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Introduction Clarke, Gold and Pedersen are validated methods to assess awareness of hypoglycaemia. Identifying impaired awareness of hypoglycaemia (IAH) is critical for supporting people with structured education and diabetes technologies, to reduce harm of hypoglycaemia. This study compares the Clarke score, Gold score and Pedersen methods and their correlations with features of hypoglycaemia unawareness and patient characteristics, to evaluate the accuracy of the methods in identifying IAH. Methods This retrospective, observational questionnaire-based study collected routine clinical data from 100 people with type 1 diabetes. The questionnaire included the three validated scoring methods, frequency of severe and nocturnal hypoglycaemia, knowledge and worry of hypoglycaemia and hypoglycaemia symptom scores using the Edinburgh Hypoglycaemia Scale. Data were analysed for IAH prevalence and the associations with features of IAH. The concordance of Clarke, Gold and Pedersen methods was evaluated using Spearman’s correlation coefficient. Results The prevalence of IAH in this cohort identified by Clarke, Gold and Pedersen methods was 18%, 19% and 61% respectively. The mean autonomic symptom score in people with IAH was significantly reduced using the Clarke method (P = 0.0002) but not on Gold (P = 0.12) and Pedersen methods (P = 0.79). For people with IAH assessed using the Clarke method, scores for night-time worry regarding hypoglycaemia (P = 0.04) and self-reported frequency of nocturnal hypoglycaemia (P = 0.001) were increased. Spearman’s correlation coefficients between Pedersen and Clarke and Pedersen and Gold were Rs = 0.555 (P

OBJECTIVE To investigate the effect on pregnancy outcome of integrating a comprehensive management plan for patients with type 1 diabetes (T1D) into the World Health Organization universal maternal care infrastructure. RESEARCH DESIGN AND METHODS A comprehensive preconception-to-pregnancy management plan for women with T1D was implemented in 11 centers from 8 Chinese cities from 2015 to 2017. Sequential eligible pregnant women (n = 133 out of 137 initially enrolled) with T1D and singleton pregnancies attending these management centers formed the prospective cohort. The main outcome was severe adverse pregnancy outcome comprising maternal mortality, neonatal death, congenital malformations, miscarriage in the second trimester, and stillbirth. We compared pregnancy outcomes in this prospective cohort with two control groups with the same inclusion and exclusion criteria: a retrospective cohort (n = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort (n = 116) of all eligible pregnant women with T1D receiving routine care from 2015 to 2017 in 11 different centers from 7 cities. RESULTS The rate of severe adverse pregnancy outcome was lower in the prospective cohort (6.02%) than in either the retrospective cohort (18.30%; adjusted odds ratio [aOR] 0.31 [95% CI 0.13–0.74]) or the contemporaneous comparison cohort (25.00%; aOR 0.22 [95% CI 0.09–0.52]). CONCLUSIONS The substantial improvements in the prospective cohort are evidence of a potentially clinically important effect of the comprehensive management plan on pregnancy outcomes among Chinese pregnant women with pregestational T1D. This supports the development of similar approaches in other countries.

Diabetes of the exocrine pancreas (DEP) is a form of diabetes that occurs due to pancreatic disease. It is far more common than has been previously considered, with a recent study showing 1.8% of adults with new-onset diabetes should have been classified as DEP. The majority is misdiagnosed as type 2 diabetes mellitus (T2DM). Patients with DEP exhibit varying degrees of exocrine and endocrine dysfunction. Damage to the islet of Langerhans effects the secretion of hormones from the β, α, and pancreatic polypeptide cells; the combination of low insulin, glucagon, and pancreatic polypeptide contributes to rapid fluctuations in glucose levels. This form of "brittle diabetes" may result in the poorer glycemic control observed in patients with DEP, when compared with those with T2DM. Diabetes of the exocrine pancreas has a different natural history to other forms of diabetes; patients are more likely to require early insulin initiation compared with those with T2DM. Therefore, individuals with DEP should be advised about the symptoms of decompensated hyperglycemia, although they are less likely to develop ketoacidosis. Clinicians should screen for DEP in patients with acute or chronic pancreatitis, following pancreatic resection, or with co-existing cystic fibrosis or hemochromatosis. Incident diabetes may herald the onset of pancreatic ductal carcinoma in a small subset of patients. Once identified, patients with DEP can benefit from specific lifestyle advice, pancreatic enzyme replacement therapy, metformin treatment, appropriate insulin dosing, and monitoring. Further research is needed to establish the ideal treatment regimens to provide optimal clinical outcomes for this unique form of diabetes.

