Screening for type 2 diabetes: a short report for the National Screening Committee.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) has been increasing, owing to increases in overweight and obesity, decreasing physical activity and the changing demographic structure of the population. People can develop T2DM without symptoms and up to 20% may be undiagnosed. They may have diabetic complications, such as retinopathy, by the time they are diagnosed, or may suffer a heart attack, without warning. Undiagnosed diabetes can be detected by raised blood glucose levels. AIM: The aim of this review was to provide an update for the UK National Screening Committee (NSC) on screening for T2DM. METHODS: As this review was undertaken to update a previous Health Technology Assessment review published in 2007, and a more recent Scottish Public Health Network review, searches for evidence were restricted from 2009 to end of January 2012, with selected later studies added. The databases searched were MEDLINE, EMBASE, MEDLINE-in-Process & Other Non-Indexed Citations, Science Citation Index and Conference Proceedings Citation Index. The case for screening was considered against the criteria used by the NSC to assess proposed population screening programmes. RESULTS: Population screening for T2DM does not meet all of the NSC criteria. Criterion 12, on optimisation of existing management, has not been met. A report by the National Audit Office (NAO) gives details of shortcomings. Criterion 13 requires evidence from high-quality randomised controlled trials that screening is beneficial. This has not been met. The Ely trial of screening showed no benefit. The ADDITION trial was not a trial of screening, but showed no benefit in cardiovascular outcomes from intensive management in people with screen-detected T2DM. Criterion 18 on staffing and facilities does not appear to have been met, according to the NAO report. Criterion 19 requires that all other options, including prevention, should have been considered. A large proportion of cases of T2DM could be prevented if people avoided becoming overweight or obese. The first stage of selection would use risk factors, using data held on general practitioner computer systems, using the QDiabetes Risk Score, or by sending out questionnaires, using the Finnish Diabetes Risk Score (FINDRISC). Those at high risk would have a measure of blood glucose. There is no perfect screening test. Glycated haemoglobin (HbA1c) testing has advantages in not requiring a fasting sample, and because it is a predictor of vascular disease across a wider range than just the diabetic one. However, it lacks sensitivity and would miss some people with diabetes. Absolute values of HbA1c may be more useful as part of overall risk assessment than a dichotomous 'diabetes or not diabetes' diagnosis. The oral glucose tolerance test is more sensitive, but inconvenient, more costly, has imperfect reproducibility and is less popular, meaning that uptake would be lower. CONCLUSIONS: When considered against the NSC criteria, the case for screening is less strong than it was in the 2007 review. The main reason is the absence of cardiovascular benefit in the two trials published since the previous review. There is a case for selective screening as part of overall vascular risk assessment. Population screening for T2DM does not meet all of the NSC criteria. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Glycaemic control and body mass index in late-adolescents and young adults with Type 1 diabetes mellitus: a population-based study.

AIMS: Studies of children with diabetes up to the age of 15 years report deteriorating glycaemic control in the early teenage years. The aim was to investigate glycaemia and body mass index in older teenagers and young adults. METHOD: A Scottish, regional, population-based, cross-sectional study of 255 young people (117 female, 138 male) with Type 1 diabetes, aged 15-25 years (mean +/-sd 19.8 +/- 2.8 years, diabetes duration: 8.8 +/- 5.4 years) registered on a diabetes database. Glycaemic control, body mass index (BMI) and insulin regimens were assessed in three age groups [group 1 (n = 96) 15-18 years; group 2 (n = 74) 18.1-22 years; and group 3 (n = 85) 22.1-25 years]. RESULTS: Subjects in the oldest age group had a significantly lower mean HbA(1c) than those in the youngest age group (8.8 +/- 1.7 vs. 9.9 +/- 1.9%; P < 0.001). Mean BMI was higher in group 3 (25.2 +/- 3.4 kg/m(2)) compared with group 1 (23.9 +/- 3.1 kg/m(2); P < 0.001). HbA(1c )levels were higher in the younger subjects and women. Lower HbA(1c) levels were associated with a higher BMI (r = -0.324, P < 0.001) in men only. Overall, 74% took three or more injections a day, of whom 60% were on basal/bolus therapy. The proportion on basal/bolus insulin therapy increased with age and duration of diabetes. CONCLUSION: Compared with adolescents, young adults with Type 1 diabetes have better glycaemic control and higher BMI. This was associated with lower insulin requirements.

Making literature searches easier: a rapid and sensitive search filter for retrieving randomized controlled trials from PubMed.

