastric autoantibodies, on the other hand, were associated with a null allele at the C4A locus. It is probable that while interaction between certain HLA-DR3 and DR4-containing supratypes is important in conferring susceptibility to Type 1 diabetes, other manifestations of autoimmunity are associated with supratypes containing C4AQ0, and in particular the diabetogenic supratype HLA-B8-C4AQ0-C4B1-BfS-DR3.

Alleles↗
PubMed1984

Assessing the risk of diabetic retinopathy.

We used multiple logistic regression to analyze cross-sectional data on 1,006 patients with diabetes mellitus who were examined in a rural diabetic screening program. The factors found to have independent and significant associations with the presence of retinopathy were duration of diabetes, albuminuria, serum creatinine, glycosylated hemoglobin, and plasma glucose levels, blood pressure, and percentage of desirable weight. By comparing the contribution of each significant factor to the deviance from the regression models, we estimated the relative importance of each. Duration of diabetes was by far the most important predictive factor. The logistic model provided a good fit to the observed prevalence rates in various risk groups but was less satisfactory for predicting the presence or absence of retinopathy in individual patients. The discovery of presently unknown risk factors may improve this situation.

Adolescent↗
PubMed1983

HLA and complement allotypes in Type 1 (insulin-dependent) diabetes.

A group of patients with Type 1 (insulin-dependent) diabetes mellitus was investigated for HLA-A, B and DR antigens as well as C4 and factor B polymorphism. A significant excess of DR3/DR4 heterozygotes was observed (27% versus 17% by Hardy-Weinberg expectation). The factor B allele BfF1 was present in 13% of patients with Type 1 diabetes (gene frequency of 0.08 versus 0.01 in control subjects). A rare C4 B allele, C4 B2.9, was found in 18% of patients with Type 1 diabetes (n = 63) compared with 1.1% of control subjects (n = 176). Total C4 deficiency at the C4 A locus (C4 AQ0,0) was present in 10% of patients with Type 1 diabetes compared with 0% of control subjects. Examination of HLA, C4 and Bf phenotypes in patients with Type 1 diabetes suggested that three high risk supratypes, HLA-A1 B8 BfS C4 AQ0 C4 B1 DR3; HLA-B18 BfF1 C4 A3 C4 BQ0 DR3; HLA-A2 CW3 BW62 BfS C4 A3 C4 B2.9 DR4 are markers for susceptibility alleles.

Adult↗
PubMed1982

Acetylator status and diabetic neuropathy.

Acetylator status was determined in 112 normal and 116 diabetic subjects. Forty-eight percent of the normal subjects were fast acetylators compared with 74% of the Type 1 (insulin-dependent) diabetic and 54% of the Type 2 (non-insulin-dependent) diabetic subjects. This result for Type 1 diabetic patients was significantly different from the normal subjects, while that for Type 2 patients was intermediate between the two. In contrast to a previous report, there was no significant association of acetylator status with peripheral neuropathy in subjects with either Type 1 or Type 2 diabetes. Acetylator status could be a genetic marker for Type 1 diabetes, but the increased proportion of fast acetylators in both groups suggested the possibility of an artefact due to high glucose levels. The rate of acetylation of sulphadimidine was significantly greater in both fast and slow acetylators with diabetes compared with normal subjects and there was a significant association between high plasma glucose and acetylator status. Prospective studies will be necessary to confirm whether acetylator status is a true genetic marker for diabetes.

Acetylation↗
PubMed1981

Glyoxalase phenotypes in patients with diabetes mellitus.

Caucasian diabetic patients in Australian surveys showed a significant difference in the distribution of glyoxalase phenotypes. Insulin dependent diabetic patients with age of onset less than 40 years had a relative excess of glyoxalase homozygote 1-1 and a deficiency of types 2-1 and 2-2. Non-insulin dependent diabetic patients were not significantly different from non-diabetic subjects in the distribution of glyoxalase phenotypes. Insulin dependent diabetic patients without the complications of retinopathy or neuropathy also showed a significant excess of glyoxalase type 1-1 in relation to the control group. Genes controlling glyoxalase polymorphism appear to be associated with the variations of diabetes and its complications.

Australia↗
PubMed1981

Impaired glucose tolerance and growth hormone in chronic liver disease.

Of 30 patients with chronic liver disease 16 showed some degree of impairment of glucose tolerance, and 16 patients had lack of suppression of raised fasting growth hormone levels or showed an anomalous rise after oral glucose. No relationship, however, existed between the state of glucose tolerance and the presence of abnormal growth hormone levels. Plasma glucose in those with normal growth hormone response at 0, 1/2, 1, 1-1/2, and 2 hours, after 50 g glucose were 5.55 +/- 0.41 mmol/l, 8.71 +/- 0.59, 10.66 +/- 0.99, 10.28 +/- 1.37, 8.90 +/- 1.40 (mean +/- SEM; n = 14). Under the same conditions those with abnormal growth hormone responses showed values of 5.32 +/- 0.59, 7.83 +/- 0.81, 9.41 +/- 0.95, 9.46 +/- 0.99, 8.69 +/- 0.98. At no time were the differences significantly different as judged by Student's t test. Measurement of serum insulin indicated a relative deficiency in patients with impaired tolerance. It is concluded that the abnormal growth hormone is not directly responsible for the impaired glucose tolerance.

Blood Glucose↗
PubMed1981

The association of bacteriuria and reduced serum pyridoxal concentrations in patients with diabetes mellitus.

Of 1017 patients admitted to the Royal Perth Hospital Diabetic Survey 142 were found to have significant bacteriuria. In these bacteriuric patients serum pyridoxal concentrations were significantly reduced (P = less than 0.001) when compared with 142 diabetic patients matched for age (+/- 5 years) and sex but without infection of the urinary tract. Measurements were repeated up to 6 mth after antibacterial treatment and serum pyridoxal concentrations were still low. Pyridoxal has a role in immunological competence, and it is possible that the increased incidence of urinary tract infection in patients with diabetes reflects impaired immunological competence due to pyridoxal deficiency.

Bacteria↗