Background We sought to assess the long-term evolution of left ventricular (LV) function using two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) for the detection of preclinical diabetic cardiomyopathy, in asymptomatic type 1 diabetic patients, over a 6-year follow-up. Design and methods Sixty-six asymptomatic type 1 diabetic patients with no cardiovascular risk factors were compared to 26 matched healthy controls. Conventional, 2D and 3D-STE were performed at baseline. A subgroup of 14 patients underwent a 6-year follow-up evaluation. Results At baseline, diabetic patients had similar LV ejection fraction (60 vs 61%; P = NS), but impaired longitudinal function, as assessed by 2D-global longitudinal strain (GLS) (-18.9 ± 2 vs -20.5 ± 2; P = 0.0002) and 3D-GLS (-17.5 ± 2 vs -19 ± 2; P = 0.003). At follow-up, diabetic patients had worsened longitudinal function compared to baseline (2D-GLS: -18.4 ± 1 vs -19.2 ± 1; P = 0.03). Global circumferential (GCS) and radial (GRS) strains were unchanged at baseline and during follow-up. Metabolic status did not correlate with GLS, whereas GCS and GRS showed a good correlation, suggestive of a compensatory increase of circumferential and radial functions in advanced stages of the disease - long-term diabetes (GCS: -26 ± 3 vs -23.3 ± 3; P = 0.008) and in the presence of microvascular complications (GRS: 38.8 ± 9 vs 34.3 ± 8; P = 0.04). Conclusions Subclinical myocardial dysfunction can be detected by 2D and 3D-STE in type 1 diabetic patients, independently of any other cardiovascular risk factors. Diabetic cardiomyopathy progression was suggested by a mild decrease in longitudinal function at the follow-up, but did not extend to a clinical expression of the disease, as no death or over heart failure was reported.

Insulin therapy (IT) is initiated for patients with type 2 diabetes mellitus when glycaemic targets are not met with diet and other hypoglycaemic agents. The initiation of IT improves glycaemic control and reduces the risk of microvascular complications. There is, however, an associated weight gain following IT, which may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to 9 kg insulin-associated weight gain (IAWG) is reported to occur in the first year of initiating IT, predominantly caused by adipose tissue. The potential causes for this weight gain include an increase in energy intake linked to a fear of hypoglycaemia, a reduction in glycosuria, catch-up weight, and central effects on weight and appetite regulation. Patients with type 2 diabetes who are receiving IT often have multiple co-morbidities, including obesity, that are exacerbated by weight gain, making the management of their diabetes and obesity challenging. There are several treatment strategies for patients with type 2 diabetes, who require IT, that attenuate weight gain, help improve glycaemic control, and help promote body weight homeostasis. This review addresses the effects of insulin initiation and intensification on IAWG, and explores its potential underlying mechanisms, the predictors for this weight gain, and the available treatment options for managing and limiting weight gain.

Diabetes in pregnancy is predominantly either pre-existing type 1 or type 2 diabetes mellitus, or gestational diabetes, the latter defined as diabetes or glucose intolerance first diagnosed during the pregnancy. Gestational diabetes usually arises in the late second trimester and is common, affecting from 2–6% to 15–20% of pregnant women depending on diagnostic criteria and country of origin. Gestational diabetes is most commonly diagnosed on the basis of an oral glucose tolerance test performed at 24–28 weeks’ gestation by a plasma glucose at 0 minutes of more than 5.1 (or >5.6, depending on the authority) mmol/L, or at 120 minutes of more than 8.5 (or >7.8) mmol/L. The effect of pregnancy on maternal glycaemic control ceases very quickly post-partum, hence women with pre-existing diabetes taking insulin should immediately revert to their pre-pregnancy regimen after birth, but with a lower insulin dose.

The effect of modifying dietary fatty acid (FA) composition on insulin sensitivity remains unclear. We aimed to investigate whether changes in plasma phospholipid (PL) FA composition, as a result of dietary intervention, correspond with changes in insulin sensitivity. The RISCK study was a 6-month randomised controlled dietary intervention study, which assessed the effect of modifying dietary fat and the glycaemic index (GI) of carbohydrates on insulin sensitivity. Total NEFA levels, fasting plasma PL FA profiles and an insulin sensitivity index (Si), derived from intravenous glucose tolerance minimal-model analysis, were available from 533 participants, all at elevated risk of type 2 diabetes. Bivariate correlations between changes in saturated PL FA (SFA), MUFA (as a percentage of total plasma NEFA) and changes in Si were assessed according to treatment group. Age, sex, ethnicity, percentage change in body mass and change in dietary GI were controlled for. Increasing total NEFA concentration was associated with worsening Si (r −0·152; P = 0·001). In the high-MUFA/low-GI diet group, change in PL-MUFA was positively and independently associated with change in Si (r 0·297; P = 0·002). Among MUFA, change in oleic acid (18 : 1) was most strongly correlated with change in Si (r 0·266; P = 0·005), as was change in minor FA 24 : 1 (r 0·244; P = 0·011) and 17 : 1 (r 0·196; P = 0·042). In the high-SFA/high-GI group, change in SFA concentration was not significantly associated with change in Si. In conclusion, increases in the proportion of plasma PL-MUFA following a high-MUFA dietary intervention were associated with improvements in insulin sensitivity.

ObjectivesThe management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT.Research design and methodsIn a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL).ResultsMean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference −4.3 kg, 95% CI −6.3 to 2.3, pConclusionsPatients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success.Trial registration numberISRCTN21335883.

