Search PubMed⌕ Search

Biomedical subjects

C C Patterson

Publications and source records attributed to C C Patterson.

At least 37 records · Page 2Linked to original sources

Prevalence and awareness of excess weight in 13 and 14 year olds in Northern Ireland using recent international guidelines.

UNLABELLED: Concern has been expressed in recent years over the rising trends in overweight and obesity, particularly in children in developed countries. No recent data were available for Northern Ireland, therefore measurements of height and weight were included in a study in Northern Ireland originally designed as part of an international study to estimate the prevalence of symptoms of asthma and atopy in childhood. Twenty-six schools across the province were sampled. 2484 children aged mainly 13 and 14 y completed questionnaires, and 2307 were weighed and measured. Using recently proposed international guidelines on defining overweight and obesity in children the prevalence of overweight in boys was 16%, with 4% being obese. In girls 16% were also overweight and 2% were obese. This concurs with figures for English and Scottish schoolchildren up to 12 y of age from 1994. Less than one-sixth of obese boys but more than one-third of obese girls were on weight-reducing diets (the majority self-prescribed), reflecting differing attitudes towards excess weight. CONCLUSION: In line with figures in younger children from England and Scotland this study shows that 16% of boys and girls from Northern Ireland are classed as overweight using recent international guidelines. Only 15% of obese boys compared with 38% of obese girls stated that they were on weight-reducing diets.

Adolescent↗

Association of serum AACT levels and AACT signal polymorphism with late-onset Alzheimer's disease in Northern Ireland.

alpha1-antichymotrypsin (AACT) is a serine protease inhibitor that has been associated with amyloid plaques in the brains of patients with Alzheimer's disease (AD). It has been reported that AACT serum levels are higher in AD patients than in age and sex matched controls. In addition, polymorphisms in the signal peptide and 5' of the AACT gene have been reported to increase the risk of developing AD. Serum AACT has also been suggested to be associated with cognitive decline in elderly subjects. Our objective was to investigate whether a relationship existed between serum AACT levels, AACT genotypes and risk for AD in a case control association study using 108 clinically well defined late onset AD cases and 108 age and sex matched controls from Northern Ireland. We also wished to determine whether higher serum AACT affected levels of cognition as had been previously reported. Serum AACT levels were found to be significantly raised in cases compared to controls (t=3.8, df=209, p<0.001). However, we detected no relationship between serum AACT levels and cognitive decline. We report allelic association of the AACT signal polymorphism with AD (chi(2)=3.70, df=1, p=0.04) but we failed to show any correlation between AACT serum levels and genotype.

Age Factors↗

Do polymorphisms of apoB, LPL or apoE affect the hypocholesterolemic response to weight loss?

To assess whether there is a differential hypocholesterolemic response to weight loss for subjects carrying polymorphisms of the apolipoprotein B and other genes. A before and after comparison of lipid parameters following a calorie controlled diet for an intervention period of 12 weeks. A lipid clinic based in a large teaching hospital. The difference in slope coefficients relating the percentage change in lipid parameters to the change in body weight (adjusted for age, gender and initial body mass index (BMI)), for genotype subgroups defined by polymorphisms of the 5'VNTR apoB gene, two mutations of the LPL gene and ApoE. One hundred and forty six subjects completed the intervention diet. While, on average, the intervention was successful (mean weight loss 3.9%), there was no statistically significant difference in the slope coefficients relating lipid change to weight loss for most of the genotypes tested. The slope difference for long versus short 5'VNTR alleles of the apoB gene was 0.445 (-1.307, 2.198) for apolipoprotein B and -0. 104 (-1.486, 1.278) for total cholesterol. However, subjects carrying at least one varepsilon4 allele were significantly hypo-responsive to weight loss, difference in slope coefficients -1.087 (-2.09, -0.084) and -1.320 (-2.589, 0.051) for total cholesterol and apoB, respectively. Although, this study is one of the largest of its kind, it has not replicated the findings of other smaller studies. These findings do not provide support for the use of genotype-targeted dietary advice in routine practice.