AIMS: To develop and test the sensitivity and precision of a rapid and simple search filter (RSSF), suitable for busy clinicians wanting to find randomised controlled trials (RCTs) in PubMed. Ideally it should retrieve all the RCTs, but as few irrelevant studies as possible, and be easy to use. METHODS: The RSSF consisted of the search term 'Randomized Controlled Trial' limited to the Publication Type field. Journals that published the highest numbers of diabetes RCTs between 2000 and 2005 were identified, and then handsearched in order define a set of known RCTs. The sensitivity of the RSSF was tested by measuring the proportion of the known RCTs retrieved, and the precision by checking the proportion of the retrieved studies which were RCTs. The RSSF was compared to a highly sensitive search strategy (HSSS) developed for PubMed. Embase was checked for trials not in PubMed. RESULTS: Sixteen journals were found to contain half of all published RCTs in diabetes. 820 diabetes RCTs were identified by handsearching. Measured against these, the RSSF gave a sensitivity of 96.0% (95% CI, 94.8% to 97.1%), and a precision of 93.6% (95% CI 91.7% to 95.0%). Compared to the HSSS, the RSSF reduced the filtering required by 87%. An Embase search for diabetes RCTs found 36 (2.1%) not in PubMed. CONCLUSIONS: A rapid simple search filter for PubMed can find almost all diabetes RCTs, while excluding most studies not required, thereby greatly reducing the time cost of searching and filtering results, and of searching other databases.

Sources of evidence for systematic reviews of interventions in diabetes.

AIMS: To analyse the effect on systematic reviews in diabetes interventions of including only trials that are indexed in medline, and to assess the impact of adding trials from other databases and the grey literature. METHODS: All systematic reviews of diabetes interventions which included a meta-analysis of randomized controlled trials, and were published since 1996, were selected. The impact on the meta-analysis of including only those trials indexed in medline, and the effect of then adding trials from other sources, was assessed. Where possible this was measured quantitatively, by redoing the meta-analysis, otherwise a qualitative estimate was made. RESULTS: Forty-four systematic reviews met our inclusion criteria. There were 120 articles reporting trial data which were not indexed in medline. These came from 52% of the reviews. In 34% of the reviews, basing a meta-analysis on a search of only medline would miss trials that could affect the result. Sources of non-medline data which had the biggest effect on the meta-analyses were journal articles from central and embase (mainly in Diabetes, Nutrition and Metabolism) and unpublished data (mainly from industry). The exceptions were journal articles on herbal medicine, mostly indexed in Chinese language databases. CONCLUSIONS: A search of only the medline database is insufficient for systematic reviews of diabetes, because in about 34% of reviews the missed trials could affect the results of the meta-analysis. It is recommended that central (on the Cochrane Library) also be searched. Scanning meeting abstracts, and seeking unpublished data are also recommended if the intervention has only recently been introduced.

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.

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.

Protein restriction for diabetic renal disease.

OBJECTIVES: To determine whether protein restriction slows or prevents progression of diabetic nephropathy towards renal failure. SEARCH STRATEGY: Computerised databases MEDLINE (1976-1996) and EMBASE (1974-1996) were searched using keywords diabetes mellitus, diabetic nephropathy, dietary proteins, diet, protein restricted and uremia. Recent issues of selected journals (Diabetic Medicine, Diabetologia, Diabetes Care, Kidney International, Nephrology Dialysis and Transplantation) were handsearched for papers not yet in the computerised databases. Reference lists of papers were also checked. SELECTION CRITERIA: This review was not limited to randomised controlled trials. All trials involving people with insulin-dependent diabetes following a lower protein diet for at least 4 months were considered since the straight line nature of progression as reflected by GFR means that patients can act as their own controls in a before and after comparison. DATA COLLECTION AND ANALYSIS: Data were extracted for length of follow up, level of protein restriction, renal function and dietary compliance. No studies of the impact of protein restriction on outcomes such as the need for dialysis or transplantation were found. The trials reported only the effect on short-term indicators such as creatinine clearance. MAIN RESULTS: Overall a protein restricted diet (0.3-0. 8g/kg) does appear to slow the progression of diabetic nephropathy towards renal failure. REVIEWER'S CONCLUSIONS: The results show that reducing protein intake appears to slow progression to renal failure, but some questions remain unanswered. The first is what level of protein restriction we should be used? The trials aimed for a daily intake of between 0.3 to 0.8g/kg of protein. The second concerns compliance in routine care - what level would be acceptable to patients? The third concerns long term outcomes -the present trials use proxy indicators such as creatinine clearance rather than outcomes such as time to dialysis or prevention of ESRF. All trials were carried out in subjects with insulin-dependent diabetes. It remains to be seen if a lower protein intake would slow the progression of nephropathy affecting the non-insulin dependent diabetic population.