Moving the NHS towards an integrated care service is a key priority according to a number of recently released strategies, plans and policy documents.1–4 Indeed, the 2014 NHS Five-Year Forward View (5 yr FV) is built on a consensus among patient and front-line staff that this is how care must be provided in the future.5 Central to this is the expectation that services for long-term medical conditions can and must be delivered outside the hospital setting.6 While this may at first appear to threaten hospital consultants, in reality it provides an opportunity for all medical specialties to help shape clinical service provision and provide accessible specialist care at a population level. A report from the Royal College of Physicians (RCP) on integrated care, due later in 2015, includes contributions from clinicians practicing in a variety of specialties, as well as from a cross-section of consultants and GPs involved in medical and specialty training, patients, trainees and senior policy makers, all addressing what steps need to be in place if integrated care is to deliver the intention envisaged in the NHS five-year plan. Ahead of this publication, we summarise insights gained from our preliminary work. In a 2009, a systematic review of 326 peer-reviewed papers identified 175 different definitions and concepts of integrated care.7 In a 2011 joint report to the Department of Health by the King's Fund and Nuffield …

Aims: To assess urinary C-peptide creatinine ratio (UCPCR) used in a modified Matsuda equation to measure insulin sensitivity (IS) in pregnancy. Research design and methods: In this cross-sectional study, two Insulin sensitivity (IS) measurements were calculated in 73 pregnant women at ~ 28 weeks of gestation by two separate methods using modified Matsuda equations. The first using the 0 and 120 min serum C-peptide concentration during a 75 g oral glucose tolerance test (OGTT) and the second using the 0 and 120 min UCPCR values. The calculated IS measurements from the two methodologies was evaluated using the Person’s test and linear regression analysis. The relationship between ISOGTT UCPCR and the fasting second void UCPCR and 120 min UCPCR was assed using Pearson correlation and linear regression analysis after logarithmic transformation of the variables. Statistical analysis was performed using SPSS V.22. Results: The IS measured using serum C-peptide (ISOGTTc-pep) in the modified Matsuda equation correlated with the IS measurement using serum UCPCR (ISOGTT-UCPCR) (r 0.704, p

Background NICE Guidelines for prevention of diabetes include identifying people at risk followed by cost-effective intervention if necessary. Based on assessment of risk via a questionnaire and/or blood test the intervention may comprise a brief discussion of risk factors and preventive advice or referral to intensive lifestyle intervention. Design and setting In this cross-sectional study 59 subjects recruited from local GP practices were invited by letter to attend a screening for a diabetes prevention study. Method Following a telephone screening during which subjects were asked whether they had been informed if they were at high-risk of type 2 diabetes, eligible subjects completed a Risk Perception Survey for Developing Diabetes (RPS-DD), a validated diabetes risk score and underwent an oral glucose tolerance test (OGTT) at a medical screening. Results As measured by the Diabetes UK Risk Score, 44.1% were at high risk, 42.4% moderate risk and 13.6% at increased risk. 42% of patients had been informed they were at high-risk by a health professional. Those who had been informed of their risk had significantly higher perceived risk scores ( p p p =0.004), but were not more aware that diet ( p =0.42) and weight management ( p =0.57) can play a role in preventing diabetes. Conclusions People at high-risk of diabetes are not being informed of their risk status as recommended by NICE guidelines. There is scope for education for health professionals and the public.

Our aim was to review the data from the National Pregnancy in Diabetes (NPID) audit, and to identify the challenges and opportunities for improving pregnancy outcomes in women with diabetes. We reviewed three years of NPID data and relevant diabetes and obstetric literature, and found that there has been little change in pregnancy preparation or outcomes over the past 3 years, with substantial clinic-to clinic variations in care. Women with Type 2 diabetes remain less likely to take 5 mg preconception folic acid (22.8% vs. 41.8%; P < 0.05), and more likely to take potentially harmful medications (statin and/or ACE inhibitor 13.0% vs. 1.8%; P < 0.05) than women with Type 1 diabetes. However, women with Type 1 diabetes are less likely to achieve the recommended glucose control target of HbA1c < 48 mmol/mol (6.5%) (14.9% vs. 38.1%; P < 0.05). The following opportunities for improvement were identified. First, the need to integrate reproductive health into the diabetes care plans of all women with diabetes aged 15–50 years. Second, to develop more innovative approaches to improve uptake of pre-pregnancy care in women with Type 2 diabetes in primary care settings. Third, to integrate insulin pump, continuous glucose monitoring and automated insulin delivery technologies into the pre-pregnancy and antenatal care of women with Type 1 diabetes. Fourth, to improve postnatal care with personalized approaches targeting women with previous pregnancy loss, congenital anomaly and perinatal mortality. A nationwide commitment to delivering integrated reproductive and diabetes healthcare interventions is needed to improve the health outcomes of women with diabetes.

Objectives To compare the cost-effectiveness (CE) of the National Institute for Health and Care Excellence (NICE) 2015 and the WHO 2013 diagnostic thresholds for gestational diabetes mellitus (GDM). Setting The analysis was from the perspective of the National Health Service in England and Wales. Participants 6221 patients from four of the Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study centres (two UK, two Australian), 6308 patients from the Atlantic Diabetes in Pregnancy study and 12 755 patients from UK clinical practice. Primary and secondary outcome measures planned The incremental cost per quality-adjusted life year (QALY), net monetary benefit (NMB) and the probability of being cost-effective at CE thresholds of £20 000 and £30 000 per QALY. Results In a population of pregnant women from the four HAPO study centres and using NICE-defined risk factors for GDM, diagnosing GDM using NICE 2015 criteria had an NMB of £239 902 (relative to no treatment) at a CE threshold of £30 000 per QALY compared with WHO 2013 criteria, which had an NMB of £186 675. NICE 2015 criteria had a 51.5% probability of being cost-effective compared with the WHO 2013 diagnostic criteria, which had a 27.6% probability of being cost-effective (no treatment had a 21.0% probability of being cost-effective). For women without NICE risk factors in this population, the NMBs for NICE 2015 and WHO 2013 criteria were both negative relative to no treatment and no treatment had a 78.1% probability of being cost-effective. Conclusion The NICE 2015 diagnostic criteria for GDM can be considered cost-effective relative to the WHO 2013 alternative at a CE threshold of £30 000 per QALY. Universal screening for GDM was not found to be cost-effective relative to screening based on NICE risk factors.