Adult↗

Season and outdoor ambient temperature: effects on birth weight.

OBJECTIVE: To determine the extent to which meteorologic factors explain seasonality in birth weight in a developed country. METHODS: Recorded birth weights were collected for all singleton live births after 36 weeks of pregnancy in Northern Ireland between 1971 and 1986. Data on daily maximum and minimum temperatures, rainfall, and hours of bright sunshine were obtained from a local climatologic station for the same period. For each birth, mean daily maximum and minimum temperatures, rainfall, and hours of bright sunshine were calculated for the trimesters of the pregnancy. Linear regression models were constructed with birth weight as the dependent variable and month of birth as a predictor variable. Months of birth were entered in the models as dummy variables. Adjustment was made for year of birth, duration of gestation, maternal age, number of previous pregnancies, sex, and social class of infants at birth and for meteorologic variables relating to each trimester. RESULTS: A clear seasonal pattern in birth weight was observed, with lowest mean birth weight in late spring and summer. Adjusted mean birth weights were 25.5 g, 29.6 g, and 31.6 g lower in May, June, and July, respectively, than in January. This seasonal variation occurred in both sexes, and in female births, it disappeared almost entirely after adjustment for mean daily maximum temperature during the second trimester of pregnancy. CONCLUSION: Infants born during late spring and summer are lighter than those born in winter, which might be the result of exposure to low winter temperatures during midgestation. Pregnant women should keep themselves warm during midpregnancy.

Birth Weight↗

Stewardship or clinical freedom? variations in dialysis decision making.

BACKGROUND: It is generally agreed that acceptance criteria for dialysis have varied and changed over time and that implicit rationing, to some extent forced on clinicians by limited capacity, has been widely practised. Our objective was to study the basis and extent of variation in dialysis decision making among nephrologists in one NHS region. DESIGN AND METHODS: In a clinical judgement analysis, linear regression models were employed to reflect the impact of clinical and non-clinical cues on nephrologists' decisions to offer dialysis to 60 'paper patients' under current capacity constraints and under an assumption of no capacity limit. A short questionnaire was also completed by eight nephrologists to elicit their expressed decision drivers, which were subsequently compared with those tacitly derived from the appraisal of the 60 clinical vignettes. RESULTS: Doctors showed substantial variation in their propensity to offer dialysis and in their perceptions of the benefits of dialysis. Even for the five patients where the discordance in propensity to offer dialysis was least, the range in perceived gain in life expectancy was from 24 to 264 months (mean 91 months). The decision models had relatively good explanatory power with an average r(2) of 0.67 (0.39-0.90) and 0.70 (0.47-0.95) for decisions made under current capacity constraints and under an assumption of no limit capacity respectively. Surprisingly, for most doctors, the patient's age had very little impact on dialysis decisions but the magnitude of the beta-coefficients for the patient's mental state (mean -30.7) was of a similar order of magnitude to the coefficient for the principal 'renal' drivers (e.g. the mean coefficient for uraemic symptomatology under current capacity constraints was 47.7). The influence of other non-renal factors on the doctor's likelihood to offer dialysis was largely independent of the capacity assumption. A comparison of the doctor's stated decision drivers with those tacitly derived from their decision models showed only modest correlation. CONCLUSIONS: The extent to which doctors vary in their propensity to offer dialysis is substantial. Very few non-clinical cues appear to influence the decision to offer dialysis. The most important non-renal factor in determining dialysis decisions was the patient's mental state.

Decision Making↗

Effect of genotype on changes in intelligence quotient after dietary relaxation in phenylketonuria and hyperphenylalaninaemia.