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.

Rising incidence of type 1 diabetes in Scottish children, 1984-93. The Scottish Study Group for the Care of Young Diabetics.

OBJECTIVES: To calculate the incidence of type 1 diabetes in Scottish children aged less than 15 years between 1984 and 1993; to examine changes in incidence; and to calculate the prevalence of diabetes at the end of this period. DESIGN: Three data sources were used to construct the Scottish Study Group for the Care of Young Diabetics register: active reporting of all new cases; reports from the Scottish Morbidity Register 1; and local registers. SUBJECTS: All children resident in Scotland diagnosed with primary insulin dependent diabetes mellitus when less than 15 years of age between 1984 and 1993. MAIN OUTCOME MEASURES: Annual incidence and prevalence rate for Scotland; time trend in incidence over the 10 years; differences in incidence between the three different age groups; and completeness of the register. RESULTS: The average annual incidence for Scotland was 23.9/100,000 children. The prevalence rate was 1.5/1000 in 1993. A total of 2326 cases was identified from the three sources. Capture-recapture analysis suggests a case ascertainment of 98.6%. The annual incidence rates increased at a rate of 2% each year (rate ratio = 1.02, 95% confidence interval (CI) 1.01 to 1.03). The incidence was higher in boys than girls (rate ratio = 1.08, 95% CI 1.00 to 1.18), and the incidence rates increased with age: 15.3/100,000/year for age 0-4 years, 24.4/ 100,000/year for age 5-9 years, and 31.9/ 100,000/year for age 10-14 years. CONCLUSIONS: The incidence of type 1 diabetes in Scotland is increasing and the prevalence is relatively high. These findings have important implications for health service resource allocation. The Scottish Study Group for the Care of Young Diabetics' register provides a base for monitoring and research.

Hypothermia in the north east of Scotland.

The aim of the study was to establish the incidence of hypothermia in the Grampian region, and to examine the accuracy of routine reporting of hypothermia on hospital discharge records. From 1990-1994, 167 patients were admitted with an SMRI diagnosis of hypothermia. An admission temperature of under 35 degrees C was recorded in 47 (28%); rectal in 37 (confirmed hypothermia) and not specified on non-rectal in 10 (possible hypothermia). Most admissions were during the winter months in only 18 cases of the 47 patients with confirmed or possible hypothermia was a secondary cause not apparent. Isolated hypothermia is rare in Grampian. In most cases other disease is the underlying cause.

A case-control investigation of perinatal risk factors for childhood IDDM in Northern Ireland and Scotland.

OBJECTIVE: To identify perinatal risk factors for childhood insulin-dependent diabetes mellitus (IDDM) and determine if they differ between early-onset and late-onset disease. RESEARCH DESIGN AND METHODS: We selected 258 diabetic children in Northern Ireland and 271 diabetic children in Scotland from population-based registers. For each diabetic child, five matched control subjects were drawn from the same population. All perinatal data were recorded routinely at birth. Odds ratios (ORs) were estimated for parental age, social class, breast-feeding, deprivation measures, and other perinatal variables. RESULTS: Scottish data indicated an increased risk among children born to older mothers (OR = 2.43, 95% confidence interval [CI] 1.49-3.97 for mothers > or = 35 years of age relative to those < 25 years of age). Northern Ireland data showed no such effect. Only Northern Ireland data showed an excess risk in children of professional or managerial families (OR = 1.51, 95% CI 1.11-2.04). A small but nonsignificant reduction in risk among breast-fed children was observed only after adjustment for social class (OR = 0.76, 95% CI 0.54-1.07). Deprivation measures were associated with reductions in risk. Children delivered by cesarean section were at increased risk in both Northern Ireland (OR = 1.66, 95% CI 1.10-2.50) and Scottish (OR = 1.70, 95% CI 1.12-2.59) data. In Northern Ireland data only, children of first pregnancies were at increased risk (OR = 1.41, 95% CI 1.03-1.93). Both data sets indicated that a first pregnancy was a more important risk factor for early-onset disease than for late-onset disease. CONCLUSIONS: Many reported risk factors are weak and show inconsistencies between studies. They may be secondary to more direct, as-yet-undiscovered risk factors. Although irrelevant in the majority of cases, the increased risk associated with delivery by cesarean section deserves further study.