The provision of out of hospital high quality specialty care given in a truly integrated healthcare system is dependent on clinicians of the future being trained and willing to deliver this. There is currently a miss-match in what the politicians wish around integrated care and what the clinical workforce, both undergraduate and postgraduate, are being currently trained for and aspire to. Greater exposure to community work in medical training and greater emphasis on the importance of integrated care is required from the different medical specialties and royal colleges to raise the profile of consultant working in non-hospital settings. It will only be when training in all aspects of integrated care provision is firmly embedded in the undergraduate and postgraduate medical curriculum that integrated care will flourish.

Hypothesis In pregnancy, urinary C peptide creatinine ratio (UCPCR) reflects endogenous insulin secretion in women with normal glucose tolerance and type 1 diabetes. Research design and methods UCPCR and serum C peptide were measured in 90 glucose-tolerant women at 0 and 120 min during a 75 g oral glucose tolerance test (OGTT) at 28 weeks of gestation. UCPCR was measured in 2 samples obtained over 10 weeks apart in 7 pregnant women with longstanding type 1 diabetes. Results UCPCROGTT and serum C peptideOGTT of glucose-tolerant women were significantly correlated at 0 and 120 min (rs0.675, 0.541 respectively, p

Diabet. Med. 28, 797–804 (2011) Abstract Objectives To develop and evaluate a standardized data set for measuring pregnancy outcomes in women with Type 1 and Type 2 diabetes and to compare recent outcomes with those of the 2002–2003 Confidential Enquiry into Maternal and Child Health. Methods Existing regional, national and international data sets were compared for content, consistency and validity to develop a standardized data set for diabetes in pregnancy of 46 key clinical items. The data set was tested retrospectively using data from 2007–2008 pregnancies included in three regional audits (Northern, North West and East Anglia). Obstetric and neonatal outcomes of pregnancies resulting in a stillbirth or live birth were compared with those from the same regions during 2002–2003. Results Details of 1381 pregnancies, 812 (58.9%) in women with Type 1 diabetes and 556 (40.3%) in women with Type 2 diabetes, were available to test the proposed standardized data set. Of the 46 data items proposed, only 16 (34.8%), predominantly the delivery and neonatal items, achieved ≥ 85% completeness. Ethnic group data were available for 746 (54.0%) pregnancies and BMI for 627 (46.5%) pregnancies. Glycaemic control data were most complete—available for 1217 pregnancies (88.1%), during the first trimester. Only 239 women (19.9%) had adequate pregnancy preparation, defined as pre-conception folic acid and first trimester HbA1c≤ 7% (≤ 53 mmol/mol). Serious adverse outcome rates (major malformation and perinatal mortality) were 55/1000 and had not improved since 2002–2003. Conclusions A standardized data set for diabetes in pregnancy may improve consistency of data collection and allow for more meaningful evaluation of pregnancy outcomes in women with pregestational diabetes.

Red cell acetylcholinesterase (AChE) activity and Ii antigenicity have been compared in patients with acute leukaemia and myeloproliferative syndromes. In acute leukaemia in relapse increased i agglutinability was found, often associated with low AChE levels, whereas in myeloproliferative syndromes increased i agglutinability was associated with increased AChE activity and increased red cell creatine. These findings are consistent with a young red cell population as similar changes were found in patients with severe haemolytic anaemia. It is proposed that two different mechanisms might be operating to produce increased i agglutinability.

Compared tothe general antenatal population major congenital malfor-mations were increased two-fold and perinatal mortalityrates four-fold. Pregnancy outcomes were similarly pooramong the 2,407 women with type 1 and the 1,401women with type 2 diabetes. A major finding from thisaudit was that women with pre-gestational diabetes wereinadequately prepared for pregnancy, with poor evidencefor, or documentation of, pre-pregnancy counselling, pre-conception use of folic acid or safe glycaemic targets beingachieved prior to pregnancy. This lack of pre-pregnancy carewas especially true for women with type 2 diabetes who asa group had higher levels of social deprivation and greaterethnic diversity than those with type 1 diabetes.

()3.7 mmol ⁄ l; p < 0.0001), and within-patient fasting glucose variability ()0.5 mmol ⁄ l; p < 0.0001). In the majority of patients (82%), these improvements in glycaemic control were achieved with once daily administration of insulin detemir. There was a small reduction in mean body weight ()0.7 kg; p < 0.0001), which was most apparent in patients with a higher body mass index (BMI) at baseline. A significant negative relationship between weight change and baseline BMI was observed (greater the BMI, greater the weight reduction). Multiple regression analysis showed that BMI and HbA1c at baseline, and change in HbA1c, were all predictors for weight change (p < 0.0001 for all), with BMI being the strongest predictor. Conclusions: Patients with type 2 diabetes nao¨ve to insulin can be effectively treated with once-daily insulin detemir (± OADs) to achieve improved glycaemic control with no adverse effect on weight and a low risk of hypoglycaemia. These short-term results are consistent with the findings of clinical trials. What’s known It has been well documented that insulin therapy can result in significant weight gain. Furthermore, this insulin-associated weight gain can act as a barrier to effective treatment of diabetes. This is due to a number of factors such as increased insulin resistance, cardiovascular risks, poor compliance and reluctance to start insulin treatment (in patients with type 2 diabetes).