BACKGROUND: Associations between genotype and intellectual outcome in patients with phenylketonuria are complicated because intelligence is influenced by many variables, including environmental factors and other genetic determinants. Intellectual changes with age, both on and after relaxation of diet, vary within the patient population. This study aims to determine whether a significant association exists between genotype and change in intelligence after relaxation of diet. METHODS: 125 patients with hyperphenylalaninaemia and phenylketonuria whose diet was relaxed after 8 years of age. Verbal, performance, and full scale intelligence quotients at 8, 14, and 18 years were expressed as standard deviation scores (IQ-SDS), and genotype as predicted residual enzyme activity (PRA) of phenylalanine hydroxylase. RESULTS: IQ-SDS at 8, 14, and 18 years were significantly below normal; no association was found between PRA and IQ-SDS. Significant reductions in verbal and full scale IQ-SDS occurred between 8 and 14 years and 8 and 18 years. There was a significant association between PRA and the reduction in verbal, performance, and full scale IQ between these years. Multiple regression analysis of 18 year results, using 8 year results as covariates, supported the association between PRA and IQ-SDS; after adjustment for phenylalanine control, both up to and after the age of 8 years, the full scale IQ-SDS at 14 and 18 years was 0.15 higher for each 10% increase in PRA. CONCLUSIONS: Genotype might be useful in predicting the likelihood of intellectual change in patients with hyperphenylalaninaemia and phenylketonuria whose diet is relaxed after the age of 8 years.

Adolescent↗

Comparison of weight in middle age, weight at 18 years, and weight change between, in predicting subsequent 14 year mortality and coronary events: Caerphilly Prospective Study.

OBJECTIVE: The prevalence of obesity is increasing in many European countries and in the United States. This report examines the mortality and morbidity associated with being overweight and obese in the Caerphilly Prospective Study and the relative effects of weight in middle age and self reported weight at 18 years. DESIGN: All men aged 45 to 59 years from the town of Caerphilly, South Wales and outlying villages were identified and 2512 men were examined for the first time between 1979 and 1983. Men were asked to recall their weight at 18 years of age (when the majority had been examined for National Service) so that weight then, weight at screening, and the difference could be related to their 14 year follow up from screening. A total of 2335 men could recall their weight at 18 years. By 14 years of follow up from screening 465 men had died and 382 had had coronary events. RESULTS: Mean body mass index in men who reported their weight at 18 years was 22.3 (SD 2.8) kg/m(2) and only 41 of these men (1.8%) were classified as obese (index >/= 30 kg/m(2)). The index did not predict all cause mortality when examined by quintile. For major ischaemic heart disease (non-fatal or fatal ischaemic heart disease) the relative odds was 1.73 (95% CI 1.21, 2.48) in the top fifth of the distribution (body mass index >/= 24.2 kg/m(2)) compared with the bottom fifth (body mass index <20.1 kg/m(2)). In men with an index >/= 30 kg/m(2) however, the relative odds were 2.03 (95% CI, 1.03, 4.01) for all cause mortality and 2.17 (95% CI, 1.08, 4.34) for major ischaemic heart disease, adjusted for age, smoking habit and social class. When men were recruited to the study, from 1979 to 1983; the mean body mass index had increased to 26.2 (SD 3.6), a mean increase of 3.9 kg/m(2) or 11. 2 kg; 299 men (12.1%) were classified as obese and showed significantly increased relative odds of both all cause mortality (1. 53 (95% CI 1.14, 2.06) and major ischaemic heart disease (1.55 (95% CI 1.13, 2.11)), adjusted for age, smoking habit and social class relative to the non-obese men. The effect of gain in weight from 18 years to recruitment was also examined; all cause mortality showed highest mortality in the fifth of the distribution who experienced weight loss or minimal weight gain. For major ischaemic heart disease an inconsistent, weak trend was shown, the relative odds rising to a maximum of 1.26 (0.89, 1.80) in the top fifth of weight gain compared with the bottom fifth. Weight gain showed strong associations with potential cardiovascular risk factors measured at recruitment; insulin, triglyceride, glucose, diastolic and systolic blood pressure and high density lipoprotein-cholesterol. CONCLUSIONS: Body mass at 18 years of age of 30 kg/m(2) or more conferred increased risk for all cause mortality and major ischaemic heart disease during 14 years of follow up of men aged 45 to 59 years. By the baseline examination the prevalence of obesity (body mass index >/=30) had increased from 1.8% to 12.1%; obese men also showed an excess risk of major ischaemic heart disease and overall mortality, but these risks were lower than those predicted from 18 years of age. Weight gain was strongly associated with smoking habit, the greatest weight gain being among ex-smokers and the least among light smokers. Weight gain from 18 years of age to baseline examination showed little relation with subsequent mortality and risk of major ischaemic heart disease when adjusted for age, smoking habit and social class. The lowest mortality rate occurred in the "fifth" of men who gained a mean weight of 16.1 kg. Weight gain is closely associated with some adverse cardiovascular risk factors; in particular with insulin, triglyceride, glucose and diastolic blood pressure.