Trends in morbidity and mortality from peptic ulcer disease: Tayside versus Scotland.

Recent studies have shown that the prophylactic use of H2-receptor antagonists reduces both ulcer recurrence and the risk of ulcer complications. Despite these results, epidemiological studies have failed to show any evidence of an effect of gastric anti-secretory drugs on complicated ulcer disease in the community. Since 1979, it has been the policy of the gastroenterology department at Ninewells Hospital in Tayside to recommend long-term, continuous therapy with H2-receptor antagonists for patients with peptic ulcer; in contrast, prophylactic therapy is less commonly used in the rest of Scotland. The difference in the management of peptic ulcer between Tayside and Scotland presented an opportunity to study the population effects of the widespread use of continuous H2-receptor antagonists on the morbidity and mortality from ulcer disease. This study compared the trends in hospital admissions, gastric surgery, haemorrhage, perforation and mortality from ulcer disease using data supplied by the Information and Statistics Division of the Common Services Agency, Scottish Health Service, Edinburgh. During the 1980s, hospital admissions for peptic ulcer declined significantly in Tayside, whereas in Scotland there was no obvious downward trend. Gastric surgery for ulcer disease declined throughout Scotland although the fall was significantly steeper in Tayside than in the rest of Scotland. For the population in general, the rate of perforation decreased faster in Tayside than in the rest of Scotland, although the difference was not significant. The rate of admissions for ulcer haemorrhage declined substantially in Tayside whereas there was little change in Scotland as a whole. The decrease in mortality from ulcer disease in all groups except younger females was more marked in Tayside than in Scotland, although the differences were not significant. The magnitude of the differences between Tayside and Scotland, and in particular the consistency of these results across a broad range of indicators of ulcer disease, suggests that the policy of prescribing long-term, continuous therapy with H2-receptor antagonists has reduced both uncomplicated and complicated peptic ulcer in the community in Tayside.

An audit of the quality of cancer registration data.

The accuracy of cancer registration data in the East of Scotland (Tayside) Cancer Registry was audited by comparing 200 consecutive registrations (about 10% of the annual total) with the 'gold standard' of the Histopathology records. ICD codes were independently generated by a pathologist by examining final pathology reports and then compared to those codes given by the local cancer registrar. Discrepancies were graded by the pathologist and the epidemiologist according to severity. Major errors of coding were few. Minor and moderate differences in coding occurred because of the nature and structure of the coding system and the manner in which data are retrieved. The level of detail required by the Cancer Registry needs to be evaluated.

Audit of the quality of hospital discharge data.

An audit of the quality of computerised hospital discharge data, in General Medicine and Paediatrics in Dundee, showed that the national data set was often inaccurate. Structured discharge summaries checked by senior medical staff are recommended.

Microangiopathy as a prognostic indicator in diabetic patients suffering from acute myocardial infarction.

Diabetic patients have an increased mortality following myocardial infarction (MI) due to left ventricular failure rather than larger infarcts or dysrhythmias. As this may be due to diabetic microangiopathy affecting the myocardium, we have examined the case records of diabetic clinic patients admitted to the Coronary Care Unit (CCU) with proven MI and compared the hospital outcome of those with and without retinopathy or nephropathy, i.e. markers for generalised microangiopathy. Sixty four consecutive records were traced, for the period when diabetic treatment policy was standardised in CCU, 24 patients had retinopathy (7 proteinuria). When compared to non-retinopathy patients they had similar ages 67 +/- 12 yr [+/- SD] v 63 +/- 9yr) but were of longer duration of diabetes p less than 0.05). There were no differences between the groups in size or site of infarct, previous infarct or hypertension history, blood glucose on admission or diabetic treatment before or after admission. Death occurred in 29% of retinopathy patients compared to 3% of non-retinopathy patients (p less than 0.01). Cardiac failure complicated 75% of retinopathy patients and 25% of non-retinopathy patients (p less than 0.001). Dysrhythmia occurred in 50% and 33% of patients respectively (P = NS). Nine patients had clinical peripheral vascular disease and five of these died. This study, of a selected group of diabetic clinic attenders admitted to CCU with acute MI, demonstrates that microangiopathy and peripheral vascular disease are important prognostic factors in determining hospital outcome as these patients are at increased risk of cardiac failure and death.