PREDICTIVE (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation) is a large, multi-national, open-label, prospective, observational study assessing the safety and efficacy of insulin detemir in clinical practice. A total of 20,531 patients with type 1 or 2 diabetes from 11 countries were prescribed insulin detemir and followed up after a mean of 14.4 weeks. The primary endpoint was incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary endpoints were: haemoglobin A(1c) (HbA(1c)), mean self-monitored fasting glucose, within-patient fasting glucose variability and body weight change. Two hundred and fourteen patients (1%) reported SADRs, including major hypoglycaemia. The incidence of major hypoglycaemic episodes was reduced from 3.0/patient-year at baseline to 0.7/patient-year at follow-up in type 1 patients (p < 0.0001), and from 0.8 to 0.1/patient-year in type 2 patients (p < 0.0001). Insulin detemir improved glycaemic control in type 1 and type 2 patients, with reductions in mean HbA(1c) (0.5% and 0.9%, respectively, p < 0.0001 for both), fasting glucose (1.7 and 2.6 mmol/l, p < 0.0001 for both) and within-patient fasting glucose variability (0.7 and 0.5 mmol/l, p < 0.0001 for both). There was a small decrease in mean body weight in both type 1 and 2 patients (-0.1 kg, p < 0.01 and -0.4 kg, p < 0.0001 respectively). Insulin detemir was used once- or twice-daily in 49% and 50% of type 1 patients, and 77% and 23% of type 2 diabetes patients, respectively. The 14-week observations from PREDICTIVE support clinical trial data showing that insulin detemir improves glycaemic control, with a lowered risk of hypoglycaemia and no weight gain.

Background Fat infiltration of the liver, muscle and pancreas is associated with insulin resistance and risk of diabetes. Weight loss reduces ectopic fat deposition and risk of diabetes, but is difficult to sustain to due to compensatory increases in appetite. Fermentable carbohydrates have been shown to decrease appetite and food intake, and promote weight loss in overweight subjects. In animal studies, fermentable carbohydrate reduces ectopic fat independent of weight loss. We aimed to investigate the effect of the fermentable carbohydrate inulin on weight maintenance, appetite and ectopic fat in subjects with prediabetes. Methods Forty-four subjects with prediabetes were randomized to 18 weeks’ inulin or cellulose supplementation. During weeks 1–9 (weight loss phase) all subjects had four visits with a dietitian to guide them towards a 5 % weight loss. During weeks 10–18 (weight maintenance phase) subjects continued taking their assigned supplementation and were asked to maintain the weight they had lost but were offered no further support. All subjects attended study sessions at baseline, 9 and 18 weeks for measurement of weight; assessment of adipose tissue and ectopic fat content by magnetic resonance imaging and magnetic resonance spectroscopy; glucose, insulin and GLP-1 levels following a meal tolerance test; and appetite by ad libitum meal test and visual analogue scales. Results Both groups lost approximately 5 % of their body weight by week nine (−5.3 ± 0.1 % vs −4.3 ± 0.4 %, p = 0.13, but the inulin group lost significantly more weight between 9 and 18 weeks (−2.3 ± 0.5 % vs −0.6 ± 0.4 %, p = 0.012). Subjects taking inulin had lower hepatic (p = 0.02) and soleus muscle (p

Background: Fermentable carbohydrates (FCHO) have been shown to improve insulin sensitivity in normoglycaemic and insulin-resistant subjects. However, there are no data on subjects with prediabetes. We aimed to investigate the effect of the FCHO inulin, on glucose homeostasis in subjects with prediabetes. Methods: In a double-blind and placebo-controlled crossover study, 40 volunteers with prediabetes were randomly allocated to take 30 g/day of inulin or cellulose for 2 weeks in a crossover trial, following a 4-week dose-escalation run-in. Fasting insulin and glucose were measured for all subjects. Fifteen of the 40 subjects also underwent a meal tolerance test to assess insulin sensitivity, free fatty acids and glucagon-like peptide-1 concentrations. A subanalysis was carried out to examine any differences between the prediabetes subtypes. Results: Inulin was associated with a significant increase in (0-30 min)incremental AUC (iAUC) for insulin (treatment: p < 0.04) and (0-60 min)iAUC for insulin (treatment: p < 0.04) compared to control. There was a significant reduction in insulin resistance measured by the homeostatic model assessment in the isolated-impaired fasting glucose (p < 0.05) but not in the isolated-impaired glucose tolerance groups (p = 0.59). Conclusion: The FCHO, inulin, may have unique metabolic effects that are of particular benefit to people at risk of diabetes, which warrant further investigation.

