Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study.

Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23 834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30-49 years, who probably mainly had type II. Relative risks of cancer overall were close to unity, but ovarian cancer risk was highly significantly raised in patients with diabetes diagnosed under age 30 years (standardised incidence ratio (SIR)=2.14; 95% confidence interval (CI) 1.22-3.48; standardised mortality ratio (SMR)=2.90; 95% CI 1.45-5.19), with greatest risks for those with diabetes diagnosed at ages 10-19 years. Risks of cancer at other major sites were not substantially raised for type I patients. The excesses of obesity- and alcohol-related cancers in type II diabetes may be due to confounding rather than diabetes per se.

Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus, Scotland, 1979-95.

AIMS: To assess pregnancy outcomes, in particular birthweight, in a large population-based cohort of women in Scotland with pre-gestational insulin-treated diabetes mellitus. METHODS: Data about diabetes from the Diabetes UK cohort were linked to data on births from the Scottish Hospital In-Patient Record System. This identified 1112 eligible singleton deliveries during 1979-95 to 706 insulin-treated women. RESULTS: One thousand and eighty-four (97.5%) deliveries resulted in a live-born infant and 28 (2.5%) in a stillbirth. There were 13 (1.2%) neonatal deaths. The mean birthweight of the live-born infants was 3421 g, 1.06 standard deviations greater than that of infants in the Scottish general population after correcting for sex and gestational age. Forty-three per cent of live-born babies in the study were large (> Scottish 90th percentile) and 4% small (< 10th percentile) for their sex and gestational age. Macrosomia, defined as birthweight > or = 4000 g, occurred in 23% live-born babies and its prevalence was significantly inversely related to duration of maternal diabetes. However, the mean birthweight of infants born to mothers with diabetes for 20 or more years was still 0.90 standard deviations greater than in the general population. Prevalence of macrosomia increased with increasing number of previous pregnancies, but was not associated with maternal height or smoking habits. Stillbirth and neonatal death rates were, respectively, 4.7 (95% confidence interval = 3.3, 6.8) and 2.4 (1.4, 4.1), times higher than those in the general population. CONCLUSIONS: The frequency of adverse pregnancy outcomes in women with pre-existing insulin-treated diabetes was much higher than in the Scottish general population, and changed little during the study period. A detailed quantification of the independent effect of duration of mother's diabetes on birthweight revealed a continuous inverse correlation between these two variables.

Mortality of South Asian patients with insulin-treated diabetes mellitus in the United Kingdom: a cohort study.

AIMS: To investigate mortality in South Asian patients with insulin-treated diabetes and compare it with mortality in non South Asian patients and in the general population. METHODS: A prospective cohort study was conducted of 828 South Asian and 27 962 non South Asian patients in the UK with insulin-treated diabetes diagnosed at ages under 50 years. The patients were followed for up to 28 years. Ethnicity was determined by analysis of names. Standardized mortality ratios (SMRs) were calculated, comparing mortality in the cohort with expectations from the mortality experience of the general population. RESULTS: SMRs were significantly raised in both groups of patients, particularly the South Asians, and especially in women and subjects with diabetes onset at a young age. The SMRs for South Asian patients diagnosed under age 30 years were 3.9 (95% CI 2.0-6.9) in men and 10.1 (5.6-16.6) in women, and in the corresponding non South Asians were 2.7 (2.6-2.9) and 4.0 (3.6-4.3), respectively. The SMR in women was highly significantly greater in South Asians than non South Asians. The mortality in the young-onset patients was due to several causes, while that in the patients diagnosed at ages 30-49 was largely due to cardiovascular disease, which accounted for 70% of deaths in South Asian males and 73% in females. CONCLUSIONS: South Asian patients with insulin-treated diabetes suffer an exceptionally high mortality. Clarification of the full reasons for this mortality are needed, as are measures to reduce levels of known cardiovascular disease risk factors in these patients.

Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes.

AIMS/HYPOTHESIS: Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. METHODS: A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. RESULTS: There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39. CONCLUSIONS/INTERPRETATION: The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.

The role of analogies in learning to read.

A number of factors contribute to proficient word recognition, including phonological awareness and the ability to make orthographic analogies. The present study considered the relative contribution analogy abilities make toward early reading ability. Two analogy tasks and measures of phonological awareness, orthographic knowledge, visual memory, general language ability, and non-verbal intelligence were administered to 20 second grade good readers and 20 third and fourth grade poor readers. The analogy tasks did make a significant contribution to early reading ability; however, the analogy tasks were not very different from the measures of reading they predicted. In other words, it seems difficult to isolate the use of analogies from basic phonological decoding abilities.

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.

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.

Lipids and apolipoprotein profiles in men with aneurysmal and stenosing aorto-iliac atherosclerosis.