Adolescent↗

Proximal femoral fracture in Northern Ireland between 1985-1997--trends and future projections.

The aims of this study were to identify changing trends with time of the incidence of proximal femoral fracture and to enable future number of hip fractures to be projected. Hospital theatre records in Northern Ireland were surveyed in 1985, 1991, 1994 and 1997 to establish the number of surgical procedures for proximal femoral fracture. The age and sex specific rates for males and females aged 50+ years were calculated. Analysis of age and sex specific incidence rates was undertaken using linear regression and Poisson regression. A 1.6% increase per annum (95% CI 1.0-2.2) was noted in males and females from 1985 to 1997. Projected increases in rates of proximal femoral fracture were calculated using population projection for 2001, 2006, 2011 and 2016. Modelling (a) assuming the age standardised rates in 1997 remain static and continue predicted a 55% fracture increase in males and a 29% increase in females by 2016, (b) assuming the secular increases continued predicted a 93% fracture increase in males and a 67% increase in females and (c) assuming further linear growth on a log-scale predicted a fracture increase in males of 135% and 99% in females. The number of proximal femoral fractures in Northern Ireland is increasing faster than that anticipated due to demographic changes alone, supporting a secular increase which was evident throughout the period of time studied, in contrast to that reported from other regions in the United Kingdom.

Age of Onset↗

Influence of hospital and clinician workload on survival from colorectal cancer: cohort study.

OBJECTIVE: To determine whether clinician or hospital caseload affects mortality from colorectal cancer. DESIGN: Cohort study of cases ascertained between 1990 and 1994 by a region-wide colorectal cancer register. OUTCOME MEASURES: Mortality within a median follow up period of 54 months after diagnosis. RESULTS: Of the 3217 new patients registered over the period, 1512 (48%) died before 31 December 1996. Strong predictors of survival both in a logistic regression (fixed follow up) and in a Cox's proportional hazards model (variable follow up) were Duke's stage, the degree of tumour differentiation, whether the liver was deemed clear of cancer by the surgeon at operation, and the type of intervention (elective or emergency and curative or palliative intent). In a multilevel model, surgeon's caseload had no significant effect on mortality at 2 years. Hospital workload, however, had a significant impact on survival. The odds ratio for death within 2 years for cases managed in a hospital with a caseload of between 33 and 46 cases per year, 47 and 54 cases per year, and >/=55 cases per year (compared to one with </=23 cases per year) were respectively 1.48 (95% confidence interval 1.03 to 2.13), 1.52 (1.08 to 2.13), and 1.18 (0.83 to 1.68). CONCLUSIONS: There was no detectable caseload effect for surgeons managing colorectal cancer, but survival of patients treated in hospitals with caseloads above 33 cases per year was slightly worse than for those treated in hospitals with fewer caseloads. Imprecise measurement of clinician specific "events rates" and the lack of routinely collected case mix data present major challenges for clinical audit and governance in the years ahead.