Aim: This study aimed to evaluate the impact of local approval times on the schedule of a large multicentre study in the UK. Method" We reviewed the approval times of 178 applications that were made to the UK National Health Services Trusts (across 159 hospitals and 19 primary care trusts). Results: The mean time for approval was 82 days; more than half the submissions (94; 53%) took longer than 60 days for a decision. The reason for taking over 60 days varied but review of the trial documentation revealed that delays occurred in the Hospital R&D Office for 25 (14%) submissions, at the hospital or primary care trust level for 14 (8%) submissions, while the investigator was responsible for 23 (13%) applications taking longer than 60 days. Conclusion: Local submissions are a source of delayed start up in many centres participating in clinical trials; however, reasons for delay are not consistent across the applications and cannot be attributed to one specific part of the local approval process.

Elevated postprandial glycaemia has been linked to CVD in a number of different epidemiological studies involving predominantly non-diabetic volunteers. The MiniMed continuous glucose monitor, which measures blood glucose every 5 min, over a 24 h period, was used to investigate changes in blood glucose readings before and after instigating a diet with low glycaemic index (GI) for 1 week in free-living healthy individuals. Nine healthy people (age 27 (sem 1·3) years, BMI 23·7 (sem 0·7) kg/m2, one male, eight females) completed the study. A reduction in GI (59·7 (sem 2) v. 52·1 (sem 2), Pv. 4·4 (sem 0·3) mmol/l, Pv. 5·1 (sem 0·2) mmol/l, P=0·004), area under the 24 h glucose curve (8102 (sem 243) v. 750 (sem 235) mmol/l per min, P=0·004) and area under the overnight, 8 h glucose curve (2677 (sem 92) v. 2223 (sem 121) mmol/l per min, P=0·01). The present study provides important data on how a simple adjustment to the diet can improve glucose profiles that, if sustained in the long term, would be predicted from epidemiological studies to have a favourable influence on CVD.

Postprandial concentrations of glucose, insulin and triacylglycerols (TG) correlate to risk for CHD. Carbohydrates affect many metabolites that could have a potential effect on cardiovascular risk factors. The objective of the present study was to examine, using a randomised prospective study, the acute (day 1) and ad libitum medium-term (day 24) effects of four diets: a high-fat diet (HIGH-FAT; 50 % fat, >34 % monounsaturated fatty acids); a low-glycaemic index (GI) diet (LOW-GI; high-carbohydrate, low-GI); a high-sucrose diet (SUCROSE; high carbohydrate increase of 90 g sucrose/d); a high-GI diet (HIGH-GI; high-carbohydrate, high-GI). Daytime profiles (8 h) (breakfast, lunch and tea) of lipid and carbohydrate metabolism were completed during day 1 and day 24. Seventeen middle-aged men with one or more cardiac risk factors completed the study. There was no change from day 1 or between diets in fasting glucose, lipids or homeostatic assessment model (HOMA) on day 24. The HIGH-FAT compared with the three high-carbohydrate diets was associated with lower postprandial insulin and glucose but higher postprandial TG and non-esterified fatty acids (NEFA). There was a significant increase in the 6 h (15.00 hours) TG concentration (day 1, 2·6 (SEM 0·3) MMOL/L v. DAY 24, 3·3 (sem 0·3) mmol/l; PPP

Maturity-onset diabetes of the young (MODY) encompasses a collection of distinct forms of diabetes, which are inherited in an autosomal-dominant mode from the maternal or paternal side of the family or occasionally occur as a de novo mutation. All the genes involved affect either β-cell sensing or insulin secretion (1). The clinical presentations of MODY are heterogeneous, reflecting the different gene mutations involved, and the glucose dysregulation observed ranges from a relatively innocent rise in the fasting glucose to frank diabetes with neurological involvement (2,3). An exact MODY prevalence within the general diabetes population has proven difficult to assess because of underrecognition and lack of routinely available and affordable diagnostic tools. A further confounder is that the reported regional prevalence of specific MODY mutations varies considerably (4). Conservative estimates suggest that between 0.14–1.8% of all cases of diabetes could be attributable to MODY (4). It is to be expected that among women screened for gestational diabetes mellitus (GDM) the prevalence of MODY will be higher, reflecting both the proportionately lower prevalence of type 2 diabetes in women of this age group and the probability that those with undiagnosed MODY will screen positive (5). From the few population studies reported, mutations in the hepatocyte nuclear factor 1 α ( HNF1a ) gene (MODY 3) and glucokinase ( GCK ) gene (MODY 2) account for the majority of cases (6). MODY 2 is characterized by its high penetrance, early onset, and lifelong fasting hyperglycemia. It is due to mutations in the pancreatic GCK gene, which acts as the β-cell glucose sensor, setting the glucose threshold at which amplification of insulin …

Summary Aims To review the evidence for the importance of glycaemic index of dietary carbohydrate in disease prevention and control Methods A critical appraisal of the literature published in English between and cited on Medline between January 1966 and October 1999. Results Using basic, intervention and epidemiological studies from experienced teams, evidence that the glycaemic index of diet may influence outcome in terms of cardiovascular risk, risk of metabolic syndrome diseases and pregnancy was found Conclusions Consideration of glycaemic indices in making dietary recommendations may be expected to produce additional health benefit.