The plasma lipids, lipoproteins and apolipoproteins have been compared in two groups of men with aorto-iliac atherosclerosis: Aneurysmal disease (n = 42) and stenosing disease (n = 86). The mean age of the men aneurysmal disease was 67.5 +/- 5.8 years and the mean age of the men with stenosing disease was 65.0 +/- 6.1 years: There was no significant different in body mass indices or smoking habits between the groups. The patients with aneurysmal disease had lower levels of plasma cholesterol than patients with stenosing disease (5.53 +/- 1.17 versus 6.11 +/- 1.20 mmol/L, P less than 0.05), but carried more cholesterol in VLDL compared to patients with stenosing disease (1.00 +/- 0.90 versus 0.60 +/- 65 mmol/L, P less than 0.05). Significantly lower concentration of apolipoprotein AI and HDL-cholesterol in patients with aneurysmal disease (ApoAI 1.01 +/- 0.31 versus 1.18 +/- 0.31 mmol/L, P less than 0.02, HDL 0.93 +/- 0.53 versus 1.13 +/- 0.34, P less than 0.05) was another characteristic difference between these two groups of patients with peripheral arterial disease. Otherwise, there were no obvious differences in the levels of plasma triglyceride, VLDL-triglyceride, LDL-cholesterol, and apolipoproteins B, C-III and E between the two groups. Although lipid and apolipoprotein profiles may not discriminate between aneurysmal and stenosing disease, different types of lipoprotein particles may contribute to the atherosclerotic process characterising both diseases.

Plasma lipid and apolipoprotein profiles of women with two types of peripheral arterial disease.

The purpose of this study was to establish whether women with peripheral arterial disease can be distinguished from controls on the basis of plasma lipid and apolipoprotein profiles. One group of patients with peripheral arterial disease (n = 20) was characterized by a localized aortic stenosis referred to as the 'small aorta syndrome' (SAS). The other group of patients with peripheral arterial disease (n = 23) had a diffuse segmental pattern of stenoses referred to as the 'stenosing peripheral arterial disease' (SPAD). After correcting for the effects of age and body mass index, the SAS group had elevated plasma total cholesterol (TC) levels when compared to normal controls (P less than or equal to 0.008), while the SPAD group had triacylglycerol (TG) levels different from controls (P = 0.02). Both groups of patients were characterized by reduced levels of apolipoprotein A-I (P less than or equal to 0.04) and increased levels of apolipoprotein C-III (P less than or equal to 0.002). Apolipoproteins B and E were also elevated in both groups of patients but not significantly. Mutivariate analyses indicated that the A-I/C-III ratio correctly discriminated 97.8% of the SAS and the A-I/C-III ratio plus A-I discriminated 89.8% of the SPAD patient from the controls. In addition, multivariate analyses showed that the variables age, TC/Apo B, Apo B/C-III and TG/C-III discriminated SPAD from SAS patients with a correct classification of 93.2%. Results of this study showed that the measurement of apolipoproteins A-I, B and C-III in conjunction with TC and TG is of potential use for differentiating patients with peripheral arterial disease from normal controls as well as for distinguishing patients with SAS from those with SPAD. It seems that particular patterns of peripheral arterial disease in women may be associated with slightly different alterations in the plasma lipoprotein system.

Smoking and arterial reconstruction.

Fasting levels of serum triglyceride, serum cholesterol, lipoprotein, uric acid, fibrinogen and carboxyhaemoglobin (COHb) were measured in 64 patients with stenosing arterial disease before reconstructive surgery, and were compared with those for normal, age- and sex-matched controls. All except fibrinogen were significantly higher in the patients with arterial disease than in the controls. The outcome of arterial reconstruction, assessed both clinically and by Doppler pressure measurement, was compared in terms of these risk factors. The reconstruction of 12 patients failed between 3 months and 5 years, leaving 52 patients with patent reconstructions at the end of the follow-up period. There was no difference between the two groups in terms of any of the risk factors, except for COHb. The COHb level (associated with inhalation of cigarette smoke) was significantly higher in the reconstruction failure group than in the reconstruction success group. We believe that patients should stop smoking cigarettes before reconstructive arterial surgery is undertaken.

Standard exercise test to assess peripheral arterial disease.

The fall in ankle systolic pressure after exercise serves as an objective indicator of the severity of haemodynamically important peripheral arterial disease. Twenty-six patients were studied to establish the effects of different work loads on the pressure response and to develop a test to standardise these effects. The patients walked for one or two minutes at 4 km/h and one or two minutes at 6 km/h, and the fall in pressure was the same when measured immediately after exercise. The time taken for the pressure to return to the pre-exercise value varied. As the fall in pressure occurs after only one minute of exercise at 4 km/h on a 10% slope, this might be adopted as a standard test. It is acceptable to the patient, since claudication, angina, and shortness of breath rarely occur. It is sensitive enough to detect mild or asymptomatic disease and is useful in following up patients.