Adult↗

Risk of Alzheimer's disease is associated with a very low-density lipoprotein receptor genotype in Northern Ireland.

The epsilon-4 allele of apolipoprotein E (APOE) is associated with increased risk of Alzheimer's disease (AD), but the pathogenic mechanism is unknown. The 5-repeat allele of a CGG repeat polymorphism in the 5' untranslated region of the very low-density lipoprotein receptor (VLDL-R) gene, a receptor for apoE, has been found to be associated with increased risk of AD in a Japanese population. Other groups have been unable to replicate this in American Caucasian populations. A case-control study utilizing a clinically well-defined group of late-onset AD patients (n = 108) and age- and sex-matched control subjects (n = 108) from Northern Ireland was performed to test this association in a relatively homogeneous population. The 9,9 genotype of the VLDL-R was found to be significantly increased in patients compared to controls (P = 0.003; Pcorr = 0.035), leading to an increased risk of AD to subjects with this genotype (OR = 3.9; 95% CI, 1.52-11.25). In contrast to results from the Japanese study, the 5-repeat allele was found to be significantly reduced in the patient group when compared to controls (P = 0.008; Pcorr = 0.047). The results from this study suggest that individuals who have the 9,9 genotype of the VLDL-R gene are at increased risk of AD in Northern Ireland.

Aged↗

Genetic association studies of tumour necrosis factor alpha and beta and tumour necrosis factor receptor 1 and 2 polymorphisms across the clinical spectrum of multiple sclerosis.

Allelic association studies with microsatellite markers around the tumour-necrosis factor (TNF) genes have demonstrated significantly different allele distributions of TNF markers (a and b) between relapsing-remitting/secondary progressive multiple sclerosis (MS) (RR/SPMS) patients and normal controls. Considering the suspected genetic and immunological heterogeneity in MS, we tested this association in primary progressive MS (PPMS) patients. Elevated levels of serum soluble TNF receptors (sTNF-R) are reported in patients with gadolinium enhancing lesions, and animal models suggest a possible therapeutic role of sTNF-RI in MS. Thus we performed similar association studies using markers for the TNF-R genes. Gene association studies were carried out on 199-216 normal controls, 174 RR/SPMS patients and 102 PPMS patients using polymorphic dinucleotide repeat TNF markers (a, b and d), and separate markers for TNF-RI and TNF-RII. Forward primers were fluorescently labelled, polymerase chain reaction (PCR) products were analysed on a fluorescent fragment analyser, and Genescan 672 software was used for allele sizing. Samples were typed for HLA-DR antigens using PCR technology and sequence-specific oligonucleotide probes. TNFa marker allele distributions differed significantly between PPMS patients and controls (P = 0.028), largely attributable to an increase in the 118-bp TNFa allele in PPMS patients (P = 0.00024). Allele distributions were similar in PPMS and RR/SPMS patients (P = 0.91). Logistic regression analysis, however, indicated that these associations were not independent of that with HLA-DRB1*15. For the TNFb marker, the 127-bp allele showed association with both patient categories (PPMS vs. controls, P = 0.010; RR/SPMS vs. controls, P = 0.027), whilst the 128-bp allele occurred more frequently in controls (PPMS vs. controls, P = 0.036: RR/SPMS vs. controls, P = 0.0009). As with the TNFa 118 bp allele, the association with TNFb was not independent of the HLA association. No association occurred with the TNFd marker, and there were also no significant differences in allele frequencies between MS groups and controls regarding the marker for TNF-RI or TNF-RII. In Northern Irish patients the TNF contribution to MS genetic susceptibility is therefore similar across the clinical spectrum of the disease but is not independent of the association with HLA-DRB1*15.

Adult↗

Dinucleotide repeat polymorphisms in EDN1 and NOS3 are not associated with severe diabetic retinopathy in type 1 or type 2 diabetes.