Diet influences the prevalence of coronary heart disease (CHD). Insulin sensitivity and concentrations of HDL cholesterol, two metabolic predictors of CHD, are also influenced by diet. Dietary carbohydrates with a high glycaemic index cause a high postprandial glucose and insulin response, and are associated with decreased insulin sensitivity and an increased risk of CHD. This study examined whether the glycaemic index of dietary carbohydrates is a determinant of serum HDL-cholesterol concentrations.Dietary, anthropometric, and biochemical data from the 1986-87 Survey of British Adults (n=2200) were reanalysed by a multiple regression model, which examined the relation between serum total cholesterol, HDL-cholesterol, and calculated LDL-cholesterol concentrations and various dietary characteristics, including the type of carbohydrate, the glycaemic index, and fat intake.Among the 1420 participants with complete data, there was a significant negative relation between serum HDL-cholesterol concentration and the glycaemic index of the diet for both men (regression coefficient -0.00724 [95% CI -0.0101 to -0.00434], p=0.02) and women (-0.01326 [-0.0162 to -0.0102], p0.0001). No other significant relation was found with total cholesterol or LDL-cholesterol concentration or with any other dietary carbohydrate or fat constituent.In a cross-sectional study of middle-aged adults, the glycaemic index of the diet was the only dietary variable significantly related to serum HDL-cholesterol concentration. Thus, the glycaemic index of the diet is a stronger predictor than dietary fat intake of serum HDL-cholesterol concentration.

The association between insulin resistance and coronary heart disease (CHD) is strong in the British Indian-Asian population. Adipocyte metabolism may contribute to both insulin resistance and CHD. We examined insulin-stimulated glucose uptake in adipocytes and in vivo insulin sensitivity using the fasting insulin resistance index (FIRI) in 60 subjects (45 Caucasian and 15 Asian) with CHD and 30 Caucasian subjects without CHD. In 25 CHD subjects (18 Caucasian and 7 Asian), the relationship between adipocyte insulin sensitivity and non-esterified fatty acid (NEFA) suppression to oral glucose was examined. Compared with controls, the CHD subjects had higher values of fasting insulin [51 (46 to 54) pmol l(-1) vs 36 (31 to 41) pmol l(-1) p< 0.01] and FIRI [1.65 (1.5 to 1.79) vs 1.06 (0.89 to 1.23), p < 0.01]. Among the CHD subjects, the Asians had higher values than Caucasian [insulin 58 (48 to 67) pmol l(-1) vs 48 (44 to 53) pmol l(-1) p < 0.01, FIRI 1.89 (1.44 to 2.13) vs 1.62 (1.4 to 1.79), p< 0.01)]. Insulin-stimulated glucose uptake in adipocytes was lower in the CHD than control subjects [56 (50 to 62) vs 115 (75 to 132) attomol min(-1).mm2, p < 0.05], being most reduced among the Asians. It was positively correlated with postprandial NEFA suppression and negatively with insulin release. In conclusion, abnormalities of adipocyte function and insulin sensitivity occur in CHD and may contribute to its aetiology.

Abnormalities in cutaneous blood flow (CBF) in otherwise healthy subjects with Type 1 diabetes mellitus (DM) have been demonstrated in response to local insults to the skin. To investigate whether defects also occurred in response to a regular daily activity, CBF was measured with laser Doppler flowmetry (LDF), before and 20 min after starting a mixed meal in 13 male Type 1 DM subjects with no clinical evidence of neuropathy, nephropathy or macroangiopathy and compared to 7 non-diabetic controls. Diabetic subjects and controls were of similar age and body mass index (mean ± SD, 33.7 ± 7.4 vs 37.1 ± 9.2 years and 25.2 ± 2.9 vs 24.5 ± 2.9 kg m−2, respectively). In subjects with DM, HbA1c was 8.3 ± 0.6 % (normal range 4–5.5 %) and duration of diabetes was 18 (8–38) years, median (range). Following a mixed meal the CBF fell in the controls by 36 % (24 to 56), median (range), compared to 3 % (−5 to 18) in Type 1 DM subjects, P < 0.0005. These results show there is a normal physiological fall in CBF following food ingestion which is attenuated in Type 1 DM. These abnormalities of vasoconstriction in the peripheral microcirculation are present after 8 years of diabetes and precede the development of clinically apparent neuropathy or vascular disease. © 1998 John Wiley & Sons, Ltd.

AIMS—Abnormalities in colour perception occur early in the development of diabetic retinopathy. Whether these changes can be influenced by increasing circulating oxygen saturation was studied in comparison with non-diabetic controls. METHODS—Protan and tritan colour thresholds were measured using a computer graphics system in 37 insulin dependent diabetic subjects, with no or minimal background retinopathy, and 27 matched controls. Colour thresholds were performed after subjects inhaled either gaseous air or 100% oxygen for a minimum of 5 minutes. RESULTS—Diabetic subjects had higher colour vision thresholds when inhaling air when compared with controls (protan (mean 3.93 (SEM 0.39), v 2.36 (0.16), p

Aims To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function. Methods An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. Results After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: β = −0.357; waist circumference: β = −0.380; body fat mass: β = −0.375) and disposition index (BMI: β = −0.215; waist circumference: β = −0.248; body fat mass: β = −0.221) and positively associated with acute insulin response to glucose [BMI: β = 0.200; waist circumference: β = 0.195; body fat mass β = 0.209 (P values

The large-for-gestational-age (LGA) infant, defined as > 90th birthweight percentile, is associated with mild disturbances of maternal glucose tolerance. In the UK the same birthweight percentile charts are used for all ethnic groups when assessing LGA infants. The influence of maternal hyperglycaemia on LGA infants of Asian (Indian Subcontinent) mothers in the UK is likely to be under-reported, as Asian birthweights tend to be lower than White/Europid birthweights. We assessed the number of LGA infants born consecutively to 21 Asian and 26 White/Europid mothers with gestational diabetes mellitus (GDM), delivered between 37 and 42 weeks gestation, and also in 34 Asian and 121 White/Europid mothers with a positive screening test for GDM but a normal 75 g oral glucose tolerance test (OGTT). Large-for-gestational-age infants were identified using both the standard UK percentile charts of the Medical Research Council and percentile charts constructed from 30,418 Asian and 162,477 White/Europid singleton births, delivered between 37 and 42 weeks gestation to non-diabetic mothers delivered in the North West Thames Region of England. The standard Medical Research Council percentile charts, compared with the ethnically derived charts, identified fewer LGA Asian (7/56 vs 15/56) but more White/Europid infants (33/147 vs 21/147). When correcting for ethnicity more Asian than White/Europid GDM mothers delivered LGA infants (9/21 vs 3/26, chi 2 = 4.76, p < 0.05). The maternal 2 h OGTT plasma glucose was a significant independent contributor to birthweight in the Asian (r2 = 0.319, p < 0.0005) but not the White/Europid infants, in whom gestational age and maternal height were significant independent contributors to birthweight (r2 = 0.158, p < 0.0001). We conclude that ethnic influences are important when defining LGA infants and that mild disturbances of maternal glycaemia have a greater influence on the birthweight of Asian than White/Europid infants.

Diabetes in pregnancy is increasing and therefore it is important to raise awareness of the associated health risks to the mother, the growing fetus, and the future child. Perinatal mortality and morbidity is increased in diabetic pregnancies through increased stillbirths and congenital malformation rates. These are mainly the result of early fetal exposure to maternal hyperglycaemia. In the mother, pregnancy may lead to worsening or development of diabetic complications such as retinopathy, nephropathy, and hypoglycaemia. This review defines pregestational and gestational diabetes and the associated health risks to the growing fetus and mother. Management is discussed, focusing on clinical evidence based guidelines published by the American Diabetic Association and the UK National Institute for Health and Clinical Excellence on the management of pregnant women with pre-existing diabetes.

Objective To compare the use of glyburide and insulin in the treatment of gestational diabetes. Design Randomized controlled trial. Setting Maternal health clinics in San Antonio, Texas. Patients Women with mild gestational diabetes (n = 404) at 11-33 weeks gestation. Only women with a singleton pregnancy were eligible. Intervention Glyburide (starting dose 2.5 mg, increased as necessary to achieve target glycaemic control to a maximum of 20 mg) or insulin (0.7 U per kg body weight, three times daily, increased as necessary). If blood glucose goals were not met after 2 weeks of treatment with the maximal dose of glyburide, treatment was switched to insulin. Main outcome measures Primary outcome was achievement of a desirable level of glycaemic control (strict target ranges were set for mean, fasting, preprandial and postprandial blood glucose, measured by frequent home monitoring). Neonatal outcomes were also assessed. Main results Eighty-two percent of women in the glyburide group and 88% of women in the insulin group achieved the target blood glucose values (difference = -6%, 95% confidence interval (CI) -13% to +1%, P = 0.07). Considerably less women in the glyburide group had blood glucose values below 40 mg (2.2 mmol/l) per decilitre (2% vs. 20%, difference -18%, 95% CI -24% to -13%, P < 0.0001). In the glyburide group, 4% of women were switched to insulin as the maximal dose failed to produce target blood glucose values. There were no significant differences in neonatal outcomes, including cord serum insulin. Conclusion Treatment of women with gestational diabetes, after the first trimester of pregnancy, with glyburide rather than insulin can achieve similar glycaemic control, with less hypoglycaemia.

Diabetes occurs in approximately 2–5% of all pregnancies. As the UK antenatal population becomes older, more obese and more ethnically diverse the number of pregnant women with pre-existing type 2 diabetes and gestational diabetes will increase. Whether diabetes precedes the pregnancy or arises within it, the risk of accelerated fetal growth, stillbirth and neonatal hypoglycaemia are all increased. As a generalization, adverse pregnancy outcomes increase with increasing maternal glycaemia. Hyperglycaemic-mediated oxidative stress has been implicated as a cause for the increased congenital malformation rates and early fetal loss associated with diabetic pregnancies. While fetal hyperinsulinaemia, secondary to maternal hyperglycaemia, is the cause of accelerated fetal growth and neonatal hypoglycaemia. Achieving optimal maternal glycaemic control prior to and throughout pregnancy is a pivotal goal in the management of all diabetic pregnancies. This degree of control requires all diabetic women contemplating a pregnancy to have access to preconception counselling and being managed with intensive insulin regimens throughout pregnancy. The medical and obstetric surveillance of pregnant diabetic women should be undertaken in a specialized multidisciplinary clinic, where diabetic complications, such as retinopathy and nephropathy, can be regularly assessed, as can fetal growth and development. As birth trauma and stillbirth are all more frequent in diabetic pregnancies elective delivery between 38–39 weeks is usually advised. At birth there is an increased risk of transient metabolic disturbances and in later life an increased risk of adolescent obesity, the metabolic syndrome and type 2 diabetes in young adulthood.