PURPOSE: Endothelin-1, and constitutive endothelial nitric oxide synthase, have been implicated in the pathogenesis of diabetic retinopathy. We therefore screened polymorphisms within the genes encoding these two vasoactive agents in a sample of individuals with 15 years of diabetes and no retinopathy (ETDRS level 10 or better) and those with severe retinopathy (ETDRS level 50 or worse). METHODS: PCR primers for highly polymorphic sites within the EDN1 and NOS3 genes were used to genotype individuals with type 1 or type 2 diabetes with severe or no retinopathy. Allele frequencies were compared between groups using chi-squared analysis and adjusting for multiple comparisons. RESULTS: No significant differences were observed in allele frequencies for these two markers between the patients who had retinopathy and the patients who did not. CONCLUSION: Polymorphic variability in the EDN1 and NOS3 genes does not appear to have a major impact on determining susceptibility or resistance to diabetic retinopathy.

Adult↗

The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus.

AIMS: To assess mortality in patients with diabetes incident under the age of 30 years. METHODS: A cohort of 23 752 diabetic patients diagnosed under the age of 30 years from throughout the United Kingdom was identified during 1972-93 and followed up to February 1997. Following notification of deaths during this period, age- and sex-specific mortality rates, attributable risks and standardized mortality rates were calculated. RESULTS: The 23 752 patients contributed a total of 317 522 person-years of follow-up, an average of 13.4 years per subject. During follow-up 949 deaths occurred in patients between the ages of 1 and 84 years, 566 in males and 383 in females. All-cause mortality rates in the patients with diabetes exceeded those in the general population at all ages and within the cohort were higher for males than females at all ages except between 5 and 15 years. The relative risk of death (standardized mortality ratio, SMR), was higher for females than males at all ages, being 4.0 (95% CI 3.6-4.4) for females and 2.7 (2.5-2.9) for males overall, but reaching a peak of 5.7 (4.7-7.0) in females aged 20-29, and of 4.0 (3.1-5.0) in males aged 40-49. Attributable risks, or the excess deaths in persons with diabetes compared with the general population, increased with age in both sexes. CONCLUSIONS: This is the first study from the UK of young patients diagnosed with diabetes that is large enough to calculate detailed age-specific mortality rates. This study provides a baseline for further studies of mortality and change in mortality within the United Kingdom.

Adolescent↗

The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus.

AIMS: To measure cause-specific mortality, by age, in patients with insulin-treated diabetes incident at a young age. METHODS: A cohort of 23 752 patients with insulin-treated diabetes diagnosed under the age of 30 years, from throughout the United Kingdom, was identified during 1972-93 and followed to February 1997. Death certificates have been obtained for deaths during the follow-up period and cause-specific mortality rates and standardized mortality ratios by age and sex are reported. RESULTS: During the follow-up period 949 deaths occurred and at all ages mortality rates were considerably higher than in the general population. Acute metabolic complications of diabetes were the greatest single cause of excess death under the age of 30 years. Cardiovascular disease was responsible for the greatest proportion of the deaths from the age of 30 years onwards. CONCLUSIONS: Deaths in patients with diabetes diagnosed under the age of 30 have been reported and comparisons drawn with mortality in the general population. To reduce these deaths attention must be paid both to the prevention of acute metabolic deaths and the early detection and treatment of cardiovascular disease and associated risk factors.

Adolescent↗

Childhood Type 1 diabetes mellitus and parental occupations involving social mixing and infectious contacts: two population-based case-control studies.

AIMS: To test the hypothesis that increased exposure to infections, through parental jobs involving high levels of social mixing, reduces the risk of childhood Type 1 diabetes mellitus. METHODS: Two population-based case-control studies of children diagnosed with Type 1 diabetes mellitus from Yorkshire (0-15 years) and Northern Ireland (0-14 years) included 220 and 189 cases and 433 and 465 controls, respectively. Parental occupations were coded using a standard occupational classification. Each job was allocated to high, medium or low levels of social mixing according to a predefined categorization. Odds ratios (OR) for the risk of childhood Type 1 diabetes were estimated for parental social mixing by age at diagnosis. RESULTS: Childhood Type 1 diabetes mellitus was not associated with high levels of parental occupational social mixing (Yorkshire - mothers: OR 1.07, 95% confidence interval (CI) 0.76-1.50; fathers: 1.15, 0.75-1.76; Northern Ireland - heads of household, usually the father: 0.78, 0.49-1.25). A larger proportion of mothers (39%) compared to fathers (18% Yorkshire, 17% Northern Ireland) had jobs involving high levels of social mixing. Mothers with high social mixing jobs conferred a nonsignificant reduced risk of Type 1 diabetes among children diagnosed under 5 years of age (0.58, 0.24-1.38) compared to those diagnosed at age 5 years and above (1.14, 0.77-1.69). CONCLUSIONS: No association between parental occupational social mixing and the risk of childhood Type 1 diabetes mellitus was detected for all ages combined. Mothers were more likely to have jobs involving high levels of social mixing than fathers. The possible protective effect of maternal high occupational social mixing on children diagnosed below 5 years of age merits further investigation.

Adolescent↗

Fasting plasma glucose and subsequent macrovascular disease after 10 years follow-up: a collaborative study on two populations.

The American Diabetes Association recently proposed a new, lower, cut-point of 7.0 mmol/l for diagnosis of diabetes mellitus. We examined data from the Caerphilly and Speedwell cohorts to determine possible cut-points of fasting plasma glucose for increased risk of subsequent ischaemic heart disease (IHD). Men (n = 4860) from the general population of a town in South Wales and a practice-based population in Bristol aged 45-63 years were first examined in 1979-83, and re-examined at intervals, and these data relate to follow-up at about 10 years (120 months, Caerphilly) (112 months, Speedwell). Clinically recognized diabetics (n = 94) experienced a higher mortality rate and an excess number of major IHD events. Among non-diabetics, mean blood glucose was 5.0 mmol/l and a significant excess of major IHD events occurred above this point even when the data were fully adjusted for all other IHD risk factors. Risk of major IHD was greatest for non-diabetic men with plasma glucose levels between 7.0 and 7.7 mmol/l. Under 7.0 mmol/l, the excess event rate was modest, however. Glucose levels were not associated with excess all-cause mortality among these non-diabetic men. These data, based on the excess risk of macrovascular disease experienced by a British cohort of non-diabetic men, accord with the proposals to base the diagnosis of diabetes on a cut point of 7.0 rather than 7.8 mmol/l.

Blood Glucose↗

Genotyping and functional analysis of a polymorphic (CCTTT)(n) repeat of NOS2A in diabetic retinopathy.

Accumulating evidence shows that the severity and rapidity of onset of diabetic retinopathy are influenced by genetic factors. Expression of the nitric oxide synthases is altered in the retinal vasculature in the early stages of diabetic retinopathy. We analyzed the allele distribution of a polymorphic pentanucleotide repeat within the 5' upstream promoter region of the NOS2A gene in samples of diabetic patients. In diabetic patients from Northern Ireland, the 14-repeat allele of the NOS2A marker was significantly associated with the absence of diabetic retinopathy. Carriers of this repeat had 0.21-fold the relative risk of developing diabetic retinopathy than noncarriers of this allele. They also had significantly fewer renal and cardiovascular complications. The ability of differing numbers of (CCTTT)(n) pentanucleotide repeats to induce transcription of the NOS2A gene was analyzed using a luciferase reporter gene assay in transfected colonic carcinoma cells. Interleukin 1beta (IL-1beta) induction was most effective in constructs carrying the 14-repeat allele. When cells were incubated in 25 mM glucose to mimic the diabetic state, IL-1beta induction was inhibited in all cases, but to a significantly lesser extent with the 14-repeat allele. These unique properties of the 14-repeat allele may confer selective advantages in diabetic individuals, which may delay or prevent microvascular complications of diabetes.

Adult↗